DEPARTMENT OF MEDICINE 2016 Annual Report DIVISIONS AND INSTITUTES

The Divisions »» Allergy John Ohman, MD »» Cardiology James Udelson, MD »» Clinical Decision Making» John Wong, MD »» Clinical Nutrition Edward Saltzman, MD »» Endocrinology Ron Lechan, MD »» Gastroenterology Joel Weinstock, MD »» Geographic Medicine and Infectious Disease David Snydman, MD »» Hematology/Oncology Andrew Evens, DO »» Internal Medicine and Adult Primary Care Deborah Blazey-Martin, MD »» Nephrology Andrew Levey, MD »» Pulmonary, Critical Care and Sleep Medicine Nicholas Hill, MD »» Rheumatology Timothy McAlindon, MD

The Institutes »» Institute for Clinical Research and Health Policy Studies Harry Selker, MD »» Molecular Cardiology Research Institute Richard Karas, MD, PhD »» Molecular Oncology Research Institute Philip Tsichlis, MD

Photography by Martha Stewart Photography. Design and production by Mark Vincent Communications, Inc. — www.markvincent.net. TABLE OF CONTENTS

The Department of Medicine Chairman’s Message 4 Departmental Leadership 6 Departmental Organization Chart 7 Clinical Activity 11 Research Activity 13 Internal Medicine Training Program 15

The Divisions Allergy 18 Cardiology 20 Clinical Care Research 36 Clinical Decision Making 38 Clinical Nutrition 42 Endocrinology, Diabetes and Metabolism 46 Gastroenterology 54 Geographic Medicine and Infectious Diseases 60 Hematology/Oncology 72 Internal Medicine and Adult Primary Care 88 Geriatrics 96 William B. Schwartz Division of Nephrology 98 Pulmonary, Critical Care and Sleep Medicine 106 Rheumatology 114

The Institutes Institute for Clinical Research and Health Policy Studies 124 Molecular Cardiology Research Institute (MCRI) 138 Molecular Oncology Research Institute (MORI) 148

Publications 152

3 CHAIRMAN’S MESSAGE

It is with pleasure that I offer the Annual Report for the Department of Medicine for 2016, a year that ended with a major strategic accomplishment for Tufts Medical Center.

In December, 2016, the board of Hallmark Health System, with 368 beds in Lawrence Memorial Hospital and Melrose- Wakefield Hospital, voted to joined Wellforce, the parent company of Tufts Medical Center and Lowell General Hospital. The goal is to offer an academic medicine presence in the two community hospitals and to increase the availability to their patients of specialty services at Tufts Medical Center.

In the Department of Medicine leadership at Tufts Medical center, Dr. David Snydman replaced Dr. Richard Karas as Vice-Chair for Research and Mark Haas replaced Allison Ankeny as Department Administrator.

Reflecting the nationwide trend in reducing hospital admissions, inpatient clinical activity in 2016 was similar to that in 2015 whereas outpatient activity increased by 8%. The increase was evident in most divisions. Research grant awards were largely unchanged from 2015.

The Division of Internal Medicine and Adult Primary Care added 2 primary care physicians, 1 urgent care physician, and 1 social worker to the Academic Medical Deeb N. Salem, MD, FACP, FACC, FACCP— Center practice. To facilitate patient access, the division extended outpatient clinic The Sheldon M. Wolff Professor and Chairman, Department of Medicine working hours and added a weekend clinic. There was a 14% increase in the primary care patient panel and visit volume and a 53% increase in new patient volume. The division received a grant from NEQCA to improve population control of hypertension and a certified diabetes education collaboration with Lowell General Hospital was initiated. In the section of Geriatrics, a new geriatric- orthopedic service was added.

The Cardiology Division, in conjunction with the CardioVascular Center and the Division of Cardiac Surgery, ranked among the top 10 centers in the US by volume of transplants and quality of outcomes. The Division was also among the top 3 US centers in the treatment of hypertrophic cardiomyopathy, with a growing volume of surgical myectomies. The transcutaneous aortic valve replacement (TAVR) program and the regional referral network for complex procedures all continued to grow.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Dr. Wong, chief of the Division of Clinical Decision Making was named co-chair of the Workgroup on Preventive Care for the AMA’s Physician Consortium for Performance Improvement.

The Division of Endocrinology received 9 new grant awards for clinical and basic science research. The national clinical trial of the NIH-supported vitamin D and type-2 diabetes (D2d) study completed enrollment of over 2400 participants.

In a sad loss for the institution, Dr. Susan Hadley, a well-loved member of the Division of Geographic Medicine and Infectious Diseases, died in 2016. Debra Poutsiaka was chosen by division fellows as the first Susan Hadley Clinician Educator awardee. Drs. Brian Chow, Tine Vindenes and Lindsay Margoles, joined the division as faculty.

Dr. Cindy Varga joined the Division of Hematology/Oncology, bringing additional expertise in the management of plasma cell neoplasms including multiple myeloma and amyloidosis.

In the Division of nephrology, Dr. Andrew Levey, was inducted into the Association of American Physicians. A new Qualification Marker developed by Dr. Perrone for use in studies of the treatment of polycystic kidney disease was adopted by the FDA. Dr. Weiner was appointed Chair of the Quality, Patient Safety and Clinical Practice Committee of the American Society for Nephrology and Dr. Scott Gilbert was appointment Chair of the Society’s Workforce and Training Committee. Dr. Klemens Meyer received the Nancy Johnson Heart Award from Dialysis Clinics, Inc.

Dr. Hill, Chief of the Division of Pulmonary, Critical Care and Sleep medicine, was appointed chair of the Steering Committee of the NIH-sponsored Pulmonary Vascular Diseasomics project and received the Distinguished Faculty Award from the medical school. Dr. Preston was appointed chair of the Educational Committee of the Pulmonary Hypertension Association. Dr. Garpestad was appointed Associate Chief Medical Officer at Tufts Medical Center. The division added several junior faculty PhDs conducting basic research.

In the Division of Rheumatology, Dr. William Harvey became Director of Informatics Integration in the Tufts CTSI program. He also joined the Board of Directors of the American College of Rheumatology. Dr. Chenchen Wang received an Excellence in Integrative Medicine Award from the European Society of Integrative Medicine. The division added one faculty member.

The three institutes at the medical center are separate from but closely allied with the divisions in the Department of Medicine. All three institutes maintained their prominent roles in the publication of research papers, teaching, and participation in expert panels.

Many other awards and honors were received by members of the Department of Medicine in 2016. In the pages that follow, we invite you to read more about our efforts in furthering the missions of clinical care, teaching and research.

Sincerely yours,

Deeb Salem

5 DEPARTMENTAL LEADERSHIP

Deeb N. Salem, MD, of the New England Journal of Medicine in 2003 and FACC, FACCP became Vice Chair of that Committee in the spring of 2009. In 2010, Dr. Salem was elected Chairman of the Dr. Deeb Salem has had a distinguished Mass Medical Society’s Committee on Sponsored career as an academic cardiologist. In Programs and Chairman of the Tufts University School of 1987, he was appointed Professor of Medicine's Graduate Medical Education Committee. He Medicine at Tufts University School of currently is on the Executive Advisory Board of the New Medicine. He served as Chief of Cardiology at the Tufts England Journal of Medicine, Chairman of the New England Medical Center from 1987 to 1995 and was NEQCAFinance Committee and is a member of the Tufts appointed the Sheldon M Wolff Professor and Chairman Medical Center's Quality of Care Committee, Finance of the Department of Medicine at Tufts University School Committee and Strategic Planning Committee. In 2014, of Medicine and Physician-in- Chief of Tufts Medical Dr. Salem was elected to the Board of Trustees of the Center in 1999. He is a Fellow of the American College of Massachusetts Hospital Association and in 2015 became Cardiology, the American College of Physicians, and the a member of the Wellforce Finance Committee. American College of Chest Physicians.

Dr. Salem was the founding President of the New England Michael Barza, MD Affiliate of the American Heart Association. His Dr. Michael Barza is Vice Chair for academic accomplishments include over one hundred Clinical Affairs at Tufts Medical Center and eighty scientific publications. He is recognized as a and Professor of Medicine at Tufts national expert in coronary artery disease, valvular heart University School of Medicine. In disease and congestive heart failure. Dr. Salem received a 2012, he was named the Sara Murray Distinguished Alumni Award from Boston University Jordan Professor of Medicine at Tufts University School School of Medicine in 1998, a Distinguished Faculty of Medicine. Award from Tufts University School of Medicine in 1998, Dr. Barza joined the faculty of Tufts-New England an American Heart Association Great Communicator Medical Center in 1972. He served as Associate Chief of Award in 1999 and an American Heart Association. the Division of Geographic Medicine and Infectious Distinguished Leadership Award in 2000. He received the Disease as well as hospital epidemiologist. He is a Fellow Massachusetts Physician Health Service Distinguished of the American College of Physicians and of the Service Award in 2003. In 2007, Dr. Salem was the Infectious Diseases Society of America. recipient of the American Heart Association’s Paul Dudley White Lifetime Achievement award. In August of Dr. Barza has been an author or coauthor of over 220 2007, Dr. Salem received the Champions in Healthcare, peer-reviewed papers in infectious diseases. Supported Lifetime Achievement Award from the Boston Business by NIH grants, he undertook a number of fundamental Journal. He has repeatedly been listed in Boston studies of the pharmacology of antibiotics in the eye. He Magazine as one of “Boston’s Best” physicians. In 2010 also became known as a superior clinician and teacher Dr. Salem was awarded the Working Wonders Lifetime with a special interest in complex infections. He is Achievement Award by Tufts Medical Center. In May of named in all recent editions of the national compendium 2016, Dr. Salem received the Massachusetts Medical of “Best Doctors”. In 1998, Dr. Barza left T-NEMC to go to Society’s Award for Excellence in Medical Service. the Carney Hospital where he served as Chief of Medicine through 2014. In 2008, while retaining his He is on the Executive Board of the Board of Trustees of positions at Carney Hospital, he returned to Tufts Tufts Medical Center and is an emeritus member of the Medical Center to assume his current positions. Board of Directors of the Northeast Affiliate of the American Heart Association. Dr. Salem is also on the Having a longstanding interest in the publication of Board of Director of the Wang Chinatown YMCA, the scientific information, Dr. Barza has served as Editor of Asian American Civic Association, the New England Antimicrobial Agents and Chemotherapy, Associate Quality Care Alliance (NEQCA), the Tufts Medical Center Editor for the Yearbook of Infectious Diseases and Senior Physicians Organization and the Tufts Health Care Editor of Infectious Diseases in Clinical Practice, and Institute. He was elected to the Publications Committee was a member of the Institute of Medicine scientific

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Department Org Chart

Vice Chair, Faculty Affairs and Quality Improvement Karen M. Freund, MD, MPH

panel on Human Health Risks with Penicillin or health, cancer prevention, and health disparities, with over Tetracyclines in Animal Feed. He served as Deputy 20 years of continuous federal funding. She is currently Editor of Clinical Infectious Diseases, a premier funded to analyze the impact of Massachusetts health infectious disease journal, from 2000-2016. reform on stability of insurance coverage and quality of care for cancer, diabetes, and other chronic conditions. Dr. Barza has made major teaching contributions to She is also investigating efforts to improve care transitions the School of Medicine. He has taught for over 25 years in and reduce preventable admissions. She has conducted the Infectious Disease Pathophysiology course and has research on leadership in an NCI-funded multi-site trial of consistently received outstanding evaluations by students. patient navigation to reduce cancer health disparities by He is the recipient of the Distinguished Faculty Award for providing timelier and higher quality cancer diagnostic 2007, the Zucker Clinical Teaching Prize for Outstanding evaluation and cancer treatment. Accomplishment in 2008 and Outstanding Tufts University School of Medicine Lecturer for 2009-2010. Dr. Freund has extensive expertise in the development of interdisciplinary team science, and in oversight of Karen M. Freund, MD, MPH institutional training programs. She has mentored over 40 trainees, including 10 underrepresented minority Dr. Karen M. Freund is Vice Chair of faculty members, in their pursuit of independent Faculty Affairs and Quality Improvement funding. She has directed a number of highly effective in the Department of Medicine at Tufts research training programs, including ten years Medical Center and Professor of of expertise with interdisciplinary institutional Medicine at Tufts University School of K programs. She currently directs the Tufts CTSI Medicine. She holds secondary appointments in Tufts KL2 institutional career development program. Clinical and Translational Science Institute, Public Health Her prior NIH funding has included understanding and Community Medicine, and the Sackler School of the predictors of academic career advancement Graduate Biomedical Sciences. She also has an American for minority and women faculty, utilizing a 17-year Cancer Society Clinical Research Professorship. longitudinal follow-up of the National Faculty Survey. Dr. Freund has broad translational science expertise in clinical trials, comparative effectiveness and health policy research. Her clinical areas of expertise include women’s

7 Dr. Freund is a member of the AHRQ Health Care Research Richard Kopelman, MD Training study section and NIH Health Disparities and Richard Kopelman, MD, is the Vice- Equity Promotion study section. She is on the editorial Chairman for Education in the boards of Women’s Health Issues, Women’s Health and Department of Medicine. He is the Gender Based Medicine, Journal of Cancer Survivorship, Louisa C. Endicott Professor of Medicine and Cancer Epidemiology, Biomarkers and Prevention. at Tufts University School of Medicine. Dr. Freund holds an AB from Harvard College, MD from Dr. Kopelman began his academic career at Tufts as one Stanford University School of Medicine, and MPH from of the first faculty members in the newly created Division Boston University. of General Medicine in the early 1980s. He has been acting chief of that division on several occasions. He has Jerome P. Kassirer, MD been Director of the Medical House Staff Training Dr. Kassirer has been a member of the Program since 1981, overseeing the growth of the house faculty of Tufts University School of staff from 30 members to its current total of 75 interns and Medicine for more than five decades, residents. He has been an active member of the and served as Vice Chairman of the Association of Program Directors in Internal Medicine Department of Medicine for 20 years. and is a past Council member and participant in His research has encompassed diverse fields including numerous committees and task forces. For the past acid-base balance, medical decision- making, and several years he has been the leader of the Assembly of cognitive science. Dr. Kassirer has served as a governor University Program Directors in that organization. and regent of the American College of Physicians, chair His academic pursuits have been in the areas of of the American Board of Internal Medicine, and from hypertension and clinical problem solving. With Dr. 1991 to 1999, as Editor-in-Chief of the New England Kassirer he was the co-editor of the Clinical Problem Solving Journal of Medicine. He currently serves on the Human series in Hospital Practice for many years and subsequently Factors Subcommittee of the National Commission on co-authored two editions of Learning Clinical Reasoning Forensic Science. with Drs. Kassirer and Wong. In addition to his administrative He is the recipient of numerous awards, several honorary responsibilities Dr. Kopelman maintains an active practice degrees including one from the Universite Rene in general internal medicine and for the past several years Descartes in Paris, and is a Master of the American has been regularly listed in the Best Doctors in America and College of Physicians. He is a member of the Institute of by Boston Magazine in its lists of top physicians. He recently Medicine of the National Academy of Sciences, the received the Dema Daley Founders Award from the Association of American Physicians, and the American Association of Program Directors of Internal Medicine. Academy of Arts and Sciences. Dr. Kopelman received his undergraduate degree magna He is currently a Special Assistant to the Dean and cum laude in economics from Harvard College in 1970 and Distinguished Professor at Tufts University School of his medical school degree from Duke University School of Medicine. He is also a Consultant, Department of Medicine in 1974. He did his house staff training at Tufts- Medicine at Stanford University and the Center for New England Medical Center followed by a fellowship in Outcomes Research and Evaluation at Yale University. hypertension at Massachusetts General Hospital. Dr. Kassirer has written extensively about health care, David R. Snydman, MD for-profit medicine, and financial conflict of interest. He is the author of the Oxford University Press book, David R. Snydman, MD was named as “On the Take: How Medicine’s Complicity with Big the Vice-Chairman for Research for the Business Can Endanger Your Health.” and a co-author Department of Medicine in October 2016. of the Lippincott book “Learning Clinical Reasoning.” He earned an MD degree from the His new book, “Unanticipated outcomes: A Medical University of Pennsylvania School of Memoir" is in press, and will be available early in 2017. Medicine. After internship and residency at New England Medical Center, he spent two years in the Epidemic Intelligence Service of the Centers for Disease Control, following which he returned to New England Medical Center to complete a fellowship in infectious diseases.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Dr. Snydman joined the faculty of Tufts Medical Center in Cleveland Clinic. Mark has always maintained a close 1979 as a Teaching and Research Scholar of the American relationship with the Tufts community, serving the past College of Physicians, one of only a handful of physicians 17 years as an Instructor for the School of Medicine in the selected nationally. He was appointed Chief of the Division Public Health and Professional Degree programs. Mark in 1998. He has been an outstanding investigator, clinician, teaches the required Budgeting and Management class to mentor and administrator. He has also been the Hospital all MPH, MD/MPH, and DVM/MPH candidates. He also Epidemiologist for more than two decades. Dr. Snydman started a popular elective offered in the medical school on developed an interest in the immunocompromised host health information technology and healthcare and is an internationally recognized expert in informatics. Mark received his BS and his MBA from transplantation infectious diseases in general and Boston University cytomegalovirus infections in particular. He developed Cytomegalovirus Immune Globulin for licensure in Danielle Riggs, BS collaboration with the Massachusetts Biologic Public Danielle Riggs joined the Department Health Laboratory, the first non-HIV treatment IND of Medicine administrative leadership biologic product approved by the FDA. For his seminal team in the fall of 2008 as the Director work he was awarded a citation from the Commonwealth of Research Administration & Finance. of Massachusetts in 1994. She oversees the pre- and post-award In 1998, Dr. Snydman was the recipient of the Natalie V. administration for all federal, foundation and industry and Milton O. Zucker Prize from TUSM for outstanding grant funds and clinical trials throughout the Divisions faculty research. He has been on the advisory council of the of Medicine. In addition, she serves as Tufts Medical NIH-sponsored Collaborative Antiviral Study Group and Center’s Executive Director of Research Administration, has been a consultant to the FDA. In 2004 he received a working closely with the Vice President of Research Distinguished Faculty Award from TUSM. In recognition Administration, on operations policies/procedures, and of his mentorship program for both faculty and fellows, implementation. She was previously the Director of Dr. Snydman was recognized by the Infectious Diseases Administration and Finance for the Molecular Oncology Society of America as the recipient of the 2015 Walter E. Research Institute and was Associate Director of Finance Stamm mentor award. He has been continuously supported for the Tufts Cancer Center, where she helped grow the in research by the NIH for over 20 years and by cancer research program. Danielle holds a bachelor’s foundations, not-for-profit entities, and industry. degree from Stonehill College.

His current research interests are primarily in C. difficile associated infections, the microbiome in C. difficile associated disease, and cytomegalovirus infections. He is the author of 221 peer reviewed original papers and has been an editor of 21 books.

Mark Haas, BS, MBA Mark Haas joined the Department of Medicine as the new Executive Director in 2016. Mark returns to Tufts Medical Center after having worked as the Business Operations Manager for General Medical Associates (now Primary Care of Boston) more than a dozen years ago. In the interim he has held leadership positions at Massachusetts General Hospital and South Shore Hospital. Mark also brings more than a dozen years of practice management experience after spending time at Brigham & Women’s Hospital, the Upham’s Corner Community Health Center, and the

9 TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 CLINICAL ACTIVITY The Department’s clinical revenue is derived from several activities. The Department is organized as part of the sources: inpatient daily care and consults, outpatient care, Tufts Medical Center Physician Organization as Pratt procedures, and certain off-site revenue for clinical Medical Group. The table below summarizes the inpatient activity for the Department of Medicine for versus FY16.Discharges for the department were essentially flat in FY16 versus FY15. Inpatient Activity at Tufts Medical Center

Attending Service Fiscal Year 2015 Actual Fiscal Year 2016 Actual % Change Cardiology 1,659 1,571 -5.3% Gastroenterology 662 578 -12.7% Internal Medicine and 912 935 2.5% Adult Primary Care Geographic Medicine and 590 586 -0.7% Infectious Disease Hematology/Oncology 891 944 5.9% Nephrology 973 1,031 6.0% Pulmonary, Critical Care and 773 775 0.3% Sleep Medicine Geriatrics 607 593 -2.3% Grand Totals 7,067 7,013 -0.8%

The table below shows the outpatient visit volumes for the different division in the Department of Medicine. Overall the ambulatory visit volume continued a trend of growth. The volume increased by an impressive 8% in FY16 after having increased 4.3% in FY15. Outpatient Activity at Tufts Medical Center

Division Fiscal Year 2015 Actual Fiscal Year 2016 Actual % Change Cardiology 12,127 13,282 9.5% Endocrine 7,641 8,027 5.1% Gastroenterology 7,880 6,795 -13.8% Primary Care – Boston (GMA) 67,288 76,022 13.0% Primary Care – Quincy 13,226 12,901 -2.5% Primary Care – Framingham 4,777 4,787 0.2% Geographic Medicine and 5,017 5,250 4.6% Infectious Disease GI/Nutrition-Obesity Clinic 108 126 -16.7% Hematology/Oncology 6,971 7,762 11.3% Nephrology 5,429 5,645 4.0% Pulmonary, Critical Care 4,826 5,389 11.7% and Sleep Medicine Rheumatology 5,738 6,460 12.6% Grand Totals 141,028 152,446 8.1%

Net patient services professional revenue grew by 1% in FY16 versus FY15.

11 Clinical Professional Revenue

Division Fiscal Year 2015 Actual Fiscal Year 2016 Actual % Change Cardiology 6,996,729 6,892,573 -1.5% Endocrine 1,209,748 1,309,634 8.3% Gastroenterology 4,008,922 3,482,775 -13.1% General Internal Medicine 10,031,298 10,915,278 8.8% (includes all Primary Care sites) Geographic Medicine and 2,722,131 2,660,058 -2.3% Infectious Disease GI/Nutrition-Obesity Clinic 59,079 46,283 -21,7% Hematology/Oncology 2,722,131 2,914,893 7.1% Nephrology 3,388,055 3,483,901 2.8% Pulmonary, Critical Care and 2,960,645 2,658,218 -10.2% Sleep Medicine Rheumatology 835,122 924,868 10.7% Grand Totals 34,933,860 35,288,481 1.0%

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 RESEARCH ACTIVITY The Department of Medicine has a wide variety of Clinical Research and Health Policy Studies (located at clinical and basic research programs. Most basic 35 Kneeland Street). Each of these research-focused research is conducted in the Tupper Research Institute, institutes has close ties with the Department of Medicine. whereas clinical and outcomes research programs are The table below summarizes the grant and contract based primarily at 35 Kneeland Street and in Tufts activity across the Divisions and Institutes in FY 2016, Medical Center. Many members of the Department of with increase/decreases from the prior year noted in Medicine conduct their research within the Molecular parentheses. Further specific details are shown in the Cardiology Research Institute (located in Tupper individual Division/Institute reports. Building), the Molecular Oncology Research Institute (located at 75 Kneeland Street), and the Institute for

2016 Research Awards 1

Division R Series K Series U Awards Training Contracts Foundation Clinical 2 (incl. (incl. Grants & Sub- & Internal Trials supplements) supplements) (iT & F series) contracts Grants

Cardiology 1 (0) 0 (0) 0 (0) 0 (0) 10 (+1) 3 (+1) 41 (+8) Clinical Decision Making 0 (-1) 0 (0) 0 (0) 0 (0) 6 (+2) 0 (-1) N/A Endocrinology 3 (0) 0 (0) 1 (0) 0 (0) 0 (0) 2 (0) 1 (+1) Gastroenterology 1 (-1) 1 (0) 0 (0) 0 (0) 5 (+3) 3 (0) 14 (+4) Geographic Medicine and 8 (+3) 2 (0) 1 (0) 1 (-2) 13 (+2) 3 (0) 14 (+3) Infectious Disease Internal Medicine & Adult 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (-1) 0 (0) Primary Care Hematology/Oncology & 1 (0) 0 (0) 0 (0) 0 (0) 3 (-1) 0 (-3) 40 (+2) Cancer Center Nephrology 4 (-2) 1 (+1) 2 (+1) 2 (0) 15 (+4) 6 (+2) 11 (-2) Pulmonary 1 (-1) 10 (+1) 0 (0) 0 (0) 12 (+8) 0 (0) 26 (-4) Rheumatology 6 (+2) 2 (0) 1 (0) 0 (0) 4 (+13) 2 (+1) 12 (-4) Institute for Clinical Research and Health 2 (-1) 0(0) 3 (1) 0 (0) 37(-5) 22 (3) N/A Policy Studies Molecular Cardiology 10 (-3) 1 (0) 0 (0) 1 (0) 15 (3) 11 (0) N/A Research Institute Molecular Oncology 10 (-1) 1 (0) 4 (-1) 0 (0) 10 (+6) 7 (+1) N/A Research Institute

1 Support from the National Institutes of Health constitutes the major source of funding for the Department of Medicine. The table above is a summary of the number of individual active Grants & Contracts and Clinical Trials awards for the Department of Medicine as of the close of 2016. 2 Clinical Trial numbers reflect trials with activity during the fiscal year (not # of executed agreements).

13 RESEARCH ACTIVITY (continued)

FY 16 Total Grants and Contracts Revenue ($36M)

$12,000,000

$10,000,000

) $8,000,000

$6,000,000 (in thousands

$4,000,000

$2,000,000

$0 y y CC GI MORI MCRI CDM ology diology ICRHPS GeoMed Car Pulmonar Nephr HemOnc/ Rheumatology Rheumatolog

FY 2016 Revenue Sources (Medicine Divisions & Institutes)

19%

Federal 10% Foundation/Other 71% Corporate 72%

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 THE INTERNAL MEDICINE TRAINING PROGRAM

The internal medicine training program at Tufts Medical in a diverse population of patients with unusual as well as Center attracts superior applicants from medical schools common illnesses. House officers are supervised and taught across the United States. Each year, 24 interns are recruited by attending physicians with exceptional expertise in the from a pool of over 2,000 applicants with diverse backgrounds, subspecialties of interest. Many graduates become primary talents and aspirations. The program is unusual for the care physicians. Others, who seeksubspecialty training, match configuration of the ward services along subspecialty lines. with excellent fellowship programs. Over the upcoming The hospital has a strong primary care referral base as year, the program will add a combined medical education well as many well-known subspecialists, which results track in conjunction with the pediatric residency program.

15 TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 THE DIVISIONS

The Department of Medicine is organized in 13 divisions. Although most fall into traditional categories, the Division of Clinical Care Research and the Division of Clinical Decision Making are unusual in their scope. The Division of Geographic Medicine and Infectious Diseases signals its international interests by its name. Many of the divisions have impressive histories as can be seen in their introductory overviews.

17 DIVISION OF ALLERGY

The outpatient clinics provide evaluation and treatment of allergic diseases through referrals from physicians » » DIVISION OF ALLERGY OF DIVISION within the hospital and from an increasing base of community physicians. The outpatient clinics provide evaluation and treatment of allergic diseases through referrals from physicians within the hospital and from an increasing base of community physicians. A wide range of diseases are seen and evaluated. Assessment of the allergic component of asthma, chronic rhinitis, food allergy, drug allergy and eczema accounts for approximately 50% of outpatient activity. Division members also John Ohman, MD treat diverse conditions such as anaphylaxis from insect stings, exercise induced anaphylaxis, angioedema and eosinophilic syndromes including eosinophilic esophagitis and vasculitis.

Over the last year referrals for evaluation and treatment of chronic urticaria and related conditions such as mastocytosis and mast cell activation syndrome have increased. Newer treatments such as omalizumab are being prescribed for more severe forms of chronic urticaria.

Specialized treatments are available through the Allergy Division including allergen immunotherapy for inhalant and insect sting allergy. Outpatient oral desensitization procedures have been developed for drug allergies. These procedures include aspirin desensitization for asthmatic patients with nasal polyps.

Adult immunodeficiency is evaluated and immunoglobulin replacement is prescribed and monitored.

Inpatient consultations for drug allergy and other allergic disorders are provided. Antibiotic allergy in patients with serious infections is a frequent reason for urgent consultation. Inpatient desensitization is prescribed and monitored by the division, and accounts for a significant percent of inpatient consults.

The Sinusitis Center, a joint program of the Allergy Division and Otolaryngology Division, offers expedited evaluation of patients with chronic sinusitis. Complex treatment programs are coordinated including allergen immunotherapy for treatment of allergic component, immunoglobulin replacement for immunodeficiency, aspirin desensitization and surgery.

Highlights of 2016

»» Referrals to the allergy clinics increased by 20% in 2016 over 2015.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF ALLERGY OF DIVISION

Faculty

Name Academic Rank Special Responsibility John L. Ohman, MD, FACP Clinical Professor, Medicine Chief of Division Weihong Zheng, MD Assistant Professor, Medicine

Community Outreach Programs extended evaluations of complicated patients. House staff members expressing interest in Allergy and Clinical Division staff has given presentations to schools, Immunology have been supported in applications for community health centers, such as the YMCA, and on fellowship training in Allergy and recent house staff local TV and radio stations about the prevention and members have been accepted to fellowships in well- treatment of allergic diseases. The staff reaches out to recognized programs including Scripps Clinic, Brigham the Mandarin and Cantonese speaking population of and Women’s Hospital and Baylor College of Medicine Boston through health fairs, seminars and educational and University of Virginia College of Medicine. articles in Chinese language newspapers like Sampan, to increase local awareness of the services offered by The staff has provided General Medical Associates with the Allergy Division. Educational Seminars in topics pertinent to Allergy. The staff regularly conducts consultations with Hospital Teaching Programs Staff and physicians within the New England Quality Care Alliance. Residents from Internal Medicine rotate through the Allergy Division. Those with a particular interest in Allergy and Clinical Immunology are given opportunities to participate in extra clinical sessions and are also encouraged to do literature reviews and

19 DIVISION OF CARDIOLOGY

The Division of Cardiology at Tufts Medical Center is a world-wide leader in patient care, research and » » DIVISION OF CARDIOLOGY OF DIVISION education in cardiology. Under the guidance of its first chief, Dr. Herbert Levine, the Division of Cardiology developed into a Center of Excellence in each of the major subdivisions of cardiology, including clinical cardiology, cardiac catheterization and intervention, noninvasive cardiac imaging, and electrophysiology. Later, under the direction of Deeb Salem MD, and subsequently Marvin Konstam MD, Tufts Medical Center began a program in advanced heart failure and cardiac transplantation, which has become a top James Udelson, MD national program in volume and outcomes. Today, under the leadership of James Udelson MD, the Division of Cardiology continues to progress. The advanced heart failure and cardiac transplantation program is the largest in New England, the Hypertrophic Cardiomyopathy (HCM) Center remains among the most active in the world, and the cardiac catheterization, electrophysiology and cardiovascular imaging laboratories show steady growth in the number of patients served and in the use of advanced techniques.

The Division of Cardiology maintains outreach programs across New England. Attending physicians provide cardiovascular expertise to numerous regional sites. Cardiology fellows spend time at neighboring institutions to complement their training. In addition, visiting students, residents, fellows and attending staff from other institutions spend time at Tufts Medical Center to learn the latest techniques in cardiovascular care.

Cardiologists at Tufts Medical Center participate in a wide variety of clinical, translational and basic science research projects sponsored by the NIH, industry, and other sources. There is extensive collaboration and shared faculty with the Molecular Cardiology Research Institute. Clinical trials are underway to study improved techniques for structural and percutaneous interventions, durable and percutaneous ventricular assist devices, new configurations of automated external defibrillators, nuclear imaging for assessment of infarct viability and remodeling, approaches to the assessment of vascular function, and novel therapies for atherosclerosis among many others.

Teaching at all levels remains a strong part of the Division’s academic mission. All faculty are involved in bedside and didactic teaching as well as serving as education and research mentors. The Division of Cardiology faculty is consistently rated amongst the highest for teaching Tufts University students and house officers. Highlights of 2016

»» One of only 2 centers in the US to finish 2016 »» Superior graduate medical educational training top 10 for cardiac transplant volume (56 cases) in all disciplines of cardiovascular medicine and outcomes »» Outpatient community outreach within the model »» One of the 3 busiest Hypertrophic of the distributed academic medical center Cardiomyopathy Centers in the US, including a »» Numerous Tufts Medical Center cardiologists growing volume of surgical myectomies listed as Boston Magazine’s 2016 Top Doctors »» Growing referral network for complex catheter- Outpatient community outreach within the model based coronary, structural, heart failure and of the distributed academic medical center electrophysiology procedures »» Numerous Tufts Medical Center cardiologists »» Continuing growth of multi-disciplinary transcutaneous listed as Boston Magazine’s 2015 Top Doctors aortic valve replacement (TAVR) program

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Interest Marvin Konstam, MD Professor Chief Physician Executive, Cardiovascular Center; Heart Failure Chief, Division of Cardiology James Udelson, MD Professor Director, Nuclear Cardiology Hanna Ahmed, MD Assistant Professor General Cardiology; Cardiovascular Imaging Assistant Clinical James Alderman, MD Interventional Cardiology, Heart Center of MetroWest

Professor » » DIVISION OF CARDIOLOGY OF DIVISION Assistant Clinical Elizabeth Ascher, MD General Cardiology, Heart Center of MetroWest Professor Molecular Cardiology Research Institute Associate Program Director, Cardiovascular Education and Robert Blanton, MD Assistant Professor Fellowship Training Director, General Cardiology Clinic

Patrick Blomberg, MD Assistant Professor Electrophysiology, Heart Center of MetroWest

Assistant Clinical William Castelli, MD General Cardiology, Heart Center of MetroWest Professor

Laurence Conway, MD Assistant Professor Interventional Cardiology

Assistant Clinical Eric Davidson, MD Cardiovascular Imaging, Heart Center of MetroWest Professor Medical Director, Cardiac Transplantation Program David DeNofrio, MD Associate Professor Medical Director, Cardiomyopathy Center Program Director, Advanced Heart Failure Fellowship Brian Downey, MD Assistant Professor General Cardiology, Cardiovascular Imaging Mohamad El-Zaru, MD Assistant Professor Interventional Cardiology; General Cardiology, Norwood

N. A. Mark Estes, MD Professor Director, Cardiac Electrophysiology

Jonas Galper, MD, PhD Professor Molecular Cardiology Research Institute Assistant Clinical Christopher Gange, MD Interventional Cardiology, Heart Center of MetroWest Professor Assistant Clinical Harvey Goldfine, MD Cardiovascular Imaging, Heart Center of MetroWest Professor Jessica Haffajee, MD Assistant Professor General Cardiology, Norwood Hospital Director, Electrophysiology Fellowship Program; Director, Munther Homoud, MD Associate Professor Cardiac Monitoring Center Molecular Cardiology Research Institute; Director, CardioVascular Gordon Huggins, MD Associate Professor Fellowship Program Iris Jaffe, MD, PhD Associate Professor Executive Director, Molecular Cardiology Research Institute Executive Director, CardioVascular Center for Research and Navin Kapur, MD Assistant Professor Innovation Elisa Kent Mendelsohn Professor of Molecular Medicine, Tufts Richard Karas, MD, PhD Professor University School of Medicine Michael Kiernan, MD Assistant Professor Medical Director, Ventricular Assist Device Program Director, Cardiac Catheterization Laboratory; Director, Carey Kimmelstiel, MD Associate Professor Interventional Cardiology Fellowship Program

21 Faculty (continued)

Name Academic Rank Title and Special Interest Assistant Clinical General Cardiology, Cardiovascular Imaging, Heart Center of George Kinzfogl III, MD Professor MetroWest Alan Kono, MD Assistant Professor Heart Failure Associate Chief of Cardiology Associate Chief Medical Officer for GME Jeffrey Kuvin, MD* Professor

» Director, Cardiovascular Education and Fellowship Training » DIVISION OF CARDIOLOGY OF DIVISION Co-Director, Center for Adults with Congenital Heart Disease Douglas Laidlaw, MD Assistant Professor Cardiac Electrophysiology Mark Link, MD* Professor Director, Heart Station Assistant Clinical General Cardiology, Cardiovascular Imaging, Heart Center of Donald Love, MD Professor MetroWest Christopher Madias, MD Assistant Professor Co-Director, Cardiac Arrhythmia Center Director, Hypertrophic Cardiomyopathy Center; Co-Director, Martin Maron, MD Assistant Professor Cardiovascular CT and MRI Barry Maron, MD Professor Director of Clinical Research, Hypertrophic Cardiomyopathy Center Nicole Orr, MD Instructor General Cardiology, Norwood Director, Valve Clinic; Director, Cardiovascular Ultrasound Natesa Pandian, MD Professor Research; Co-Director, Comprehensive Cardiovascular Imaging Director, Cardiovascular Imaging Center; Director, Ayan Patel, MD Professor Echocardiography Laboratory; Director, Women’s Heart Center Pranitha Reddy, MD Assistant Professor Echocardiography Associate Director, Hypertrophic Cardiomyopathy Center; Ethan Rowin, MD Assistant Professor Director, Cardiac MRI Yuheng Ruan, MD Assistant Professor General Cardiology, Cardiovascular Imaging Marwa Sabe, MD Assistant Professor Heart Failure Deeb Salem, MD Professor Chairman of Medicine Gordon Saperia, MD Assistant Professor General Cardiology Sushil Singh, MD Assistant Professor Cardiac Electrophysiology Jeffrey Shih, MD Assistant Professor Heart Failure Assistant Clinical Howard Sussman, MD General Cardiology, Heart Center of MetroWest Professor Jenica Upshaw, MD Assistant Professor Director, Cardio-Oncology Program; Heart Failure David Venesy, MD Assistant Professor Heart Failure Amanda Vest, MBBS MPH Assistant Professor Heart Failure Jonathan Weinstock, MD Assistant Professor Director, Cardiac Rhythm Management Devices Medical Director, Cardiac Care Unit Medical Director, Valve and Structural Heart Health Center Andrew Weintraub, MD Assistant Professor Associate Director, Cardiac Catheterization Laboratory Associate Director, Vascular Medicine Center Sophie Wells, MD Assistant Professor General Cardiology; Cardiovascular Imaging Benjamin Wessler, MD Assistant Professor Director, Valve Clinic; General Cardiology; Cardiovascular Imaging Assistant Clinical David Young, MD General Cardiology, Heart Center of MetroWest Professor

*Left the institution in 2016

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Major Clinical Programs The Division of Cardiology at Tufts Medical Center of stroke within several large multicenter trials in which remains committed to the academic missions of the Tufts catheterization laboratory are leaders in excellence in patient care, research and teaching. The enrollment. Collaboration between the Tufts Molecular following are the major clinical programs in Cardiology: Oncology Research Institute and Drs. Kimmelstiel, Weintraub and Kapur has led to multiple mechanistic »» The Interventional Cardiology Program studies focusing on pharmacologic approaches to platelet »» The New England Cardiac Arrhythmia Center inhibition during coronary intervention. This »» The Heart Failure and Cardiac Transplant Center

collaboration currently is studying the effects of a cell- » » »» The Comprehensive Cardiovascular Imaging Center penetrating pepducin—a trial where the drug being CARDIOLOGY OF DIVISION »» The Hypertrophic Cardiomyopathy (HCM) Center studies was invented by the Tufts basic scientists. »» The Preventive Cardiology Center The Tufts Cardiac Catheterization Laboratory is a »» The Women’s Heart Center national leader in the implantation of ventricular support »» The Heart Station devices, several of which have been initially developed in Dr. Kapur’s Surgical Research Laboratory. These clinical programs are among the premier The Hypertrophic Cardiomyopathy Center provides a large cardiovascular programs in the country. This report number of physiologic studies for HCM and alcohol septal summarizes the Division’s clinical activities and recent ablation. Dr. Navin Kapur directs the acute circulatory program developments, as well as the academic growth. support program at Tufts, which focuses on the clinical The Interventional Cardiology Program application of percutaneous mechanical support devices (pMSD) for cardiogenic shock and advanced heart failure. As Carey Kimmelstiel, MD – Director a dual board- certified interventional cardiologist and The nationally-renowned Interventional Cardiology advanced heart failure/transplant specialist, Dr. Kapur has Program provides advanced technologies and therapies developed a combined training pathway option for fellows to for patients with cardiovascular disease. The become Interventional Heart Failure (IHF) specialists. Since Interventional Cardiology staff regularly perform state- 2009, this IHF pathway has grown in reputation and Tufts of-the-art procedures such as septal ablation for Medical Center has established an international presence hypertrophic cardiomyopathy (HCM), valvuloplasty, through the SCAI, AHA, TCT, CRF, ACC, and ESC as a leader catheter based valve replacement, percutaneous in the field of interventional therapies for heart failure. mechanical support for high risk coronary intervention Tufts Medical Center was one of only 15 sites in the US and advanced heart failure. The program also offers involved in the Recover Right Trial investigating a pMSD transcatheter treatment of a variety of congenital defects designed for right ventricular failure. Tufts is also the only such as patent foramen ovale, and atrial septal defects, as site in Boston participating in the PARACHUTE IV Trial well as endovascular treatment of peripheral arterial evaluating a novel interventional device for apical left disease and aortic coarctation. ventricular aneurysms and participates in the COAPT The Interventional Cardiology Program participates in trial evaluating the Mitra-clip devices for functional major multi-center clinical trials as well as in mitral regurgitation in heart failure. Through investigator- initiated research. The laboratory has collaborations with the division of Cardiac Surgery, Heart continued to recruit patients into trials of newer- Failure, and several industry partners, the catheterization generation drug-eluting stents, most recently entering the laboratory is developing novel approaches to diagnosis realm of bioabsorbable stents as well as pharmacologic and management of percutaneously and surgically studies examining the impact of adjunctive therapies on implanted cardiac assist devices. The Kapur Lab also has platelet function. established important funded research projects with several industry leaders in the field of pMSDs (Cardiac The lab routinely collaborates with other specialties to Assist, Heartware, Thoratec, and Abiomed). investigate the impact of cardiovascular therapies in patients with extracardiac syndromes. An example of The Interventional Cardiology Training Program at Tufts collaboration is the cath lab’s involvement with the Medical Center has received consecutive Fellow Department of Neurology, which has led to data in-Training Grant Awards from the SCAI and Abbott documenting the effects of PFO closure on the incidence Industries for excellence in fellow education since 2009.

23 The laboratory participates in benchmarking outcomes with the American College of Cardiology and the National Catheterization Data Registry.

Dr. Andrew Weintraub, Associate Director of the Cardiac Catheterization Laboratory, supervises the diagnostic and therapeutic services offered to patients with lower and upper extremity vascular disease, carotid artery disease, and hypertension secondary to renal artery stenosis. »

» The interventional cardiology service also participates in DIVISION OF CARDIOLOGY OF DIVISION the multi-disciplinary Valvular and Structural Heart Health Center. This service evaluates patients with valvular and structural heart disease who are considered high risk for conventional surgical procedures. It integrates multi- modality testing and state of the art therapies for these exceptional risk patients.

Dr, Weintraub is director of the Tufts TAVR program , a high-volume program which has received accolades for excellent outcomes in the field of percutaneous aortic valve replacement. The Tufts TAVR Program has recently been selected to participate in a randomized study assessing the effects of TAVR on patients with heart failure symptoms.

The New England Cardiac Arrhythmia Center

N. A. Mark Estes, MD – Director The New England Cardiac Arrhythmia Center offers outpatient consultative services for patients with The staff electrophysiologists oversee a fellowship arrhythmias and conducts research on arrhythmias. program consisting of three fellows in clinical cardiac The Center is staffed by five full time and four visiting electrophysiology. Members of the Arrhythmia Center board-certified electrophysiologists. Physicians and have served on guidelines writing groups and held staff provide comprehensive evaluation and management leadership positions in national and international of patients with cardiac arrhythmia with an emphasis on professional organizations. The fellows routinely present communicating timely with patients and members of the abstracts at national meetings and the attending health care team. Nurse practitioners respond to routine physicians serve as invited faculty at the major national patient inquiries and educational needs. Daily and international meetings. outpatient pacemaker and implantable cardioverter Staff electrophysiologists participate extensively in defibrillator clinics are available for those with clinical research. The EP attendings have participated implantable devices. The Center provides trans- on the Executive Committees and as Principal telephonic monitoring of pacemakers and loop monitors. Investigators on the major cardiac rhythm device trials Three cardiac electrophysiology laboratories provide the including the CABG Patch, DEFINITE, MADIT II, full spectrum of invasive electrophysiology studies, MADIT-CRT,MADIT-RIT, and MADIT S-ICD as well as radiofrequency ablations, defibrillator and pacemaker the NIH-funded “Multidisciplinary Study of Right implantations, tilt table tests, and cardioversions. Two Ventricular Dysplasia” (ARVD). This last-named trial is a ablation laboratories provide advanced imaging and multi-center study of the cardiac, clinical, and genetic mapping capabilities to address supraventricular aspects of arrhythmogenic right ventricular dysplasia arrhythmias and many ventricular arrhythmias. With the (ARVD). Dr.Estes conducts research on the prevention of advanced mapping system, more radiofrequency ablation sudden death by means of Automated External cases are being referred for cure of supraventricular and Defibrillators (AEDs) with several publications related to ventricular arrhythmias as well as atrial fibrillation. program development, clinical utility, legislative policy, and legal risks of the devices.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Dr. Mark Link's research into sudden death from chest for this specific indication. The two main LVADs that are wall impact (commotio cordis) has advanced efforts to employed at this institution are the Thoratec HeartMate II prevent sudden deaths resulting from precordial chest and the HeartWare HVAD devices. In 2016, 65 LVADs were blows. Over 30 publications have been produced recently placed for the treatment of Stage D heart failure. from this laboratory. Together with colleagues in the The Center maintains heart failure outreach programs at Tufts-MCRI, he performs electrophysiological Lahey Clinic, Rhode Island Hospital, the University of investigations on knock-out mouse models. He is Massachusetts Medical Center and Dartmouth Hitchcock investigating the association between air pollution and Medical Center. In addition, cardiologists from Lahey atrial and ventricular arrhythmias. He also investigates Clinic, Dartmouth-Hitchcock, Beth Israel Deaconess »

arrhythmias in patients with Hypertrophic Cardiomyopathy. » Medical Center, University of Massachusetts Medical CARDIOLOGY OF DIVISION Dr Link is a member of the 2015 AHA Writing Group for Center and Rhode Island Hospital participate in the Advanced Cardiac Life Support (ACLS) Guidelines, as inpatient and outpatient services at Tufts Medical Center. well as the Writing Committee for the 2011 AHA Cardiovascular fellows from a variety of neighboring Hypertrophic Cardiomyopathy Guidelines and 2012 AHA institutions spend time at Tufts Medical Center to learn PPM and ICD Implant Guidelines. Dr. Link is also the more about the management of advanced heart failure. principal investigator of the RAID trial, assessing the The Advanced Heart Failure and Transplant Cardiology efficacy of ranolazine in prevention of ICD shock. Dr. Fellowship Program was one of the first programs in the Weinstock served as the principal investigator in the country receive ACGME accreditation for its expertise in Replace Trial and has a similar role in the ongoing Echo heart failure training. CRT and VEST Trials. The Center participates in several clinical research The Heart Failure and Cardiac investigations of new therapies for the treatment of all Transplant Center stages of heart failure as well as new immunosuppressive David DeNofrio, MD – Director agents for heart transplantation. The Center has been an active study site for the National Heart and Lung The Heart Failure and Cardiac Transplant Center is nationally renowned for its clinical and research Institute’s Heart Failure Clinical Trials Network and is activities. The Center is a national leader in therapies for currently engaged in multiple Network protocols. In severe heart failure, including cardiac transplantation addition, we are part of The Clinical Trials in Organ and mechanical ventricular assist device therapy. Transplantation (CTOT) project. This is a cooperative research program sponsored by the National Institute of The Center’s cardiac transplantation program performed Allergy and Infectious Diseases (NIAID). CTOT is an 56 transplant procedures in the 2016 calendar year. This investigative consortium for conducting clinical and was the highest volume program of any heart transplant associated mechanistic studies that will lead to improved center in the region and one of the top 10 centers in the outcomes for transplant recipients. The Center continues country. Following approval by the Center for Medicare to participate in multiple national and international and Medicaid Services (CMS) in 2001, the transplant device technologies, including LVADs, for the treatment of program has met or exceeded CMS thresholds each year end-stage heart failure. for both transplant volume and outcomes. With a steady stream of new referrals for transplantation, the program The CardioVascular Imaging Center: The performed approximately 150 formal transplant Cardiovascular Imaging and Hemodynamic evaluations in 2016. In addition, the center was Laboratory (Echocardiography Lab) recognized as one of only 8 other programs in the US to obtain a 5 star rating for outcomes based on Scientific Ayan R. Patel, MD – Director Registry of Transplant Recipient (SRTR) data.The Center This laboratory is nationally known for its innovative also maintains a vibrant mechanical ventricular assist approaches to cardiac diagnosis and has made major device program to support patients with Stage D heart advances in the echocardiographic and Doppler failure. Since 1998 over 437 patients have been supported assessment of myocardial, valvular, congenital, and using ventricular assist devices for both “bridge-to- ischemic heart disease. transplantation” and “destination therapy” indications. The Laboratory provides a unique array of advanced Following the approval by CMS of the left ventricular services including: three-dimensional transthoracic and assist device (LVAD) program in 2003, a steadily transesophageal imaging; stress echocardiography for increasing number of procedures have been performed specialized evaluation of heart failure, valvular disease,

25 cardiac hemodynamics and assessment of ischemia; it Cardiac Magnetic Resonance Imaging and also has extensive experience in the use of myocardial Cardiac Computed Tomography contrast imaging for evaluation of cardiac function. Ethan Rowin, MD – Director, Cardiac MR,; Martin In addition, the laboratory provides imaging guidance Maron, MD, Y. Kent Yucel, MD and Neil Halin, DO – for non-coronary structural interventions, such as Co-Directors. Martin Maron’ MD, Director Cardiac CT transcatheter aortic valve replacement and percutaneous Tufts Medical Center has the most advanced cardiac mitral valve repair. magnetic resonance imaging available with two Phillips The clinical research activities of the laboratory include magnets that are cardiac MRI capable. The cardiac MRI three-dimensional assessment of cardiac chambers and » program focuses on imaging for cardiomyopathies as » DIVISION OF CARDIOLOGY OF DIVISION the relationship with hemodynamics, investigation of well as structure/function analysis and myocardial three-dimensional speckle tracking for evaluation of viability. In addition, a complete non-invasive cardiac disease, the use of imaging for evaluation of assessment of the coronary arteries is performed with a valvular disease, and vascular ultrasound assessment of 10- second breath hold without the need for beta- peripheral vascular endothelial function. Fellows play blockers with the use of the 64-slice Siemens Definition an integral role in the clinical and research activities of dual source scanner for CT angiogrpahy. Fellows the laboratory. participate in all aspects of advanced imaging, including image acquisition and analysis. Nuclear Cardiology Laboratory

James Udelson, MD – Director The Hypertrophic Cardiomyopathy Center Clinical imaging interpretation in this laboratory Martin S. Maron, MD – Medical Director; Barry J. routinely is performed using 4DM-SPECT software, Maron, Director Clinical Research; Ethan Rowin, providing readers with fully quantitative analysis to MD,– Co-Director support image interpretations. The lab is accredited by 2016 marks the 13th year of the first comprehensive ICANL (Intersocietal Commission on the Accreditation Hypertrophic Cardiomyopathy (HCM) Center in the of Nuclear Laboratories). Northeast. The Center provides state-of-the-art diagnostic and therapeutic modalities for patients with The Cardiac Imaging Core Laboratory completed work HCM, the most common genetic cardiovascular disease. on the multi-center NHLBI-funded Occluded Artery Surgeons working with the HCM center perform over 90 Trial ancillary nuclear study (OAT-NUC), in which surgical myectomies per year for relief of left ventricular patients from the parent OAT trial underwent SPECT outflow obstruction. The Division’s interventional imaging for assessment of infarct zone viability and cardiology team was the first in the Boston area to influence on remodeling. The IMMEDIATE Trial perform an alcohol septal ablation for relief of heart assessed infarct size from SPECT imaging in a subset of failure symptoms in patients with obstructive HCM and the patients enrolled in the NHLBI study of glucose- is a leader in this area with over 25 alcohol ablations insulin-potassium given to patients with acute coronary performed each year. The HCM Center’s cardiologists syndromes in ambulances. The Core Lab also served as a provide multidisciplinary patient care for problems as central quality control and analysis center for SPECT diverse as heart failure, syncope, arrhythmias and imaging performed in conjunction with 2 major prevention of sudden death. federally-funded comparative effectiveness trials - the PROMISE trial, randomizing 10,000 patients with The Center is a major research center for patients with suspected CAD to an initial evaluation with functional HCM. Dr. Martin Maron is the national study PI for the testing (including stress SPECT perfusion imaging) or to first prospective randomized clinical trial evaluating the an anatomic evaluation strategy (CT angiography), and efficacy of a novel drug for treatment of symptomatic RESCUE, a 4,000 patient trial of those with suspected HCM (LIBERTY-HCM). Dr. Maron and Rowin are lead investigators on another novel drug for HCM currently CAD randomized to an initial evaluation with stress being evaluated in a phase II study at Tufts. The group SPECT perfusion imaging or to CT angiography. Growth has also recently defined to the natural history of HCM areas include radionuclide imaging to assess cardiac to demonstrate that this disease is now associated with amyloidosis and ongoing efforts to optimize assessment low mortality disease in the contemporary era of of Emergency Department patients with chest pain and cardiovascular treatments and management. Other suspected acute coronary syndromes. areas of focus are the use of implantable cardioverter defibrillators (ICD) to prevent sudden death, the role of

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 27 left ventricular outflow tract obstruction to prognosis, The Women’s Heart Center and the use of cardiac MRI in diagnosis and prognosis. Ayan R. Patel, MD – Director To date, over 120 manuscripts have been published from the HCM center at Tufts. The center has become The goal of the Women’s Heart Center is to provide established as one of the top HCM centers in the world. consultative support to primary physicians and Plans are underway to create the HCM Research Center cardiologists, regarding prevention, diagnosis, and to adderss basic and translational projects with the aim management of cardiovascular diseases in women. The of identifying mechanisms of the disease that can be center provides expertise in the management of lipid therapeutically targeted. disorders and other cardiovascular risk factors,

» management of cardiac disease in women, and » DIVISION OF CARDIOLOGY OF DIVISION The Preventive Cardiology Center cardiovascular imaging/diagnostic testing in women. Nutritional counseling is also available in collaboration Robert M Blanton, MD – Director with the Frances Stern Nutrition Center. The General Cardiology Clinic (GCC), formerly termed the Preventative Cardiology Clinic (PCC), provides risk Teaching Activities factor assessment and management for patients with heart disease and those at an increased risk for Gordon Huggins, MD-Director, Cardiovascular cardiovascular disorders. The staff is composed of a Education and Fellowship Training multi-disciplinary team of cardiologists, fellows, and The Division of Cardiology is dedicated to the highest other health professionals. Staff members have level of teaching and training of medical, dental, nursing instituted a number of new measures to enhance and PA students, house staff and fellows. Members of the medication compliance. Division participate in all aspects of teaching, including lectures, bedside diagnosis, small group discussions,and The Center functions as the primary outpatient training other interactive methods of teaching at all levels. experience for cardiovascular fellows at Tufts Medical Center. Numerous clinical research projects are based in Cardiology faculty are involved with individual the GCC, including the evaluation of vascular preceptorships and "selectives" with first year medical endothelial function to assess cardiovascular risk. students. In addition, cardiologists teach small group Further, a number of clinical trials are based in GCC. lecture series on topics in cardiology. Faculty provide The group also participates in multi-center research didactic education on the cardiovascular physical projects focused on lipids and other novel prevention examination and also provide research mentorship to therapies. The team was one of the top enrolling centers students throughout their medical school years. for the IMPROVE-IT Study, a multi-center, multi- Cardiology fellows work with students as they learn national study examining ultra-low LDL levels in physical diagnosis. patients at risk for atherosclerosis, and STABILITY, a Gordon Huggins, MD serves as the director of the study focusing on a novel anti-inflammatory mechanism cardiovascular pathophysiology course for second year. The to treat coronary artery disease. The group has also course for Tufts medical students is a comprehensive series participated in novel lipid-altering research with PCSK9 of lectures, clinical-pathology conferences and small group Inhibition, and has recently completed enrollment in the discussions. Cardiology staff and fellows are involved in ODYSSEY OUTCOMES study to test the effect of teaching third students and fourth year medical sub-interns additional lipid lowering with the PCSK9 inhibitor on inpatient ward services and in the outpatient setting. alirocumab in patients with prior acute coronary Cardiology fellows also teach electrocardiography and syndrome. An additional recently commenced study is mentor students on clinical rotations. the CAMELLIA- TIMI61, which evaluates the effect of long-term treatment with Belviq (lorcaserin) on the Bedside and didactic teaching of internal medicine house incidence of major adverse cardiovascular events in officers occurs daily during attending rounds as well as obese and overweight subjects with cardiovascular dedicated teaching conferences. Numerous attending disease or multiple cardiovascular risk factors. cardiologists and fellows have received recognition for outstanding teaching by the house staff. Numerous house officers present research at national research meetings and publish articles in the field.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Cardiovascular fellowship training and education at Tufts subspecialty training programs, provides advanced Medical Center is under the direction of Gordon Huggins, training in all aspects of cardiovascular disease. Fellows MD. Dr. Huggins is also the Co-Director of the Tufts MD participate in research within the Division, from basic PhD Combined Degree program and he directs an active science to translational and clinical projects. All fellows translational medicine research program in the Molecular participate in an annual research proposal competition. Cardiology Research Institute. Dr. Robert Blanton is the In addition, fellows present findings at regional and Associate Director of the Fellowship Program and national meetings and publish their work in peer- Candace Scanlon is the Education Coordinator. reviewed journals. Fellows are also active in quality improvement. Graduating fellows from the Division of Fellowship positions remain extremely competitive. The »

Cardiology move on to successful careers in all aspects » three-year general cardiology fellowship program, plus CARDIOLOGY OF DIVISION of academic and clinical cardiology.

Research Grant Support

Recipient Funding Source Purpose of award NIH CTSI KL2 Scholar Cardiac Cell Entry-Inhibition and Protection Therapy for Chronic Tufts University Chagas Disease Robert Blanton, MD Novel Protein Kinase GI Substrates in Cardiac Remodeling and NIH Blood Pressure Control Cardurion PDE9 Inhibitor Genetics, Mechanisms and Clinical Phenotypes of NIH N. A. Estes, MD Arrhythmogenic Caardiomyopathy NIH Late Sodium current blockade in high-risk ICD patients Study of new mechanisms in dopaminergic cell death in mouse Jonas Galper, MD, PhD Michael J Fox Foundation models for Parkinson’s disease Heart Failure Network: New England, New York and Quebec NIH Regional Clinical Center

NIH Basic Mechanisms of Human Calcific Aortic Valve Disease Gordon Huggins, MD Salivary Amylase Gene (AMY 1) as Predictor of Weight and Diet in Miriam Hospital LookAhead & DPP Precision Medicine for Dilated Cardiomyopathy in European and Ohio State University African Ancestry American Heart Extra-Renal Mineralocorticoid Receptors in Hypertension and Association, Established Atherosclerosis Investigator Award The Role of Vascular MR-Regulated Genes in Vascular Function NIH Iris Jaffe, MD, PhD and Disease Smooth Muscle Mineralocorticoid Receptors in Vascular Aging and NIH Hypertension Sex Differences in SMC-MR Role in Vascular Aging and NIH Hypertension Karyopharm Testing efficacy of KPT compounds on inhibiting phenylephrine- Therapeutics induced cardiac myocyte hypertrophy Iris Jaffe/Robert Blanton Acute and Sustained Cardiac and Vascular Effects of Serelaxin in Novartis the Angiotensin II/L-NAME Heart Failure Model

29 Reasearch Grant Support (continued)

Recipient Funding Source Purpose of award Changing the Paradigm of AMI Therapy: The Bench to Bedside Abiomed Approach

Abiomed CVAD Registry Protocol Agreement

The hemodynamic effects of the (circulatory) device in animal Navin Kapur, MD Boston Scientific models of heart failure » »

DIVISION OF CARDIOLOGY OF DIVISION Maquet Clinical Hemodynamic Study of MEGA-IABP Function NIH Endoglin: A Novel Target of Therapy for Right Heart Failure NIH Endoglin: A New Target of Therapy for Heart Failure The Role of PKG-1a in cGMP Signaling Mechanisms through the Richard Karas, MD, PhD / Merck Evaluation of the Effects of cGMP Modulations in Normal and Robert Blanton, MD Disease Studies in the PKG1-LZM Mouse Merck TAC LKR140269 Mechanical circulatory support: Measures of adjustment and Michael Kiernan, MD NIH quality of life A Prospective, Multicenter, Single-arm Study Designed to Assess the Safety of 3-month Dual Antiplatelet Therapy (DAPT) in Boston Scientific Subjects at High Risk for Bleeding Undergoing Percutaneous Coronary Intervention (PCI) With the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Long-term Treatment with BELVIQ Carey Kimmelstiel, MD (lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Eisai Pharmaceuticals Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects with Cardiovascular Disease or Multiple Cardiovascular Risk Factors A Randomized, Double-Blind, Placebo-Controlled, Parallel- Group Study to Evaluate the Effect of SAR236553/REGN727 on the Sanofi Pharmaceuticals Occurrence of Cardiovascular Events in Patients who have Recently Experienced an Acute Coronary Syndrome (Odyssey). HCMR- Novel Predictors of Outcome in Hypertrophic NIH Cardiomyopahty Exercise in Genetic Cardiovascular Conditions (Lifestyle and NIH Exercise in Hypertrophic Cardiomyopathy "LIVE-HCM"/Lifestyle and Exercise in the Long QT Syndrome "LIVE-LQTS Safety, Tolerability, Preliminary Pharmacokinetics and MyoKardia, Inc. Pharmacodynamics of Single Ascending Oral Doses of MYK-461 in Martin Maron, MD Patient Volunteers With Hypertrophic Cardiomyopathy A Phase 2 Open-label Pilot Study to Evaluate Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability MyoKardia, Inc. of MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Gilead Sciences Study to Evaluate the Effect of GS-6615 on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Recipient Funding Source Purpose of award Natalie V. Zucker “Evaluation of the Impact of Left Ventricular Assist Device Support Research Grant, Tufts on Glycemic Control in Patients with Diabetes and Advanced Heart Medical Center, $5000 Failure: Correlation of Hemoglobin A1c and Glycated Albumin Tests” “How Does Body Composition Change After Placement of a Left CTSI Pilot Study Amanda Vest, MBBS, MPH Ventricular Assist Device in Advanced Systolic Heart Failure” A prospective, multicenter, double-blind, randomized, placebo- »

controlled parallel – group study to assess the efficacy and safety » Actelion CARDIOLOGY OF DIVISION of macitentan in patiens with pulmonary hypertension after left ventricular assist device implantation. Examining the Prevalence of TTR Mutations in Subjects Suspected Alnylam Pharmaceuticals of Having Cardiac Amyloidosis

Ayan Patel, MD A Phase 3 Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Alnylam Pharmaceuticals ALN-TTRSC in Patients with Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC) Natalie V. Zucker Research Grant, Tufts Medical Center A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Jenica Upshaw, MD Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat Merck in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF) - VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Heart Failure Society of Heart Failure Disease Management Strategies to Reduce America Hospitalizations and Improve Health related Quality of Life CRT Implant Strategy Using the Longest Electrical Delay for Non- St Jude Medical left Bundle Branch Block Patients (ENHANCE CRT) Jonathan Weinstock, MD Safety and Effectiveness Trial for the Nanostim Leadless St Jude Medical Pacemaker A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Long-term Treatment with BELVIQ (lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Eisai Pharmaceuticals Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects with Cardiovascular Disease or Multiple Jeffrey Kuvin, MD Cardiovascular Risk Factors A Randomized, Double-Blind, Placebo-Controlled, Parallel- Group Study to Evaluate the Effect of SAR236553/REGN727 on the Sanofi Pharmaceuticals Occurrence of Cardiovascular Events in Patients who have Recently Experienced an Acute Coronary Syndrome (Odyssey). James Udelson, MD NHLBI Subcontract for SPECT image core lab for the PROMISE trial “Evaluation of the Impact of Left Ventricular Assist Device Support Natalie V. Zucker on Glycemic Control in Patients with Diabetes and Advanced Heart Amanda Vest, MBBS MPH Research Grant, Tufts Failure: Correlation of Hemoglobin A1c and Glycated Albumin Medical Center, $5000 Tests”

31 Honors and Awards

Robert Blanton, MD »» Reviewer, American Journal of Cardiology, Heart Rhythm »» Invited reviewer, Department of Defense: Congressionally »» Editorial Board, Heart Rhythm Directed Medical Research Program, cardiovascular focused Gordon Huggins, MD program awards. »» Chair, Scientific Review Committee for non-cancer studies David DeNofrio, MD at Tufts Medical Center »» Heart Failure Society of America, Education Committee »» Vice Chair, Institutional Review Board Tufts Medical Center

» Member

» »» Co-Director, Tufts University School of Medicine MD PhD DIVISION OF CARDIOLOGY OF DIVISION »» American College of Cardiology, Program Committee Program Member for Heart Failure »» Director, Tufts University School of Medicine Cardiac »» Boston Magazine’s Top Doctors List for Cardiology Pathophysiology Course

N. A. Mark Estes, MD Iris Zamir Jaffe, MD, PhD »» Editorial Boards, Circulation, Arrhythmias and »» Editorial Board of Endocrinology Electrophysiology, Circulation, Journal of the American »» Associate Editor, Clinical Science College of Cardiology, American Journal of Cardiology, US »» American Society of Clinical Investigation Elected Member Cardiology, Journal of Cardiovascular Electrophysiology, Pacing and Clinical Electrophysiology, Hellenic Journal of »» American Heart Association Established Investigator Cardiology, Associate Editor, Journal of Interventional Award Cardiac Electrophysiology, Heart Rhythm »» AHA High Blood Pressure Research Council Mid-Career »» Section Editor, Controversies in Cardiology, Circulation Award for Research Excellence »» Editor in Chief, Cardiology Up to Date »» Milton O. and Natalie V. Zucker Prize for Research »» Co-Chair ACC/AHA Task Force on Performance Measures »» Charter Member NIH Study Section: Vascular Cell and for Atrial Fibrillation Molecular Biology »» Named in “Best Doctors in America”, Best Doctors in Navin Kapur, MD Boston Member: Scientific Affairs Committee of Tufts University »» ACC Quality in Technology Committee School of Medicine »» HRS Performance Measures Task Force »» Editorial Board Member: Catheterization and »» European Cardiac Arrhythmia Society Distinguished Cardiovascular Interventions Achievement Award »» Editorial Board Member: Journal of Invasive Cardiology »» ACC/AHA Performance Measures Writing Group »» Editorial Board Member: Heart : Journal of the British »» ACC/AHA/HRS SVT Guidelines Writing Group Cardiovascular Society »» ACC/AHA/HRS Eligibility and Disqualification Richard Karas, MD, PhD Recommendations for Competitive Athletes With »» Chief Scientific Officer, Tufts Medical Center Cardiovascular Abnormalities Writing Group »» Vice Chairman for Scientific Affairs, Department of Jonas Galper, MD, PhD Medicine »» Editorial Board Journal of Biological Chemistry »» Executive Director, Molecular Cardiology Research »» Patient Care assessment committee, Tufts Medical Center Institute »» MCRI training grant committee, vice chair »» Chairman, Evaluation and Policy Subcommittee, National Research Committee, American Heart Association »» ESTA Study Section NIH Ad hoc Reviewer »» AHA National Research Committee Munther Homoud, MD Michael Kiernan, MD »» Recognized for Excellence in Teaching, Tufts University School of Medicine »» American Heart Association, Council on Clinical Cardiology Committee on Heart Failure / Transplantation »» Division of Cardiology Fellowship Teaching Award »» Boston Magazine “Top Doctors” List

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF CARDIOLOGY OF DIVISION

»» American Heart Association, Council on Clinical Cardiology »» Abstract Grader: American College of Cardiology; Committee: Fellow in Training / Early Career American Heart Association; Transcatheter Therapeutics Subcommittee »» Manuscript reviewer: Cardiology, Journal of Investigative »» AHA Writing Group: Biomarkers for the prevention, Medicine, Journal of Thrombosis and Thrombolysis, assessment, and management of heart failure: a Journal of Interventional Cardiology, Circulation, American consensus statement from the American Heart Heart Journal, Catheterization and Cardiovascular Association. Interventions, Journal of the American College of »» AHA Writing Group: Cardiovascular function and treatment Cardiology, New England Journal of Medicine, Circulation: in ß-thalassemia major: a consensus statement from the Cardiovascular Interventions American Heart Association. »» Grant reviewer/grader – SCAI FIT (Fellowship in Training) »» AHA Writing Group: Recommendations for the Use of Grant Mechanical Circulatory Support »» Named in “Best Doctors in America” and Best of Boston »» AHA Writing Group: Antibody Mediated Rejection in Magazine Cardiac Transplantation »» National Co-PI of ION Drug-Eluting Stent Trial »» Co-Chair: NIH Heart Failure Network Cardiorenal »» SCAI Fellow in Training Grant Syndrome Working Group »» Abbott Fellow in Training Grant Carey Kimmelstiel, MD »» Abstract Captain – Interventional Cardiology Poster »» Editorial Board: Journal of Thrombosis and Thrombolysis Session-American College of Cardiology Scientific Editorial Board - Catheterization and Cardiovascular Sessions 2016 Interventions

33 » » DIVISION OF CARDIOLOGY OF DIVISION

Marvin Konstam, MD »» American College of Cardiology, Competency Management »» Member, Association of University Cardiologists Committee »» Clinical Practice Guideline Committees, Heart Failure »» American Heart Association, Vice-Chair, Laennec and Society of America, Agency for Health Care Policy and Post-Graduate Education Committee Research, and AHA/ACC »» American Heart Association, Professional Education »» Member, CMS/The Joint Commission/ACC/AHA AMI/ Committee Heart Failure Technical Expert Panel »» American Heart Association, Paul Dudley White Award »» Member, ACGME Advisory Committee for Advanced Heart Committee Failure and Transplant Cardiology »» NRMP Specialties Matching Service, Liaison for »» Chair, American College of Cardiology, Council on Cardiovascular Disease Academic Cardiology »» ACGME Standing Panel for Accreditation Appeals »» Co-Chair National Heart Lung and Blood Institute, »» Nominating Committee, Tufts Medical Center Physicians’ Workshop on Heart Failure Prevention Organization Board of Trustees

Jeffrey Kuvin, MD »» Chair, International Advisory Committee, Kuvin Centre for the Study of Infectious and Tropical Diseases, Hebrew »» Boston Magazine’s “Top Doctors” (Cardiology) University of Jerusalem, Israel »» Chair, American College of Cardiology, Lifelong Learning Oversight Committee »» American College of Cardiology, COCATS Task Force

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Mark Link, MD »» Chairman, Mass Medical Society’s Committee on »» Task Force 2: Hypertrophic Cardiomyopathy, Other Sponsored Programs Cardiomyopathies, and Myocarditis; Task Force 8: »» Chairman, Tufts University School of Medicine Continuing Arrhythmias and Conduction Defects; Chair: Task Force 11: Education Committee Emergency Action Plans, Resuscitation, CPR, and AEDs; »» Massachusetts Hospital Association, Board of Trustees Chair: Task Force 12: Commotio Cordis; Task Force 15: James Udelson, MD Classification of Sport: Dynamic, Static and Impact »» Editor-in-Chief, Circulation: Heart Failure »» Boston Magazines “Best Doctors”- »» Associate Editor, Circulation »» Associate Editor-Journal Watch Cardiology » »

»» Editorial Board – JACC, JACC Imaging, Journal of Nuclear CARDIOLOGY OF DIVISION »» Editorial Board-EP Lab Digest Cardiology, Current Cardiovascular Imaging Reports, Heart »» Editorial Board-Heart Rhythm Failure Reviews, US Cardiology, Trends in Cardiovascular »» Editorial Board-Journal of Innovations in Cardiac Rhythm Medicine Management »» U.S. Food and Drug Administration, Special Government »» Clinical Events Committee for multi-center trials Employee Martin Maron, MD »» Member, Association of University Cardiologists »» Editorial Board: American Journal of Cardiology »» Member, Association of Professors of Cardiology »» Editorial Board: Journal of the American College of »» Ad-hoc Member, Cardiovascular and Renal Drugs Advisory Cardiology Panel, Center for Drug Evaluation and Research, United States Food and Drug Administration Natesa Pandian, MD »» Co-Chair, ACC/ACR Writing Committee for Appropriate »» ACC Writing Group on Rheumatic Fever Use Criteria to Assess Imaging Modalities to Evaluate »» ACC Scientific Sessions, Program Committee Chest Pain in the Emergency Department »» Invited Faculty , ACC Annual Scientific Sessions, San Diego, »» Heart Failure Society of America, Executive Council March 2015 »» Best Doctors in Boston, Boston Magazine »» Invited Speaker, Medical Grand Rounds, Einstein Medical »» Associate Editor, Practice Update in Cardiology Center, Philadelphia, April 2015 »» Co-Chair, ASNC/SNMMI Think Tank on Cardiovascular »» Invited Faculty at the ASE Board Review Course, Molecular Imaging Philadelphia, April 2015 »» Invited Faculty at Inter-Hospital Cardiac Anesthesia Amanda Vest, MD Conference, Boston, April 2015 »» Heart Failure Society of America (HFSA) Guideline »» Invited Faculty at the ASE Annual Scientific Sessions, Committee Boston, June 2015 Jonathan Weinstock, MD »» Program Director, Echocardiography Today & Tomorrow, »» US News and World Report, Top Doctor St. Wolfgang, Austria June 2015 »» Abstract Reviewer, American Heart Association Scientific »» Invited Faculty Indian Academy of Echocardiography, Sessions Mumbai, Oct 2015 »» Manuscript Reviewer, Heart Rhythm, Journal of »» Invited Faculty at Echo Hong Kong International Interventional Cardiac Electrophysiology, Heart Rhythm Conference, Hong Kong, Nov 2015 Case Reports

Ayan Patel, MD Andrew Weintraub, MD »» Associate Editor: Circulation Heart Failure »» Listed, Best Doctor in America »» FASE, American Society of Echocardiography »» Listed, Best Doctors in Boston Deeb Salem, MD »» Manuscript Reviewer, Circulation Heart Failure, Circulation »» Massachusetts Hospital Association Trustees Advisory Interventional Cardiology Council Service Award »» Wang YMCA of Chinatown Legacy Award

35 DIVISION OF CLINICAL CARE RESEARCH

The Division of Clinical Care Research has no clinical programs of its own. Physician-researcher Division » » DIVISION OF CLINICAL CARE RESEARCH CARE CLINICAL OF DIVISION members have appointments in Medicine, Pediatrics, Psychiatry, and Surgery where they are active participants in clinical activities. Those with primary appointments in clinical divisions of the Department of Medicine are the following:

»» Harry Selker, MD Harry Selker, MD Internal Medicine and Adult Primary Care, Pratt Diagnostic Center »» Elena Byhoff, MD Internal Medicine and Adult Primary Care »» Karen Freund, MD Internal Medicine and Adult Primary Care »» David Kent, MD Internal Medicine and Adult Primary Care »» Susan Parsons, MD Hematology-Oncology »» Benjamin Wessler, MD Cardiology

For further details regarding their clinical, teaching and research responsibilities, please see the reports of those divisions and of the Institute for Clinical Research and Health Policy Studies.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 37 DIVISION OF CLINICAL DECISION MAKING » » DIVISION OF CLINICAL DECISION MAKING, INFORMATICS AND TELEMEDICINE AND INFORMATICS MAKING, DECISION CLINICAL OF DIVISION “Tufts Medical Center has the only unit in the world that ties the principles of logical decision analysis to the care of individual patients. It is concerned with identifying strategies of patient care that minimize unnecessary tests and procedures, increase patients’ participation in decisions affecting their care, and decrease the cost of medical care.” — The Best Hospitals in America: The Authoritative Reference Guide for Patients, Their Families and Medical Professionals.”

The Division of Clinical Decision Making began as collaboration between computer scientists John Wong, MD at the Massachusetts Institute of Technology and physicians at Tufts Medical Center and Tufts

University School of Medicine. Under the guidance of Drs. Stephen Pauker and Jerome Kassirer, the Division was formally established in 1980 to conduct research, teach students, train physicians and provide consultations. The Clinical Consultation Service responds to requests from physicians who are uncertain as to the optimal management strategy for a patient and provides advice based on literature review and formal decision analysis explicitly weighing the risks and benefits of the alternatives.

The division has become a critical component of sophisticated medical systems and a crucial element of medical school teaching. Many would agree that there is simply too much information available now for even subspecialists to master in their own field. The student, the practitioner and the research scientist must learn how to efficiently access the huge volume of information available, how to digest it critically, and how to use the information to make clinical decisions.

Highlights of 2016

»» Committee Member, Institute of Medicine, »» Member, Human Factors Subcommittee of the Diagnostic Error in Health Care (Dr. Wong) National Committee on Forensic Science (Dr. Kassirer) »» Co-chair, American Medical Association Physician Consortium for Performance »» Past President, Society for Clinical and Improvement Work Group on Preventive Care Experimental Hypnosis (Dr. Pauker) (Dr. Wong) »» Committee Member, Institute of Medicine, End of Life (Dr. Pauker)

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » »

Faculty TELEMEDICINE AND INFORMATICS MAKING, DECISION CLINICAL OF DIVISION

Name Academic Rank Title and Special Responsibility John B Wong, MD Professor Division Chief Brian J Cohen, MD Assistant Professor Medical Director, Pratt Diagnostic Center Jerome P Kassirer, MD Distinguished Professor Senior Advisor Stephen G Pauker, MD Professor Division Chief Emeritus

Major Clinical Programs

Clinical Decision Consultation Service potential pitfalls in solving clinical problems. The student The Division provides consultations to physicians who are participates in clinical consultations and learns how to uncertain as to the optimal management strategy for an critically evaluate the medical literature. individual patient. The service provides advice based on literature review and formal decision analysis. The process Research explicitly weighs the harms and benefits of the alternatives The Division focuses its research on clinical decision analysis, and often the preferences of the specific patient. Typical comparative effectiveness research, and health policy analysis. consultations involve complex clinical problems or problems The studies examine clinical and policy questions involving the that entail difficult tradeoffs: patients with combinations of information content of the medical history, physical conditions that make traditional strategies of care problematic, examination and diagnostic tests, determination of the optimal instances in which there is conflicting information, and diagnostic test or test sequence, selection of the best therapy, decisions that need to reflect strongly individual patient and evaluation of new medical technologies (tests, devices or preferences. drugs). It uses the tools of decision analysis, utility assessment, literature review and synthesis (meta-analysis), medical Teaching Activities informatics, Markov model development, Monte Carlo simulation, Bayesian interpretation of diagnostic tests, Evidence-based Medicine measurement of patient preferences, cost-effectiveness Tufts 1st year medical students are introduced to the general analysis, and discrete event simulation. principles of evidence-based medicine (how to formulate well- constructed questions and then find and evaluate information). Members of the Division are familiar with the use of techniques for assessing patient preferences and incorporating them into Clinical Decision Making clinical decision making. Current research projects include In this elective course, 4th year Tufts medical students learn the assessments of coronary heart disease treatments, colon cancer rudiments of clinical decision-making, including the screening, HIV and hepatitis C screening, screening for interpretation of clinical data and test results using Bayes’ rule, hypercholesterolemia in adolescents, epilepsy treatment, the analysis of the risks, harms and benefits of clinical decision aids for shared decision making, anticoagulation for decisions, the estimation and use of probabilities and of atrial fibrillation, cost-effectiveness of Tai Chi for osteoarthritis prognosis, and the evaluation of outcomes. Students also and fibromyalgia, guideline evaluation, and methodological review the cognitive processes involved in clinical reasoning, recommendations for performing decision analysis modeling. exploring the steps used by expert clinicians and identifying

39 Clinical Research Support

Recipient Funding source Purpose of award AHRQ Methods Research and Support in Decision and Simulation Modeling CMS ECHO: Increasing Capacity to Deliver Care to High Cost Medicaid Populations NIH/NCCAM Tai Chi and Physical Therapy for Knee Osteoarthritis NIH/NCCAM Tai Chi and Physical Therapy for Fibromyalgia NIH/NCCAM Mentoring and Research in Patient-Oriented Integrative Medicine » » DIVISION OF CLINICAL DECISION MAKING, INFORMATICS AND TELEMEDICINE AND INFORMATICS MAKING, DECISION CLINICAL OF DIVISION NIH/NCRR Clinical and Translational Science Institute Award RCT of an integrated Treatment of Persons with Co-Occurring HCV and Alcohol NIH/NIAA Abuse John Wong, MD NIH/NIAAA Value of Personalized Risk Information NIH/NIDA Incidence of HIV Infection in a Cohort of IV Drug Users Integrating Causal Inference, Evidence Synthesis, and Research Prioritization PCORI Methods Comparative Effectiveness of Adolescent Lipid Screening and Treatment PCORI Strategies A Method for Patient-Centered Enrollment in Comparative Effectiveness PCORI Trials: Mathematical Equipoise PCORI Funded Clinical Research Network Project with the Chicago Community Trust

Health Care Policy and Clinical Practice The Division has been involved with numerous The Division has also translated guidelines into quality consensus conferences, guideline development improvement and performance measures through the processes and appropriateness of care assessment for the AMA Physician Consortium for Performance National Institutes of Health (NIH), Office of Medical Improvement Work Group (AASLD/AGA/AHA/ACC/ Applications Research (OMAR), Institute of Medicine AMA) on Hepatitis C, Coronary Artery Disease, (IOM), American College of Cardiology (ACC), American Hypertension, Heart Failure, and Cardiac Imaging. In College of Chest Physicians (ACCP), American College of addition, the Division has been engaged in Patient Physicians (ACP), Outcome Measures in Rheumatology Outcome Research Teams (PORTs) sponsored by the then (OMERACT), American Association for the Study of Liver Agency for Health Care Policy and Research (AHCPR) on Disease, (AASLD), Centers for Disease Control and Chronic Ischemic Heart Disease and Diabetes Mellitus. Prevention (CDC), Medicare Evidence Development Lastly, the Division has developed decision aids for Advisory Committee (MedCAC), the CDC Working Group shared decision making through the non-profits Evaluating Genetic and Genomic Testing (EGAPP), Informed Medical Decisions Foundation and Healthwise European League Against Rheumatism (EULAR), World to increase patient knowledge and help patients Health Organization (WHO), and US Federal Drug understand the critical role that their preferences may Administration (FDA). play in their care decisions.

Honors and Awards

John Wong, MD, FACP »» Chair, Hepatitis C: Diagnostics, Epidemiology, Natural »» Committee Member, Institute of Medicine, Diagnostic Error History Abstract Review Committee for Association for the in Health Care Study of Liver Disease and for Digestive Disease Week »» Co-chair, American Medical Association Physician »» Chair, Awards Committee, Society for Medical Decision Consortium for Performance Improvement. Work Group on Making Preventive Care

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF CLINICAL DECISION MAKING, INFORMATICS AND TELEMEDICINE AND INFORMATICS MAKING, DECISION CLINICAL OF DIVISION

»» Task Force Member, American College of Cardiology Jerome Kassirer, MD, MACP Foundation Appropriate Use Criteria for Multi-modality »» Member, Human Factors Subcommittee of the National Imaging in Cardiac Structure and Function in Non-Valvular Committee on Forensic Science Heart Disease »» Senior Editorial Advisor for Circulation: Cardiovascular »» Task Force Member, American College of Cardiology Quality and Outcomes Foundation Appropriate Use Criteria for Multi-modality »» Visiting Professor at Stanford University; collaborating with Imaging in Cardiac Structure and Function in Valvular Arnold Milstein's group on Care Redesign Heart Disease »» Consultant, Center for Outcomes Research and Evaluation, »» Systematic Review Member, American Association for the Yale University Study of Liver Disease (AASLD), Hepatitis B Guidelines »» Invited Expert Panel Member, Workshop on Risk Evaluation Stephen Pauker, MD, MACP, FACC, FACMI, ABMH and Mitigation Strategies (REMS): Building a Framework »» Past President, Society for Clinical and Experimental Hypnosis for Effective Patient Counseling on Medication Risks and »» Certified Consultant in Hypnosis, Active Commitment to Benefits, Duke-Margolis Center for Health Policy Excellence (SCEH-ACE), Society for Clinical and Experimental »» Keynote Speaker, Institute of Medicine Improving Hypnosis Diagnosis in Health Care. Improving Periodontal Diagnosis: »» Re-Certification Approved Consultant, American Society of Translating Practice into Data for Person-Centric Clinical Hypnosis Healthcare, American Practitioners Engaged in Applied »» Committee Member, Institute of Medicine, End of Life Research and Learning (PEARL Network), American Dental »» Member, Institute of Medicine Association »» Member, CDC Working Group for Evaluation of Genomic Applications for Populations and Prevention (EGAPP) »» Member, American Board of Medical Hypnosis Examining Body

Brian Cohen, MD »» Castle Connolly Top Doctor

41 DIVISION OF CLINICAL NUTRITION

Nutrition plays a key role in disease risk as well as in healing. There is increasing evidence for novel roles of nutrients in inflammation, » »

DIVISION OF CLINICAL NUTRITION CLINICAL OF DIVISION immune function, carcinogenesis, and cognitive decline. Members of the Division of Clinical Nutrition are nationally known nutrition researchers and clinicians who provide an array of consultative nutrition services to acutely and chronically ill patients.

Tufts University is a national and international leader in nutrition care, education and research. Tufts Medical Center and Tufts University School of Medicine have long had a strong focus on the clinical, training, and research aspects of human nutrition. The campus features a Edward Saltzman, MD remarkable array of resources, including the Division of Clinical Nutrition at Tufts Medical

Center, the Frances Stern Nutrition Center (FSNC), the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (HNRCA), and the Friedman School of Nutrition and Science and Policy.

Faculty

Name Academic Rank Title and Special Responsibility Edward Saltzman, MD Associate Professor Chief Johanna Dwyer, PhD Professor Director, Frances Stern Nutrition Center Joel Mason, MD Professor Director, GI Nutrition Clinic Irwin Rosenberg, MD University Professor

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF CLINICAL NUTRITION CLINICAL OF DIVISION

Major Clinical Programs Teaching Activities Adult Nutrition Support Service Division members participate extensively in the education of students at Tufts University School of The adult Nutrition Support Service (NSS), under the Medicine. Dr.Saltzman directs the second-year course in direction of Dr. Saltzman, provides expert nutritional Nutrition and Medicine. Residents and Fellows in consultation for inpatients who require enteral or multiple medical subspecialties rotate through the parenteral nutrition support and for patients who inpatient Nutrition Support Service and GI Nutrition require continued nutrition support after discharge. The clinic. Dietetic interns who are training to become attending staff also provides interpretation of indirect Registered Dieticians in the Frances Stern Nutrition calorimetry (metabolic rate) studies. Center have required rotations on the inpatient Nutrition GI Nutrition Clinic Support Service. Under the supervision of Dr. Mason, a nationally Members of the division are also active in the Friedman recognized expert in nutritional management of School of Nutrition and Science Policy, where Dr. malabsorptive disorders, this clinic provides care for Saltzman is Academic Dean for Education. Division patients with complex nutritional disorders. members provide classroom teaching and serve as mentors for doctoral students. Tufts Medical Center Committee on Nutrition To insure that nutrition practices at Tufts Medical Center are uniform and consistent with current best practices, the Nutrition Committee monitors provision of nutrition care throughout the medical center and contributes to development of policies and procedures.

43

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Research Activity Several members conduct research at the HNRCA, one of six USDA supported national nutrition research centers. Dr. Mason directs the Vitamins and Carcinogenesis Laboratory. Dr. Saltzman is Medical Director of the Metabolic Research Unit, the HNRCA's inpatient unit, and is a member of the Energy Metabolism laboratory at the HNRC. Dr. Dwyer serves a Senior Nutrition Scientist in the Office of Dietary Supplements, National Institutes » » of Health. NUTRITION CLINICAL OF DIVISION

Honors and Awards

Johanna Dwyer, PhD »» Editor, Nutrition Today

Joel Mason, MD »» Elected to the Board of Directors, American Society for Nutrition »» Co-chair of the national annual conference, Advances and Controversies in Clinical Nutrition

Irwin Rosenberg »» Editor in Chief, Food and Nutrition Bulletin

Edward Saltzman, MD »» Member, Board of Directors, American Society for Nutrition

45 DIVISION OF ENDOCRINOLOGY, DIABETES AND METABOLISM » » ENDOCRINOLOGY, DIABETES AND METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION The Division of Endocrinology at Tufts Medical Center offers clinical services ranging from comprehensive diabetes management to subspecialty outpatient clinics devoted to pituitary, bone, thyroid, and adrenal disorders and endocrine neoplasia. In addition to a wide variety of teaching activities for medical students, residents and endocrinology fellows, the Division offers selective courses in clinical endocrinology and endocrine research for medical students. Ronald Lechan, MD The Division has a distinguished history dating to the 1940’s when Dr. Edwin B. Astwood became its first Chief. During his tenure, a number of advances were made including the introduction of drugs for the treatment of hyperthyroidism, the use of thyroid hormone therapy for the treatment of thyroid nodules, the isolation and preparation of ACTH for clinical use and the purification of human growth hormone, allowing the first treatment for pituitary dwarfism.

In 1972, Dr. Seymour Reichlin, a world-renowned leader in the field of neuroendocrinology and disorders of the thyroid gland, became Chief of the Division. Outstanding achievements made during his tenure included the development of the first radioimmunoassay for thyrotropin-releasing hormone (TRH), identification of the origin of the hypothalamic tuberoinfundibular system, elucidation of the somatostatin and TRH genes and studies on the mechanisms of action of somatostatin, TRH and prolactin secretion, demonstration of the role of the immune system in neuroendocrine regulation, studies on the evaluation and treatment of hyperprolactinemia, and the diagnosis and treatment of patients with MEN II syndrome.

With the formation of the Human Nutrition Research Center on Aging, the Endocrinology Division gained prominence for its studies of disorders of lipids, calcium metabolism and obesity. In 1990, Dr. A.E. Boyd, III became Chief and brought expertise in diabetes mellitus and molecular biology. The Division grew rapidly when Dr. Boyd merged the Division of Molecular Medicine with the Division of Endocrinology. After Dr. Boyd’s untimely death in 1995, Dr. Ronald Lechan assumed leadership of the Division. During this time, the Division has continued its research interests in bone metabolism, diabetes, neuroendocrinology, obesity and adipocyte function, and has substantially grown its clinical program to involve offsite programs in Quincy, Norfolk and the Merrimack Valley. Division members have received numerous grants, awards, prestigious lectureships and committee memberships.

Highlights of 2016 »» Clinical and basic science research programs »» Grant renewal from the Gerald J. and Dorothy R. awarded 9 new grants. Friedman Foundation for Medical Research to support fellowship training in Endocrinology, »» Vitamin D and type 2 diabetes (D2d) study, Diabetes and Metabolism a NIH-supported multi-center clinical trial coordinated out of the Division of »» Ongoing efforts to establish satellite Endocrinology, completed recruitment of endocrinology subspecialty clinics in local 2,423 participants communities outside of the Boston area and telemedicine consult program with Patient Advocates in Maine

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Responsibility Chief of Division Director, Fellowship Program Ronald M. Lechan, MD, PhD Professor Director, Neuroendocrine Clinic Co-director, Neuroendocrine & Pituitary Program Lisa Ceglia, MD Assistant Professor Director, Bone Clinic

Michael Dansinger, MD Assistant Professor Director, Diabetes Reversal Program » » ENDOCRINOLOGY, DIABETES AND METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION Bess Dawson-Hughes, MD Professor Director, Bone-Metabolism Laboratory, HNRC Csaba Fekete, MD, PhD Adjunct Professor Professor of Neurobiology, Hungarian Academy of Science Dr. Robert C and Veronica Atkins Professor in Metabolism and Nutrition Andrew S. Greenberg, MD Professor Director, Obesity and Metabolism Laboratory at Jean Mayer USDA Human Nutrition Research Center at Tufts University Julie Howe, NP Nurse Practitioner and Certified Diabetes Educator Director, Thyroid Clinic and Ultrasound and Fine Needle Aspiration Jacqueline Kung, MD Assistant Professor Thyroid Clinic Director, Diabetes Clinic Anastassios G. Pittas, MD, MS Professor Associate Director, Fellowship Program General Endocrinologist Aruna Saraswat, MD Professor Emeritus Consultant for Tufts Medical Center Primary Care-Quincy and Norfolk Specialty Care Center Seymour Reichlin, MD Professor Emeritus Director, Diabetes Clinic Director, Internal Medicine Residency Endocrine Rotation Director, 4th Richard Siegel, MD Associate Professor Year Medical Student Endocrine Elective Co-Director, From Health To Disease III: 2nd Year Medical Student Endocrine Course Jeffrey Tatro, PhD Associate Professor Researcher Roberto Toni, MD, PhD Adjunct Professor Professor of Human Anatomy, University of Parma School of Medicine General Endocrinologist Jeffrey Vercollone, MD Assistant Professor Consultant for Tufts Medical Center Primary Care-Quincy Mary Wenners, NP Nurse Practitioner and Certified Diabetes Educator Paula Dabenigno, RN Certified Diabetes Educator

Major Clinical Programs The Division of Endocrinology offers complete »» Obesity (in collaboration with the Obesity Consultation diagnostic and therapeutic services for common and Center, Dr. Richard Siegel) complex endocrine disorders. A variety of subspecialty »» Neuroendocrinology and Endocrine Neoplasia outpatient clinics provide expert and investigational (Dr. Ronald Lechan) treatments, namely: »» Diabetes Reversal Program (Dr. Michael Dansinger) »» Bone Disease (Dr. Lisa Ceglia) »» General Endocrinology (Drs. Lisa Ceglia, Jacqueline Kung, »» Thyroid Disease and Thyroid Cancer (Dr. Jacqueline Kung) Aruna Saraswat, Richard Siegel, Jeffrey Vercollone) »» Diabetes and Metabolism (Drs. Richard Siegel, Anastassios Pittas, Lisa Ceglia, Aruna Saraswat, Jeffrey Vercollone)

47 The inpatient consultation team offers management for fine needle aspiration biopsy of thyroid nodules, diabetes and all endocrine disorders for hospitalized interpretation of bone densitometry studies, and patients. Under the direction of Dr. Richard Siegel, protocols interpretation of continuous glucose monitoring data. for insulin management in the intensive care units and The Division is also active in teaching house staff and insulin order forms have been developed and implemented medical students. Among the offerings are the following: on medical and surgical floors to improve diabetes management in the hospital. Dr. Siegel offers a novel »» Selective courses in clinical endocrinology and endocrine telemedicine consultation program with Patient Advocates research for medical students, supervised by Drs. Richard in Maine, focused on the care of patients with diabetes Siegel and Ronald Lechan »

» mellitus. Under the direction of Dr. Michael Dansinger, the »» Formal instruction in the endocrine pathophysiology ENDOCRINOLOGY, DIABETES AND METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION Diabetes Reversal Program at Tufts Medical Center was course to second year medical students in the From introduced, now into its 10th year, in which diet and exercise Health to Disease III: Endocrine Course, co-directed has achieved remission in approximately a third of patients by Dr. Richard Siegel with type 2 diabetes. Mary Wenners, NP and Julie Howe, NP »» Lectures at Noon Conference and participation in Morning have overseen the insulin pump program as well as an Asian Report for Internal Medicine Residents Outreach Screening Program to identify patients in the local »» A series of didactic lectures for first year Fellows in the community with diabetes mellitus. Under the direction of endocrinology training program Dr. Jacqueline Kung, the thyroid cancer program includes mutational testing and gene expression classifier testing on »» Electives in the endocrinology clinics and on the fine needle biopsy aspirates of thyroid nodules. endocrinology consultation services for both medical students and Internal Medicine Residents. In collaboration with the Departments of Neurosurgery, »» One-on-one mentoring in lifestyle coaching to medical Radiology and Ophthalmology, a multidisciplinary residents and medical students who rotate through the neuroendocrine pituitary program was developed under the lifestyle-based Diabetes Reversal Program. direction of Drs. Ronald Lechan and Carl Heilman to facilitate the evaluation and care of patients with hypothalamic and Faculty members have also been mentors, served on PhD pituitary disorders. The Division is also working and MS Thesis Committees, and participated in teaching in collaboratively with the Division of Internal Medicine and the Medical School, Sackler School of Graduate Biomedical Adult Primary Care to improve the care of patients with type 1 Sciences, USDA Human Nutrition Center, Dental School, and type 2 diabetes mellitus, and, under the direction of Dr. Friedman School of Nutrition and Health Policy, University Lisa Ceglia, with the Department of Orthopedics to improve of Parma and Hungarian Institute of Science. bone health for patients with recent bone fractures. The Dr. Ceglia served as mentor for a PhD candidate at the Division has established satellite clinics in Quincy and Friedman School of Public Policy and Nutrition Science Norfolk, overseen by Dr. Aruna Saraswat and Dr. Jeffrey on potassium bicarbonate supplementation in the Vercollone, and in the Merrimack Valley, overseen by Dr. prevention of muscle loss during weight-reducing diet. Jacqueline Kung, to assist NEQCA physicians with the care of Dr. Greenberg directed the predoctoral training program their patients with diabetes and other endocrine disorders. for nutrition students at the Friedman School. Dr. Aruna Teaching Activities Saraswat volunteered as a faculty evaluator for medical student Objective Structure Clinical Exam (OSCE) The Division offers fellowship training in Endocrinology, encounters. Dr. Siegel directs the 4th year Medical Diabetes and Metabolism, accepting two new Fellows Student Endocrine Elective, is Co-Director of the each year into a 2-year clinical or 3 year clinical/research pathophysiology endocrine course for 2nd year medical program. One new Fellow each year is supported by a students, is preceptor of the Medicine III rotation in grant from The Gerald J. and Dorothy R. Friedman New Endocrinology for Tufts School of Dental Medicine, and York Foundation for Medical Research. Included in the has participated in the Clinical Pathology Core Lecture teaching activities are formal lectures on topics in Series on diabetes mellitus, and at the GMA Noon endocrinology, instruction in thyroid ultrasound and Conference Series on Diabesity Update. Dr. Dansinger

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 was involved in overseeing evidence-based didactic »» Demonstration that in older women with low vitamin D training of dietitians in lifestyle coaching at Boston Heart status and moderate risk of disability, vitamin D Diagnostics, and Dr. Kung served as a preceptor for Tufts supplementation had modest beneficial effects on muscle Medical Student Free Clinic Sharewood Project. Division fiber size and significant increases in intramyonuclear members were also involved in teaching at the American vitamin D receptor expression. Thyroid Association Annual meeting, lecturing to PhD »» Demonstration that transgenic expression of a dominant students in the Janos Szentagothai Neuroscience active AMPK2 mutation in mice results in obesity through Department at Semmelweis University and at the activation of central ghrelin signaling. University of Parma. In addition, Dr. Roberto Toni »» Demonstration that the parabrachial nucleus has »

developed a series of multimedia web lectures on human »

bidirectional connections with most refeeding-activated METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION embryology and the anatomy of the head and neck (www. neuronal groups in the CNS, suggesting that short anfamedmuseo.unipr.it). feedback circuits exist in this satiety network. Research Activities »» Demonstration that reducing renal acid load with KHCO3 supplementation significantly increases the expression of The commitment to research by the faculty continues to microRNAs involved in osteogeneis, osteoblast be a major focus of the Division. Success in this endeavor differentiation and myogenesis. is indicated by the publication record of the faculty that »» Demonstration of a significant association between includes 44 peer reviewed papers, book chapters and increases in miR-21 and 133b and decreases in bone reviews in 2016. resorption and calcium excretion. Support for faculty research is derived from 13 NIH »» Demonstration of a role for transient receptor potential grants, 3 grants from the USDA, 1 grant from the ADA, 1 vanilloid 3 (TRP3) channels in the mesolimbic-dopamine grant from the European Union, 1 grant from the Italian food reward pathway. Ministry of Research, 1grant from the Gerald J. and »» Demonstration that ablation of the gene, ACSL5, in mice Dorothy R. Friedman Foundation for Medical Research, increased systemic energy expenditure, reduced body fat 2 grants from the Boston Heart Diagnostics, as well as a accumulation and improved insulin sensitivity. variety of industry and institutional grants. Nine new »» Evidence that ablation of tumor progression locus 2 (TPL2) grants were awarded to Division members this year. results in decreased hepatic steatosis and expression of de Highlights of recent research accomplishments include: novo lipogenesis-related markers as well as reduction of endoplasmic reticulum stress biomarkers, suggesting »» Demonstration that advanced testing using LDL and HDL TPL2 could be a molecular target for hepatocellular particles is dramatically more sensitive for showing carcinoma prevention. improvements in CVD risk factors related to lifestyle »» Demonstration that high, monthly doses of vitamin D are change than LDL or HDL cholesterol associated with increased risk of falls. »» Demonstration that a widely promoted web-based risk test »» Evidence based on NBHA diagnostic criteria that 16% of would label more than 73 million Americans as being at men and 29.9% women age 50+ have osteoporosis. high risk for “prediabetes”, indicating how common conditions can be easily medicalized. »» Demonstration that treatment with vitamin D compounds results in sustained increases in vitamin D receptor (VDR) »» Demonstration that the Diagnostics Lifestyle Program is expression in human skeletal muscle. effective for reducing CVD risk factors in an outpatient clinical setting and that CVD risk factor reductions parallel »» Evidence that shorter sleep duration and insomnia the degree of weight loss, dietary adherence, food logging symptoms are not associated with lower bone mineral and coach involvement. density levels in older adults.

49 Basic Research

Recipient Funding source Purpose of award European Union* Effect of Thyroid Hormone Antagonist, NH3, in THAI Mouse Line Hungarian National Brain Csaba Fekete, MD Effect of Glutamate on Electrical Parameters of Tanycytes Research Program* (PI) NIH* (Co-Investigator) Tanycytes and hypothalamic inflammation associated with obesity » » ENDOCRINOLOGY, DIABETES AND METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION Clinical Research

Recipient Funding source Purpose of award

NIH (Co-Investigator) Vitamin D and type 2 diabetes (D2D study) (with Dr. Pittas) Lisa Ceglia, MD Effects of 25(OH)D supplementation in younger postmenopausal DSM Nutritional Products (PI) women Effectiveness of lifestyle program for former NFL players at risk for Boston Heart Diagnostics (Co-PI) heart disease Heart Michael Dansinger, MD Effectiveness of lifestyle program for firefighters and police officers at Boston Heart Diagnostics (PI) risk for heart disease NIH (PI) Musculoskeletal benefits of bicarbonate in older adults NIH (Co-Investigator) Vitamin D and Type 2 Diabetes (D2D) (with Dr. Pittas) USDA (PI) Studies of nutrition and the aging skeleton Impact of supplemental vitamin D on serum 25OHD levels and short Pfizer (PI) Bess Dawson-Hughes, MD term indicators of physical function NIH* (PI) Bone Material Strength in Normoglycemic and Hyperglycemic Adults Vitamins D and K and Neuropathologically-Defined Alzheimer and NIH* (Co-Investigator) Other Dementias in Older Patients NIH (Co-Investigator) Role of Vitamin D in Established Type 2 Diabetes (with Dr. Pittas) Gerald J. and Dorothy R. Friedman Clinical and research training in Endocrinology, Diabetes and Foundation for Medical Research* (PI) Metabolism Ronald Lechan, MD, PhD Study of pathophysiology and molecular biology of NIH, TCGA Trial (PI) pheochromocytoma and paraganglioma Assessment of coagulation Factors in Nonalcoholic Fatty Liver Disease NIH* (Co-Investigator) Richard Siegel, MD (NAFLD) and Related Conditions Tufts Health Plan Foundation* Care Coordination in Asian Elders

American Diabetes Association (PI) D2d Co-Support Award

Multi-center randomized trial of vitamin D supplementation for NIDDK (PI) prevention of type 2 diabetes Anastassios Pittas, MD NIDDK (PI) Role of vitamin D in established type 2 diabetes Department of Defense (Co- Development of more effective approaches to sustain weight loss Investigator) Center for Sport and Exercise Roberto Toni, MD, PhD Role of Obesity in Working Performance of Military Personnel Medicine, University of Parma* (PI)

* New Award in 2016

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Recipient Funding source Purpose of award Nutrition and Cancer Center CDK6-mediated Repression of RUNX1 is Required for Negative Pilot Grant* (Co-PI) Regulation of White Fat Browning disease Role of Adipocyte TLR4 and IRF8 in Obesity Associated Adipose Tissue Tufts University* (Co-PI) Inflammation and Metabolism USDA (Co-Investigator) Bioactive Components of tomato and their Anti-inflammatory Action Andrew Greenberg, MD

NIH, NIDDK (PI) Research training program in nutrition and chronic disease » » NIH (Co-director) Boston Nutrition Obesity Research Center METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION NIH (PI) Role of ACSL5 in liver and intestinal triacyglycerol metabolism Regulation of Adipocyte and Adipose Tissue Metabolism in Obesity USDA (PI) Related Inflammation and Metabolic Disorders

NIH (PI) Tanycytes and hypothalamic inflammation associated with obesity

NIH* (PI) Role of Parasubthalamic Nucleus (PSTN) in Appetite Regulation Ronald M. Lechan, MD, PhD Anatomical and functional analysis of POMC neuronal rescue by NIH (PI) tanycytes

Museum Network System, Morphology and Endocrinology in Art (MORPHENDO) University of Parma Italian Ministry of Culture, Art Development of restoration procedures for 17th-19th century anatomical and Music specimens Italian Ministry of Research and Development of biotechnology and bioengineering strategies to develop Roberto Toni, MD University (MIUR) (PI) ex situ bioartificial organs University of Parma School of Molecular mechanisms regulating growth and differentiation of Medicine neuroendocrine cells Italian Fund for Basic Research Development of biotechnologies and bioengineering strategies to (FIRB) (PI) develop bioartificial bone

* New Award in 2016

51 » » ENDOCRINOLOGY, DIABETES AND METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION

Honors and Awards

Dr. Lisa Ceglia »» Speaker, IOF-ESCEO Annual Meeting on Osteoporosis, »» PhD Thesis Committee, Friedman School of Nutrition and Malaga Health Policy »» Speaker, IOF-Asia-Pacific Conference, Singapore »» Speaker, Rheumatology Grand Rounds, Tufts Medical »» Speaker, International Symposium on Nutritional Aspects Center, Boston, MA of Osteoporosis, Montreal, Canada Dr. Michael Dansinger »» Speaker, Vitamin D workshop, Boston »» Speaker, Carolina Academy of Family Physicians, Hilton »» Speaker, ASBMR Annual Meeting, Atlanta, GA Head, SC »» Speaker, DO-HEALTH Annual Meeting, Zurich

»» Speaker, Boston Heart Diagnostics Customer Conference, Dr. Csaba Fekete Boston, Chicago, Dallas, San Francisco, Phoenix, Orlando »» Head, Neuroscience Section of the Hungarian Association »» Council of Directors, True Health Initiative of Endocrinology and Metabolism »» Member of the Expert Panel, CDC Worksite Health »» Editorial Board, Frontiers in Endocrinology Systems and ScoreCard Translational Endocrinology Dr. Bess Dawson-Hughes »» Editorial Board, Journal of Chemical Neuroanatomy »» Editorial Board, Bone »» Speaker, Annual Meeting of the European Thyroid »» Editorial Board, Osteoporosis International Association, Copenhagen, Denmark »» Editorial Board, Calcified Tissue International »» Speaker, 4th Scientific Meeting of the European GnRH Network, Budapest, Hungary »» Chair, Calcium Map Global Project by IOF »» Member, WHO Working Group on Definition and Management of Sarcopenia

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Dr. Andrew Greenberg Dr. Anastassios Pittas »» Associate Director of Boston Nutrition Obesity Center »» Chair, NIH Study Section on Clinical & Integrative Diabetes (BNORC) and Obesity

Dr. Jacqueline Kung »» Member, American Diabetes Association Research Grant Review Committee »» Member, Trainees and Career Advancement Committee, American Thyroid Association »» 2016 Boston’s Best Doctors »» Chair, Information Technology Subcommittee, American Dr. Aruna Saraswat Thyroid Association »» Division Representative, Tufts Medical Center Quality »

»» Co-Chair Clinical Track Subcommittee, American Thyroid Improvement Committee » ENDOCRINOLOGY, DIABETES AND METABOLISM AND DIABETES ENDOCRINOLOGY, OF DIVISION Association Dr. Richard Siegel »» Practicum Faculty, Thyroid Ultrasound Course, American »» Boston Magazine Best Doctors 2016 Thyroid Association Annual Meeting, Denver, CO »» Outstanding Tufts University School of Medicine Lecture, »» Volunteer Attending Physician, Tufts Medical Student Free 2015-2016 Clinic Sharewood Project Dr. Jeffrey Tatro Dr. Ronald Lechan »» Inventor on licensing agreement pertaining to worldwide »» Organizing Committee and Co-Chair, Friedman Fellows sales of α-MSH antiserum Symposium on Nutrition and Human Health, New Orleans, LA Dr. Roberto Toni »» Editorial Board, Acta Biomedica »» Scientific Director, Museum of Biomedical, »» Boston Magazine 2016 list of Top Doctors Biotechnological and Translational Sciences, University of Parma »» Castle Connolly America’s Top doctors »» Editorial Board and Section Editor on History of »» 2106 Vitals” Patients’ Choice Award Endocrinology, L’Endocrinologo »» Selected by International Biographical Center as Top 100 »» Member, Scientific Committee, PhD Program in Molecular Health Professionals 2016 Medicine at the University of Parma School of Medicine »» External Expert, PhD Program in Molecular Medicine, »» Chief Consultant, Center for Sport and Exercise Medicine University of Parma School of Medicine of the University of Parma »» Member, International FIPA Consortium to study familial »» Scientific Director, Museum of Biomedicine and Historical pituitary adenomas Library of biomedicine, University of Parms »» Member, National Study Group on Environmental Endocrinology, Italian Society of Endocrinology »» Speaker, ICOM 2016, Parma, Italy

53 DIVISION OF GASTROENTEROLOGY

The Division of Gastroenterology was established in the 1960s under the direction of Dr. James Patterson, a » » DIVISION OF GASTROENTEROLOGY OF DIVISION dermatologist who became a gastroenterologist as a result of his interest in the skin manifestations of digestive diseases. Dr. Marshall Kaplan, who had established a reputation at the NIH as an investigator of liver disease, succeeded Dr. Patterson as Division Chief in 1972.During Dr. Kaplan’s thirty year tenure, the Division became widely known for the management of

Joel Weinstock, MD primary biliary cirrhosis and sclerosing cholangitis and developed an academic andresearch focus. Dr. Kaplan also was an Associate Editor of the New England Journal of Medicine. In 2006, Dr. Joel Weinstock, who was well known for basic investigations of intestinal immunology, became Chief of the Division. His appointment brought novel approaches to the treatment of inflammatory bowel disease and a strong basic science interest in the mechanisms of immune regulation in the gut.

In 1984, the Division became one of the first awardees of an NIH Silvio O. Conte Digestive Disease Research Center grant. This basic research program, known as the GRASP Center, formed the central link among digestive disease researchers throughout the medical center, the medical school and the veterinary school. The founding director of the GRASP Center was Mark Donowitz MD; Andrew Plaut became director in 1987.

Many former members of the Division have made major contributions to the field of gastroenterology and three have been presidents of the American Gastroenterological Association.

The members of the Division combine clinical and basic research talents. Members receive funding from the NIH and pharmaceutical industry and patients are referred from a network of internists and gastroenterologists throughout New England. Aside from the particular strengths in cholestatic liver disease and inflammatory bowel disease, the Division offers advanced endoscopic procedures for a variety of gastrointestinal disorders. The liver transplant program has merged with the program at Lahey Clinic so that the surgical procedures are now done at Lahey Clinic but the identification of candidates and the pre-and post-operative care remain at Tufts Medical Center.

Highlights of 2016

»» Joel Weinstock, MD – Best Doctors 2016 – »» Lori Olans, MD – Best Doctors 2016 – “Boston Magazine” “Boston Magazine”

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Responsibility » » Joel V. Weinstock, MD Professor Division Chief GASTROENTEROLOGY OF DIVISION Harmony Alison, MD Assistant Professor Director, Endoscopy Unit Martin Beinborn, MD, PhD Assistant Professor Associate Director, Clinical Programs Peter Bonis, MD Adjunct Professor Aaron Dickstein, MD Clinical Assistant Professor Moises Guelrud, MD Clinical Professor Alan Kopin, MD Professor Director, Molecular Pharmacology Research Director, Food Allergy Center Assistant Professor, Co-Director, Food Allergy Center at Floating John, Leung, MD Medicine & Pediatrics Hospital for Children Affiliated Faculty, Tufts Innovation Institute Professor of Medicine and Nutrition; Director, Joel B. Mason, MD Professor Vitamins & Carcinogenesis Laboratory, USDA Human Nutrition Research Center at Tufts University Lori Olans, MD Assistant Professor Andrew Plaut, MD Professor Jatin Roper, MD Assistant Professor Mark J. Sterling Instructor of Medicine Kathleen Viveiros, MD Assistant Professor Director, Fellowship Program Robert Yacavone, MD Assistant Professor

Major Clinical Programs The clinical activities of the Gastroenterology Division of »» Colonoscopy and colonoscopic polypectomy, Tufts Medical Center include outpatient and inpatient chromoendoscopy and magnification endoscopy management of gastrointestinal disorders and liver diseases. »» Management of patients with chronic liver disease The Division has an international reputation in chronic including chronic hepatitis, cirrhosis, gallstones, primary cholestatic liver diseases and in inflammatory bowel disease, sclerosing cholangitis and primary biliary cirrhosis. leading to referrals from worldwide. »» Chronic cholestatic liver disease The Division has special expertise in: »» Inflammatory bowel disease

»» Esophageal motility studies and 24-hour pH monitoring of Physicians in the Division of Gastroenterology have the esophagus pioneered innovative medical treatments for primary biliary »» Endoscopic treatment of Barrett’s esophagus cirrhosis and primary sclerosing cholangitis. These therapies »» Peptic ulcer disease appear to induce remission in some patients with previously »» Gastrointestinal endoscopy, including transduodenal bile untreatable disease. duct and advanced pancreatic endoscopic therapy

55 The Food Allergy Center at Tufts Medical Center and Floating Hospital for Children was established in 2013 in collaboration with the pediatric and adult GI Division. It provides integrative, patient-oriented, multidisciplinary care for both adults and children with known or suspected food allergies/ intolerances. Division members treat diverse conditions like food anaphylaxis, eosinophilic esophagitis and eosinophilic gastroenteritis. »

» Teaching Activities DIVISION OF GASTROENTEROLOGY OF DIVISION The Division of Gastroenterology is extensively involved in the education of medical students. In the preclinical years, the division is responsible for the GI pathophysiology course. In the clinical years the division teaches students on both the Gastroenterology subspecialty floor and on the inpatient consultation service.

Interns and residents at Tufts Medical Center rotate through the GI subspecialty ward and may also choose an elective on the GI consultation service. These experiences expose residents to a wide variety of gastrointestinal disorders.

The Gastroenterology Fellowship Program is a joint fellowship program between Tufts Medical Center and St. Elizabeth’s Medical Center of Boston, both of which are affiliates of Tufts University School of Medicine. This collaboration has significantly enriched the educational experience of the teaching program. Most of the trainees seek academic careers.

Residents from the internal medicine training program rotate through the Allergy Division. Those with a particular Other interests include malabsorption disorders, and the interest in Allergy and Clinical Immunology are given clinical evaluation of nutritional disorders and weight loss; opportunities to participate in extra clinical sessions and are sexually transmitted intestinal and liver disease, including also encouraged to do literature surveys and extended hepatitis and parasitic infections; and chronic secretory evaluations of patients with complicated illnesses. House diarrhea. The inflammatory bowel disease clinic applies an staff expressing interest in Allergy and Clinical Immunology interdisciplinary approach for the care of complex diseases have been supported in applications for fellowship training including faculty fromthe Departments of Colorectal Surgery, in Allergy and recent house staff members have been Radiology and Pathology. There is expertise in a wide accepted to such fellowships in well- recognized programs spectrum of inflammatory disorders including ulcerative including Scripps Clinic, Brigham and Women’s Hospital, colitis, Crohn’s disease, lymphocytic colitis, collagenous Baylor College of Medicine and University of Virginia College colitis and many others. of Medicine.

The GI motility service offers the latest techniques for the Divisional staff regularly conduct consultations with study of motility problems of the gastrointestinal tract. physicians within the New England Quality Care Alliance, Physician experts applying this advanced technology aid in and educate dietary interns rotating through the Food the evaluation of non-cardiac chest pain, gastroesophageal Allergy Center on management of food allergies and food reflux disease, defecation disorders and more. intolerances.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF GASTROENTEROLOGY OF DIVISION

Community Outreach Programs diseases. The staff reaches out to the Mandarin and Cantonese speaking population of Boston through health Division staff has given presentations to schools, community fairs, seminars and educational articles in Chinese language health center, such as the YMCA, and on local TV and radio newspapers like Sampan, to increase local awareness of the stations about the prevention and treatment of allergic services offered by the Allergy Division.

Clinical Research

Recipient Funding Source Purpose of Award

STOOL Study: A multi-center, longitudinal study sponsored by OpenBiome that Aaron Dickstein, MD OpenBiome aims to prospectively investigate short- and long-term safety and efficacy of FMT in treating recurrent C. difficile.

Basic Research

Recipient Funding Source Purpose of Award A prospective, multi-center, longitudinal and exploratory pediatric and adult study to determine the correlation of clinical outcome measures with the established biomarker of peak mucosal eosinophil count (Phase 1), and National Institutes of Health to compare the transcriptomes (eosinophilic esophagitis- transcriptome, (NIH) eosinophilic gastritis-transcriptome and eosinophilic colitis- transcriptome) with their respective peak mucosal eosinophil counts and respective clinical outcome measures. John Leung, MD A prospective, non-blinded randomized trial comparing patient reported Patient-Centered Outcomes outcomes scores in novel empiric elimination dietary therapies in eosinophilic Research Institute (PCORI) esophagitis (EoE) in order to assess the therapeutic viability of minimally restrictive empiric elimination diets. A prospective, randomized, single center, controlled study to show a NEQCA LCO 2015 Performance smartphone based remote home visit program is not inferior to APMI’s home and System Improvement visit program by increasing medication adherence (to >75%) and reducing Program ED/urgent care visits, while reducing cost by 50%.

57 Basic Research (continued)

Recipient Funding Source Purpose of Award Swiss National Science Foundation (grant no. 32003B_135665/1) AstraZeneca AG (Switzerland) Aptalis A multicenter study to develop, validate and evaluate an eosinophilic

» Dr. Falk Pharma GmbH (Germany) esophagitis activity index for pediatric and adult patients » DIVISION OF GASTROENTEROLOGY OF DIVISION Glaxo Smith Kline AG Nestlé S. A. (Switzerland) The International Gastrointestinal Eosinophil Research This is a randomized, placebo-contolled, parallel-group, double-blind trial of John Leung, MD Shire Pharmaceutical, Inc Oral Budesonide Suspension (OBS) in Adolescent and Adult Subjects (11 to (continued) 55 Years of Age, Inclusive) with eosinophilic esophagitis. A prospective, randomized, single center, controlled study in pediatric patients age 6-18 who have poorly controlled asthma and whose parents/ Tufts Medical Center guardians have access to a smartphone (or similar device) with video and internet capability to asses the viability of remote visits in controlling asthma symptoms and ED visits. A randomized, placebo-controlled, parallel-group, multi-site, double- Merck Sharp & Dohme Corp., a blind trial of MK-3641 in children with ragweed pollen-induced allergic subsidiary of Merck & Co., Inc. rhinoconjunctivitis, with or without asthma, to be conducted in conformance with Good Clinical Practices A multicenter, double-blind, placebo- controlled study is investigate the Regeneron Pharmaceuticals, Inc efficacy, safety, pharmacokinetic, and immunogenicity of dupilumab in adult patients with eosinophilic esophagitis. National Institute of Food and Combination of curcumin and vitamin B6 for the prevention of obesity- Joel Mason, MD Agriculture (NIFA) induced colon cancer: animal studies Investigation of immune regulation in the gut pertaining regulatory T cells and NIH-RO1 DK 058755 the effect on the control of IBD Investigation of the role of dendritic cells in the control of inflammation in the Joel Weinstock, MD NIH-RO1-KD091987 intestines and how it relates to IBD The Schneider Family The Inflammatory bowel disease Gilman Family

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF GASTROENTEROLOGY OF DIVISION

Honors and Awards

John Leung, MD »» 2016 – American College of Gastroenterology – SCOPY Award for Best Foreign Language Video, “Chinese Colonoscopy Prep

Joel Mason, MD »» 2016 – Lecture at annual meeting of International Food Technology: “Obesity and Colon Cancer”

Moises Guelrud, MD »» 2016 – Castle Connolly Top Doctors

Mark Sterling, MD »» 2016 – Quality Improvement Officer for the Division of Gastroenterology at Tufts Medical Center

59 DIVISION OF GEOGRAPHIC MEDICINE AND INFECTIOUS » » GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION DISEASES

The Division of Geographic Medicine and Infectious Diseases at Tufts Medical Center is known for its excellence in clinical care, teaching, and research. The Division was created in 1957. Its first Chief, Dr. Louis Weinstein, was an internationally renowned clinician and teacher whose clinical acumen and charismatic teaching style attracted many young physicians to the relatively new subspecialty of infectious diseases. Graduates of his training program occupied significant positions in academia. During the tenure of his successor, Dr. Sherwood Gorbach, the cause and pathogenesis of C. difficile David David Snydman, MD Snydman, MD, FACP, FIDSA, FAST associated disease were discovered by Drs. John Bartlett and Te-Wen Chang. In 2007, Dr. Gorbach was awarded the Alexander Fleming Prize, a lifetime achievement award, from the Infectious Diseases Society of America. Dr. Sheldon Wolff, the Chairman of Medicine at Tufts- New England Medical Center and an internationally recognized infectious disease expert (and Fleming Prize recipient), together with Charles Dinarello of the Experimental Medicine Division, discovered interleukin-1.

In 1986, the Divisions of Geographic Medicine, Experimental Medicine, and Infectious Diseases were merged into the Division of Geographic Medicine and Infectious Diseases. The chief, Dr. Gerald Keusch, was well known for his work on the pathogenesis of enteric infections, the effects of malnutrition on the immune response, and vaccine development. He, too, has been awarded the Fleming Prize by IDSA.

Dr. David R. Snydman became chief of the Division in 1998. Dr. Snydman is known for the first clinical description of Lyme disease, the first isolation of an organism consistent with B. burgdorferi from the joint of a patient with chronic Lyme arthritis, and the development of Cytomegalovirus Immune Globulin, which is used in transplantation. Dr. Snydman has expanded the division’s expertise in transplantation infectious disease, HIV care, and clinical research while maintaining the international programs and basic science focus in research. Under his leadership, the Division secured its’ fourth NIH training grant, this one in clinical research training in infectious diseases. In addition, the faculty has obtained 10 research career development awards from the NIH and 3 faculty career mentor awards, and trains 3-5 new fellows each year. Tufts University School of Medicine and Tufts Medical Center is the site for the editorial offices of Clinical Infectious Diseases, a journal of the Infectious Disease Society of America. The Editor and Deputy Editor and several Associate Editors are faculty members.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Highlights of 2016

»» David R. Snydman, MD, FACP, FIDSA was named »» Susan Hadley, MD, FIDSA was honored Vice-Chairman for Research in the Department of posthumously with a Professor Emerita Medicine Medicine award from Tufts University School of Medicine in May 2016. »» Sherwood Gorbach, MD, Professor Emeritus of Medicine and Public Health, had the honor of »» Geneve Allison, MD, FACP was named to the Best having an organism named after him, Doctors in Boston by Castle Connolly. Gorbachella massiliensis. »» Brian Chow, MD, Tine Vindenes, MD, MPH, and

»» Debra Poutsiaka, MD, PhD, was named the first Lindsay Margoles, MD, joined the division. » » Susan Hadley, MD Clinician Educator Awardee by DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION the fellows.

Faculty

Name Academic Rank Title and Special Responsibility Chief of Division David R. Snydman, MD, FACP, FIDSA, Professor Hospital Epidemiologist FAST Vice Chair for Research Department of Medicine Director of OPAT (OutPatient Intravenous Antibiotic Therapy) Genève Allison, MD, MSc, FACP Assistant Professor Program Robert Arbeit, MD Professor Consultation Attending, Idera Pharmaceuticals Michael Barza, MD Professor Vice Chair for Clinical Affairs, Department of Medicine Fellowship Program Director Helen W. Boucher, MD, FACP, FIDSA Professor Director, Heart Transplant and Ventricular Assist Device Infectious Diseases Program Victor Boyartchuk, PhD Assistant Professor HPV Clinic, José A. Caro, MD Assistant Professor Course Director for the Infectious Diseases Rotation for 4th Year Medical Students Brian D.W. Chow, MD Assistant Professor Intercity Conference Director, Jennifer K.L. Chow, MD, MS Assistant Professor Associate Director, Ventricular Assist Device and Heart Transplant Infectious Disease Program Antimicrobial Steward, Antimicrobial Management Program Shira Doron, MD, MS, FIDSA Associate Professor Associate Hospital Epidemiologist Yoav Golan, MD, MS, FIDSA Associate Professor Professor Emeritus, Public Sherwood L. Gorbach, MD Health and Medicine Jeffrey K. Griffiths, MD, MPH & TM Professor James Hellinger, MD, MSc Assistant Professor Steven Y. Hong, MD, MPH, MAR Assistant Professor Deputy Chief of Party, Society for Family Health, Namibia Molecular Biology and Microbiology, Tufts University School Linden T. Hu, MD, FIDSA Professor of Medicine. Principal Investigator Microbial Pathogenesis Training Grant Michael R. Jordan, MD, MPH Assistant Professor Consultant to WHO Anne V. Kane, MD Assistant Professor Director, Phoenix Lab

61 Faculty (continued)

Name Academic Rank Title and Special Responsibility Laura Kogelman, MD, FIDSA Associate Professor Director of ID Clinic and Traveler’s Health Services Pathophysiology Course Director, Morbidity and Mortality Rakhi Kohli, MD, MS Assistant Professor Conference Director Xin Li, PhD Assistant Professor Lindsay Margoles, MD Assistant Professor »

» Director, Inpatient Skin Management and Risk Reduction GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION Natalie E. Nierenberg, MD, MPH Assistant Professor Team Center for Vascular, Wound Healing & Hyperbaric Medicine Roberta O’Connor, PhD Assistant Professor Debra D. Poutsiaka, MD, PhD, FIDSA Associate Professor Co-director Mycobacterial Treatment Unit – Tufts MC David R. Stone, MD Associate Professor Attending Physician, Tufts Medical and Lemuel Shattuck Hospital Cheleste Thorpe, MD Associate Professor Institutional Biosafety Committee Chair Edouard Vannier, PhD Assistant Professor Tine Vindenes, MD, MPH Assistant Professor Global Care Medical Group, PC Associate ID Fellowship Program Director, Gretchen Volpe, MD, MPH Assistant Professor Antimicrobial Stewardship Director of Clinical HIV Research Program Associate Chair Dept. of Public Health Director, Christine Wanke, MD Professor Division of Nutrition and Infection Professor School of Nutrition Honorine D. Ward, MD Professor Assistant Clinical Professor Attending Physician, South Shore Hospital Simone Wildes, MD, FACP Assistant Professor HIV/HCV co-infection clinic

Teaching Activities The Division provides comprehensive teaching for all levels disease physicians. A rigorous didactic curriculum of the medical school and for postgraduate education. encompasses HIV medicine, nosocomial and community acquired infections, transplantation-related infections and Dr. Teena Kohli is the director of the Infectious Disease infections acquired during travel abroad. The second pathophysiology course for the second year medical school program year is devoted partly to research. Trainees can curriculum. elect to acquire additional expertise in one of four tracks, Drs. Kohli, Kogelman, and Wurcel were recognized as top namely infection control, antimicrobial stewardship, lecturers by Tufts University School of Medicine. transplant infectious diseases, or HIV. Research fellowships are available in global health with an NIH The fellowship program is comprehensive and includes sponsored D 43, or in microbial pathogenesis (T 32) or as training in transplant infectious diseases. From three to part of an endowed fellowship in infectious diseases five fellows are recruited each year. The training program is named after a former faculty member, Frank Tally, MD. considered by the Infectious Disease Society of America to (the Tally fellowship). be a model for such programs. Graduates of the program hold faculty positions at major The goal of the fellowship program is to train the next academic medical centers, as well as at the United States generation of academic infectious diseases specialists. The clinical training comprises 12 months of inpatient FDA, CDC, and in the pharmaceutical industry. consultation and a weekly clinic supervised by infectious

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION

Research Activities purification, preparation of complex bacterial media, and preparation of competent cells and plasmid State of the art research conducted by divisional faculty maxipreps by the cesium gradient technique. In in bacterial, HIV, other viral and parasitic diseases response to the Human Microbiome Project, Drs. Kane spans basic science, clinical research, outcomes, and and Ward founded the Microbiota Working Group to translational research in the US and abroad. The annual encourage microbiota projects in the Division. Dr. Kane research budget for the division exceeds $4 million. has added services to the core which are designed to The tables below provide an indication of the scope of facilitate research such as DNA extraction from clinical these awards. samples and the subsequent generation and purification Anne Kane, MD, manages the Phoenix Lab, a microbial of PCR amplicons of 16S ribosomal DNA for deep products and services core facility for the Tuft sequencing. She has for several years lectured to community. The core services are all based on the graduate students in the Friedman School on the role of growth of micro-organisms and include large and small- the intestinal microbiota in human health. scale bacterial culture, protein expression and

63 Clinical Research Awards

Recipient Funding Source Purpose of grant Algorithm-based Therapy of Catheter-associated Staphylococcus NIH – HHSN272200900023C Septicemia Protocol Chairperson, Clinical Endpoints Committee (CEC) Industry – Actelion Protocol AC-061A301/AC-061A302 Multi-center, randomized, double-blind studies to compare the efficacy and safety of Industry – Actelion Protocol AC- cadazolid versus vancomycin in subjects with Clostridium difficile- 061A301/AC-061A302 » associated diarrhea (CDAD). » GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION Chairperson, Data Monitoring Committee Antibacterial Resistance Leadership Group Member, Gram-positive NIH – 1UM1AI104681 subcommittee World-wide Randomized Antibiotic EnveloPe Infection Medtronic Protocol Prevention Trial, (WRAP-IT), Helen Boucher, MD Member, Data Monitoring Committee A Phase 3, Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled Study to Assess the Efficacy and Safety of Maribavir Shire Protocol 620-302 Compared to Valganciclovir for the Treatment of Cytomegalovirus (CMV) Infection in Hematopoietic Stem Cell Transplant Recipients Member, Data Monitoring Committee A Phase 3, Multicenter, Randomized, Open-label, Active- controlled Study to Assess the Efficacy and Safety of Maribavir Compared to Investigator-assigned Treatment in Transplant Shire Protocol 620-303 Recipients with Cytomegalovirus (CMV) Infections that are Refractory or Resistant to Treatment with Ganciclovir, Valganciclovir, Foscarnet or Cidofovir, Member, Data Monitoring Committee Industry HPV and Anal Cancer in HIV+ Patients José A. Caro, MD Center for AIDS Research Developmental Award: Tissue Biomarkers and Cellular Immunity as (CFAR) 2016 Predictors of Anal HSIL in HIV positive MSM Resistance Development in Antibiotic – Treated Pet Dogs and their Shira Doron, MD, MS Tufts One Health Committee Owners

Role of Bile Acids in Human Susceptibility to Clostridium difficile NIH (R21) Infection Trends of Ceftaroline (CPT) Activity Among Consecutive Methicillin- Forest Labs resistant Staphylococcus aureus (MRSA) Blood Isolates and Correlation with Vancomycin (VAN) Activity Mortality and Hospital Length of Stay (HLOS) among Patients with Community-Acquired Pneumonia (CAP): A Propensity Score-Matched Forest Labs Yoav Golan, MD, MS Analysis of Ceftaroline fosamil (CPT-F)-Treated vs. Ceftriaxone-treated patients. Validation of a simple clinical rule to predict recurrence of infection by Merck & Co. C. difficile. Step 2: Defining risk factors for multiple recurrences ofC. difficile infection. A risk of recurrence-stratified comparison of fidaxomicin vs. vancomycin in adults with Clostridium difficile infection (CDI) and the cost- Cubist Pharmaceuticals effectiveness of fidaxomicin vs vancomycin or metronidazole in the treatment of infection by Clostridium difficile

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Recipient Funding Source Purpose of grant Namibia ART Patient Tracing Intensification and Predictors of Loss to 1K23AI097010-01A1, NIH/NIAID Follow-up Pilot Study of an Alcohol Screening and Brief Intervention to Reduce U2G, CDC/PEPFAR Hazardous Alcohol Consumption in Namibia’s ART Programme HIV Drug Resistance Amongst Patients Failing Second-line Antiretroviral U2G, CDC/PEPFAR Therapy in Namibia » »

Demonstration Project on Feasibility and Effectiveness of Community DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION Steven Y. Hong, MD, MPH U2G, CDC/PEPFAR Adherence Clubs in Namibia’s ART Programme, 04/01/2017 – 03/31/2018, Principal Investigator Outreach HIV Services Targeting Men and their Sexual Partners: Demonstration Project in Khomas Region of Mobile Clinic Community- U2G, CDC/PEPFAR Based HIV and Multi-Disease Testing Intervention, 04/01/2017 03/31/2018, Principal Investigator The Society for Family Health, Deputy Chief of Party / Director: Clinical Services, 04/01/2017 – USAID, 03/31/2018 Preventing HIV and STDs in Women Over 50; Phase 2 SBIR NIA 5R44AG034707-03 – Creating educational videos to promote safe sex among culturally diverse divorced women over 50. Laura Kogelman, MD A pilot feasibility project for: Toward a new clinical trial: Advanced NIH/NIAID ‘infection proof’ anti-HIVgene- modified T cells Period: January 2016-ongoing Role: Co-Investigator Characterization of the mechanism of action of a marine secondary Roberta O’Connor, PhD Russo Dual Investigator Award metabolite with activity against Toxoplasma and Cryptosporidium Investigation of a novel sepsis biomarker, presepsin, in distinguishing Debra Poutsiaka, MD, PhD Mochida Pharmaceuticals SIRS from sepsis

NIAID Clinical research training grant in infectious disease

US National Survey of susceptibility of Bacteroides fragilis, National Industry Sources Survey of C. difficile antimicrobial susceptibility and epidemiology. Summit Ridinilazole phase II trial Phase 2 trial microbiology including Microbiome analysis, ribotype David R Snydman, MD Summit diversity, spore and vegetative cell isolation, vancomycin resistant Enterococci, and survey of C. difficile susceptibility Seres Testing of Isolates National Survey of C. difficile susceptibility to Fidaxamicin Merck Analysis of Ribotype diversity over time among C. difficile in the US Actelion National Survey of C. difficile susceptibility to Cadazolid TUSM Earl P. Charlton Fund Gretchen Volpe, MD Food insecurity, Obesity, and Antiretroviral adherence in an HIV clinic. Research Award

65 Clinical Research Awards

Recipient Funding Source Purpose of grant

Fogarty HIV and Nutrition Training Program with University of Namibia

Training Program in Innovations in Global Health (with Dr. H Ward and Fogarty Christian Medical College) Joint Indo-US Collaborations, on HIV, ART, Intestinal Microbiota Food R21 and Nutrition Technical Assistance » » GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION USAID/WHO Funding to prepare Nutrition and HIV Guidelines

The Impact of Omega Three Fatty Acids on Vascular Function and cIMT R01 NIH/NHLBI Christine Wanke, MD in HIV Infected Individuals

R01 NIH/NICHHD Nutrition and HIV Progression

2 R01 NIH/NHLBI Protease Inhibitor Related Dyslipidemia

NIH/NIAID Brown-Tufts University Center for AIDS Research: Nutrition Core

Brown/Tufts/Miriam Fogarty AIDS International Training and Research NIH/Fogarty Program A Multi-arm, Phase 3, Randomized, Placebo Controlled, Double Blind Industry - BMS clinical research Clinical Trial to Investigate the Efficacy and Safety of BMS-663068 study in Heavily Treatment Experienced Subjects Infected with Multi-drug Resistant HIV-1 Health Services grant to increase care for persons with hepatitis C virus (HCV) as a comorbid condition of substance abuse through a program Alysse Wurcel, MD, MS HRSA-16-074, HRSA of patient co-management between Duffy Health Center in Hyannis and Tufts Medical Center in Boston The Economic Burden of HIV and HCV Infection in Hospitalized Inmates. The goal of this study is to compare costs of hospitalization for inmates P30AIO42853, NIAID with HCV to those without HCV, and investigate whether HIV/HCV co- infection further increases the costs of hospitalization.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Basic Research Support In addition to clinical research, Division faculty carry out basic research in Lyme disease and babesiosis, cryptosporidiosis, and Shiga toxin.

Recipient Funding Source Purpose of grant Victor Boyartchuk, PhD 5R21 AI097855-02 Analysis of TGSL, A Novel Regulator of Macrophage Survival

R01AI122286 NIH/NIAID Persister Cells of Borrelia burgdorferi

R21AI126757 NIH/NIAID Role of innate immune intolerance in the pathogenesis of Lyme disease » » GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION Coping with Stress: Next Generation Approaches to Borrelia burgdorferi R01AI131656 NIH/NIAID Host Adaptation Steven and Alexandra Cohen Pilot Field Trial of Reservoir Targeted Vaccine Foundation Steven and Alexandra Cohen Identification ofB. burgdorferi genes involved in adaptation to the tick Linden Hu, MD Foundation host by massive parallel sequencing Physiological Interaction Between Probiotic Bacteria and Porphyromonas 5R01 DE024308-02 gingivalis R42AI078631 NIH Delivery system development for a reservoir targeted vaccine Role of carbon availability in environmental adaptation by Borrelia 1R21 AI111317-01 burgdorferi 5T32 AI007329-22 Infectious Disease Training – Pathogenesis/Host Response 5U01 AI109656-01 Searching for persistence in Lyme Disease Xin Li, PhD 7R01 AI103173-02 Critical Roles of Iron and Copper Detoxification inBorrelia Burgdorferi NIH sponsored U01 subcontract Diverse Drug Lead Compounds from Bacterial Symbionts in Tropical Roberta O’Connor, PhD from Oregon Health and Science Marine Mollusks University NIH, NIAID An Ex Vivo 3-D Pre-Clinical Human Enteroid Model for Cryptosporidium

NIH NIAID Role of GAG-Binding Proteins in Cryptosporidium Infection A bioengineered 3D primary human intestinal model for NIH NIAID Cryptosporidium NIH FIC Tufts-CMC Framework Program for Global Health Innovation Tufts CTSI A Point-of-care platform for Cryptosporidiosis Honorine D. Ward, MBBS Tufts Collaborates/Tufts The Relation of Cohabitation with Production Animals to Gut Microbiota University and Stunting in Children A novel 3-D bioengineered human intestinal model for Cryptosporidium Tufts Innovation Institute propagation Bill and Melinda Gates An Integrated Human Enteroid Model of Environmental Enteric Foundation Dysfunction Bill and Melinda Gates A Bioengineered Model of Human Intestinal Cryptosporidiosis Foundation The Gordon and Llura Gund Identification of genetic determinants of susceptibility to babesiosis in Family Foundation humans Edouard Vannier, PhD The Dorothy Harrison Egan Characterization of novel therapeutic targets for severe babesiosis Foundation

67 Honors and Awards

Geneve Allison, MD, FACP »» The Current State of the Antibiotic Pipeline, Washington, DC »» First author paper selected by the journal’s editorial team »» IDSA-FDA Meeting on Facilitating Antibacterial Drug as the Outstanding Paper in the 2016 Development for Patients with Unmet Need and »» Emerald Literati Network Awards for Excellence: Allison Developing Antibacterial Drugs that Target a Single GM, Weigel B, Holcroft C. Does electronic medication Species, Rockville, MD reconciliation at hospital discharge decrease prescription »» Panel member, FDA Workshop: Coordinated development medication errors? Int J Health Care Qual Assur. of new antimicrobial drugs and antimicrobial susceptibility » »

GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION 2015;28(6):564-73. test (AST) devices, Rockville, MD »» Chair, Medication Safety Committee, Tufts Medical Center »» CDDEP-IDSA-PEW-GARP-BASC-DZIF-NIPH-Wellcome »» Director, Outpatient Parenteral Antibiotic Therapy, Tufts Forum on Sustainable Access to Effective Medical Center »» Antibiotics before the UN High Level Meeting on »» 2016 Co-chair, International Working Group on OPAT, Antimicrobial Resistance, New York, NY International Society of Chemotherapy Infection and »» Use of New Antibiotics: FDA Indications and Beyond. Cancer Gram-positive Antimicrobials. ID Week, New Orleans, LA »» IDSA (Infectious Disease Society of America) – Update on Brian D.W. Chow, MD OPAT e-Handbook and OPAT Guidelines, October 2016, »» “Effectiveness of Influenza Vaccination and Statins against New Orleans, LA Laboratory Confirmed Influenza.” Huong Q. McLean, PhD, Helen Boucher, MD, FACP, FIDSA MPH; Brian D. Chow, MD; Jeffery J. VanWormer, PhD; »» Promoted to Professor of Medicine Burney A. Kieke, MS; Jennifer P. King, MPH; Edward A. »» Member, IDSA Clinical Practice Guidelines for Belongia, MD. Options IX Meeting for the Control of Staphylococcus aureus Bacteremia Influenza, Chicago, IL, August 2016. »» Member, Task Force on Industry Relations Infectious »» “Health care provider attitudes and barriers regarding HPV Diseases Society of America vaccination: Factors associated with increasing HPV vaccine coverage before and after an intervention »» Chair, Academic Affairs Committee, College of the Holy program.” Huong Q. McLean, PhD, MPH, Becky S. Cross Birchmeier, RN, MS, Brian Chow, MD, Elizabeth R. Vickers, »» Abstract Reviewer for IDWeek and ASM Microbe MPH, Michael M. McNeil, MD, Julianne Gee, MPH, Shannon »» Global Infectious Diseases: New Challenges and Solutions Stokley, DrPH, Edward A. Belongia, MD, Jeffrey J. Keynote Address. Boston University School of Law VanWormer, PhD. IDWeek 2017, New Orleans, LA, October »» Mock Drug Development Exercise (CME), Annual 2016. Postgraduate Course in Clinical Pharmacology, Drug »» Pediatric Infectious Diseases Society Vaccine Advocacy »» Development and Regulation, Boston, MA. Committee »» Alexandria Summit- Infectious Diseases. Antimicrobial »» American Academy of Pediatrics PREP: Infectious Resistance. Washington, DC. Diseases Editorial Board »» Duke Margolis Antimicrobial Expert Workshop, Exploring Practical Implementations of Economic »» Incentives for Antimicrobial Development in the U. S., Washington, DC »» Panel member, AHRQ/CDC Expert Panel Meeting, Atlanta, GA »» FDA Workshop: Developing Antimicrobials for Unmet Medical Needs, Silver Spring, MD »» PEW Charitable Trust - American Society for Microbiology - Wellcome Trust Congressional Briefing:

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Shira Doron, MD, MS, FIDSA Linden T. Hu, MD, FIDSA »» Consultant, MDPH, Implementation of state antimicrobial »» Member, NIH study section (HIBP) resistance program Society for Healthcare Michael Jordan, MD, MPH »» Epidemiology of America Antimicrobial Stewardship »» Global surveillance of HIV drug resistance: approaches and subcommittee linkage with monitoring of the HIV continuum of care. »» Consultant, DPH for CDC grant to develop content for Invited presentation at the ECDC/WHO Joint Meeting on statewide stewardship implementation European HIV/AIDS Surveillance10-11 March 2016, » » »» Adjunct appointment Immunology Department at Sackler Bratislava, Slovakia DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION School of graduate biomedical sciences for service to »» Early Warning Indicators of HIV drug resistance: linkage to MERGE-ID students. care and monitoring. Invited presentation to the Namibia Invited talks: Ministry of Health and Social Services, HIV Care and »» New England Critical Care Pharmacists, March Treatment Program. Held at Safari Hotel, Windhoek, »» The Hospital and Healthsystem Association of Namibia. August 2016. Pennsylvania, March »» Early Warning Indicators of HIV drug resistance. Invited »» SHEA, May presentation to Patient Monitoring Meeting, Held at World »» ASM/MICROBE, June Health Organization, Geneva. September 2016. »» Regional HMCC talk on Ethical Consideration in Ebola »» Global Action Plan on HIV resistance monitoring. Invited Management, December presentation to ECDC expert consultation meeting – Surveillance of HIV drug resistance in the EU/EEA 27-28 »» Go Team sessions, Nov October 2016. Stockholm, Sweden. »» Delvalle Institute EID Training session, Sept. Panel member. David R. Snydman, MD, FACP, FIDSA, FAST Steven Y. Hong, MD, MPH, MAR »» Best Doctor’s in America Selection 2015-16 »» Member, Tufts Global Health Faculty Council »» Invited Presentation entitled “Treating CMV in Solid Organ »» Center for AIDS Research: HIV Prevention Core Faculty, Transplant: Resistance and Therapeutic Options at the Lifespan/Tufts/Brown Center for AIDS Research American Society for Transplantation Meeting, Boston, Ma »» Center for AIDS Research Namibia Country Director June 2016 »» Member, Republic of Namibia HIV Drug Resistance »» Abstract Reviewer for ECCMID, and AST Technical Working Group »» Wellcome Trust grant reviewer »» Member, Republic of Namibia ART Adherence Technical »» Associate editor of the Immunocompromised Host section Working Group of Clinical Infectious Diseases »» World Health Organization (WHO) Consultant for HIV drug »» IDSA Intra-abdominal Guidelines Committee resistance in sub-Saharan Africa »» Shire Endpoints Committee for Maribavir Studies »» National Institutes of Health Clinical Research Loan »» Sequiris DSMB Chair for Influenza vaccine trial Repayment »» Takeda DSMB member for vedulizumab sc trials in Crohns »» University of Namibia School of Medicine Fogarty Grant and Ulcerative Colitis sponsored Symposium on Responsible Conduct of Research Main Speaker David Stone, MD »» Ministry of Health and Social Services workshop on »» QI Division Leadership Committee Tufts Medical Center Responsible Conduct of Research-Speaker »» Board of Directors Span Inc. Transitional Care Program for »» Official launch of Namibia’s Ministry of Health and Social HIV in Boston. Services HIV Clinical Mentors’ Program and Induction »» State Pharmacy and Therapeutics Committee/ Workshop-Speaker Corrections in Massachusetts

69 Edouard Vannier, PhD Honorine Ward, MD »» Invited Speaker at the 2nd Lyme Disease and Tick-Borne »» Section Editor, Parasitology, BMC Infectious Diseases Illnesses Conference, Massachusetts General Hospital, »» Editorial Board, Infection and Immunity Boston, May 14-15, 2016. Presentation was entitled »» Editorial Board, Microbes and Infection “Babesiosis: Critical Issues”. »» Reviewer, NIH Study Section, Special Emphasis Panel, »» Invited Speaker at the 65th Annual Meeting of the Global Infectious Diseases American Society of Tropical Medicine and Hygiene, »» Reviewer: Infection and Immunity, Journal of Infectious Atlanta, November 13-17, 2016. Presentation was entitled Diseases, Clinical Infectious Diseases, American Journal of “The Rationale for an Antibody-based Therapy in Severe » Tropical Medicine and Hygiene, Nature, Nature »

GEOGRAPHIC MEDICINE AND INFECTIOUS DISEASES INFECTIOUS AND MEDICINE GEOGRAPHIC OF DIVISION Babesiosis”. Microbiology et al. Christine Wanke, MD »» Member, Cryptosporidiosis/Microsporidiosis Subject »» Member of IDSA Committee for Preparation of Enteric Group, Guidelines for the Prevention and Treatment of Infection Guidelines. Opportunistic Infections in HIV-Infected Adults and »» Chartered Member of Study Section ICPI. Adolescents NIH, CDC, and HIVMA/IDSA, Office of AIDS »» Reviewer for JID, AIDS, JAIDS, JAMA Research Advisory Council »» Member of Special Emphasis Review Panel for CTSA »» Member, Programs and Faculty Committee: Tufts Sackler Proposals School of Graduate Biomedical Sciences »» Presented Ethics in Research at the University of Namibia »» Presented on Infection Control at National Institute of Research in Tuberculosis, Chennai, India

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016

71 DIVISION OF HEMATOLOGY/ONCOLOGY

The Division of Hematology/Oncology was established in the 1940s by Dr. William Dameshek, who was a world-renowned » »

HEMATOLOGY/ONCOLOGY OF DIVISION hematologist and founder of the American Society of Hematology (ASH). Dr. Robert S. Schwartz, world renowned for his studies on the immune system and demonstration of pharmacologic immunosuppression, assumed the directorship of the Division of Hematology and oversaw its merger in 1978 with the Division of Oncology. His contributions ushered in the era of organ and bone marrow transplantation. In 1990, Dr. Schwartz was named Deputy Editor of the New England Journal of Medicine. His successor, Dr. Bruce Furie, together with Dr. Barbara Furie, made numerous major contributions to the fields of hemostasis, thrombosis Andrew Evens, DO, MSc, FACP and cell adhesion, including the discovery of P–selectin, an important platelet and vascular adhesion molecule. From 1998 to 2006, Dr. John Erban, an internationally recognized clinical breast cancer researcher, served as Division Chief, followed in 2006 by Dr. Richard Van Etten. He was succeeded in 2013 by Dr. Andrew Evens, an internationally recognized clinical and translational researcher in lymphoproliferative malignancies. Dr. Evens was also appointed Director of the Tufts Cancer Center at Tufts Medical Center.

Collectively, the Division has trained a multitude of leaders in hematology and oncology, many of whom now head major cancer centers, divisions of hematology and oncology, and major research programs throughout the world. Many trainees of the division hold leadership positions in professional societies including the American Society of Hematology (ASH), the American Society of Clinical Oncology (ASCO), and the American Association of Blood Banks. Division faculty oversee the treatment of patients with a wide array of cancers in both ambulatory and inpatient settings and have important roles in post-graduate education as well as clinical and translational research for the Tufts Cancer Center.

Highlights of 2016

»» Dr. Cindy Varga joined the division, bringing expertise in »» Cancer Center’s Asian population navigate their healthcare plasma cell neoplasms including amyloidosis and multiple »» The Program for Adolescents and Young Adults (AYA) with myeloma. cancer and hematologic diseases received philanthropic »» 12 physicians from the Cancer Center, including 4 support from the Reid R. Sacco AYA Cancer Alliance hematologists, named among Boston Magazine’s“Top »» The Division has over 100 clinical trials in cancer and Doctors” hematology with cumulative budgets exceeding $5 million »» A unique Community Oncology Disparities Initiative »» The Bone Marrow Transplant program at Tufts Medical continued with philanthropic support from the Yawkey Center received full re-accreditation from Foundation for the Foundation, the Asian Accreditation of Cellular Therapy (FACT) in 2016. »» Healthcare Foundation of Massachusetts, and the Avon »» Several philanthropic gifts were received in 2016 to support Foundation to support the creation of a Patient Navigation research programs and patient care as detailed below. Program helping Tufts

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » HEMATOLOGY/ONCOLOGY OF DIVISION

Recent Cancer Center Gift Highlights Gastric Carcinoma Research Fund Breast Cancer Research Ms. Elizabeth A. McNiel made three gifts totaling $40,000 for the Gastric Carcinoma Research Fund Zaniboni Breast Cancer Fund in 2016. Funds raised from the registration of the “cure breast cancer” charitable license plate totaled over $130,000. Amyloidosis and Myeloma Research Program The Zaniboni Scholar Award is made possible through The Demarest Lloyd Jr. Foundation made a gift of The Massachusetts Cure Breast Cancer License Plate $161,000 in support of Dr.Comenzo’s translational Initiative, established October 31, 2006. All Faculty research program. Additional Research Support Ms. Carol A Feldsher made a gift of $25,000 in 2016. The Estate of Mr. William Moore made a gift of Asian Healthcare Foundation of Massachusetts $138,000 to support research in the Division of The Asian Healthcare Foundation of Massachusetts Hematology/Oncology provided the cancer center with a $50,000 donation to Michael and Marci Moreau donated $26,000 to support defray cost of hiring a multilingual patient navigator. breast cancer care and research Prostate Cancer Research Fund Ms. Julie Person made a gift of $250,000.

73 Faculty

Name Academic Rank Title and Special Responsibilities Chief, Division of Hematology/Oncology Director, Andrew M. Evens, DO, MSc, FACP Professor Tufts Cancer Center Eugene Berkman, MD Professor, Emeritus Former Chief, Division of Hematology/Oncology Director, Hematology/Oncology Fellowship Program; Zaniboni Scholar in Breast Cancer Rachel Buchsbaum, MD Associate Professor Associate Chief Medical Officer for Graduate Medical » »

HEMATOLOGY/ONCOLOGY OF DIVISION Education Research Associate Director, Hemostasis and Thrombosis Research Diane Connolly, PhD Assistant Professor Laboratory Medical Director, Blood Bank and Transfusion Service, Stem Cell Processing Laboratory Neely Cell Therapy and Raymond Comenzo, MD Professor Collection Center Founding Director, John C. Davis Myeloma and Amyloid Program Associate Director, Hemostasis and Thrombosis Research Lidija Covic, PhD Assistant Professor Laboratory Associate Director for Clinical Science and Clinical Director, John K. Erban, MD Professor Tufts Cancer Center Assistant Professor of Medicine Suriya Jeyapalan, MD, MPH Director, Medical Neuro-Oncology and Neurology Director of The Neely Cell Therapy Collection Center and Grace Shih-Hui Kao, MD Associate Professor Stem Cell Processing Laboratory Chairman, Institutional Review Board, Tufts Health Sciences Campus Andreas Klein, MD Associate Professor Associate Chief, Division of Hematology/Oncology Acting Chairman and Principal Investigator, Cancer Center Tissue Repository Oversight Committee Senior Consultant in Hematology Hans Klingemann, MD, PhD Adjunct Professor of Medicine Vice President for R&D, NantKwest, Inc Athan Kuliopulos, MD, PhD Professor Director, Hemostasis and Thrombosis Research Laboratory Anita Kumar, MD Assistant Professor Malignant Hematology and Health Outcomes/Survivorship Associate Chief, Division of Hematology/Oncology; Leader, Robert Martell, MD, PhD Adjunct Associate Professor Hepatobiliary Tumor Board and Head/Neck cancers Paul Mathew, MD Associate Professor Prostate Cancer and Genitourinary Malignancies Kenneth B. Miller, MD Professor Associate Chief, Division of Hematology/Oncology Senior Consultant in Hematology Tariq Mughal, MD Adjunct Professor of Medicine Founder, Alpine Oncology Foundation; and Vice President, Foundation One, Medical Affairs Lori Pai, MD, DMD, MPH Assistant Professor Lung Cancer and Melanoma Expert

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Name Academic Rank Title and Special Responsibilities

Associate Director for Population Science and Community Involvement, Tufts Cancer Center Director, Reid R. Sacco AYA Cancer Program Director, Patient Susan Parsons, MD, MRP Professor Navigation Program Director, Center for Health Solutions, Institute for Clinical Research and Health Policy Studies » »

Program Director, GI Oncology HEMATOLOGY/ONCOLOGY OF DIVISION Wasif Saif, MD Professor Program Leader, Experimental Therapeutics Senior Consultant in Hematology David Schenkein, MD Adjunct Professor of Medicine Chief Executive Officer, Agios Pharmaceuticals Robert Schwartz, MD Professor Emeritus Emeritus Chief, Division of Hematology/Oncology Clinical Director, Leukemia Program Kellie Sprague, MD Assistant Professor Clinical Director, Bone Marrow and Stem Cell Transplant Program Associate Director, Hematology/Oncology Fellowship Gary Strauss, MD, MPH Professor Program Medical Director, Lung Cancer Program Philip Tsichlis, MD Jane F. Desforges Professor Executive Director, Molecular Oncology Research Institute Lynne Taylor, MD Adjunct Associate Professor Neuro-Oncology and Palliative Care Cindy Varga, MD* Assistant Professor Plasma cell neoplasms program leader

*New faculty in 2016

Major Clinical Programs The faculty of the Hematology/Oncology Division A Holistic and Integrative Therapy program was supervises over 25,000 outpatient visits and treatments continued in the Tufts Cancer Center primarily with annually and oversees three complex inpatient services: funding from the Donaldson Charitable Trust the Bone Marrow Transplant/Hematologic Malignancies Foundation. The Integrative Therapy program is led in service, the Inpatient Oncology Service, and the part by Mary Beth Singer MS, ANP-BC, AOCN, ACHPN; it Hematology/Oncology Consultation service. Clinical aims to decrease symptom distress, promote healing, laboratory services under the direction of Division and improve the overall experience of cancer treatment members include a blood bank with stem cell processing for patients. Acupuncture and massage are provided free capability and a special Hematology Laboratory that of charge to cancer patients each week by certified processes blood and bone marrow specimens for clinical clinicians from Pathways to Wellness. Additionally, an and research purposes. The Neely Center Cell Processing annual lectureship and patient-focused workshop on and Collection Center provides state of the art services in fatigue, related symptoms, and supportive therapies has cell collection, processing, and therapy, apheresis, and been established and a program of research led by transfusion support for the entire Medical Center. The Nadine Linendoll, PhD, RN, was initiated focused on 20-bed infusion center provides state-of-the-art infusion cancer related fatigue and the impact of integrative support for chemotherapy, parenteral solutions, and therapy on cancer. antibiotics, in addition to education and psychosocial services. In addition, the Center for Extracorporeal Photopheresis provides novel therapy with a nationally recognized clinical research program in allogeneic stem cell transplantation and cell processing.

75 The Reid R. Sacco Adolescent and Young Adult (AYA) »» Lymphoma Program – Andrew Evens, DO, MS, FACP, Program for Cancer and Blood Diseases at Tufts Medical Medical Director Center was established and launched in 2013. The AYA »» Melanoma and Cutaneous Malignancies Program – Lori clinic, led by Dr. Susan Parsons, provides Pai, MD, Medical Director age-appropriate, comprehensive care in a designated »» Neely Cell Therapy Center and Extracorporeal physical space where our team focuses on both the Photopheresis Program – Raymond Comenzo, MD, clinical and transitional needs of cancer survivors ages Director; Grace Kao, MD, Associate Director 18-39 years. This program was started through generous »» The Neely Center for Clinical Cancer Research – John support from the Reid R. Sacco AYA Alliance. This Erban, MD, Medical Director »

» program represents one of the few such specialty HEMATOLOGY/ONCOLOGY OF DIVISION programs in New England dedicated to the care of »» Plasma Cell Neoplasms – Raymond Comenzo, MD, patients within this age group. Director Multidisciplinary Cancer Care is the paradigm for cancer Teaching Activities treatment offered by the Division. Physicians participate in several multidisciplinary clinics with concurrent and Faculty from the Hematology/Oncology Division participate coordinated care by multiple cancer specialists provide extensively in the teaching of medical students, house officers, multispecialty care and access to psychosocial and and fellows at Tufts Medical Center. Teaching of Tufts genetic counseling. Below are additional University School of Medicine (TUSM) students includes both multidisciplinary programs at Tufts. preclinical lectures and clinical clerkship teaching. Dr. Rachel Buchsbaum is course director for the TUSM course entitled Multidisciplinary programs and clinics for “Introduction to Hematology and Oncology, and serves as the cancer treatment (in 2016) include Vice-Chair of the TUSM Curriculum Committee. Dr. Susan »» Adolescent Young Adult Program for Cancer and Blood Parsons is co-course director of the Public Health Integration Diseases – Susan Parsons, MD, Director course for first, second, and third year students in the combined MD/MPH program at TUSM. She also is course »» Benign Hematological Disorders Clinic – Hande Tuncer, MD director of the Research Ethics course in the Clinical and Clinical Director Translational Science Graduate Program at the Sackler School »» Bone Marrow and Stem Cell Transplant Program – Kellie of Graduate Biomedical Sciences at Tufts University (Sackler). Sprague, MD Director Several faculty members are mentors and thesis advisors for »» Brain Tumor and Neuro-Oncology Program – Suriya PhD graduate students enrolled in Sackler programs. Jeyapalan, MD, Medical Director Currently, there are 5 PhD students doing thesis research in »» Breast Cancer and The Breast Health Center – Roger laboratories/research programs of Division faculty. Graham, Director and John Erban, MD, Medical Oncology The Division is also the home of the Hematology/Oncology Director Fellowship Training Program at Tufts Medical Center that is »» GI Oncology – Wasif Saif, MD Medical Director the centerpiece of Division teaching activities. As the Institute »» Genitourinary Malignancies Tumor Board – Paul Mathew, of Medicine and the American Society of Clinical Oncology MD, Director have predicted a major physician shortage in hematology/ »» Head and Neck Tumor Clinic – Robert Martell, MD, PhD oncology in the next decade, the Fellowship Program serves a critical educational need. Five clinical fellows per year are »» Hematologic Malignancies Program – Andreas Klein, MD, selected from over 300 applicants. The first year is devoted to Director clinical training in hematology and oncology, with an intense »» Hepatobiliary Tumor Clinic – Robert Martell, MD, PhD, focus on ambulatory care. Members of the Division join Clinical Director physicians from other specialties and ancillary services to »» Lung Cancer Multidisciplinary Clinic – Gary Strauss, MD, offer fellowship training and complex therapy in a MPH, Clinical Director multidisciplinary environment. In the second and third years

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 of the Program, fellows are exposed to the inpatient Clinical Research consultation service and the bone marrow transplant/ hematologic malignancies service, both of which provide Clinical research in hematology and oncology takes the essential clinical experiences and rigorous training in form of cooperative group trials, industry-sponsored managing complex diseases. Fellows maintain a continuity trials, and investigator-initiated trials. Tufts Medical outpatient clinic one half-day per week. During their clinical Center is a member of the Eastern Cooperative Oncology year, fellows are exposed to the breadth of basic and Group (ECOG), a prominent national clinical oncology translational cancer research at Tufts Medical Center through research consortium. A number of the Division faculty the MORI Lecture series, Cancer Center Grand Rounds, and serve in key leadership positions on ECOG committees direct contact with clinician-scientist faculty. These and are principal investigators for ECOG National clinical » » HEMATOLOGY/ONCOLOGY OF DIVISION experiences allow fellows to begin to plan research projects for trials. For example, Dr. Evens led NCT01216683: A 3-Arm their second year. Randomized Phase II Trial of Rituximab/Bendamustine (BR) Followed by Rituximab vs Bortezomib (Velcade®)-BR The research portion of the Clinical Fellowship begins in the (BVR) Followed by Rituximab vs. BR Followed by second year. Typically, about half of the fellows in each class Lenalidomide (Revlimid®)/ Rituximab in High Risk express an interest in basic and translational research, while Follicular Lymphoma. Dr. Parsons is a member of the the other half pursue clinical research projects. Under the study committee for Children’s Oncology Group trial supervision of an advisory committee, fellows make periodic AHOD1331, a randomized controlled trial of brentuximab presentations of their research progress to Division faculty. In vedotin in the treatment of children and adolescents with the third year, the writing of at least one research paper that high risk Hodgkin Lymphoma. She leads two embedded summarizes the trainee’s data and findings is a major priority. studies within the trial on chemotherapy-induced In 2016, 6 fellows in the Division presented their research work peripheral neuropathy and cost effectiveness analysis. at national meetings and international meetings, 5 fellows published papers related to their research projects, and 1 Together, the Division and Cancer Center have over100 fellow earned an achievement award (Dr. Flores, 2015 Danny active therapeutic clinical trials in cancer and Danielson Translation Innovation Award). hematology and 20+ new cancer clinical studies are awaiting activation. Many of these clinical studies are Over 140 Hematology/Oncology Fellows have been trained in “investigator- initiated trials (IITs) and are examining the Division, with approximately 40% of these trainees directly novel and targeted anti-cancer treatments, including supported during their research years by the Training Grant. immunotherapy (see table below). The cumulative Of Program graduates, 20 are now Division Chiefs, head major budgets for these clinical studies total over $5 million programs at NCI–designated Cancer Centers or at the National with the annual clinical trial funding in 2015 based on Cancer Institute, or hold leadership positions at major patient accrual was ~$1,000,000. This clinical research pharmaceutical companies. Of 24 program graduates in the activity supports basic and translational research within last 5 years, 18 are on the faculty of academic medical centers the Division. and one is a program leader in a major pharmaceutical company. Directed by Rachel Buchsbaum, MD, the Tufts All patients in the clinic and inpatient areas are asked to Hematology/Oncology Fellowship program received a full consent to donation of specimens (blood, bone marrow, 5-year accreditation with commendation by the Accreditation biopsy material) for research purposes as part of an IRB– Council for Graduate Medical Education at its last site review approved protocol, and these specimens are de–identified and continuing subsequent accreditation under the ACGME and banked. The Tissue Repository, a Core Facility of the Next Accreditation System. Tufts Cancer Center, is a valuable resource for meeting the translational research interests of qualified Tufts Medical Research Activities Center investigators. The following is a highlight of Faculty members and fellows of the Division of selected clinical cancer trials, with an emphasis on IITs Hematology/Oncology as well as investigators at MORI that are being conducted within the Division. continue vibrant research endeavors in cancer. Researchspans the spectrum from basic, translational, and patient- oriented research to numerous therapeutic and interventional clinical trials in cancer and blood diseases. Below is a summary of these research efforts in 2016.

77 Clinical Research/Clinical Trials (partial listing)

Investigator Sponsor/Trial number Title Finding the X Factor: how breast cancers conscript the tumor Tufts Medical Center TMC/CTSI microenvironment. Rachel Buchsbaum, MD Biomarker Breast: Development of a minimally invasive biomarker for Tufts Medical Center (TMC) breast cancer. Tufts Medical Center (TMC) A Diagnostic Screening Trial: Seeking AL Amyloidosis Very Early (SAVE)

» Minimal Residual Disease as a Possible Predictive Factor for Relapse in

» Tufts Medical Center (TMC) HEMATOLOGY/ONCOLOGY OF DIVISION Patients with AL Amyloidosis C16021: A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients Millennium With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation C16011: A Phase 3, randomized, controlled, open-label multicenter safety and efficacy study of dexamethasone plus MLN9708 or physician’s choice Millennium of treatment administered to patients with relapsed or refractory systemic light chain (AL) amyloidosis. An Open-label, multicenter, phase 1B study of JNJ-54767414 (HuMaxA Janssen CD38) (Anti-CD38 Monoclonal Antibody) in combination with backbone regimens for the treatment of subjects with multiple myeloma. E3A06: Randomized phase III trial of Lenalidomide vs. Observation alone in ECOG patients with asymptomatic high risk smoldering multiple myeloma. A Phase I, open label dose escalation study of intravenous administration of Prothena Raymond Comenzo, MD single agent NEOD001 in subjects with light chain (AL) amyloidosis. PRONTO: A Phase 2b, Randomized, Double-blind, Placebo-controlled Prothena Study of NEOD001 in Previously Treated Subjects with Light Chain (AL) Amyloidosis who have Persistent Cardiac Dysfunction VITAL: A phase III, randomized, multicenter, double-blind, placebo controlled, 2 arm, efficacy and safety study of NEOD001 Plus standard Prothena of care vs. placebo vs standard of care in subjects with light chain (AL) amyloidosis. NEOD001-OLE001: Open-label Extension Study to Evaluate the Long-term Prothena Safety and Tolerability of NEOD001 in Subjects with Light Chain (AL) Amyloidosis STORM: A Phase IIb, open-label, single arm study of Selinexor (KPT-330) Karyopharm Therapeutics KCP- plus low dose dexamethasone in patients with multiple myeloma quad- 330-012 refractory to previous therapies. Pre-clinical studies of Daratumumab in stem cell mobilization and Tufts Medical Center (TMC) transplant for patients with clonal plasma cell diseases. Pre-clinical studies of elotuzmab in stem cell mobilization and transplant Tufts Medical Center (TMC) for patients with clonal plasma cell diseases.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Investigator Sponsor/Trial number Title PALLAS: Palbociclib Collaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib with Standard Adjuvant Endocrine Therapy Versus PrECOG Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer E1Z11: A Cohort Study to Evaluate Genetic Predictors of Aromatase ECOG

Inhibitor Musculoskeletal Symptoms (AIMSS) » » HEMATOLOGY/ONCOLOGY OF DIVISION NRG BR003: A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel with or NRG / CTSU without Carboplatin for Node-Positive or High-Risk Node-Negative Triple- Negative Invasive Breast Cancer HCRN BRE12-158: A Phase II Randomized Controlled Trial of Genomically Hoosier Cancer Research Directed Therapy After Preoperative Chemotherapy in Patients with Triple Network Negative Breast Cancer BRAVO: A phase III, randomized, open label multicenter, controlled trial Tesaro of niraparib vs physician’s choice in previously treated HER2 negative, John Erban, MD germline BRCA mutation positive breast cancer patients. MGA271-01: A phase I, open label, dose escalation study of MGA271 (Fc- optimized Humanized Anti-B7-H3 Monoclonal Antibody) in patients with Macrogenics refractory B7- H3-Expressingneoplasms or neoplasms whose vasculature expresses B7-H3. MGAH22-02: A Single Arm, open label phase II study of MGAH22 (Fc- optimized Chimeric Anti-HER2 monoclonal antibody) in patients with Macrogenics relapsed or refractory advanced breast cancer whose tumors express HER2 at the 2+ level by immunohistochemistry and lack evidence of HER2 gene amplification by FISH. MGAH22-04/SOPHIA: A Phase 3, Randomized Study of Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment Macrogenics of Patients with HER2+ Metastatic Breast Cancer Who Have Received Two Prior Anti-HER2 Therapies and Require Systemic Treatment Inflammatory Breast Cancer Initiative: Creation of an Inflammatory Breast Tufts Medical Center (TMC) Cancer Research Database

79 Clinical Research/Clinical Trials (partial listing) continued

Investigator Sponsor/Trial number Title C16017: An Open-label, Multicenter, Phase 2 Study of Oral MLN9708 in Millennium Adult Patients With Relapsed and/or Refractory Follicular Lymphoma AFM11-101: A Pharmacodynamically guided, dose-escalation, phase 1 study to assess the saftey of AFM11 (recombinant antibody construct against Affimed human CD19 and CD3) in patients with relapsed and/or refractory CD19 positive B-cell NHL »

» E1411: Intergroup Randomized Phase II Four Arm Study In Patients With HEMATOLOGY/ONCOLOGY OF DIVISION ECOG Previously Untreated Mantle Cell Lymphoma E1412: Randomized Phase II Study of Lenalidomide R-CHOP (R2CHOP) vs R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, ECOG and Prednisone) in Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma E4412: E4412: A Phase I Study with an Expansion Cohort of the ECOG Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma Andrew Evens, DO NU11H01: A Phase II Trial of Sequential SGN-35 Therapy With Adriamycin, Northwestern University Vinblastine, and Dacarbazine (S-AVD) for Older Patients with Untreated Hodgkin Lymphoma NU12H09: A Phase I-II Trial of Brentuximab Vedotin Plus Rituximab as Northwestern University Frontline Therapy for Patients With CD30+ and/or EBV+ Lymphomas Impact of routine surveillance imaging (RSI) on outcomes in patients with Tufts Medical Center (TMC) diffuse large B-cell lymphoma (DLBCL) Tufts Medical Center (TMC) Outcomes of Gray Zone Lymphoma in the Contemporary Era Rates of HBV Screening and HBV-Reactivation in Patients Receiving Tufts Medical Center (TMC) Rituximab Based Therapy Tufts Medical Center (TMC) Comparative study of canine and human genomics and lymphoma Non-classical Chronic Lymphocytic Leukemia (CLL): A Critical Examination Tufts Medical Center (TMC) and Comparative Analysis of Morphologic, Immunophenotypic, and Molecular Characteristics and Association with Patient Outcome A071101: A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, Alliance IND# Alliance 15380) Vaccine Given with Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM) A071401: Phase II Trial Of SMO/AKT/NF2 Inhibitors In Progressive Alliance Meningiomas With SMO/AKT/ NF2 Mutations A221101: A Phase III Randomized, Double-Blind Placebo Controlled Study of Alliance Armodafinil (Nuvigil®) To Reduce Cancer-Related Fatigue in Patients with High Grade Glioma Suriya Jeyapalan, MD NU10C03: Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Northwestern University Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Cancer METIS: Pivotal, open-label, randomized study of radiosurgery with or Novocure without Tumor Treating Fields (TTFields) for 1-10 brain metastases from non-small cell lung cancer (NSCLC) M13-813: A Randomized, Placebo Controlled Phase 2b/3 Study of ABT-414 with Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects AbbVie with Newly Diagnosed Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance 1)

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Investigator Sponsor/Trial number Title A multicenter access and distribution protocol for unlicensed NMDP cryopreserved cord blood units (CBUs) for transplantation in pediatric and adult patients with hematologic malignancies and other indications E1912: A Randomized Phase III Study of Ibrutinib(PCI-32765)-based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab ECOG (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic

Lymphocytic Leukemia (CLL). » » HEMATOLOGY/ONCOLOGY OF DIVISION E1A11: Randomized Phase III Trial of Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Carfilzomib, Lenalidomide, Dexamethasone ECOG (CRd) Followed by Limited or Indefinite Lenalidomide Maintenance in Patients With Newly Diagnosed Symptomatic Multiple Myeloma Collection of samples from CML patients undergoing treatment and Tufts MC monitoring for the development of BCR-ABL testing assays and other related diagnostic measures Plerixafor: Pilot Study of Lymphoid Tumor Microenvironmental Disruption Tufts MC Prior to Autologous Stem Cell Transplantation UNITY: A Phase 3, Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination with TGR-1202 Compared to Obinutuzumab TG Therapeutics in Combination with Chlorambucil in Patients with Chronic Lymphocytic Leukemia (CLL) Andreas Klein, MD KCP-330-009: A Phase 2b Open-label, Randomized Two-arm Study Karyopharm Therapeutics Comparing High and Low Doses of Selinexor (KPT-330) in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) GS-US-339: A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Gilead Tolerability, and Pharmacodynamics of GS 9973 in Subjects with Relapsed or Refractory Hematologic Malignancies Phase Ib Trial of Pembrolizumab (MK-3475) in Combination with Dinaciclib Merck (MK-7965) in Subjects with Hematologic Malignancies (KEYNOTE-155) Characterization of a naive T-cell (CD45RA)-depleted stem cell graft for Tufts Medical Center (TMC) allogeneic stem cell transplant with reduced risk for graft-versus-host disease Tufts Medical Center (TMC) Creation and Maintenance of a De-Identified Tissue Catalog Pilot Study of Biological Material Collection for Research in Tumor Biology Tufts Medical Center (TMC) and Behavior in Subjects Undergoing Procedures at Tufts Medical Center Does Endogenous Reactivation of Varicella Virus Boost Anti-VZV Immunity Tufts Medical Center (TMC) After Allogeneic Bone Marrow Transplantation? Biological Material Collection for Studies of Immune Function, and Tumor Tufts Medical Center (TMC) Biology and Behavior In Subjects With Hematologic Malignancies, Bone Marrow Disorders, and Healthy Donors Prostate cancer and bone metastases: Fibronectin signaling via integrin Tufts Medical Center (TMC) receptors HCRN GU14-202: Combined Targeting of the Androgen Receptor in Investigator Initiated, Castrate-Resistant Prostate Cancer with Enzalutamide and the Poly (ADP- Paul Mathew, MD supported by Tesaro Ribose) Polymerase [PARP] Inhibitor Niraparib Study Leadershipa A031201: Phase III Trial of Enzalutamide (NSC # 766085) versus Alliance Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer

81 Clinical Research/Clinical Trials (partial listing) continued

Investigator Sponsor/Trial number Title Innovative statistical methods for the integration of functional and clinical NCI outcomes Adaptor program for children with respiratory technology dependence: CHCCEF/CHICO Phase I, retrospective analysis of claims data Familial T-Cell Depleted Stem Cell Transplant in High-Risk Sickle Cell Tufts Medical Center (TMC) Anemia » Susan Parsons, MD » HEMATOLOGY/ONCOLOGY OF DIVISION How Are You Doing? Exploring HRQL Collection and Reporting at the Point Tufts Medical Center (TMC) of Care Impact of Patient Navigation on Patients' Acceptance of Recommended Tufts Medical Center (TMC) Breast Cancer Treatment Evaluation of Patient Navigation during Active Cancer Treatment: A Yawkey Foundation Retrospective Chart Review PANC009: An open-label, multicenter, single-arm, Phase 1/2 study of metronomic 5-fluorouracil in combination with nab-paclitaxel, Celgene bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma NAB1-paclitaxel (Abraxane) Plus Gemcitabine in Subjects with Locally Celgene Advanced Pancreatic Cancer (LAPC): An International, Open-Label, Multi- Center, Phase 2 study (LAPACT)

PCYC-1128-CA: A Phase 1b/2 Study of Ibrutinib Combination Therapy in Wasif Saif, MD Pharmacyclics Selected Advanced Gastrointestinal And Genitourinary Tumors

A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, and Taiho Oncology Pharmacokinetics of TAS-102 in Patients with Advanced Solid Tumors and Varying Degrees of Renal Impairment A Phase 1b/2 Dose Escalation and Expansion Trial of NC-6004 (Nanoparticle Cisplatin) plus Gemcitabine in Patients with Advanced Solid NanoCarrier Tumors or Squamous Non-Small Cell Lung, Biliary Tract, and Bladder Cancer

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Investigator Sponsor/Trial number Title RADIUSX: An open-label, multi-center, Expanded Treatment Protocol of Midostaurin (PKC412) in adult patients with newly diagnosed Fms-like Novartis tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation chemotherapy A Phase 1b Study to Evaluate the Safety and Preliminary Efficacy of PF- 04449913, an Oral Hedgehog Inhibitor, in Combination with Intensive Pfizer

Chemotherapy, Low Dose Ara-C, or Decitabine in Patients with Acute » »

Myeloid Leukemia or High-Risk Myelodysplastic Syndrome HEMATOLOGY/ONCOLOGY OF DIVISION A multi-center, randomized, double-blind, placebo controlled, study to Kellie Sprague, MD Novartis evaluate the efficacy and safety of CSJ148 compared to placebo to prevent human cytomegalovirus (HCMV) replication in stem cell transplant patients CASCADE: A randomized, double-blind phase 3 study of vadastuximab talirine (SGN-CD33A) versus placebo in combination with azacitidine or Seattle Genetics decitabine in the treatment of older patients with newly diagnosed acute myeloid leukemia (AML) A Research Database for Hematopoetic Stem Cell Transplantation, Other NMDP Cellular Therapies and Marrow Toxic Injuries. Research Sample Repository for Allogeneic Unrelated Hematopoietic Stem NMDP Cell Transplantation Phase 2, Parallel-Arm Study of MGCD265 in Patients with Locally Advanced Mirati or Metastatic Non-Small Cell Lung Cancer with Activating Genetic Alterations in Mesenchymal-Epithelial Transition Factor Lori Pai, MD SOLAR: An Open-label, Randomized Phase 3 Efficacy Study of ASP8273 vs Astellas Erlotinib or Gefitinib in First-line Treatment of Patients with Stage IIIB/IV Non-small Cell Lung Cancer Tumors with EGFR Activating Mutations

Basic/Translational Research Division members collaborate with a variety of The Division also collaborates with a number of other prominent and talented researchers and research institutes across the Tufts Health Sciences Campuses. institutes throughout the Tufts campuses. The basic and This includes the Cummings School of Veterinary translational cancer research activities at Tufts Medical Medicine at Tufts University (TCSVM), which is the only Center are based in the Molecular Oncology Research veterinary school in New England providing high- quality Institute (MORI), located at 75 Kneeland Street. MORI clinical care services and original research. The research has 16 faculty members, including five clinician- includes shared models to study cancer inanimals that scientists, and employs about 50 FTEs. Its mission is to may have direct application to humans (i.e., Comparative explore the molecular mechanisms of neoplastic Oncology). Researchers at TCSVM are members and transformation and to promote the translation of basic active participants of the National Cancer Institute research findings into the clinic. To achieve this goal, Clinical Oncology Trials Consortium. They have MORI scientists carry out research that spans the contributed to numerous clinical trials utilizing dogs, spectrum from gene discovery to target validation for cats, and other small animals with various spontaneous drug development. Please see the Institutes Section of cancers to inform human cancer therapy. There are this report for more details on MORI. several ongoing translational cancer collaborations between TCSVM and the Division.

83 The Division of Hematology/Oncology also collaborates United States. It is supported by the United States closely with the Jean Mayer USDA Human Nutrition Department of Agriculture (USDA). The interaction Research Center on Aging (HNRCA) at Tufts University. The between nutrition and the onset and progression of cancer Center is a unique national asset devoted to diseases of an has been a special interest of several scientists at the aging population, including cancer. The HNRCA is HNRCA. These investigators use cell and molecular biology operated by Tufts University through a cooperative techniques, genomics, and sophisticated animal models. agreement with the Agricultural Research Service (ARS), and is one of six human nutrition research centers in the »

» Laboratory/Translational Research Grants (partial list) HEMATOLOGY/ONCOLOGY OF DIVISION

Investigator Funding Source Grant title NIH/NCI Synthesis and Study of Complex Natural Products (R01 Subcontract) Department of Defense CDMRP Development of Technologies for Early Detection and Stratification of – Breast Cancer Breast Cancer Rachel Buchsbaum, MD Diane Connolly-Zaniboni Research Scholarship in Breast The role of Tiam-1 in the tumor microenvironment. Cancer Prothena Therapeutics Prothena Research Fellowship NIH/NCI A Development of PAR2 Pepducins for the Treatment of Atopic Dermatitis (R42 Subcontract) Lidija Covic, PhD NIH/NCI Development of PAR2 Inhibitors for the Treatment of Nonalcoholic (R42 Subcontract) steatohepatitis (NASH) EMR Adverse Drug Event Detection for Pharmacovigilance (subcontract): IH/NCI This multicenter projects aims to refine/improve existing Bio-Natural Language Processing (Bio-NLP) and develop new innovative BioNLP (U01 Subcontract) algorithms order to identify serious adverse events during cancer treatments MAP Kinase Signaling in Lymphoma: A Novel Therapeutic Paradigm: The goal of the proposed research project is to investigate the biology NIH/NCI and clinical efficacy of targeting the MAP Kinase MEK/ERK pathway in (R01 NCE) lymphoma through in vitro and in vivo mouse models as well as through an early-phase clinical trial in relapsed/refractory non-Hodgkin’s lymphoma (DLBCL). Computerized quantitative imaging assessment of tumor burden: A multidisciplinary team has been assembled comprising radiologists, NIH/NCI informaticians, and oncologists, including an industrial partnership with General Electric (GE) Medical Systems to integrate and analyze a spectrum Andrew Evens, DO of quantitative imaging biomarkers (e.g., quantitative PET). NIH/NCI Computing, Optimizing, and Evaluating Quantitative Cancer Imaging (U01 Subcontract) Biomarkers Nutrition and Cancer Pilot Pitfalls, opportunities and implications of dietary fat in targeting fatty acid Project metabolism in Tesaro, Inc. Targeting PD1 Pathway in Lymphoma Investigating the Efficacy of IPI-145 in Hodgkin’s and T Cell Lymphoma Cell Infinity Pharmaceuticals Lines The Lipid Addiction of Diffuse Large B-cell Lymphoma (DLBCL) and 3-V Biosciences, Inc. Potential Treatment Strategies with Novel Fatty Acid Synthase (FASN) Small Molecule Inhibitors Takeda/Millennium The Takeda Oncology Hematologic Malignancies Fellowship Pharmaceuticals

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Investigator Funding Source Grant title Athan Kuliopulos, MD NIH/NCI (P50) TRIP-PCI: PAR1 Pepducin-Based Interventions in Arterial Thrombosis PhD NIH/NCI (R01) The Role of IWS1 in Development and Tumorigenesis Philip Tsichlis, MD NIH/NCI (R01) Differential Regulation of RNA Processing by Akt Isoforms

Honors and Awards (partial list) » »

Dr. Buchsbaum HEMATOLOGY/ONCOLOGY OF DIVISION »» Tufts University School of Medicine Outstanding Lecturer »» Tufts University School of Medicine Notable Teaching »» Castle Connolly Boston Top Doctors

Dr. Erban »» Medical Editor Tufts Medicine »» TUSM Teaching Award-Medicine Clerkship »» Boston Magazine, Best Doctors: Section –Oncology 2016 »» Castle Connolly America’s Top Doctors for Cancer »» Medical Grand Rounds Speaker, Holy Family Hospital »» Medical Grand Rounds Speaker, Newton Wellesley Hospital »» Medical Grand Rounds Speaker, Melrose Wakefield Hospital-Hallmark Health, Melrose MASymposium Lecture and Panelist: Monte Jade NE Young Professional Association, Cambridge MA »» Lecturer, Harvard-China Food Safety Training Program, Harvard School of Public Health

Dr. Evens »» Co-Chair, 13th International Ultmann Symposium on the Diagnosis and Management of Lymphoma, The University of Chicago and The Robert H. Lurie Comprehensive Cancer Center of Northwestern University. May 2016. »» Co-Chair. Lymphoma Research Foundation (LRF) New England Lymphoma Annual Patient Workshop, Mayt, 2016; Needham, MA. »» Chair. Tufts Cancer Center: New England Cancer Moonshot Dr. Junghans Summit; June, 2016; Boston, MA. »» Medical Grand Rounds, NEBH “Surgical Blood Loss and Its »» Primary Hematology Review Panel (Standing Member and Control with Anti-Fibrinolytic Therapies” Chair), for VA Scientific Merit Review (R01). NIH and NCI. »» Chief, Section of Hematology, NEBH »» NIH/NCI Hodgkin Lymphoma Working Group primary »» Chairman, Transfusion Committee, NEBH member (Steering Committee Subgroup) »» Member, VTE Monitoring Committee, NEBH »» Named the Chan Soon-Shiong Endowed Scholar in »» Member, IRB, NEBH Precision Medicine at Tufts Medical Center, Boston, MA

85 Dr. Klein Dr. Parsons »» Castle Connolly Boston Top Doctors »» NCI Scientific Steering Committee, Cancer Care Delivery »» Primary/voting member, Education Committee, American Research (appointed member) Society of Blood and Marrow Transplantation »» NCI-ASCO Teams in Cancer Care Delivery (selected »» Primary/voting member, Subcommittee on Web-Based participant) Learning, Education Committee, American Society of »» American Cancer Society, Palliative Care and Symptom Blood and Bone Marrow Management Extramural Grant Review Committee »» Chair, Institutional Review Board, Tufts Health Sciences (standing member)

» »» Castle Connelly/America’s Top Doctors-Pediatric

» »» Regulatory Affairs Director, Tufts CTSI HEMATOLOGY/ONCOLOGY OF DIVISION Hematology/Oncology »» Chair, Tufts Cancer Center Tissue Repository Oversight Committee. »» Children’s Oncology Group-Hodgkin Lymphoma Steering Committee »» Course Co-Director, Demystifying Cancer Clinical Trials, Division of Hematology/Oncology and CTSI. »» Editorial Board, Medical Care Research and Review »» Course Co-Director and Presenter, Applying Precision Dr. Saif Medicine to the Treatment of Hematologic Disease. »» Notable Teaching Award by Tufts Medical School »» Member, New England Lymphoma Rounds Steering »» America's Top Doctors® for Cancer Committee (Sponsor: Lymphoma Research Foundation; »» Compassionate Doctor Recognition www.lymphoma.org/nelr) »» Grand Rounds, UVA Cancer Center »» Member, CTSA Consortium Consensus Scientific Review »» Grand Rounds, Wake Forest Comprehensive Cancer Center Committee (SRC) Working Group »» Grand Rounds, Dana Farber Cancer Center »» Host, BMT Online Journal C lub »» Grand Rounds, Armed Forces Institute of Pathology Dr. Kumar »» Invited Speaker, Best of ASCO »» Invited Speaker: American Society of Hematology Annual »» Grand Rounds, Penn State - Hershey Cancer Center Meeting, December 2016 »» Grand Rounds, Yale Cancer Center Dr. Matthew »» Grand Rounds, Columbia University Medical Center »» Boston Magazine Best Doctors 2016 »» Grand Rounds, Montefiore Medical Center Dr. Miller Dr. Sprague »» Top Doctors in Boston – Hematology »» Boston Magazine, Best Doctors, 2016 »» Listed – US News and World Report top 1% doctors for »» Top Doctor, Hematology, Castle Connolly 2016 cancer »» Patient Education Advisory Group: Diverse Populations, »» Grand Rounds – Brockton Hospital National Marrow Donor Program »» Grand Rounds MDS/AML Metro- West Medical Center »» Invited Speaker: New Horizons in Myelodysplastic Dr. Pai Syndromes, Applying Precision Medicine to the Treatment »» Natalie V Zucker Research Center for Women Scholars of Hematologic Diseases, Boston, MA Grant »» Invited Speaker: History of Bone Marrow Transplantation, »» Charlton Grant Award Caring for the Bone Marrow Transplant Patient Symposium, Boston, MA

Dr. Strauss »» America’s Top Doctors for Cancer, 2016 »» Grand Rounds, Steward Norwood Hospital, February 2016

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » HEMATOLOGY/ONCOLOGY OF DIVISION

Dr. Varga »» Selected to be on the Tufts Clinical and Translational Science Institute »» Selected to be on the Women in Medicine and Science Committ »» Invited speaker: Armed Forces Institute of Pathology, Rawal Pindi »» Invited speaker: University of Cincinnati, Cincinnati, OH »» Invited speaker: Best of ASCO, Orlando, FL »» Invited speaker: Penn State - Hershey Cancer Cente, Hershey, PA »» Invited speaker: ASCO Town Hall Meeting – Medscape, Chicago, IL »» Invited speaker: Yale Cancer Center, New haven, CT »» Invited speaker: Columbia University Medical Center, New York, NY »» Invited speaker: Montefiore Medical Center, Bronx, NY

87 DIVISION OF INTERNAL MEDICINE AND ADULT PRIMARY CARE » » INTERNAL MEDICINE AND ADULT PRIMARY CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION The Division of Internal Medicine and Adult Primary Care at Tufts Medical Center is the principal clinical home for adult internal medicine, family medicine, geriatrics and transitional care medicine. The division contains five sections, described below.

Tufts Medical Center Primary Care – Boston comprises multiple ambulatory internal medicine practices and is the primary care teaching practice for the Tufts Internal Medicine Residency. All of the physicians are internists or family practitioners and many have a focus on research, quality or education in addition to their clinical practices at Tufts MC Primary Care Deborah Blazey-Martin, MD, MPH - Boston.

The Pratt Diagnostic Center is a concierge model practice. Patients and their families are able to spend more time with their physician to discuss management of their chronic illnesses and health screening and prevention. Patients pay an annual fee for this service.

The division’s Community Practices, strategically located in both the South Shore and Metro West markets, opened in October of 2013. Comprised of internists and family medicine physicians, these practices are dedicated to providing excellent primary care to patients in their own neighborhoods. They expose senior internal medicine residents to community practice and teach Tufts University School of Medicine Physician’s Assistant students. They also host Tufts Medical Center specialists, bringing them closer to the patients who live in these communities.

The General Medicine Inpatient Service is a hospitalist service caring for a wide range of medical conditions. As the only non-subspecialty inpatient medical service, it serves as an important component of the resident and medical student education experience.

The Geriatrics Section offers inpatient geriatric rotations for residents, together with an educational program for nursing staff at Tufts Medical Center, and a polypharmaceutical and advanced care plan to address the special needs of elderly patients.

Highlights of 2016

»» Added 2 new primary care physicians, 1 urgent »» Extended clinic hours from 8:00 am – 8:00 pm care physician and 1 Social Worker to the Monday through Thursday and added weekend Academic Medical Center practice clinic from 8:00 am -12:00 pm every Saturday

»» Received NEQCA Hypertension Grant working with »» 14% increase in Primary Care patient panel in 2016 SPRINT trial leader Dr. Daniel Weiner to improve »» 14% increase in visit volume population HTN management »» 53% increase in new patient volume »» GMA / Nephrology Hypertension Clinic initiated

»» Certified Diabetes Education collaboration with Lowell Genera

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Responsibilities

Deborah Blazey-Martin, MD, MPH, Chief, Internal Medicine and Adult Primary Care Assistant Professor FACP Medical Director, Tufts Medical Center Community Care » » Dineli Ahearn, MD Assistant Professor Director, Primary Care Innovation CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION Sora Al Rowas, MD, MSc Assistant Professor Yee Chuan Ang, MD Assistant Professor, Geriatrician John Barravecchio, MD Assistant Professor Tufts Medical Center Primary Care – Quincy Elena Byhoff, MD, MSc Assistant Professor Institute for Clinical Research and Health Policy Studies Jeanine Carlson, MD Associate Clinical Professor Pratt Diagnostic Center Steven Carr, MD Assistant Professor Tufts Medical Center Primary Care – Quincy Niamh Carroll, MD Assistant Professor Daniel Chandler, MD Assistant Professor Director of Resident Ambulatory Education Prianka Chawla, MD, MS Assistant Professor Elaine Choi, MD Assistant Professor Jaclyn Chu, MD Assistant Professor Brian Cohen, MD Assistant Professor Medical Director, Pratt Diagnostic Center Misha Dad, MD Assistant Professor Amy Dinitz, MD Assistant Professor John Doyle, MD, Assistant Professor Medical Director of Employee Health Services Medical Director, Tufts Medical Center Primary Care – Daniel F. Driscoll, MD Assistant Professor Quincy Paul Duncan, MD Assistant Professor Richard Dupee, MD Clinical Professor Chief of Geriatrics, Pratt Diagnostic Center Vice Chair for Faculty Affairs and Quality Improvement Karen Freund, MD, MPH Professor Associate Director of Research Collaboration, CTSI Jenny Hong Gao, MD, PhD Assistant Professor Medical Director, Tufts Medical Center Primary Care – Renee Goetzler, MD, MPH Assistant Professor Framingham Linda Kaplan, MD Assistant Professor Director, Predictive Analytics and Comparative Effectiveness (PACE) Center, ICRHPS; David Kent, MD Professor Director, Sackler School of Graduate Biomedical Sciences, Clinical and Translational Science Program Jennifer Kim, MD Assistant Professor Vice-Chair for Education; Program Director, Internal Richard Kopelman, MD Professor Medicine Residency Program Diane Krause, MD, MPH Assistant Professor Joan Kross, MD, MPH Associate Clinical Professor Tufts LCO Medical Director

89 Faculty (continued)

Name Academic Rank Title and Special Responsibilities

Olivia Lanna, MD, MA Assistant Professor Tufts Medical Center Primary Care – Quincy Sandra Lau, MD Assistant Professor Mary Lee, MD, MS, FACP Professor Special Advisor for Education Innovation James Mahoney, MD Assistant Professor Tufts Medical Center Primary Care – Quincy Associate Chief of Geriatrics »

» Cinthya Marturano, MD Associate Clinical Professor INTERNAL MEDICINE AND ADULT PRIMARY CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION Director of Continuing Medical Education Catherine Milch, MD Assistant Professor Yueling Guo Moran, MD Assistant Professor Tufts Medical Center Primary Care – Quincy Jana Naef, MD Assistant Professor Jack Naggar, MD Assistant Professor Director of Community Primary Care Education, Tufts Erin Ney, MD Assistant Professor Medical Center Primary Care – Quincy Marta Onyskiv, MD Assistant Professor Tufts Medical Center Primary Care – Quincy Judy Pinsker, MD Associate Clinical Professor Karthik Ravindran, MD Assistant Professor Tufts Medical Center Primary Care – Framingham Associate Program Director of Internal Medicine Joseph Rencic, MD Associate Professor Residency Program Associate Professor, Department of Joyce A. Sackey, MD Medicine and Department of Public Dean, Multicultural Affairs/Global Health Health and Community Medicine

Kinjalika Sathi, MD Assistant Professor Assistant Director of Resident Internal Medicine Education

Kimberly Schelling, MD Assistant Professor Director Inpatient Services Chief, Institute for Clinical Research and Health Policy Harry Selker, MD Professor Studies; Pratt Diagnostic Center Staff

Shawn Shroff, MD Assistant Professor Tufts Medical Center Primary Care - Quincy

Myron Siu, MD Associate Clinical Professor Laura K. Snydman, MD, FACP Associate Professor Clerkship Director Steven Spector, MD Assistant Professor GMA and Pratt Diagnostic Center Jillian Suzukida, MD Assistant Professor Julie Tishler, MD Assistant Professor Director of Quality Improvement Caitlin Toomey, MD Assistant Professor Shirly Tozzi, MD Assistant Professor Nancy Tran, MD Assistant Professor Michael Wagner, MD Associate Professor President and CEO, Tufts Medical Center Wei Wang, MD Assistant Professor Saul Weingart, MD, PhD Professor Chief Medical Officer, Tufts Medical Center Elisabeth Wilder, MD Assistant Professor John B. Wong, MD Professor Chief, Clinical Decision Making, Informatics and Telemedicine Irina Zilberman, MD Assistant Professor

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Major Clinical Programs The Division of Internal Medicine and Adult Primary In diabetes, we automated point of care hemoglobin A1C Care continues to increase its primary care services on testing to enable clinicians to discuss diabetic control in its main campus at Tufts Medical Center. In addition, the real time and improve outcomes. In our residency division has expanded services in Geriatrics, inpatient practice, we changed our note template and improved medicine and collaborative programs on the main residents’ rate of ordering follow up appointments for campus and has extended its services into the continuity of care. Finally, we have created a community in the spirit of the distributed academic hypertension registry and report to help clinicians with

medical center model. population health management. » » INTERNAL MEDICINE AND ADULT PRIMARY CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION Tufts Medical Center Primary Care - Boston (Primary In early 2015, Tufts Primary Care launched a Patient Care – Boston) is the largest ambulatory practice at Tufts Portal to satisfy one of the requirements of the Medical Center, located in the Biewend building. The Meaningful Use Program. Previously, some patients clinic continued to grow in 2016 with increased patient utilized a product that allowed for HIPAA compliant access due to expanded evening hours from 5:00 pm - electronic communication only with their Provider. The 8:00 pm Monday through Thursday and 8:00 am - 12:00 GE Patient Portal allows for secure communications with pm Saturday mornings. In 2016 Primary Care – Boston the entire Care Team, as well as providing the ability for hired 3 new physicians including a former chief resident, a patient to see past and current medications, problems a Cantonese-speaking physician, and a clinical scholar. and lab results. As of September 30, 2016, 7,458 of our patients have reviewed their medical records or Primary Care – Boston cares for more than 37,000 exchanged secure messages on the Portal. The Patient patients resulting in 76,000 primary care office visits per Portal has also been used to quickly and securely year. 2016 saw a 14% increase in clinic visits over 2015 communicate with our patients as evidenced by a couple which brought in an average of 285 new patients per of projects: after a hospital visit each patient receives an month to Tufts Medical Center through primary care. automatic email message reminding them of the New patient growth in 2016 increased 53% over 2015 and importance of discharge instructions, the need to take 98% from fiscal year 2014. The division also coordinates prescribed medications and to contact us if they require care and is a major source of referrals to subspecialty assistance; for patients prescribed controlled substances colleagues and services within the organization. we have used the portal to share handout information Primary Care – Boston consists of about 40 internists, regarding medication safety and solicited information some with careers primarily devoted to clinical care. from the patients to help us collaboratively create Others offer clinical care but also are active in medical individual Care Plans. education, quality improvement, and administration. Still others have primary appointments in other In 2016 primary care partnered with Lowell General divisions, mainly research institutes, but practice Diabetes Center and received a certificate of clinical medicine at Primary Care – Boston. accreditation from AADE. Primary Care Boston has offered free DSME classes to Tufts Medical Center In 2016 the Quality Improvement Committee and Patients to teach them self-management of their Change Team focused on chronic narcotics prescribing, diabetes. In addition to the certificate of accreditation, diabetes control, residency continuity of care and a new we are currently training one of our RN’s to be a hypertension registry. The practice has 470 patients on Certified Diabetes Educator. Tufts Medical Center chronic opioids. Doing our part to combat the national Primary Care – Boston is also the sole educational site opioid abuse crisis, we designed and implemented a for the continuity clinics for 72 internal medicine chronic controlled substances management program residents; their training is provided by primary care with a team-based approach. A new electronic medical preceptors. Drs. Daniel Chandler (Director of Resident record template was created and implemented that Education) and Kinjalika Sathi (Assistant Director of captures new algorithms and risk assignments to ensure Resident Education) coordinate their various clinical, safe prescribing. We have improved the percentage of didactic, and administrative responsibilities with a goal our patients in compliance with annual contracts, urine to maximize their primary care education and toxicology screens and prescription monitoring checks. experience.

91 Primary Care – Boston has achieved the highest level of NCQA Patient Centered Medical Home (PCMH) recognition, Level 3 with Distinction. The award was first received in 2013 with successful recertification starting December 2016. This is uncommon in academic medical centers. Population- based medicine with the patient at the center is the rationale behind this model of care, and promotes the importance of team-based management of patients. » » INTERNAL MEDICINE AND ADULT PRIMARY CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION Care teams, composed of physicians, nurse practitioners, registered nurses, medical assistants and practice coordinators care for all patients in the panel. Outreach is facilitated by registries, information technology, health information exchanges and other means to assure that patients receive the indicated care in a culturally- and linguistically-appropriate manner. This robust team structure has been developed and rolled out across most of the practice, resulting in increased MHQP patient satisfaction scores.

The Division's vision for PCMH transformation has the following goals:

»» Emphasize high-quality, team-based preventive care and disease management, with care coordination across the health care continuum. »» Invite patients to actively engage in improving their health and well-being. »» Promote physician, nurse, and staff satisfaction by redesigning the staffing model to allow everyone to work to the top of their certifications. Primary Care – Boston continues to include »» Commit to delivering superior customer service. multidisciplinary services, embedding Drs. Lisa Ceglia »» Create and maintain an environment where trainees learn and Joe Vercollone from Endocrinology to provide to provide primary care at the highest level and enjoy the intensive diabetes consultation, management, and practice of medicine and caring for their patients. education within the practice. Amanda Weintraub, LCSW, Wil Hartigan, LCSW, and Nelson Wong, LICSW provide »» Establish a data-driven practice culture of continuous social work services with additional behavioral services improvement in the quality of care provided and the safety coordinated by Dr. Annette Hanson from Psychiatry. In of the environment of care based on transparency and 2016 the division collaborated with Dr. Daniel Weiner and accountability. the Nephrology department to institute a monthly hypertension clinic within primary care. The purpose is to bring the specialist to the practice to collaborate in the care of hypertensive patients.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 As the outpatient practice site for 72 Tufts Internal same-day appointments, onsite blood drawing stations Medicine Residents, the Division has made significant and centralized digital medical records that can connect changes and innovations. Under the leadership of Dr. patients to their entire healthcare team at Tufts Medical Daniel Chandler, the Director of Residency Education, we Center or MetroWest Medical Center. In 2016, Tufts have moved to a "3+1" model for the intern class to Medical Center Community Care was created and now increase their primary care continuity. Interns spend 3 provides dedicated recruitment and management weeks learning inpatient medicine followed by 1 week of services for these community practices. ambulatory care. This allows concentrated times when In Quincy, Tufts Medical Center specialists rotate interns are in clinic and are not interrupted by inpatient through the practice on a monthly basis making their »

demands. In addition, under the direction of Dr. Erin Ney, » services conveniently available to patients locally. CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION senior residents rotate through the Tufts Medical Center Cardiologists and endocrinologists team up with their Primary Care-Quincy practice and are exposed to both a Primary Care Physician colleagues to provide community practice and nursing home care. Dr. Chandler comprehensive, coordinated care to patients in a has continued video observations for all residents, a patient-friendly environment. mandatory quality chart review project,and has further refined the pre-clinic conference structure. Pre-Clinic The Pratt Diagnostic Center uses a concierge model to now includes new content and more versatile formats and provide a high level of service coupled with expert stresses feedback on public speaking and teaching skills diagnostic care. Under the direction of Dr. Brian Cohen, from the preceptor to the presenting resident. the program continues to thrive since its inception ten years ago. The Pratt Diagnostic Center markets its The Primary Care – Boston Anticoagulation Service services and clinical practice to members of the Boston monitors patients on warfarin and enoxaparin, and the business community. novel oral anticoagulants. The service is primarily managed by nurses in consultation with a pharmacist Teaching Activities and the primary care physicians. Patients can have blood drawn in a variety of sites convenient for them The educational programs of the division consist of the including point of care testing in Primary Care - Boston. following:

In 2016 the service managed over 500 patients with »» Residents’ Ambulatory Medicine in Tufts Medical Center excellent results in terms of compliance and time in the Primary Care - Boston therapeutic range. »» Continuity Clinic The general medicine inpatient service continues to be »» Ambulatory Block Rotations an important clinical and educational program. Under »» Geriatric Block Rotation the direction of Dr. Kimberly Schelling, Director of »» Primary Care Elective Inpatient Services, the general medicine ward rotation provides house staff the opportunity to have intensive »» General Medicine Inpatient Service (staffed by a Division of exposure to patients with complex illnesses under the Internal Medicine and Adult Primary Care attending and care of general internists and to see these physicians as composed of a 3rd year resident, 2 interns, a pharmacist, potential role models for a career in general internal and medical students). medicine. Dr.Schelling is in charge of the combined »» Third Year Medicine Clerkship for Tufts University School of inpatient Geriatric Service and Medical Consultation Medicine service. The additional service offers geriatric training, »» General Medicine Consultation Service (staffed by a promotes education, and offers consultation to other Division attending and composed of a 3rd year resident, inpatient services. internal medicine intern, and a psychiatry intern intermittently) The community practices in Framingham and Quincy are dedicated primarily to clinical care. From disease »» Geriatrics Inpatient Service (staffed by a Division attending prevention to managing chronic illness to an urgent care and composed of a 3rd year resident, an internal medicine appointment, these teams are focused on delivering intern, a psychiatry intern intermittently, and medical high-quality, efficient care to their patients in their local students) communities. Both Quincy and Framingham are in »» Fourth-year medicine sub-internships for Tufts University newly constructed spaces, which were thoughtfully School of Medicine designed for optimal patient care. Each practice offers

93 » » INTERNAL MEDICINE AND ADULT PRIMARY CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION

Many of the faculty play pivotal roles in the educational Care-Boston, and associated outpatient ambulatory programs, both for the medical school and for the elective clinics. Drs. Laura Snydman, Dan Chandler, residency training program. Dr. Richard Kopelman is the Kinjalika Sathi, and Joe Rencic provide a “Resident-as- Program Director for the Internal Medicine Residency Teacher” program to enhance the skills of residents in training program at Tufts Medical Center. Each year, the teaching medical students. The faculty of the division are program recruits 24 new interns and has a total of 72 recognized annually by medical students and residents for residents and three chief medical residents. Dr. Joseph their excellence in teaching and their fundamental Rencic is an Associate Program Director of the internal contributions to the educational programs of the medical medicine residency, with an additional research focus in school and medical center. clinical decision making and development of expertise. Dr. Laura Snydman as Clerkship Director provides oversight Research Activities for the medical students during their third and fourth year Adult Internal Medicine acts as an important source of medicine clerkships at Tufts Medical Center. Dr. Daniel patients for clinical research trials at the medical center. Chandler is Director of Resident Education for Internal With more than 37,000 patients in the practice and an Medicine and Adult Primary Care. He sets the overall electronic medical record which enables researchers to education agenda for the 72 residents that rotate through identify patients with specific diagnoses, the Division is Primary Care-Boston for their continuity and primary care able to work collaboratively with institutionally- experience throughout their 3 years of training. Dr. sponsored research projects on identifying patients for Kinjalika Sathi, as the Assistant Director of Residency research projects. Education, administers the outpatient ambulatory curriculum through the primary care clinic, Primary

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Honors and Awards Invited Lectures »» “Value of Personalized Risk Information.” NIH Health Deborah Blazey-Martin, MD, MPH Economics Common Fund: Determinants of Personalized Awards Health Care and Prevention Steering Committee Meeting. »» Top Doctor, Boston Magazine 2016 Rockville, MD, July 19, 2016. »» Committee Assignments »» “Understanding Heterogeneity of Treatment Effect: »» President’s Council of Cornell Women General Principles and the Example of PFO in Cryptogenic Stroke.” NeuroCORPS division at Columbia University. New »» NEQCA Board of Trustees York, NY. Jan 27, 2016.

»» Trustee, NEQCA Accountable Care » » Richard Kopelman, MD CARE ADULT PRIMARY AND MEDICINE INTERNAL OF DIVISION Brian Cohen, MD Awards Awards »» Dean’s Outstanding Mentor Award –Tufts University »» Castle Connolly Top Doctor School of Medicine Richard Dupee, MD, MACP, AGSF »» Fish Visiting Scholar in Medical Education 2016 – Brigham Awards and Women’s Hospital, Department of Medicine »» Mastership in the American College of Physicians Sandra Lau, MD »» Castle Connolly Top Doctor Awards »» Boston Magazine Top Doctor »» NEQCA Primary Care Award

David Kent, MD, CM, MS Karthik Ravindran, MD Awards Awards »» Technical Expert Panel, Evidence Synthesis Report on “Life »» Preceptor of the Year Award – Tufts University School of Expectancy Calculators,” Minneapolis VA Medical Center Medicine PA Program »» Vice Chair for the Evidence Review Committee (ERC) for Laura Snydman, MD the 2016 Update of the AHA/ASA "Guidelines for the Awards Management of Patients with Acute Ischemic Stroke" »» Outstanding Teaching in the Clerkship Years New Research Support »» Invited Faculty Marshall for Commencement Exercises, »» Evidence and the Individual Patient: Understanding Tufts University School of Medicine Heterogeneous Treatment Effects for Patient-Centered Care” »» Johns Hopkins-Tufts Trial Innovation Center National Institutes of Health (NIH) (1U24TR001609-01) »» “Risk Stratification and Tailoring of Prevention Programs” »» “How Well Do Clinical Prediction Models (CPMs) Validate? A Large-Scale Evaluation of Cardiovascular Clinical Prediction Models” New Editorial Boards »» Diagnostic and Prognostic Research

95 ADULT PRIMARY CARE— GERIATRICS

The Geriatrics section of the Division of Internal Medicine and Adult Primary Care was established in » » GERIATRICS CARE ADULT PRIMARY the spring of 1998 in order to enhance the training of students and residents in the subspecialty of geriatrics. Geriatrics is a robust medical subspecialty at Tufts Medical Center. The inpatient team consists of a geriatric attending, medical residents at all three levels of training, and medical students. The team provides daily assessment and care of the older patient, with intensive application of basic geriatric principles, including early functional return, delirium prevention, Richard Dupee, MD and safety. The team also staffs the Geri-Ortho service, where geriatric trauma patients, and older patients requiring elective orthopedic surgery, are provided comprehensive geriatric assessment pre-and post-operatively, in order to prevent post-operative complications, including delirium and functional loss. The palliative care service and the ethics service also play a vital role in the care of the older patient, in conjunction with the geriatrics team. Geriatrics also plays an instrumental role in the NEQCA ACO (New England Accountable Care Organization) that General Medical Associates joined in 2014.

Highlights of 2016

»» A new geriatric-orthopedic service was initiated »» Dr. Dupee was honored by the American College of Physicians with the title of Master of the College

Faculty

Name Academic Rank Title and Special Responsibility Richard Dupee, MD Clinical Professor Chief of Geriatrics Yee Chuan Ang, MD Assistant Professor Geriatrician Cinthya Marturano, MD Assistant Professor Associate Chief of Geriatrics Wei Wang, MD Assistant Professor Geriatrician

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Major Clinical Programs Geriatrics Inpatient Service Older persons are at disproportionate risk of becoming seriously ill and requiring hospital care. Moreover, the utilization of acute hospital care by older persons is increasing rapidly with the aging of the population.

Once hospitalized, older patients are at high risk for functional loss and institutionalization. » » The inpatient geriatrics service at Tufts Medical Center GERIATRICS CARE ADULT PRIMARY is designed to prevent loss of function and other serious events and conditions common to this age group following hospitalization. The goal of the inpatient geriatric program is to provide the safest care possible, with return to full function as quickly as possible.

Geriatrics Consultation Service The resident team, led by a geriatrician, is available to all medical and surgical services for inpatient consultation regarding issues and complications that frequently occur when an older patient is hospitalized, guiding the various subspecialty services in the care of these patients.

Geriatrics-Orthopedic Service The “Geri-Ortho” service is a new addition to the geriatric care model. Geriatric trauma patients, and older patients requiring elective orthopedic surgery, are provided comprehensive geriatric assessment pre-and Honors and Awards post-operatively, in order to prevent post-operative Richard Dupee, MD complications, including delirium and loss of function. »» Voted “Top Doctors in Geriatrics” Boston Magazine, and by Unlike the geriatric consultation service, these Castle-Connolly orthopedic patients are cared for directly by the geriatrics team from the time of admission. »» Received the Schwartz Center award: “For exemplifying everyday acts of compassion in health care.” MedWest Center for Memory Disorders and National Professional Society Committee Appointments Conditions of Older Adults »» Governor, American College of Physicians, Massachusetts The MedWest Center for Memory Disorders and Chapter (2010-2014) Conditions of Older Adults was established in »» President, Massachusetts Geriatrics Society (2009-2014) conjunction with Tufts Medical Center. A team of »» Health and Public Policy Committee, American College of specialists evaluates patients thought to have memory Physicians (2012-2014) deficits. It identifies and treats patients with mild »» Editorial board, “Annals of Long-term Care” (2003-present) cognitive impairment and with various stages of Alzheimer’s disease. Specific and sensitive evaluation tools are used to provide early and accurate diagnosis and treatment. Patients come from all over New England for evaluation by this service.

97 WILLIAM B. SCHWARTZ DIVISION OF NEPHROLOGY

The William B. Schwartz Division of Nephrology is internationally known for the quality of patient care, » » NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM teaching, research, and public policy contributions. In the early years of the Division, William B. Schwartz and his colleagues elucidated many basic principles of acid-base and fluid and electrolyte homeostasis which are used to this day. In recent years, the Division has carried out seminal studies in the epidemiology, progression, and treatments of chronic kidney disease and the effects of chronic kidney disease on cardiovascular disease. Members of the Division have led the development and implementation Andrew Levey, MD of clinical guidelines for the identification, classification, and treatment of kidney diseases.

In its research and its clinical programs, the Division has emphasized collaboration with other specialties (metabolism, neurology, cardiology, infectious disease, urology, and transplantation surgery) and disciplines (epidemiology, statistics). Division members collaborate with methods experts to use the research approaches appropriate for epidemiology, clinical trials, development of clinical practice guidelines, and outcomes. Members also collaborate with domain experts to focus on the research areas of: chronic kidney disease, assessment of kidney function, aging, nutrition, dialysis and transplantation, progression, polycystic kidney disease, acute kidney injury, and hypertension. Basic science studies involve the role of inflammation and oxidative stress in chronic kidney disease and the role of immunosuppressive regimens in predisposing to infections in dialysis and transplant patients.

The Division has established multidisciplinary clinics for polycystic kidney disease, kidney transplantation and home dialysis. Unique clinical programs include the Kidney Function Evaluation Clinic and the Bone Biopsy Clinic.

The teaching programs emphasize basic science-clinical correlations. Fellowships are available in clinical nephrology and in research. Participants in the research fellowship program undertake formal training in research methods culminating in a Master of Science degree at the Sackler School of Graduate Biomedical Sciences at Tufts University.

Tufts Medical Center is the site of the editorial offices of the American Journal of Kidney Diseases (AJKD), the official journal of the National Kidney Foundation. The Editor, Deputy Editor, and other Editors are members of the Division.

Highlights of 2016

»» Dr. Levey was recognized by Thomson Reuters »» Dr. Weiner was the Tufts MC Principal as a highly influential researcher for the second Investigator for the SPRINT Trial, a study which year in a row. has the potential to change the standard for the treatment of high blood pressure. »» Drs. Levey, Meyer, Perrone and Sarnak were Boston Magazine’s Top Doctors. »» Dr. Meyer was appointed to a 3-year term on ASN Dialysis Advisory Group »» Dr. Gilbert received the Dr. Jack Mitus Special Faculty Recognition from the TUSM Senior Class. »» Dr. Perrone was the lead author and Dr. Miskulin a co-author on a publication that established the first ever data standard applicable to kidney disease

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Responsibility » »

Division Chief NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM Andrew S. Levey, MD Professor Editor of the American Journal of Kidney Diseases Associate Division Chief Ronald D. Perrone, MD Professor Director, Polycystic Kidney Disease Center Medical Director, Kidney Transplantation Michael B. Cohen, MD Assistant Professor David A. Drew, MD, MS Assistant Professor Scott J. Gilbert, MD Associate Professor Director, Fellowship Training Program Nitender Goyal, MD* Assistant Professor Director, Quality Improvement Lesley A. Inker, MD, MS Associate Professor Medical Director, Kidney and Blood Pressure Center Director, Kidney Function Evaluation Center Vice Chairman of Medicine for Clinical Affairs, Bertrand L. Jaber, MD, MS Associate Professor St. Elizabeth’s Medical Center Alin A. Joseph, MD, MS Assistant Professor Amy B. Kuhlik, MD Assistant Professor Dean for Student Affairs, TUSM Eduardo Lacson, Jr., MD, MPH* Associate Professor Maurice S. Segal, MD Nicolaos E. Madias, MD Academic Dean of TUSM, St. Elizabeth’s Medical Center Professor of Medicine Director, Dialysis Services Tufts Medical Center Medical Director, DCI Boston and DCI Walden Pond Klemens B. Meyer, MD Professor Medical Director, Home Dialysis Program at DCI Ball Square Medical Director, DCI Information Systems

Dana C. Miskulin, MD, MS Associate Professor

Associate Medical Director, DCI Walden Pond Madhumathi Rao, MD, PhD Assistant Professor Director, Bone Biopsy Center Director, DCI Outcomes Monitoring Program Michelle M. Richardson, PharmD Assistant Professor Director of Communications Director of Research Mark J. Sarnak, MD, MS Professor Associate Director, Research Training Program in Nephrology Dhivya Sundaramurthy* Instructor of Medicine Associate Medical Director, DCI Boston Daniel E. Weiner, MD, MS Associate Professor Deputy Editor, American Journal of Kidney Diseases Seth Wright, MD, MS Assistant Professor Director, Continuing Medical Education

*New appointment in 2016

99 Major Clinical Programs Kidney and Blood Pressure Center (KBPC) Outpatient clinical activities take place primarily in the Center, directed by Dr. Inker. The Center emphasizes a multi- disciplinary approach to kidney disease in collaboration with the Division of Transplant Surgery, Department of Urology, the DCI outpatient dialysis unit and the Frances Stern Nutrition Center. The KBPC

» specializes in the diagnosis and management of CKD, » NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM hypertension, glomerular diseases, kidney transplantation, and peritoneal dialysis. In 2013, the KBPC began outpatient measurements of GFR and in 2015 began the bone biopsy program. The Center carries out clinical studies on chronic kidney disease (CKD), including studies of polycystic kidney disease, lupus nephritis (in conjunction with the Division of Rheumatology), immunosuppression for transplantation, cardiovascular disease in transplantation, computerized quality of life assessment, and genetic predisposition to progression.

Home Dialysis The Division has an active home dialysis program at DCI’s Ball Square facility in Somerville, comprising both peritoneal dialysis and home hemodialysis. Patients are eligible if they are able to perform the required tasks, do not live alone and have insurance adequate to cover the procedures. Because of its convenience, the program is much appreciated by patients. multidisciplinary nature of the team facilitates Center for Polycystic Kidney Disease consultations for patients who have already received The Center for Polycystic Kidney Disease at Tufts Medical transplants, as well as for patients and donors for whom Center was opened in 2006. The physicians are transplantation is being considered. Another benefit of this internationally recognized experts in treating and collaboration is the facilitation of dialysis access planning managing the complications of PKD. On average, 50 new and interventions. patients are seen each year in this program. Areas of expertise for patients with PKD include dialysis and Kidney Function Evaluation Clinic transplantation and the evaluation and management of the The Kidney Function Evaluation Center, under the complications of liver and kidney cysts including chronic direction of Dr. Inker, is a Boston-wide resource for pain, kidney stones, and cardiovascular issues such as confirmatory tests for GFR estimated from creatinine. intracranial aneurysms. Care is coordinated with the Patients whose estimates of GFR using creatinine are not Departments of Urology, Neurosurgery, Transplantation thought to be accurate are referred to the Center for Surgery and Genetics. measurement of GFR using plasma clearance of iohexol. estimated using both creatinine and cystatin C and a Kidney Transplantation Program report is sent to the referring physicians for a complete A weekly Transplant Multidisciplinary clinic is staffed by interpretation of the GFR values. For example, it may be Dr. Perrone, Medical Director of Kidney Transplantation, useful in patients who will be undergoing chemotherapy together with a transplantation surgeon. Nurse with agents that are cleared by the kidneys, potential practitioners serve as transplantation coordinators. The

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 kidney donors with high muscle mass who are thought to Inpatient Dialysis have falsely low estimated GFR, or patients with CKD who Dialysis Clinic, Inc., the hospital’s dialysis provider, performs have low muscle mass who have symptoms that could be pediatric as well as adult hemodialysis at Tufts Medical consistent with uremia. Center, with Dr. Meyer as director. Because patients receiving Bone Biopsy Center hemodialysis treatment usually are also undergoing many other tightly scheduled tests and procedures, the program is Directed by Dr. Rao, the Bone Biopsy Center works with organized so as to enhance patient f low. Continuous other nephrologists, endocrinologists, endocrine venovenous hemofiltration (CVVH) and slow continuous surgeons, orthopedic surgeons and pathologists to

ultrafiltration (SCUF) are also available. »

provide comprehensive care plans for patients with » NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM metabolic bone disease. Inpatient peritoneal dialysis is performed in intensive care units and on the North 7 inpatient ward, where the nursing To diagnose and manage these diseases, most physicians use staff are trained to perform peritoneal dialysis. Tufts a parathyroid hormone (PTH) assay, which has serious Medical Center is the only hospital in Greater Boston with a limitations. The gold standard is a bone biopsy, which helps floor on which the staff nurses are trained to perform characterize the bone quality and architecture, establishes peritoneal dialysis. turnover rates and provides an optimal treatment guide. Currently, Tufts Medical Center is the only center in New England to perform biopsies to aid in the diagnosis and Teaching Activities management of bone disease associated with kidney disease. The Division of Nephrology is committed to education at the national as well as the local level. Division members In-center Dialysis carry out clinical and basic research, serve on national The DCI Boston in-center hemodialysis unit located at Tufts boards that establish standards in clinical practice, and Medical Center operates more than 2 stations. There are lecture at local, national, and international conferences. two affiliated in-center dialysis clinics, one at Ball Square Division members participate extensively in the in Somerville, the other at Walden Pond in Concord, MA. preclinical years (renal pathophysiology, physical Both programs are routinely recognized for high quality diagnosis) and the clinical years (ward and consultation clinical care. services) of the medical school. Dr. Gilbert conducts a Inpatient Programs series of lectures on core nephrology topics for 3rd year students during their internal medicine clerkships at The Division provides routine consultation in the diagnosis Tufts Medical Center. In addition, Dr. Gilbert offers an and management of kidney diseases, as well as expertise elective in evidence-based medicine to 4th year students. for all forms of renal replacement therapy including hemodialysis, peritoneal dialysis, continuous renal Interns and residents at Tufts Medical Center rotate replacement therapy, and charcoal hemoperfusion. through the renal ward service and may choose an elective on the renal consultation service. Senior Under the direction of Dr. Perrone, the Division residents may also choose an elective in the Kidney and participates in the Tufts Medical Center Kidney Transplant Blood Pressure Center. The senior residents rank this Program. Many of the donors in this program are living outpatient experience highly. donors. Tufts Medical Center is a member of the New England Program for Kidney Exchange (NEPKE) that The Division participates in other postgraduate forums. coordinates sharing by mismatched donor-recipient pairs. Several Division members serve as research mentors to Patients who have received transplants are followed in the Masters of Science candidates in the Sackler School of KBPC. The transplant team at Tufts Medical Center has Graduate Biomedical Sciences. Dr. Gilbert coordinates carried out more than 1250 kidney transplants. nephrology lectures in the Advanced Molecular and Cellular Pharmacology Course at Tufts University School of Medicine, teaches Renal Pharmacology at the Sackler School of Graduate Biomedical Sciences and leads the Renal Section of the Nutritional Biochemistry and Physiology at the Friedman School of Nutrition Science and Policy.

101 Clinical Fellowship Training of decision support tools for treatment of anemia in Under the direction of Dr. Gilbert, the clinical fellowship dialysis patients and the implementation of an interface program offers training of unusual breadth and depth. between hemodialysis machines and the information Fellows have clinical rotations both at Tufts Medical system. Dr. Richardson directs the corporate-wide DCI Center and at St. Elizabeth’s Hospital. Over the past 15 Outcomes Monitoring Program, which uses patient years, approximately 40% of graduates of the fellowship experience data to improve care. program have continued in full-time academic positions. National Kidney Disease Education Program Another 16% have become private practitioners with Dr. Inker is a member of the National Kidney Disease substantial teaching responsibilities, many in hospitals »

» Education Program (NKDEP) of the NIDDK. She has NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM with university affiliations. The remaining graduates are participated in the efforts of the NKDEP to recommend largely engaged in private practice. reporting GFR estimates by clinical laboratories and to Research Fellowship Training standardize serum creatinine assays for more accurate The William B. Schwartz Division of Nephrology offers GFR estimation. clinical research training through the NIDDK PKD Data Standards Institutional Research Training Award in “Epidemiology, Along with colleagues from the Polycystic Kidney Clinical Trials and Outcomes Research in Nephrology”. Disease Outcomes Consortium, Dr. Perrone was the lead This award funds three research trainees per year. The author and Dr. Miskulin a co-author on an AJKD program is designed for fellows aspiring to a career as an publication that established the first ever data standard independent investigator in clinical research in applicable to kidney disease. Data standards for any nephrology. The program has been focused primarily on given therapeutic area allow for mapping and pooling of chronic kidney disease, but in recent years, there has data into a common data set and provide the basis for been a growing interest in acute kidney injury. future studies, sharing data and long-term registries. In Policy Initiatives ADPKD, having consensus data standards is the foundation for improving understanding of disease Chronic Kidney Disease in Nicaragua progression and treatment. Dr. Weiner collaborates with public health researchers from Boston University School of Public Health to Research Activity investigate chronic kidney disease among workers in Research in the Division of Nephrology is focused on rural Nicaragua. The objective is to explore the reported solving clinical problems. Each research project has high prevalence of kidney disease among working age domain experts, generally a nephrologist, a methods residents in rural northwest Nicaragua to better define expert, and collaborators from other disciplines. prevalence and to develop hypotheses regarding cause. Although the primary emphasis has been on chronic DCI Information Systems and Outcomes kidney disease, there are a growing number of projects Monitoring Program in acute kidney injury. Some of the areas of recent emphasis are: chronic kidney disease, assessment of Dr. Meyer is Medical Director for Information Systems kidney function, aging, nutrition, dialysis and for Dialysis Clinic, Inc., and is a principal architect of transplantation, progression, polycystic kidney disease, DCI’s information system, which sets an industry acute kidney injury, and hypertension. standard for quality of care and of information. The team’s current projects include continued development

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Clinical Research Activity

Recipient Funding Source Purpose of Award Assess aorta, brain, and kidney structure and function in the NIH/NIDDK AGES-Reykjavik study (with Dr. Inker) Seek markers for CKD in a representative multi-ethnic NIH/NIDDK population with measured GFR (with Dr. Inker)

National Kidney Foundation Assess GFR Decline as an Outcome for Clinical Trials in CKD

Andrew S. Levey, MD » » NIH/NIDDK Estimating GFR from a Panel of Endogenous Filtration Markers NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM

Monitoring PD adequacy using serum levels of endogenous DCI filtration markers

NIH Chronic Kidney Disease Prognosis Consortium

Association of FGF-23 and Klotho with cognitive impairment David Drew, MD, MS NIH* and cerebrovascular disease in CKD Pharmalink Proteinuria Reduction/Primary IGA Nephropathy Patients NIH* CKD Biomarker Consortium-Phase 2: Risk Markers in Blood Lesley A. Inker, MD, MS Change in alubuminuria and GFR as end points for clinical trials NKF* in early stages of CKD NIH/NIDDK Blood Pressure in Dialysis NIH Pragmatic trials in maintenance hemodialysis Dana C. Miskulin, MD, MS DCI Decision support for anemia management in HD Intelomed Measuring cardiovascular stress in hemodialysis patients DCI* The Dialysate Sodium Lowering Trial (DESALT) A multi-center, longitudinal observational study of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Otsuka to establish the characteristics and determinants of disease progression. Determine long-term safety and efficacy of oral tolvaptan in Otsuka adults with ADPKD Ronald D. Perrone, MD NIH/NIDDK PKD Clinical Trials Network Compare the efficacy and safety of Tolvaptan in patients with Otsuka ADPKD and CKD Stages 2-4 Evaluate the long-term safety of titrated immediate-release Otsuka Tolvaptan in patients with ADPKD Department of Defense* Evaluating metformin as a novel therapy for ADPKD Identifying risk factors and screening for cognitive impairment DCI* in hemodialysis patients NIH/NIDDK Investigate cognitive function in hemodialysis patients Assess relationship among chronic kidney disease, vascular NIH/NIDDK disease and aging Mark J. Sarnak, MD, MS The Aging Kidney: Chronic Injury, Impaired Functions and NIH Clinical Outcomes Kidney tubular damage and dysfunction identify a novel axis of NIH kidney disease Beyond the glomerulus: novel clinical markers of kidney health NIH* and prognosis

103 Clinical Research Activity (continued)

Recipient Funding Source Purpose of Award DCI Safety and effects of supplementation with ergocalciferol Analysis of pulse wave velocity and central aortic pressure NIH outcomes in SPRINT Randomized trial of exercise training on cognitive and physical NIH/NIDDK functioning in CKD NIH SPRINT Main Phase II » » NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM Daniel E. Weiner, MD, MS Renal disease, kidney cancer, and metalworking fluid exposure NIH in autoworkers NIH MIND and the kidneys Cardiovascular outcomes in subjects with Type 2 DM and diabetic nephropathy Janssen Evaluate the safety and efficacy of pyridorin in subjects with nephropathy due to Type 2 DM

* New grant in 2016 Basic Research

Recipient Funding Source Purpose of Award Using metabolomics to study treatment effect and toxicities of Lesley A. Inker, MD, MS Otsuka tolvaptan in the TEMPO 3:4 trial Use a proteomic approach to CKD biomarker discovery and Andrew S. Levey, MD NIH/NIDDK validation

* New grant in 2016

Honors and Awards

Andrew S. Levey, MD Scott J. Gilbert, MD »» Inducted to the Association of American Physicians »» Recognized as a “Top Doctor” by Boston Magazine »» Recognized by Thomson Reuters as a highly influential »» Chair, ASN Workforce and Training Committee researcher for three sequential years »» Member, Medical Advisory Board of the NKF serving New »» Member, NKF Scientific Advisory Board England

Ronald D. Perrone, MD »» Program Chair, Nephrology Training Program Directors Retreat, American Society of Nephrology »» Co-executive director, Polycystic Kidney Disease Outcomes Consortium »» Member, Panel for Accreditation Appeals in Nephrology »» Invited Lecture: The PKD Outcomes Consortium: TKV as a »» Accreditation Council for Graduate Medical Education Biomarker for Patient Selection, Barcelona Spain »» Member, Executive Committee of the Nephrology Training »» Invited Lecture: Management of Hypertension. Zurich Program Directors for the American Society of Nephrology Switzerland »» Outstanding teaching in Preclinical Years Award from the »» Invited lecture: Using CDISC Standard to Map Clinical Senior Class Information in ADPKD. Cambridge UK »» Invited Presentation: Rightsizing Your Fellowship Program. »» Invited lecture: Using Total Kidney Volume to Predict ASN Kidney Week Disease Progression and Guide Management of ADPKD. Ottawa Canada

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Lesley A. Inker, MD, MS Mark J. Sarnak, MD, MS »» Recognized as a “Top Doctor” by Boston Magazine »» Recognized in Boston Magazine as one of Boston’s best »» Chair, International Classification of Diseases in the US nephrologists »» Chair, Clinical Oversight Committee of KEEP »» Co-chair, Cardiovascular Health Study (CHS) Renal Work Group »» Member of the National Institute for Diabetes, Digestive and Kidney Disease: United States Renal Data System »» Co-chair, KDIGO Clinical Practice Guideline for Lipid External Advisory Committee and Vascular Access Management in CKD Consortium External Advisory Committee »» Member, Steering Committee for CKD Prognosis

»» Member, National Kidney Disease Education Program Consortium » » NEPHROLOGY OF DIVISION SCHWARTZ B. WILLIAM Laboratory Work Group. »» Invited lecture: Applying JNC 8 and KDIGO Blood Pressure »» Major Grant Awards in 2016: Please see Table of Research Recommendations in the CKD Population American Activities Society of Nephrology, San Diego, CA »» Invited lecture: Hypertension in the Elderly: Defining Eduardo Lacson, Jr., MD, MPH Meaningful Targets. NKF Spring Clinical Meeting Boston »» Delegate for ASN National Kidney Health Initiative and the MA CDC Making Dialysis Safer Coalition Daniel E. Weiner, MD, MS »» Member, ASN Quality Metrics Task Force »» Information Steering Committee of Dialysis Clinic Inc »» Member, DCI’s Clinical Science and Quality Initiatives »» Member, Renal Disease and Detoxification Committee of Nicolaos E. Madias, MD the Association for the Advancement of »» Member, Advisory Board for the Hellenic Bioscientific MedicalInstrumentation Association in the USA »» Member, American Association of Kidney Patients Medical »» Member, editorial boards of Hippokratia, Hellenic Medicine, »» Member, USRDS External Advisory Committee and Fistula International Angiology, Arterial Hypertension and Kidney: »» Member, ASN Dialysis Advocacy Group A current survey of world literature »» Chair, ASN Quality Metrics Task Force Klemens B. Meyer, MD »» Chair, 2016 National Kidney Foundation Spring Clinical »» Recognized as a “Top Doctor” by Boston Magazine »» Grant reviewer, NIA GEMSSTAR review committee »» Member, Quality Management Committee and Medical »» Member, ASN Public Policy Board »» Invited Lecture: Unique ESRD Populations: Malnourished »» Member, DCI Medical Director Research Committee and and Morbidly Obese. ASN Kidney Week Chicago IL Quality Management Committee »» Invited Lecture: The hemodialysis Prescription: from Blood »» Invited lecture: Practices that Work to Improve Dialysis Flows to Baths. NKF Spring Clinical Meeting Boston MA Outcomes. ASN Kidney Week Chicago IL »» Invited Lecture: Dialysis Nuts and Bolts: Technical Things »» Invited lecture: Edematous and Hypotensive Dialysis Every Dialysis Provider Should Know. NKF Spring Clinical Patients: What to Do? ASN Kidney Week Chicago IL meeting Boston MA »» Invited lecture: Trends in US Hemodialysis Practices: Dana C. Miskulin, MD, MS Insights from the DOPPS. NKF Spring Clinical Meeting »» Member, Quality Management Committee of Dialysis Clinic Boston MA Inc »» Chair, Endpoints Committee for the HALT-PKD Study »» Major Grant Awards in 2016: Please see Table of Research Activities

Michelle M. Richardson, PharmD »» Member, ESRD Functional Status TEP »» Invited lecture: Improving the patients experience of care. Annual Dialysis Conference Seattle Washington

105 DIVISION OF PULMONARY, CRITICAL CARE AND SLEEP MEDICINE » » DIVISION OF PULMONARY, CRITICAL CARE AND SLEEP MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION The Pulmonary Division was established in 1971. During the 31-year tenure of its first chief, Dr. Fanburg, the Division grew to comprise ten active MD members and two full-time PhD members. Dr. Fanburg established a highly regarded basic research program that focused on metabolic activities of the lungs including angiotensin converting enzyme activity as well as endothelial cell biology. More recent studies have focused on signal transduction pathways related to serotonin, its transporter and receptors, in the regulation of pulmonary vascular smooth muscle cell proliferation. Dr.Fanburg has received Nicholas Hill, MD international recognition and numerous awards for his work.

Dr. Nicholas Hill assumed the directorship in 2002 and has expanded the clinical research activities in the division, along with a more than doubling in the size of the faculty. Clinical trials are underway on pulmonary hypertension, high flow nasal oxygen and ventilator management of ARDS. There are also studies in progress to improve ventilator outcomes, especially through the use of noninvasive ventilation. This modality has gained wide acceptance for its ability to improve outcomes in patients with certain forms of respiratory failure.

The Division offers a wide array of clinical services. In the early 1990s, it became the Pulmonary and Critical Care Division when it assumed the medical care of patients in the Medical Intensive Care Unit at Tufts Medical Center. The Center for Sleep Medicine was incorporated in 2002. In addition, specialty clinics in asthma, pulmonary hypertension, TB, lung cancer and amyotrophic lateral sclerosis are conducted by the Division. The addition of Dr. Maher Tabba in 2008 brought skills in interventional pulmonology to the Division. The Division also added coverage of two intensive care units in Lowell, Massachusetts, at Lowell General Hospital and Saints Medical Center in 2013. Dr. Greg Schumaker was appointed to direct this aspect of the Division’s activities.

Highlights of 2016

»» Dr. Nicholas Hill appointed chair of the Steering »» Dr. Michael McBrine co-directs the Intensive Care Unit Committee of the NIH-sponsored Pulmonary Vascular at Beth Israel Deaconess Hospital-Plymouth in Diseaseomics (PVDomics) project Plymouth, MA, as well as co-directing our Pulmonary Fellowship Program »» Dr. Nicholas Hill received the Distinguished Faculty Award from Tufts University School of Medicine »» The Division has added two junior faculty PhDs doing basic research; Dr. Krishna Penumatsa working on the »» Dr. Ioana Preston appointed Chair of the Educational biological effects of transglutamase 2, and Dr. Jamie Committee of the Pulmonary Hypertension Wilson working on the role of FOX signaling in Association and Director of the Pulmonary pulmonary hypertension Hypertension Center at Tufts Medical Center »» Peter Polgar, PhD joined the Division, bringing »» Dr. Erik Garpestad appointed as Associate CMO in expertise on cell permeable peptides as potential addition to his role as Associate Chief of Pulmonary therapeutic tools Division

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Responsibility Division Chief Nicholas Hill, MD Professor Director, Respiratory Therapy Department Nadine Al-Naamani, MD* Assistant Professor Christina Anderlind, MD Assistant Professor Pulmonary Consultant, Shattuck Hospital Haval Chweich, MD * Assistant Professor CCU intensivist » »

Director, ICU Pharmacology Research Program MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION John Devlin, Pharm D Adjunct Associate Professor Special and Scientific staff Matthew Duprey, Pharm D Sponsored Research Staff Scott Epstein, MD Professor Dean of Educational Affairs, TUSM Barry Fanburg, MD Professor Director, Pulmonary Research Geraldine Finlay, MD Adjunct Associate Professor Senior Editor, Up-To-Date, Pulmonary Attending Associate Division Chief Erik Garpestad, MD Associate Professor MICU Director Associate Chief Medical Officer for Quality Maher Ghamloush, MD Assistant Professor Director, Pathology Conference Series Program Director, Sleep Medicine Fellowship Khalid Ismail, MD Assistant Professor Director, The Center for Sleep Medicine Usamah Kayyali, PhD, MPH, DPAT Associate Professor Special and Scientific staff Sucharita Kher, MD Assistant Professor Director, Divisional Outpatient Services Sebastian Kurz, MD, PhD Assistant Professor Pulmonary Attending Po-Shun Lee, MD Associate Staff Pulmonary Outpatient Clinic Michael McBrine, MD Assistant Professor ICU Co-director, Beth Israel Deaconess Hospital-Plymouth Krishna Penumatsa, PhD* Assistant Professor Special and Scientific staff Director, Pulmonary Hypertension Center Ioana Preston, MD Associate Professor Director, Pulmonary Function Lab Imrana Qawi, MD Assistant Professor Director, Pulmonary/Critical Care Ultrasound Services Medical Director, Bronchoscopy Service Kari Roberts, MD Associate Professor Associate Program Director, Internal Medicine Residency Program Russel Roberts, Pharm D Adjunct Associate Professor Senior Clinical Pharmacy Specialist Medical Director, Rapid Response Team, Tufts MC Greg Schumaker, MD Assistant Professor ICU Director, Lowell General Hospital Section Chief of Critical Care, Lowell General Hospital Amy Simon, MD Adjunct Associate Professor Director, Asthma Center Program Director, Fellowship Program Maher Tabba, MD, FACP Associate Professor Director, Pulmonary Interventional Service Deniz Toksoz, PhD Associate Professor Special and Scientific staff Rod Warburton, BA* Assistant Professor Research Lab Supervisor Jamie Wilson, PhD * Assistant Professor Special and Scientific staff Felix Yu, MD * Assistant Professor

* New member in 2016

107 Major Clinical Programs Teaching Activities The Critical Care Program, under Dr. Erik Garpestad, The Division teaches the second-year pathophysiology oversees the delivery of medical critical care at Tufts course at Tufts University School of Medicine, providing Medical Center. The program provides daytime coverage didactic lectures and leading small discussion groups. by a board-certified intensivist seven days a week, as well Third-year clerkships are available on the pulmonary as nightly phone coverage by fellows and attendings. The ward service. A number of pulmonary attending Division also provides daytime coverage and overall physicians have been recognized by medical students for direction of two ICUs at Lowell General Hospital and their teaching.

» Saints Medical Center, respectively, under the direction

» Fourth-year clerkships are available in the MICU at Tufts DIVISION OF PULMONARY, CRITICAL CARE AND SLEEP MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION of Greg Schumaker, MD. Dr. Michael McBrine serves as Medical Center. Electives are also available on the Co-Director of the ICU at Beth Israel Deaconess Hospital- pulmonary consultation service, as well as in the Sleep Plymouth in Plymouth, MA. Laboratory and on the Pulmonary Interventional Service The Center for Sleep Medicine, under Dr.Khalid Ismail, under Maher Tabba. Medical residents experience rotations provides diagnostic and therapeutic services for patients on the Pulmonary ward and MICU services, and may choose with a variety of sleep-related disorders. It consists of an electives on the Pulmonary consultation service. Division eight-bed, fully accredited sleep laboratory at Tufts members have received many teaching awards. Medical Center. It serves as an important educational There are ACGME-accredited fellowships in Pulmonary resource for the Pulmonary and Critical Care Fellowship and Critical Care medicine, as well as in Sleep Medicine. Program. The Division also offers unaccredited fellowships in The Bronchoscopy Service, under Dr. Kari Roberts, offers interventional medicine and pulmonary vascular diagnostic and therapeutic bronchoscopies for inpatients disease. There are three fellows in each year of the and outpatients attending Tufts Medical Center. three-year Pulmonary Critical Care fellowship, and there is an option for additional years for those wishing a The Pulmonary Interventional Service, under Dr. Maher more in-depth research experience. The Sleep Tabba, offers a wide range of advanced pulmonary Fellowship has one position per year. interventional procedures that include percutaneous placement of tracheostomy tubes, placement of stents for Fellows rotate through the ICUs and consultation airway narrowing, medical thoracoscopy and other rotations at Tufts MC during their first year. During the pleural procedures including thoracoscopy drainage and second and third years, fellows serve as the in-house pleurodesis. Plans are in place to obtain f luorescent intensivist at the Intensive Care Units at Lowell General technology to identify occult airway cancers. pursued basic science or clinical research careers and Saints Medical Center, and pursue research interests. The Division also offers numerous outpatient general and These can be in a wide range of areas including basic, specialty clinics for asthma, sleep disorders and translational and clinical pulmonology, and fellows are pulmonary hypertension encouraged to collaborate with investigators at other institutions if additional expertise is sought. Each year, the Barry Fanburg Award for Excellence in Pulmonary and Critical Care Medicine is presented to a senior fellow selected for his or her exceptional and outstanding performance during fellowship. Most graduates have taken clinical academic positions or have gone into clinical practice, and some have pursued basic science or clinical research careers.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Research Activities Clinical Research Support The ongoing clinical research projects within the Division have an annual budget of approximately $225,000.

Recipient Funding Source Purpose of Award Pulmonary Division Database and DNA tissue bank in pulmonary hypertension Chest Foundation Respironics Enhancing utilization of non-invasive ventilation in critical care Pulmonary Division Sleep during non-invasive ventilation in the ICU » » Effect of noninvasive open ventilation (NIOV) on work of breathing MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION Breathe Technologies in COPD patients A dose-ranging study of the efficacy and safety of bardoxolone methyl REATA Pharmaceuticals in patients with pulmonary arterial hypertension Nicholas Hill, MD Fisher & Paykel Health Pilot study of optiflow as a NIV rest therapy A Phase 2 randomized, double-blind, placebo-controlled multi- Gilead center study to assess the efficacy and safety of GS-6624 in subjects with idiopathic pulmonary fibrosis A multicenter, randomized, double-blind, placebo-controlled trial to Therapeutics evaluate the safety and efficacy of inhaled Treprostinil in subjects with pulmonary hypertension due to parenchymal lung disease An open-label extension study of inhaled Treprostinil in subjects with United Therapeutics pulmonary hypertension due to parenchymal lung disease The Steroid Sparing Effects of Omalizumab in Non-Cystic Fibrosis Sucharita Kher, MD Novartis ABPA ANGEL study. Ambrisentan in portopulmonary hypertension. A Gilead multicenter open label trial testing the efficacy and safety in the special population of POPH ASK study. A Phase 2, dose-ranging, randomized, double-blind, Gilead placebo-controlled study of GS-4997 in subjects with pulmonary arterial hypertension Actelion OPUS Registry/Opsumit® (Macitentan) Users Registry Actelion SPHERE study. Uptravi® (Selexipag): the Users Drug Registry TRITON study. The efficacy and safety of initial triple versus initial dual oral combination therapy in patients with newly diagnosed Actelion pulmonary arterial hypertension: a multi-center, double-blind, placebo-controlled, Phase 3b study. Ioana Preston, MD GRIPHON OL study. Long-term single-arm, open-label study to Actelion assess the safety and tolerability of Selexipag (ACT-293987) in patients with pulmonary arterial hypertension. Motion – a Phase IV, prospective, single arm, open-label study to Bayer HealthCare measure outcomes in patients with PAH not on active treatment Respite – An open-label, international multicenter, single arm, Bayer HealthCare uncontrolled, phase 3b study of riociguat response to treatment with phosphosdiesterase-5 inhibitors (PDE-5i) LIBERTY study. A phase 2, randomized, double-blind,placebo- Eiger controlled study of UBEnimex in patients with pulmonary arterial hypertension (WHO Group 1) PHAROS study: Pulmonary hypertension assessment and George Washington Univ recognition of outcomes in scleroderma Pulmonary Division Database and tissue bank for study of pulmonary hypertension Kari Roberts, MD NIH/NHLBI Estrogen signaling in portopulmonary hypertension

109 Basic Research/NIH Funded Research Support For the past 45 years the Division has been actively and PhDs, have performed these studies. Members of the involved in NIH-supported research programs that have Division regularly participate in national advisory and utilized biochemical, cell biologic and molecular grant review committees. The Division's current annual biologic systems to study pulmonary disease. A variety research grant support is $400,000. of investigators from the Division, including both MDs

Recipient Funding Source Purpose of Award » »

DIVISION OF PULMONARY, CRITICAL CARE AND SLEEP MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION Choir, Steering Committee, PVDomics Network – Redefining NIH/NHLBI Pulmonary hypertension through pulmonary vascular disease.

National biological sample and data repository for pulmonary NIH/NHLBI arterial hypertension Low tidal volume universal support: feasibility of recruitment for NIH/NHLBI interventional trial acronym: LOTUS FRUIT PETAL NETWORK. Re-examination of systemic early NIH/NHLBI Nicholas Hill, MD neuromuscular blockade for ARDS: ROSE TRIAL Establishing a national bio-repository of biological samples and NIH/NHLBI genetic data of patients with WHO Group 1 PAH. (Nichols, PI; Hill, co-investigator) Developing clinical trials for prevention and treatment of ARDS. Also to effectively contribute to a multicenter network led by a NIH/NHLBI clinical coordinating center. (Steingrub, PI; Hill, co-investigator) Determine the role of the serotonin transporter in serotonylation of cellular proteins, including fibronectin, that leads to smooth Barry Fanburg, MD NIH/NHLBI muscle cell proliferation and migration and development of pulmonary hypertension (Fanburg, PI; Toksoz, co-investigator; Hill, collaborator)

American Heart Association The role of mineralocorticoid receptor (MR) in pulmonary Ioana Preston, MD hypertension. Exploring the role of MR in the development of PAH Grant-in-Aid by combining in vitro studies with in vivo animal testing Examining the role of estrogen, genetic variation in estrogen metabolizing genes, and angiogenesis in porto-pulmonary Kari Roberts, MD NIH-NHLBI hypertension. (Kawut, PI; Roberts, co-investigator) Exploring the role of the tissue transglutaminase in right ventricular stiffness in pulmonary hypertension animal model of Krishna Penumatsa, PhD Gilead Sciences pulmonary artery constriction. We will identify and characterize the sequence of signaling mechanisms that lead to right ventricular stiffness seen in this model.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Honors and Awards

Nicholas Hill, MD (selected items) »» Symposium on COPD organized by the National Research »» National Association for Medical Direction of Respiratory Institute for Tuberculosis and Lung Disease/Iranian Care (NAMDRC) 39th Annual Meeting and Educational Pulmonary Society. Invited speaker: “NIV for COPD in the Conference: Invited speaker: "Pulmonary Hypertension: Long-Term Setting—How to use it?” and “Does High Flow New Therapies,” Rancho Mirage, CA and Nasal Therapy have a Role in COPD Management?” »» NYDART Annual Springtime Respiratory Therapy Tehran, Iran Symposium & Exhibition 2016, Invited lecture: "Non- »» Pulmonary Hypertension Association on Demand CME »

Symposium. Invited speaker: “Management of Pulmonary » Invasive Therapies: The Role of High Flow Therapy and MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION Beyond.” Kingsborough Community College, Brooklyn, NY Hypertension.” Manchester, NH »» Trends in Mechanical Ventilation Conference 2016; Course »» 14th Annual Tufts Pulmonary Hypertension Symposium, Director. Speaker: “High Flow Nasal Oxygen—the new Course Director. Concurrent Patient Session; Patient Q & NIV?” Workshop: “Applications of Noninvasive Ventilation A. "The Great Debate: To Treat or not to Treat Combined and High Flow Nasal Therapy.” Waltham Woods, MA Group 2 Pulmonary Hypertension." Cambridge, MA »» Medical Grand Rounds, Boston University. “Controversies »» 2016 Winter Lung Series Conference, The University of in Pulmonary Hypertension.” Boston, MA Arizona College of Medicine. Presenter: “Group 2 »» The Canadian Respiratory Conference: A Breath of Fresh Pulmonary Hypertension; a Conundrum Wrapped in an Air. Invited Speaker: “NIV: Something Old, Something New, Enigma.” Tucson, AZ Something Blew.” Halifax, Nova Scotia »» American Thoracic Society International Conference. »» European Respiratory Society International Congress 2016. Invited speaker: “When Less is More; Making Respiratory Chair: Symposium; “Telemonitoring of Ventilator- Assistance Simpler, Safer and Cheaper.” Facilitator/ Dependent Patients Looking into the Future.” Meet the Moderator: “Respiratory Failure: High Flow Oxygen, Professor: “Dealing with Air Leaks during Noninvasive Liberation, Non-Invasive and Prolonged Ventilation,” Ventilation.” Symposium speaker: “The Physiologic Effects and “The Promised Land: Clinical Studies in PH.” of NTV and HFNT: HFNT is not Continuous Airway San Francisco, CA Pressure.”: London, United Kingdom »» XIX Foro Internacional de Medicina Critica/International »» Saint Frances Hospital and Medical Center 20th Annual Forum of Critical Medicine (Mechanical Ventilation—Sepsis Thomas J. Godar Pulmonary/Critical Care Symposium. and Selected Topics). Presenter: “Tips on Nasal High Flow; Invited speaker: “Chronic Pulmonary Arterial How it Works,” “Tips on Nasal High Flow; The New Hypertension—How Far have we Come to Understand the Noninvasive Ventilation” and “The Failing Right Ventricle.” Pathogenesis and Treatment?” Hartford, CT Mexico City, Mexico »» CHEST 2016, Annual meeting of the American College of Christina Anderlind, MD Chest Physicians. Leadership Training Course. Speaker »» Patent: Co-inventor of a Nasal Epithelium Gene Expression “Conversation with an Academic Leader, a Personal Signature and Classifier for the Prediction of Lung Cancer Journey.” Evening Symposium: “Physiologic Bases of High »» Invited lecture: "Interpretation of Pulmonary Function Flow Nasal Therapy.” Los Angeles, CA Testing," Lemuel Shattuck Hospital, Boston, MA »» Critical Care Canada Forum annual meeting. Invited »» Invited lecture: "Eosinophilic Lung Disease," Lemuel speaker: “NIV in Hypoxemic Respiratory Failure—does it Shattuck Hospital, Boston, MA still have a Role?” and “High Flow Nasal Oxygen—Where to »» Invited lecture: "ABGs," Lemuel Shattuck Hospital, use it?” Toronto, Canada Boston, MA »» The FSH Society’s 2016 Patient Connect Conference. »» Invited lecture: "Solitary Pulmonary Nodule," Lemuel Facioscapulohumeral Muscular Dystrophy. Presenter: Shattuck Hospital, Boston, MA “Respiratory Manifestation of FSH: How we Manage them.” Boston, MA »» Member of the Medication Occurrence Subcommittee, Lemuel Shattuck Hospital, Boston, MA

111 Scott Epstein, MD Sebastian Kurz, MD »» Panel Member, Liberation from Mechanical Ventilation: An »» Infection Control Committee, Tufts Medical Center Official American College of Chest Physicians/American Michael McBrine, MD Thoracic Society Clinical Practice Guideline »» Alert Space Take Force Committee, Tufts Medical Center »» TUSM/Maine Medical Center/Maine Track Steering »» Beth Israel Deaconess Plymouth Hospital Care Committee Committee »» Faculty Advisory Council on Excellence, Diversity and Krishna Penumatsa, PhD Inclusion, TUSM »» Course Director, Pulmonary Research Seminar Series,

» »» Masters in Biomedical Sciences Steering Committee, Tufts Medical Center » DIVISION OF PULMONARY, CRITICAL CARE AND SLEEP MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION TUSM »» Invited lecture: Gordon Research Conference. »» Co-Chair, First and Second Year Course Directors “Transglutaminases in Human Disease Processes. Committee, TUSM Girona, Spain »» Educational Strategic Planning II Committee (to revise Ioana Preston, MD TUSM curriculum) »» Thrombosis and Pulmonary Hypertension Summit. Invited »» Chair, Accreditation Standards Oversight Committee, speaker. "Molecular Pathways in PAH". Cancun, Mexico TUSM »» Sir John Vane Memorial meeting. Invited speaker. : "New »» Commonwealth of Massachusetts Governor's Medical Concepts in Clinical Trial Design in PAH.” London, United Education Working Group on Prescription Drug Misuse Kingdom »» Recognized as an Outstanding Tufts University School of »» International Society of Heart and Lung Transplant. Invited Medicine lecturer speaker: "Alterations in Lipid Metabolism in Pulmonary Erik Garpestad, MD Hypertension.” Washington, DC »» Co-Chair of Critical Care Committee, Tufts Medical Center »» 14th Annual Update in Pulmonary Hypertension Symposium. Course Co-Director and Speaker: “Treatment Maher Ghamloush, MD Considerations for the Hospitalized PAH Patient.” »» IRB Committee member, Tufts Medical Cente Cambridge, MA Khalid Ismail, MD »» Swiss Annual Pulmonary and Critical Care meeting. Invited speaker. "New Prostanoids in the Treatment of PAH.” »» Admissions Committee, Tufts University School of Montreux, Switzerland Medicine »» Japanese Society for Pulmonary Hypertension Annual Usamah Kayyali, PhD Meeting. Invited speaker. “Update on Treatment Algorithm »» Grant reviewer for the NIH Respiratory Integrative Biology for PAH.” Tokyo, Japan and Translational Research Study Section »» Scientific Leadership Council, Pulmonary Hypertension »» Grant reviewer for the NIH-HLBP Program Project Review Association Workgroup 014 »» IRB Committee Member, Tufts Medical Center »» Grant reviewer for the NIH-ZHL1 CSR-P (S1) Clinical »» Chair, Educational Committee, Pulmonary Hypertension Centers for Pulmonary Vascular Disease Phenomics Association »» Grant reviewer for the State of California Tobacco-Related »» Scientific Leadership Council member, Pulmonary Disease Research Program Hypertension Association Sucharita Kher, MD »» Editorial Board Member: Pulmonary Circulation, European »» Quality Improvement Academy II: Committee on "Moving Respiratory Journal, Advances in Pulmonary Hypertension through your visit". Taskforce focused on improving patient »» Grant reviewer for the American Heart Association experience during an outpatient visit. »» Member, Taskforce on Older Adults with Asthma in Massachusetts. Department of Public Health »» Women in Medicine Committee, Tufts Medical Center, Department of Medicine

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » DIVISION OF PULMONARY, CRITICAL CARE AND SLEEP MEDICINE SLEEP AND CARE CRITICAL PULMONARY, OF DIVISION

Kari Roberts, MD Greg Schumaker, MD »» Pharmacy and Therapeutics Committee, Tufts Medical »» Co-Chair, VAP Prevention Task Force, Tufts Medical Center Center »» UIT Prevention Task Force member, Tufts Medical Center »» Graduate Medical Education Committee, Tufts Medical »» Critical Care Committee member, Tufts Medical Center Center »» Chair, Critical Care Committee, Lowell General Hospital »» Patient Care Assessment Committee, Tufts Medical Center »» Cardiovascular Performance Improvement Team, Lowell »» American Thoracic Society Members in Transition and General Hospital Training Committee »» Ethics Committee, Lowell General Hospital »» American Thoracic Society Nominating Committee, »» Medical Executive Committee, Lowell General Hospital Pulmonary Circulation Assembly »» Peer Review Committee, Lowell General Hospital »» Association of American Medical Colleges, Member, »» Pharmacy and Therapeutics Committee, Lowell General Council of Faculty and Academic Societies Hospital »» Performance Improvement Council, Lowell General Hospital »» Sepsis Committee, Lowell General Hospital

Maher Tabba, MD »» IRB Committee Member, Tufts Medical Center

113 DIVISION OF RHEUMATOLOGY

The Division of Rheumatology offers comprehensive evaluation, consultation, and management of arthritis » » RHEUMATOLOGY OF DIVISION and rheumatic disease. Under the leadership of Dr. Timothy McAlindon, the division focuses on diagnosis and treatment of musculoskeletal and autoimmune rheumatic disorders. The division has had a steady increase in patient volume both internally in the main campus clinic as well as in its two satellite clinics in Norfolk (supervised by Dr. Senada Arabelovic) and Wellesley (supervised by Dr. Janeth Yinh).

Research in the Division concentrates on investigations of the pathogenesis of osteoarthritis, Timothy McAlindon, MD new quantitative methods to measure its progression, and clinical trials of disease-modifying investigational treatments. There is an active program in the use of Tai Chi for chronic rheumatic diseases including osteoarthritis, fibromyalgia, and systemic lupus erythematosus. The Center for Treatment Comparison and Integrative Analysis (CTCIA) generates evidence reports, health technology assessments, and clinical practice guidelines.

Highlights of 2016

»» Dr. Rajandeep Paik joined the Rheumatology Division »» Dr. Steven Vlad was appointed to IRB Committee

»» Dr. Timothy McAlindon received the Boston »» Jeff Driban received the New Investigator Award, Magazine “Top Doctors” Award National Athletic Trainers’ Association’s Research & Education Foundation »» Dr. William Harvey became Director of Informatics Integration, Tufts CTSI »» Dr. Chenchen Wang received the Excellence in Integrative Medicine Research Award, Clinical »» Dr. William Harvey joined the Ambulatory Research Prize, Heel Foundation, from the Initiatives Workgroup at Tufts Medical Center European Society of Integrative Medicine »» Dr. William Harvey joined the Board of Directors, American College of Rheumatology

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Faculty

Name Academic Rank Title and Special Responsibility Pediatric/Adult Transitional Clinic Associate

Fellowship Program Director » Senada Arabelovic, DO Assistant Professor » RHEUMATOLOGY OF DIVISION Course Director for Medical Student on Electives Director, Center for Treatment Comparison & Raveendhara Bannuru, MD, PhD Assistant Professor Integrative Analysis Juan Canoso, MD Adjunct Professor Clinical Anatomy Jeffrey Driban, PhD Assistant Professor Research Rajandeep Paik, MD Assistant Professor Adult Clinic William Harvey, MD, MSc Assistant Professor Clinical Director Robert Kalish, MD Associate Professor Program Director Grace Lo, MD Adjunct Assistant Professor Osteoarticular Research Program Timothy McAlindon, MD, MPH Professor Division Chief Steven Vlad, MD, PhD Assistant Professor Industry Sponsored Clinical Trials Director, Center for Complementary and Chenchen Wang, MD, MSc Professor Integrative Medicine Janeth Yinh, MD Assistant Professor Musculoskeletal Ultrasound Program Director

Major Clinical Programs

The Center for Arthritis and building networks with community physicians and Rheumatic Diseases neighborhood hospitals, offering high quality patient- The Center for Arthritis and Rheumatic Diseases oriented services, and developing clinically-relevant provides ambulatory consultation and follow-up as well research programs. as inpatient consultation services. The spectrum of Musculoskeletal Ultrasound Program rheumatic disorders treated by the Rheumatology Division encompasses musculoskeletal disorders and To improve the care of patients, the Division has adopted complex autoimmune diseases. Areas of particular the use of musculoskeletal ultrasound. This non-invasive expertise include ankylosing spondylitis, autoimmune imaging technique provides an enhanced rheumatic disorders, bone health, bursitis and musculoskeletal evaluation that avoids exposure to the tendonitis, gout, inflammatory muscle diseases, lupus, ionizing radiation associated with other imaging Lyme disease, osteoarthritis, psoriatic arthritis, techniques. Several of the faculty are skilled in its use rheumatoid arthritis, and vasculitis. Several members of and have designed a teaching series to introduce the Division have expertise in musculoskeletal trainees to this modality. Musculoskeletal ultrasound ultrasound. The Division also has a weekly urgent care allows the dynamic assessment of joint and tendon clinic to accommodate urgent referrals for diagnosis or movements in a manner not possible through other treatment of acute or severe presentations in rheumatic routine imaging modalities. Ultrasound-guidance disease. The Division's seven faculty and two fellows see facilitates the aspiration and injection of approximately 6,500 visits per year. musculoskeletal tissues, improves diagnostic accuracy and therapeutic effectiveness, and is valuable for The Division strives to advance all three aspects of its research in rheumatology. mission; patient care, education, and research. Emphasis on achieving these goals include diversifying services,

115 Pediatric/Adult Transitional Clinic Research Activities The clinic is designed to transition pediatric patients Osteoarthritis (OA) with autoimmune disorders who have been followed at the Floating Hospital for Children into an adult setting. The patients are seen by Dr. Senada Arabelovic.

Lyme Disease Specialty Clinic Dr. Robert Kalish offers a weekly Lyme disease clinic in which patients are assessed for complex issues regarding » »

RHEUMATOLOGY OF DIVISION the diagnosis and treatment of Lyme disease. Dr. Kalish has long been involved in Lyme disease research, first studying the humoral immune response in patients with Lyme arthritis in the 1990’s, and subsequently participating in a long-term follow-up study of patients Osteoarthritis (OA), particularly knee OA, is among the top with Lyme disease in the Lyme, Connecticut area. He is 15 causes of disability in the country and the main reason invited regularly to speak on Lyme disease for Medical for joint replacement at a cost of over $30 billion/year. Knee OA is typically a slowly progressive disorder but for Grand Rounds conferences. a recently-identified subset the disease progresses with dramatic rapidity. These individuals develop more frequent Teaching Activities and severe knee pain, and are 16 times more likely to require a total knee replacement. Since this is a novel observation, Tufts University medical students from each of the four it is not yet known whether accelerated knee OA (AKOA) is years rotate through the Division. First year students a distinct disease or an accelerated form of ordinary knee OA. Determining factors that differentiate or identify AKOA have the option of an elective with Dr. Kalish or other could lead to preventive strategies and uncover therapeutic faculty members. Second year students receive lectures targets. Our goals are to test if AKOA can be uniquely by the Division’s faculty in the Musculoskeletal characterized by: (i) anatomical characteristics associated with injuries and abnormal loading, (ii) biochemical Pathophysiology course directed by Dr. Kalish. Fourth factors that compromise structures (glucose homeostasis, year medical students have the option of completing a inflammation), (iii) certain types of instigating pathology, one month rotation in Rheumatology. and (iiii) distinct pathological processes. To achieve these goals, we propose to perform a nested case-control study The Rheumatology Fellowship is a two-year clinical and with three groups selected from the Osteoarthritis Initiative. research based program that provide training for The Osteoarthritis Initiative is an outstanding study that conducts annual evaluations, including magnetic resonance physicians interested in specializing in Rheumatology. images, x- rays, and clinical measurements, of people with Each year, the division enrolls one new fellow and or at risk for knee OA. The three groups to be examined will graduates physicians into successful academic and be patients with 1) knees that develop AKOA, 2) knees that develop common OA, and 3) knees with no OA. The study clinical positions. Weekly educational conferences in the will assess annual MR images in the sample to identify division include Rheumatology Grand Rounds, and quantify structural changes in the knee. Assays will be Rheumatology Case Conference/Journal Club and done to measure baseline glucose balance and systemic inflammation. Finally, serum and urine biomarker data Rheumatology Radiology Rounds. provided by the OAI will be used to measure bone and The goals of this program are to advance the cartilage turnover. These findings could lead to preventive strategies and uncover therapeutic targets. The insights understanding of OA pathophysiology and to seek new generated from this study may be applicable to regular knee disease-modifying interventions. A critical component is OA, expanding the overall field. the development of valid outcome measures for OA progression that are sensitive to change. Techniques clinical trials. Disease-modification trials of intra- being explored include quantitative imaging of articular articular corticosteroids, vitamin D, collagen cartilage, assessment of peri-articular bone morphology hydrolysate, and osteogenic protein 1 are completed or using MRI, dual x-ray absorptiometry, gait analysis, and in progress. The research program is funded by grants the testing of physical function. These approaches are from the NIH, the American College of Rheumatology addressed through epidemiologic collaborations with Research & Education Fund, and by sponsorship from the Osteoarthritis Initiative consortium and through industry.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Center for Complementary and The CTCIA has three primary areas of focus:

Integrative Medicine »» Develop state-of-the-art evidence reports and technology The primary mission of the Center for Complementary assessments. and Integrative Medicine (CCIM) is to improve health »» Assist expert panels in developing evidence-based clinical outcomes for patients with chronic medical conditions. practice guidelines. The CCIM investigates cost-effective methods of »» Employ advanced comparative effectiveness research complementary and alternative medicine therapies. The techniques to support FDA approval/regulatory processes. center strives to integrate evidence-based, multi- disciplinary therapies into conventional care plans for Network of different placebo comparisions » » chronic disease prevention and treatment, CCIM allows RHEUMATOLOGY OF DIVISION for collaboration between doctors and researchers, ultimately promoting high quality clinical care and informed and involved patient populations.

The CCIM has three major areas of focus:

»» Clinical research projects in therapies, specifically mind- body medicines. »» Ongoing professional development for predoctoral and postdoctoral candidates and related healthcare professionals. Industry-Sponsored Trials »» Integration of evidence-based therapies into conventional The industry-sponsored trial program is supported by medical practice, including Tai Chi mind-body therapy, several clinical research coordinators and research acupuncture and massage therapy. assistants. The wide range of pharmaceuticals tested Center for Treatment Comparison includes small molecules for fibromyalgia, biologic and Integrative Analysis medications for immunologic disorders and osteoarthritis, and intra-articular substances for knee The Center for Treatment Comparison and Integrative osteoarthritis. The current panel of sponsored trials Analysis (CTCIA) uses advanced evidence-based includes: methodologies to help answer a host of clinical, regulatory and health policy questions. »» A phase 2, placebo-controlled, double-blind, dose- escalation study evaluating the safety, tolerability, CTCIA specializes in the development of evidence pharmacokinetics, and pharmacodynamics of SM04690 reports and utilizes advanced meta-analysis methods to injected in the target knee joint of moderately to severe help connect research with effective practice and guide symptomatic osteoarthritis subjects informed policy decisions. The center also provides »» A phase 2a study evaluating the safety, efficacy, and assistance for international panels of experts in the pharmacodynamics effects of ABT-981 in patients with development of guidelines, supporting the development knee osteoarthritis process with evidence and methodological support. »» A Phase 2a, Multicenter, Randomized, Double-Blind, These evidence reports have had a significant impact in Placebo-Controlled Study Comparing the Safety and health policy both nationally and internationally. Using Efficacy of ABT-981 to Placebo in Subjects with Erosive innovative approaches, the center has successfully Hand Osteoarthritis assisted clients in regulatory process while securing FDA approvals and labeling changes. This year the center has »» A multi-center, parallel, double-blind, randomized, placebo- published Rheumatoid Arthritis guidelines in controlled study to evaluate the safety and effectiveness of partnership with the American College of Rheumatology. HYMOVIS®, a new viscoelastic hydrogel, for the treatment The center also published other important studies which of osteoarthritis of the knee garnered a significant amount of national and »» COAST-1: Clinical Knee Osteoarthritis Symptom Treatment international media attention. 1 Study. A Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of AXS-02 (Disodium Zoledronate Tetrahydrate) Administered Orally to Subjects with Knee Osteoarthritis Associated with Bone Marrow Lesions.

117 Research Support Highlights

Name Title Funding Source Purpose of Award Comparative safety profile on Synvisc® for Senada Arabelovic, MD Principal Investigator Genzyme knee osteoarthritis: a systematic review and network meta-analysis Clinical practice guideline development for Co-Investigator ACR rheumatoid arthritis ACR recommendations for the prevention »

» Co-Investigator ACR and treatment of glucocorticoid-induced RHEUMATOLOGY OF DIVISION osteoporosis International symposium on osteoarthritis Principal Investigator Sanofi management Raveendhara Bannuru, MD, PhD Royal Australian College RACGP Guidelines for the non-surgical Principal Investigator of General Practitioners management of hip and knee osteoarthritis Infectious Diseases Society of America, American Academy of Neurology and American Infectious Diseases Principal Investigator College of Rheumatology guideline on The Society of America Prevention, Diagnosis, and Treatment of Lyme Disease Biomarkers of Cartilage Turnover and Metabolism Greater than One Year After Investigator Department of Defense Traumatic Joint Injury and Signs of Early Pot- Traumatic Osteoarthritis Rapid Quantitative composite MRI Co-Investigator NIH measurement of Knee OA structural progression Jeffrey B. Driban, PhD Constitutional and Metabolic Factors Co-Investigator NIH associated with the development of Hand OA Periarticular Bone Density as a Biomarker for Co-Investigator NIH Early Knee OA Co-Investigator NIH Efficacy of CAM on Patient Centered Outcomes Characterization of Rapidly Progressive Knee Principal Investigator NIH Osteoarthritis Clinical Trial of Tai Chi & Physical Therapy for Co-Investigator NIH Knee Osteoarthritis Fidia, Samumed, Study Physician 5 Clinical Trials in Knee Osteoarthritis Axsome, Abbvie William Harvey, MD, MSc Effect of intra-articular steroids on structural Co-Investigator NIH progression of knee OA: an RCT Clinical Trial of Tai Chi and Aerobic Exercise for Co-Investigator NIH Fibromyalgia Rheumatology Research Amgen/Wyeth Rheumatology Fellowship Robert Kalish, MD Principal Investigator Foundation Training Award

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Name Title Funding Source Purpose of Award A multi-center, parallel, double-blind, randomized, placebo-controlled study to Principal Investigator Fidia evaluate the safety and effectiveness of HYMOVIS®, a new viscoelastic hydrogel, for the treatment of osteoarthritis of the knee Periarticular Bone Density as Biomarker for Principal Investigator NIH/NIAMS

early Knee OA » » RHEUMATOLOGY OF DIVISION Effect of Intra-Articular Steroids on Structural Principal Investigator NIH/NIAMS Progression A Phase 2a Study Evaluating the Safety, Principal Investigator Abbvie Inc Efficacy, and Pharmacodynamic Effects of ABT- 981 in Patients with Knee Osteoarthritis Rapid quantitative composite MRI Principal Investigator NIH/NIAMS measurement of Knee OA structural progression A Phase 2, Multicenter, Randomized, Double- Timothy McAlindon, MD, MPH Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Principal Investigator Samumed, LLC Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects Clinical practice guideline development for Principal Investigator ACR Rheumatoid Arthritis Constitutional and Metabolic Factors Principal Investigator NIH/NIAMS associated with the development of Hand OA Characterization of Rapidly Progressive Knee Co-Investigator NIH/NIAMS Osteoarthritis A Method for Patient-Centered Enrollment Co-Investigator PCORI in Comparative Effectiveness Trials: Mathematical Equipoise Co-Investigator NIH/NCCAM Tai Chi and Knee Osteoarthritis Co-Investigator NIH/NCCAM Tai Chi and Fibromyalgia COAST-1: Clinical Knee Osteoarthritis Symptom Treatment 1 Study. A Randomized, Double- blind, Placebo-controlled Trial to Assess the Site Principal Axsome Therapeutics, Efficacy and Safety of AXS-02 (Disodium Investigator Inc Zoledronate Tetrahydrate) Administered Orally to Subjects with Knee Osteoarthritis Associated with Bone Marrow Lesions Safety and Efficacy of ABT-981 to Placebo in Principal Investigator Abbvie Inc. Subjects with Erosive Hand Osteoarthritis Steven Vlad, MD, PhD Sub Investigator Samumed Knee Osteoarthritis A multi-center, parallel, double-blind, randomized, placebo-controlled study to Sub Investigator Fidia evaluate the safety and effectiveness of HYMOVIS®, a new viscoelastic hydrogel, for the treatment of osteoarthritis of the knee Evaluating the Safety, Efficacy, and Sub Investigator Abbvie, Inc Pharmacodynamic Effects of ABT-981 in Patients with Knee Osteoarthritis

119 Research Support Highlights (continued)

Name Title Funding Source Purpose of Award Clinical Trial of Tai Chi and Aerobic Exercise for Principal Investigator NIH/NCCAM Fibromyalgia Midcareer Investigator Award in Patient- Principal Investigator NIH/NCCAM Oriented Research Clinical Trial of Tai Chi and Physical Therapy for Principal Investigator NIH/NCCAM Knee Osteoarthritis » Chenchen Wang, MD » RHEUMATOLOGY OF DIVISION Clinical Trial of Tai Chi Mind-Body for the Principal Investigator NIH/NCCAM Treatment of Post-Traumatic Stress Disorder Traditional Chinese Mentoring and Clinical Research Training in Primary Mentor Medicine Universities Chinese Investigators Site Principle U.S. Department of Novel Interventions for Gulf War Veterans’ Investigator Veterans Affairs Illnesses

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Honors & Awards William Harvey, MD, MSc »» Medical Director of Clinical Informatics, Tufts Medical Raveendhara Bannuru, MD, PhD Center »» Academic Research Awards Committee of Tufts University »» Clinical Director, Division or Rheumatology, Tufts Medical School of Medicine Center »» Clinical and Translational Science Curriculum Committee »» ICD-10 Clinical Liaison, Tufts Medical Center for MS/PhD Graduate Program of the Tufts Clinical and »» Care Improvement Council, Tufts Medical Center Translational Science Institute and the Sackler School of »» Chair, Committee on Government Affairs, American Graduate Biomedical Sciences, Tufts University College of Rheumatology » »

»» Core Expert Panel Member and Evidence Synthesis Team RHEUMATOLOGY OF DIVISION »» Advocates for Arthritis, American College of Rheumatology Leader: Osteoarthritis Treatment Guideline Development annual political advocacy meeting with legislators on Group (OAGDG) for Osteoarthritis Research Society Capitol Hill, Washington, DC International »» Board of Directors, American College of Rheumatology »» Evidence Synthesis Methodologist: American College of Rheumatology Committee on ACR Recommendations for »» Director of Informatics Integration, Tufts CTSI the Prevention and Treatment of Glucocorticoid-induced »» Ambulatory Initiatives Workgroup, Tufts Medical Center Osteoporosis Robert Kalish, MD Jeffrey Driban, MD »» American College of Rheumatology Educational Grant »» Executive Committee Chair, Athletic Trainers’ Study Section Osteoarthritis Consortium »» Chair, American College of Rheumatology – State of the »» Work Group Chair, Osteoarthritis Prevention Work Group, Art Meeting Planning Committee Osteoarthritis Action Alliance Timothy McAlindon, MD MPH »» Committee Member, National Athletic Trainers’ Association »» Boston Magazine. “Top Doctors” Research and Education Foundation Free Communications »» Board of Directors, OARSI Subcommittee »» ACR OP Clinical Treatment Guidelines, Literature Review »» Associate Editor, BMC Musculoskeletal Disorders Team Leader »» Committee Member, Eastern Athletic Trainers’ Association Research Committee Steven Vlad, MD PhD »» Reviewer, Biospecimen Review & Allocation Committee, »» Tufts University School of Medicine Curriculum Committee Osteoarthritis Initiative, National Institute of Arthritis & »» Classification Subcommittee of the American College of Musculoskeletal & Skin Diseases Rheumatology Quality of Care Committee »» Abstract Reviewer, American College of Rheumatology Chenchen Wang MD, MSc Annual Scientific Meeting »» Vice Chairperson, World Federation of Chinese Medicine »» Grant Reviewer, Arthritis Foundation Societies (Computational Medicine) »» Steering Committee, Tufts University

121

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 THE INSTITUTES

Tufts Medical Center has three Institutes which are nationally known for their basic and clinical research activities. The Institutes do not report directly to the Department of Medicine but many of their members carry out clinical activities within the various divisions. INSTITUTE FOR CLINICAL RESEARCH AND HEALTH POLICY STUDIES » » INSTITUTE FOR The Institute for Clinical Research and Health Policy Studies (ICRHPS) is a hospital-wide enterprise that includes members of many clinical departments of Tufts Medical Center. Academic appointments and clinical activities of

CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL Institute members are conducted through the Division of Clinical Care Research (CCR) of the Department of Medicine. In addition, some faculty members have clinical appointments in departments other than the Department of Medicine.

These cross-appointments enhance research and the leadership role of the Institute in the broader Tufts campus. About half of the Institute’s research is federally supported, primarily by the National Institutes of Health (NIH) and the Patient Care Outcomes Research Institute (PCORI). The Institute’s research involves the study of clinical features of disease; the optimal use of treatments and of evidence; measurement of the outcomes of healthcare interventions; and the influence of socioeconomic, organizational, and policy factors on healthcare. Over the past 20 years, as a result of ICRHPS/ CCR-based research, Tufts Medical Center has had the world’s highest average ISI citation index in health care research, and has been most often ranked first of any institution.

Through the efforts of the ICRHPS faculty, and faculty throughout the Department of Medicine and the Tufts campus, the Tufts Clinical and Translational Science Institute (Tufts CTSI) was established in August 2008 with a grant from the NIH. The CTSI’s promotion of collaborative, full-spectrum translational research has a substantial impact on the conduct of research at Tufts and at affiliated hospitals across Massachusetts and Maine. The Tufts CTSI includes the joint Biostatistics, Epidemiology, and Research Design (BERD) Center, the Clinical and Translational Science Center (formerly the Tufts GCRC), and the Clinical and Translational Research Graduate Program of the Tufts Sackler School. The Graduate Program provides research training to fellows and to trainees throughout many Tufts Medical Center clinical departments and divisions. The BERD provides support to all Tufts departments and divisions in biostatistics, study design, data collection, writing, and related project development.

Highlights of 2016

»» Receipt of $8,083,799 in new funding for 22 new research projects in 2016

»» Ongoing conduct of 64 research projects

»» Recruitment of two clinical research faculty

»» Authorship by faculty of 172 articles in over 100 different journals

»» Recognition of faculty by participation in many national panels

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » Faculty INSTITUTE FOR

Name Academic Rank Title and Special Responsibility Division Chief Executive Director, Institute for Clinical Research and Health Harry Selker, MD, MSPH Professor Policy Studies STUDIES POLICY HEALTH AND RESEARCH CLINICAL Dean, Tufts Clinical and Translational Science Institute Director, CCHSR David Adler, MD Professor, Psychiatry and Medicine Clinician-Researcher, CHS Joni Beshansky, RN, MPH Associate Professor CCHSR Janis Breeze, MPH Instructor Epidemiologist, BERD Elena Byhoff, MD, MSc Assistant Professor Program on Equity in Health and Science James Chambers, PhD Assistant Professor CEVR CHS Hong Chang, PhD Assistant Professor Biostatistician, BERD Joshua Cohen, PhD Research Associate Professor Assistant Director, CEVR Denise Daudelin, RN, MPH Assistant Professor Project Director, CCHSR Co-PI, Tufts CTSI Karen Freund, MD Professor Director, Program on Equity in Health and Science Vice Chair of Medicine for Research Associate Professor of Medicine and Richard Hermann, MD CHS Psychiatry Assistant Professor of Surgery and Howard Jen, MD PACE Medicine Director, Clinical and Translational Research Graduate David Kent, MD, MS Professor Program, Sackler School Director, PACE CCHSR

David Kim, PhD Assistant Professor CEVR

Manlik Kwong, BS Adjunct Instructor Software Engineer, CCHSR Tara Lavelle, PhD Assistant Professor CEVR Deborah Lerner, MS, PhD Professor of Medicine and Psychiatry Director, Program on Health, Work and Productivity, CHS Amy LeClair, PhD Assistant Professor Program on Equity in Health and Science THI Laurel Leslie, MD Professor, Medicine and Pediatrics Tufts CTSI Pei-Jung Lin, PhD, MS Assistant Professor CEVR PACE Jason Nelson, MPH Instructor Biostatistician, BERD

125 Faculty (continued)

Name Academic Rank Title and Special Responsibility Peter Neumann, ScD Professor Director, CEVR Farzad Noubary, PhD Assistant Professor Biostatistician, BERD Director, CHS Director, Center for Child and Family Outcomes Susan Parsons, MD, MRP Professor of Medicine and Pediatrics Founding Director, Reid R. Sacco Adolescent and Young

» Adult Cancer Program » INSTITUTE FOR Associate Director and Epidemiologist BERD Associate Jessica Paulus, ScD Assistant Professor Director, Sackler Graduate Program

Lori Lyn Price, MAS Assistant Professor Biostatistician, BERD

Gowri Raman, MD, MS Assistant Professor CCES CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL Angie Mae Rodday, PhD Assistant Professor CHS William Rogers, PhD Research Assistant Professor CHS

Associate Director and Biostatistician, BERD CCHSR Robin Ruthazer, MPH Assistant Professor PACE

Dana Gelb Safran, ScD Associate Professor CHS Saeid Shahraz, PhD Assistant Professor PACE

Norma Terrin, PhD Associate Professor Director and Biostatistician, BERD , CHS

Hocine Tighiouart, MS Assistant Professor Biostatistician, BERD Lisa Welch, PhD Assistant Professor Evaluation Manager, Tufts CTSI Benjamin Wessler, MD, MS Instructor PACE

Research center abbreviations: BERD =Biostatistics, Epidemiology, and Research Design Center CCES = Center for Clinical Evidence Synthesis CCHSR = Center for Cardiovascular Health Services Research CEVR = Center for Evaluation and Risk in Health PACE = Predictive Analytics and Comparative Effectiveness Center CHS = Center for Health Solutions (formerly The Health Institute)

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Associate and Adjunct Staff Affiliations

Alawi Alsheikh-Ali, MD, MS Sheikh Khalifa Medical City, Abu Dhabi, UAE Mohan Bala, PhD, MBA Sanofi-Aventis Raveendhara Bannuru, MD Tufts Medical Center Peter Bonis, MD Tufts Medical Center Kathleen Bungay, PharmD Northeastern University Joseph Cappelleri, PhD Pfizer, Inc Peter Castaldi, MD Brigham and Women’s Hospital

Thomas Concannon, PhD Tufts Medical Center » » INSTITUTE FOR Jen Cook, MD, MPH Minuteman Health Ralph D’Agostino, Sr., PhD Boston University Issa Dahabreh, MD, MS Brown University Olaf Damman, MD Tufts Medical Center

Jonathan Davis, MD Tufts Medical Center STUDIES POLICY HEALTH AND RESEARCH CLINICAL Roger Fielding, MD Tufts HNRC Frederick Frankhauser, JD Tufts Medical Center Gary Freeman, MD Zoll Medical Barbara Gandek, MS QualityMetric Incorporated Seyyed Nassir Ghaemi, MD, MPH Tufts Medical Center Alexandra Glazier, JD, MPH New England Organ Bank Robert Goldberg, PhD Baystate Medical Center Elizabeth Goodman, MD Massachusetts General Hospital Alice Gottlieb, MD Tufts Medical Center William Gouveia, PharmD Tufts Medical Center Daniel Greenberg, PhD Ben Gurion University of the Negev, Israel David Greenblatt, MD Tufts University John Griffith, PhD Northeastern University Judy Hinchey, MD Caritas St. Elizabeth’s Medical Center Gordon Huggins, MD Tufts Medical Center John Ioannidis, MD Stanford University Paula Hirsch, MD Massachusetts Institute of Technology Howard Jen, MD Tufts Medical Center Graham Jones, PhD, DSc, DipIC, BS Tufts Medical Center Harmon Jordan, ScD MassPRO Georgios Kitsios, MD, MS, PhD Lahey Clinic Richard Kopelman, MD Tufts Medical Center Jeffrey Lasker, MD NEQCA Joseph Lau, MD Tufts Medical Center Mary Lee, MD Tufts University Andrew Levey, MD Tufts Medical Center Peter Lindenauer, MD, MSc Baystate Medical Center Alice Lichtenstein, DSc Tufts Friedman School/HNRC John Mason, PhD Blue Cross Blue Shield of Massachusetts Timothy McAlindon, MD, MPH Tufts Medical Center Kimberley McGuigan, PhD, MBA Pfizer, Inc Sandeep Menon, BHMS, MPH, PhD Pfizer, Inc Vandana Menon, MD, PhD, MPH, MS Outcome Sciences, Inc. Catherine Milch, MD, PhD Millenium Pharmaceuticals Nanguneri Nirmala, PhD Tufts Medical Center Stephen Pauker, MD Tufts Medical Center Brian Pereira, MD AMAG Pharmaceuticals, Inc. Inga Peter, PhD Mount Sinai Medical Center

127 Associate and Adjunct Staff Affiliations

Thomas Pfeiffer, DNS Harvard University Rosalie Phillips, MPH Tufts Public Health Baystate Medical Center

Alice Rushforth, PhD Tufts Medical Center Mark Sarnak, MD, MS Tufts Medical Center Christopher Schmid, PhD Brown University Caroline Schwartz, ScD DeltaQuest Foundation » »

INSTITUTE FOR Joanna Seddon, MD Tufts Medical Center Robert Sege, MD Boston Medical Center Patricia Sheehan, RN, MPH, MS Tufts Medical Center Radley Sheldrick, MD Tufts Medical Center David Snydman, MD Tufts Medical Center CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL Djora Soeteman, PhD Tufts Medical Center Paul Stark, ScD Tufts School of Dental Medicine Gary Strauss, MD Tufts Medical Center Athina Tatsioni, MD University of Ioannina Medical School Teruhiko Terasawa, MD Fujita Health Univ School of Medicine, Japan Thomas Trikalinos, MD, PhD Brown University Sean Tunis, MD, MSc Center for Medical Technology Policy James Udelson, MD Tufts Medical Center Katrin Ulhig, MD, MS Tufts Medical Center Chenchen Wang, PhD Tufts Medical Center Christine Wanke, MD Tufts Medical Center John Ware, PhD University of Massachusetts Medical School John Wong, MD Tufts Medical Center Elias Zintzaras, MD, PhD Univ of Thessaly School of Medicine, Greece Deborah R. Zucker, MD American Federation of Medical Research

Major Clinical Programs The Division of Clinical Care Research/ICRHPS has no »» Laurel Leslie, MD» clinical programs of its own. Physician-Researcher General Pediatrics Division members have appointments in Internal Medicine »» Susan Parsons, MD» and Adult Primary Care, Neurology, Pediatrics, and Adult and Pediatric Hematology- Oncology Psychiatry where they are active participants in clinical Reid R. Sacco Adolescent and Young Adult Cancer Program activities. Among those with primary appointments in the Division, clinical activities are as listed below: Teaching Activities »» Harry Selker, MD Internal Medicine and Adult Primary Care/ Faculty in the Division of CCR/ICRHPS teach courses Pratt Diagnostic Clinic and seminars in clinical research methods to faculty, fellows, residents, and administrative staff primarily »» David Adler, MD» through the Tufts Clinical and Translational Science Psychiatry (Tufts CTSI) Clinical Research Curriculum, MS/PhD »» Karen Freund, MD» Clinical Research Graduate Program of the Tufts Sackler Internal Medicine and Adult Primary Care School of Biomedical Sciences. »» Howard Jen, MD» The CTS graduate program, under the direction of Dr. Pediatric Surgery David Kent, aims to train the next generation of leaders »» David Kent, MD» and innovators in the application of methods of health Internal Medicine and Adult Primary Care services research, especially to direct improvement of

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 clinical practice. By teaching core clinical research skills Research Activities and facilitating the completion of an independent The seven primary research programs of the Division of research project, the program aims to help motivated Clinical Care Research are listed below, followed by trainees embark on careers as clinical and health short descriptions of their activities. services researchers. »» Biostatistics, Epidemiology and Research Design Center The CTS graduate program, the first in the nation linking an MS/PhD program in a biomedical graduate school »» Center for Cardiovascular Health Services Research with an academic medical center for clinical research »» Center for Clinical Evidence Synthesis training, has emerged as a national model. The program

»» Center for Evaluation of Value and Risk in Health » » is designed for individuals who have completed training INSTITUTE FOR »» Center for Health Solutions (formerly The Health Institute) in the medical sciences (MD, DO, DDS, DVM, etc.), or in −− Program for Child and Family Outcomes another advanced biomedical degree program; the majority of students are postdoctoral clinical fellows or −− Program on Health, Work, and Productivity faculty at Tufts Medical Center and other Tufts-affiliated −− Program on Innovation in Pediatric Policy and Practice CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL hospitals. The program confers an MS and a PhD in »» Predictive Analytics and Comparative Effectiveness Center Clinical Research and also provides individual courses to other non-matriculated students. Students select one »» Program on Equity in Science and Health of the three following concentrations which choice allows them to develop more extensive competency in Biostatistics, Epidemiology and their chosen area: Evidence-based Clinical Effectiveness Research Design Center Research, Clinical Investigation, and Health Services (Dr. Norma Terrin, Director; Faculty: Drs. Hong and Outcomes Research. Additionally, in order to Chang, Farzad Noubary, Jessica Paulus, Ms. Janis promote better interdisciplinary research education Breeze, Mr. Jason Nelson, Ms. Lori Lyn Price, Ms. through increased comprehensiveness of the program Robin Ruthazer, Mr. Hocine Tighiouart) content, the program provides students with the option The BERD Center, a joint program between ICRHPS/CCR of choosing a focus in another discipline, which would and the Tufts CTSI, promotes innovation and excellence typically represent the content area of their thesis. across the spectrum of patient-oriented research The Program has a formal mentoring system to facilitate through development of new statistical and study design fellows’ development and execution of independent methods and provision of training, education and research projects. All students enrolled in this program support in applying standard and cutting- edge design must complete an independent research project thesis. and analytic techniques. The BERD serves as the Visiting fellows, special fellows, and fellows from a academic center for biostatistics at Tufts University and variety of Tufts Medical Center Departments and its affiliated teaching hospitals. It provides a forum to Divisions also participate in fellowship offerings. Nearly develop new methods, consulting strategies, and all of the fellows who have trained in this Program are solutions to problems through internal meetings and currently active faculty at medical schools or the NIH, seminars as well as through attendance at local and and the rest serve as senior staff or consultants in health national meetings. BERD faculty are involved as services delivery and policy. investigators on their own investigator-initiated research as well as on projects throughout Tufts Medical Center, Post-doctoral training is provided by several federally- Tufts University, and other Tufts affiliates. BERD staff sponsored training and career development awards. serve nationally as consultants to institutions, federal agencies, corporations and grant proposal review panels, and as members of Data Safety and Monitoring (DSMB) boards. In addition, the faculty in the BERD is responsible for statistical and computational instruction and mentoring to students in the Sackler Clinical Research Program.

129 ischemia and the outcomes of reperfusion therapy for ST elevation myocardial infarction (STEMI) that are printed on patients' electrocardiograms. These instruments have been shown in large trials to improve emergency cardiac care. Building on this, several years ago, CCHSR ran a national randomized placebo controlled trial to determine if a long-neglected treatment for acute myocardial infarction (AMI), an intravenous solution of glucose, insulin, and potassium (GIK) given by »

» emergency medical service (EMS) very early in the INSTITUTE FOR course of acute coronary syndromes (ACS) and AMI, could reduce cardiac arrest and death. The results of this 871-participant study showed that although progression to AMI was not significantly reduced, the odds of having

CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL cardiac arrest or dying were reduced by half, and the size of the AMI was reduced by 80%. This trial spun-off multiple other studies of EMS care for ACS and of GIK. A second GIK trial is planned to confirm this result, which, if true, could potentially save the lives of tens of thousands of patients in the US, each year. Meanwhile, CCHSR has built on the EMS clinical trial infrastructure and linked multiple EMS systems and emergency departments for emergency care research and quality improvement.

Predictive Analytics and Comparative Effectiveness Center

Center for Cardiovascular Health (Dr. David Kent, Director; Dr. Jessica Paulus, Dr. Services Research Saied Shahraz, Ms. Robin Ruthazer, Dr. Benjamin Wessler, Dr. Howard Jen, Dr. Issa Dahabreh), (Dr. Harry Selker, Director; Faculty: Dr. David Kent, Ms. Denise Daudelin, Mr. Manlik Kwong, Ms. Robin The Predictive Analytics and Comparative Effectiveness Ruthazer, Ms. Joni Beshansky) (PACE) Center studies the limitations of using group- derived evidence as the basis for decision making in For 30 years, the Center for Cardiovascular Health individual patients. The approach is based on the close Services Research (CCHSR) has focused on the integration of clinical and statistical reasoning and the development of treatment strategies, decision aids, goal is to provide clinicians and patients with evidence methods, and systems aimed at improving medical care, better tailored to their particular circumstances. The especially emergency and cardiac care. It is particularly PACE Center has expertise in clinical medicine, risk known for a series of studies of factors influencing modeling, individual patient meta-analysis, and cardiac care, and for the development of clinical observational comparative effectiveness studies. Among predictive instrument decision aids which provide other projects, David Kent, MD, MS, PACE Director, is diagnosticpredictions for emergency physicians and the Principal Investigator of several federally-funded paramedics in the emergency clinical care setting. These research grants related to these issues, including several instruments can also be used retrospectively to methods grants from the Patient-Centered Outcomes determine the appropriateness of care. Related work has Research Institute (PCORI) and grants from the National included conduct of multiple larger national clinical Institutes of Health (NIH)/National Institute of effectiveness trials, including demonstrating better Neurological Disorders and Stroke (NINDS) focused on treatment and clinical outcomes for patients with acute cerebrovascular disease. Dr. Kent works with 5 coronary syndromes and acute myocardial infarction. additional faculty investigators and statisticians. Electrocardiographs now in use include predictive instruments developed by Dr. Selker for cardiac

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Center for Clinical Evidence Synthesis from the perspective of patients, physicians, and policymakers, and 3) applying cost-effectiveness (Faculty: Dr. Gowri Raman, Drs. Norma Terrin, analyses in medical and public health interventions John Wong) such as preventive measures, screening and treatment The Center for Clinical Evidence Synthesis (CCES) for Alzheimer’s disease, cancer, and other diseases and promotes the application of evidence-based methods to conditions. healthcare and biomedical topics and the development of methodologies in evidence synthesis. Members are CEVR has developed two unique databases to help experts in the fields of meta-analysis, clinical data- measure and communicate the clinical and economic value of health care strategies. CEVR is the home of The synthesis, decision, and cost-effectiveness analysis, » » clinical guideline creation and evaluation and health Tufts Cost-Effectiveness Analysis Registry, an INSTITUTE FOR services and outcomes research. CCES was an AHRQ- internationally known resource containing detailed designated Evidence-based Practice Center for 15 years information on 5,000 standardized cost-effectiveness and continues to collaborate on these projects analyses published in the peer-reviewed literature nationwide. In addition, CCES members have done (www.cearegistry.org). In addition, CEVR has developed CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL consulting and conducted evidence reviews under and maintains The Tufts Medical Center Medicare contracts from government agencies, pharmaceutical National Coverage Decisions (NCDs) Database, a first of companies, and other organizations. CCES faculty are its kind that documents decisions made by the Centers experienced teachers in critical literature appraisal and for Medicare and Medicaid Services (CMS). Recent have trained multidisciplinary audiences in the conduct projects include a CMS Innovation Award to evaluate of evidence based reviews through curricula and cloud-based technology in the critical care setting, programs in national and international settings. They analysis of the costs and benefits of treatments for serve as mentors to trainees and as consultants to leukemia, lymphoma, and myeloma; multiple academic and private entities in evidence appraisal. unmanaged co-morbidities in diabetes patients; factors influencing Medicare coverage of new technologies; Center for the Evaluation of Value modeling the impact of early Alzheimer's disease and Risk in Health detection, and understanding the influence of comparative effectiveness research on coverage and (Dr. Peter Neumann, Director; Faculty: Drs. Joshua reimbursement. Cohen, James Chambers, David Kim, Tara Lavelle, Pei Jung Lin) Center for Health Solutions The Center for the Evaluation of Value and Risk in Health (CEVR) was established in December 2005 by Peter (Dr. Susan Parsons, Director; Faculty: Drs. DavidAdler, Hong Chang, Richard Hermann, Neumann, ScD (Director) and Joshua Cohen, PhD Debra Lerner, Laurel Leslie, William Rogers, (Deputy Director) to focus on issues pertaining to value, Angie Mae Rodday) cost-effectiveness, and risk tradeoffs in healthcare decisions. The mission of CEVR is to analyze the The Center for Health Solutions, founded in 1988 as The benefits, risks, and costs of strategies to improve health Health Institute (THI) at Tufts-New England Medical and health care and to communicate the findings to Center, was home to the Medical Outcomes Study clinicians and policymakers. CEVR researchers (MOS)—a landmark study designed to measure the undertake scientific research projects, advance methods relationship between the organization and delivery of development for the field, train the next generation of medical care and the functional health outcomes of practitioners and users, and work with policymakers patients. The Center for Health Solutions’ overall worldwide to develop reasoned policy solutions. mission is to improve health by advancing measurement of, and knowledge about, the social, behavioral, medical CEVR researchers bring experience in economics and and biological factors that influence individual and decision analysis to a host of clinical and public health population health. To accomplish this goal, CHS policy issues. Research at CEVR focuses on: 1) evaluating develops tools to advance the science of outcomes and comparing diverse benefit-risk tradeoffs that are measurement from the patient’s point of view; engages in central to a multitude of healthcare decisions; 2) large-scale research projects to examine the links understanding the attitudes and perceptions of value between structure, process and outcomes of health care;

131 conducts multidisciplinary research into the complex Faculty members within CHS receive research support pathways linking health and its social, behavioral, from a variety of sources, including federal funders medical and biological determinants; and works with (NIH, AHRQ, VA, and CDC), pharmaceutical companies, clinicians, government, employers, health plans and and foundations. other public and private sector organizations to translate research into practice and policy. Program on Equity in Science and Health

The principal program areas of research encompassed (Dr. Karen Freund, Director; Drs. Elena Byhoff, by CHS’s work are the following: 1) Program on Child Laurel Leslie, Amy LeClair) and Family Outcomes, led by Susan Parsons, MD, MRP, The Program on Equity in Science and Health addresses » » INSTITUTE FOR studying the quality of life of families coping with a diversity in the biomedical workforce and disparities in chronic illness (such as cancer or mental health healthcare delivery. The mission of the program is to disorders); 2) Program on Health, Work, and address two separate but related aspects of equity Productivity, led by Debra Lerner, MS, PhD, addresses through research, 1) equity in science and biomedical the burgeoning need to improve the health of working careers, including understanding the factors associated CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL people and reduce the human and economic burden of with recruitment, promotion, and retention of women health problems on them, their families, employers, and and minority faculty in academic biomedical careers the nation, and 3) the Program on Innovation in and 2) disparities in the delivery of healthcare, Pediatric Policy and Practice, led by Dr. Laurel Leslie, especially to women and minority communities. In both addresses the effective development and implementation streams of research, the program studies the multiple of evidence-informed care of children and adolescents levels at which inequities may operate and pays close with health, developmental, and behavioral concerns attention to the social determinants of health and cared for in community settings such as schools, wellbeing. The program focuses on interventions to pediatric clinics, and child welfare/protective services. reduce and eliminate these disparities.

Research Support

Recipient Funding Source Purpose of Award Royal DSM Economic Model on Vitamin Research NIH via University of California Risk Benefit Trade-Offs for Whole Genome Sequencing $84,695 –San Francisco Estimating the Population Health Benefits of new Pfizer Pharmaceuticals Pfizer Disinvestment in US healthcare: Opportunities and Challenges James Chambers, PhD Is Coverage Policy for Rheumatoid Arthritis Treatment Genentech Consistent with the Evidence? Examining the restrictiveness of commercial payer coverage PHRMA policies for drugs and the evidence used when formulating them Factors Predicting Private Payer Coverage Policy for Medical NPC Technology: An empirical analysis Insurance Instability and Disparities in Chronic Disease NIH/NIMH Outcomes PCORI via Lahey Clinic Cervical Spondolytic Myelopathy Surgical Trial Karen Freund, MD NIH via Ohio State OSU Cancer Center Support Grant Tufts Breast Cancer Training Program to Reduce Health Susan Komen Foundation Disparities American Cancer Society Patient Navigation to Eliminate Cancer Disparities Richard Hermann, MD AHRQ via ECRI National Quality Measures Clearinghouse Project

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Recipient Funding Source Purpose of Award Evaluating Observational Data Analyses: Confounding Control PCORI via Brown University and Treatment Value of Personalized Risk Information (Dual PI: Peter Neumann) NIH including additional supplement An Online Searchable Field Synopsis of Clinical Prediction NIH Models in Cardiovascular Disease David Kent, MD Evidence and the Individual Patient: Understanding PCORI

Heterogeneous Treatment Effects for Patient-Centered Care » » INSTITUTE FOR Targeted Antithrombotic Therapy in Cryptogenic Stroke with NIH/NINDS Patent Foramen

Johns Hopkins University Administrative Supplement to Enhance Network Capacity

PHRMA Incorporating Family Spillover Effects into Cost-Effectiveness STUDIES POLICY HEALTH AND RESEARCH CLINICAL Tara Lavelle, PhD Shire Human Gen analyses: Review of practices and magnitude of benefits VA via UPenn RD Merit Award State of Tennessee The Primary Care Work and Health Initiative Depression Pilot Caregivers of Individuals Diagnosed with Schizophrenia: Impact Debra Lerner, PhD Janssen on Employment and Unmet Needs White Paper Addressing the Business Case for Investing in OneMind Institute Mental Health and Mental Healthcare Comparative Effectiveness of Adolescent Lipid Screening and Laurel Leslie, MD PCORI Treatment Strategies MS Survey: Willingness to Pay to Insure Against the Costs of Biogen IDEC Multiple Sclerosis Treatments Nationwide Frequency and Cost of Preventable Hospitalizations Alzheimer’s Foundation in Alzheimer’s Disease BADERC: Estimating Costs of Multiple Chronic Conditions NIH via MGH Pei Jung Lin, PhD among Adults with Diabetes Sanofi Impact of Multimorbidity on Health Care Utilization Purdue Pharma Cost and Prevalence of Opioid Abuse Incorporating Family Spillover Effects into Cost-Effectiveness Otsuka Pharmaceutical analyses: Review of practices and magnitude of benefits Bayer Bayer Tufts Medical Center Post- doctoral Fellowship Sunovion Sunovion Tufts Medical Center Post-doctoral Fellowship Analyze the health economic outcome variables to determine Peter Neumann, ScD Abbott health care costs Heart Failure Module 3: Financial Impact of Reducing Amgen Hospitalization Bayer SRE Manuscript Are Payer Thresholds for Value More Restrictive for NPC Biopharmaceuticals than for Medical Procedures? Jason Nelson, MPH Novartis, Gilead, Pfizer, Sanofi, Paying for Innovation: How does the timing of therapeutic costs Amgen, Biogen, Johnson& and benefits influence payer coverage? Johnson, Vertex

133 Research Support (continued)

Recipient Funding Source Purpose of Award Robert Wood Johnson Updating the Panel on Cost-Effectiveness in Health and Foundation Medicine Bill and Melinda Gates Registry on Cost per Disability Adjusted Life Years Foundation (DALY) Studies ASTRAZENACA A “Summit” with Experts on the Cost-Effectiveness of J ason Nelson, MPH National Phar Council » (continued)

» Drug Value Frameworks: Case Studies and Policy Implications INSTITUTE FOR PHRMA Abbott Adaptation of LK01 HEOR Model for Spain University of Southern CA USC Tufts Value Conference on Alzheimer’s Disease Treatments Janssen Building a Real World Evidence (RWE) Blueprint for the Future CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL Familial T-Cell Depleted Stem Cell Transplant in High Risk Sickle NIH via NYMC Cell Anemia Patient Navigation for Medically Underserved Breast Avon Foundation Cancer Patients Susan Parsons, MD Leukemia and Lymphoma Proof of Paradigm in Cost-Effectiveness Analysis Society with Novel Therapeutics Yawkey Foundation Patient Navigation Program Avon Foundation Patient Navigation During Active Treatment for Breast Cancer ILSI Flavan-3-ols: A Systematic Mapping of the Evidence Gowri Raman, PhD Risk Factor for Hospitalized Patients with Gram-negative Merck Sharp & DOHM Infections Aging, comorbid conditions, and health care utilization in NIH/NIMH via Brown U persons with HIV William Rogers, PhD Disparities in Nursing Home Care Quality in People living with NIH via Brown U HIV/AIDS NIH via Tufts U CTSA Network Recruitment Innovation Center CTSA Consortium Demonstration and Evaluation NIH/NCCATS of SRC Processes CTSA Consortium Scientific Review Committee Stakeholder NIH/NCCATS Committee (CCSSC) Consensus Project CTSA Enhancing Clinical Research Professionals’ Training and NIH/NCCATS Qualifications A Method for Patient-Centered Enrollment in Comparative Harry Selker, MD, MSPH PCORI Effectiveness Trials: Mathematical Equipoise CTSA Consortium Demonstration and Evaluation of Scientific NIH/NCATS Review Committee Processes (SRC) NIH/NCATS Clinical and Translational Science Award UL1 NIH/NCATS Clinical and Translational Science Award 1KL2 NIH/NCATS Clinical and Translational Science Award 1TL NIH via Johns Hopkins University Johns Hopkins – Tufts Trial Innovation Center

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Honors and Awards

David Adler, MD »» Health Care Research Training Study Section, Agency for Professional Society Committee Assignments and Leadership: Healthcare Research and Quality »» Professional Society Committee Assignments and Honors and Awards: Leadership: »» American Cancer Society Clinical Professorship in Health »» Member, Distinguished Fellowship Committee, Mass. Disparities Psychiatric Society New Grant Funding: »» Chairman, Committee on Psychopathology, Group for »» » “Tufts Breast Cancer Training Program to Reduce Health » » Advancement of Psychiatry Disparities”, Susan G. Komen Foundation $404,529 INSTITUTE FOR Honors and Awards: Richard Hermann, MD, MS »» 2010-2016 – Best Doctors in America Editorships: »» 2010-2016 – Best of Boston Physicians, Boston Magazine »» Co-chair, NQMC/NGC Editorial Board

James Chambers, PhD, MPharm, MSc »» Editorial Board, Joint Commission Journal for Quality and STUDIES POLICY HEALTH AND RESEARCH CLINICAL Editorships: Safety »» Editorial Board, PharmacoEconomics Open »» Invited Lectures and Presentations: New Grant Funding: »» Presenter, An Introduction to the Agency for Healthcare »» “Factors Predicting Private Payer Coverage Policy for Research and Quality Webinar Medical Technology: An empirical analysis”, National David Kent, MD Pharmaceutical Council $165,000 »» Professional Society Committee Assignments and »» “Examining the restrictiveness of commercial payer Leadership: coverage policies for drugs and the evidence used when »» CTSA Comparative Effectiveness Research Methods formulating them”, PHRMA $87,500 Workgroup Karen Freund, MD »» Member, CTSA Education and Career Development Key Editorships: Function Committee »» Editorial Board, Cancer Epidemiology, Biomarkers and »» Member, Methods Work Group of the National CTSA Prevention Strategic Goal Committee »» Editorial Board, Journal of Cancer Survivorship »» National Panels: King Trust Clinical and Health Service »» Editorial Board, Women’s Health and Gender Based Research Committee, Grant Review, Charles A. King Medicine Postdoctoral Fellowship Program, The Medical Foundation »» Editorial Board, Women’s Health Issues »» Institute of Medicine (IOM) Comparative Effectiveness National Panels: Research-Innovation Collaborative (CER-IC) »» Boston Breast Cancer Equity Coalition, founding member »» Comparativeness Effectiveness Research, Methods and Steering Committee Committee, SCTS »» American Cancer Society, national Round Table on Patient »» PFO Guideline Committee, American Academy of Navigation, founding member NeurologyMember, Scientific Advisory Board, Optum Labs, »» National Cancer Institute, Patient Navigation Research Cambridge, MA Program, Steering Committee »» Technical Expert Panel, Evidence Synthesis Report on “Life »» Health Disparities and Equity Promotion Study Section, Expectancy Calculators”, Minneapolis VA Medical Center National Institutes of Health Vice Chair for the Evidence Review Committee (ERC) for the 2016 Update of the AHA/ASA “Guidelines for the Management of Patients with Acute Ischemic Stroke”

135 Editorships: Laurel Leslie, MD, MPH »» Editorial Board, Diagnostic and Prognostic Research »» Professional Society Committee Assignments and »» Invited Lectures and Presentations: Leadership: »» “Value of Personalized Risk Information.” NIH Health −− American Academy of Pediatrics Economics Common Fund: Determinants of Personalized −− Member, Pediatrician Life and Career Experience Study Health Care and Prevention Steering Committee Meeting. Steering Committee Rockville, MD, July 19, 2016. −− Member, Council on Foster Care, Adoption, and Kinship »» “Understanding Heterogeneity of Treatment Effect: Care General Principles and the Example of PFO in Cryptogenic » −− Member, Council on Quality Improvement and Patient » INSTITUTE FOR Stroke.” NeuroCORPS division at Columbia University. New Safety York, NY Jan 27 2016. »» American Board of Pediatrics New Grant Funding: −− Member, Finance Committee, Board of Directors, ABP »» Institute for Clinical and Translational Research Training Program”, NIH/NCATS via Johns Hopkins University −− Member, Finance Committee, ABF Foundation CLINICAL RESEARCH AND HEALTH POLICY STUDIES POLICY HEALTH AND RESEARCH CLINICAL $112,453 −− Secretary/Treasurer, Board of Directors, ABP »» “Evidence and the Individual Patient: Understanding −− Vice President for Research, AB Heterogeneous Treatment Effects for Patient-Centered Care”, PCORI $249,574 Pei Jung Lin, PhD Tara Lavelle, PhD »» Professional Society Committee Assignments and Leadership: New Grant Funding: »» “Incorporating Family Spillover Effects into Cost- »» Executive Committee, Board of Directors, International Effectiveness analyses: Review of practices and magnitude Society for Pharmacoeconomics and Outcomes Research of benefits“, PHRMA $150,000 (ISPOR) Boston Chapter »» “Incorporating Family Spillover Effects into Pediatric Cost- »» Steering Committee, International Pharmacoeconomic Effectiveness Analyses: Review of practices and magnitude Conference on Alzheimer’s Disease (IPECAD) of benefits“, Shire Human Gen $150,000 Editorships »» Debra Lerner, MS, PhD »» Associate Editor, Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association National Panels: »» Scientific Advisory Board, HealthFitness, Inc. New Grant Funding: »» “Impact of Multimorbidity on Health Care Utilization and »» Board of Directors, Understanding our Differences, Costs among patients with diabetes mellitus“ Sanofi Newton, MA School Department, school-based disability $274,415 awareness and educational organization »» “Cost and prevalence of Opioid Abuse”, Purdue Pharma »» Board of Directors, The Health Project, which selects the $350,000 annual C. Everett Koop Award for workplace health promotion »» “Incorporating Family Spillover Effects Into Cost- Effectiveness Analyses in Alzheimer’s Disease: »» Ad Hoc member, TUSM Faculty Appointment Review of practices and magnitude of benefits“, Subcommittee Otsuka Pharmaceuticals, $100,000 »» Journal of Health Affairs Advisory Panel, Planning Meeting on Workplace Health and Performance »» Panel Member, Social Security Administration, Developing and Assessing Medical Evidence for Extreme Limitations in the Ability to Focus on Tasks New Grant Funding: »» “White Paper Addressing the Business Case for Investing in Mental Health and Mental Healthcare”, OneMind Institute $18,900

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Peter Neumann, ScD Gowri Raman, MD, MS »» Professional Society Committee Assignments and New Grant Funding: Leadership: »» “Flavan-3-OLD: A Field Synopsis and Qualitative Gap »» Scientific Review Committee, International Society for Analysis”, International Life Science $33,946 Pharmacoeconomics and Outcomes Research William Rogers, PhD »» Scientific Review Committee, Annual Meeting of the New Grant Funding: Society for Medical Decision Making »» “Disparities in Nursing Home Care Quality For Patients »» Co-Chair ISPOR Special Task Force on U.S. Value Living with HIV/AIDS, NIH via Brown University $37,947

Frameworks » »

Harry Selker, MD, MSPH INSTITUTE FOR Editorships »» Professional Society Committee Assignments and »» Editorial advisory panel, Expert Review of Leadership: Pharmacoeconomics and Outcomes Research »» Clinical Research Forum, Board of Directors, Co-Chairman, »» Editorial board, Health Affairs Chair, Public Policy Committee »» Editorial board, Value in Health STUDIES POLICY HEALTH AND RESEARCH CLINICAL »» Association for Clinical and Translational Science, Founder New Grant Funding: and Board of Directors, Vice President for Healthcare »» “Bayer-Tufts Medical Center Post-Doctoral Fellowship”, Implementation, Delivery, and Policy Research, Chair, Bayer $271,510 Public Policy Committee, President »» “Building a Real World Evidence (RWE) Blueprint for the National Panels: Future” Janssen $375,000 »» NIH National Center for Advancing Translational Sciences, »» “Sunovion Post-Doctoral Fellowship in HEOR” Sunovion Advisory Council $108,729 »» NIH National center for Advancing Translational Sciences, »» “Paying for Innovation: How does the timing of therapeutic Cures Acceleration Network Review Board costs and benefits influence payer coverage?” Consortium »» Health Resources in Action, Board of Directors of Amgen, Biogen-IDEC, Gilead, Vertex, Johnson and »» NIH Study Sections, Directors Pioneer Award Review Johnson, Novartis, Pfizer, and Sanofi, $350,000 “A Committee ‘Summit’ with Experts on the Cost-Effectiveness of Palivizumab”, Astrazenaca $200,000 »» Invited Lectures & Presentations: »» “Drug Value Frameworks: Case Studies and Policy »» University of Pittsburgh Department of Medicine Research Implications”, National Pharmaceutical Council/PhRMA Day, Visiting Professor $75,000 »» New Grant Funding: Johns Hopkins-Tufts Trial Innovation »» “USC Tufts Value Conference on Alzheimer’s Disease Center, NIH/NCATS via Johns Hopkins University, Treatments”, University of Southern California $100,000 $4,394,296

Susan Parsons, MD, MRP Norma Terrin, PhD »» Professional Society Committee Assignments and Editorships: Leadership: »» Statistics Editor, Clinical Infectious Diseases »» American Cancer Society, Palliative Care and Symptom »» Editorial Board, Research Synthesis Methods Peer Review Committee, Invited Committee Member »» Statistics Editor, Statistical Communications in Infectious National Panels: Diseases »» Invited Member, National Cancer Institute’s Steering Committee on Cancer Care Delivery Research »» Selected Team Member, NCI-ASCO Teams in Cancer Care Delivery Project New Grant Funding: »» Patient Navigation During Active Treatment for Breast Cancer: Surmounting the Cultural and Socio-Economic Divide for Patients of Chinese Origing”, Avon Foundation $75,000

137 INSTITUTE FOR MOLECULAR CARDIOLOGY RESEARCH (MCRI) » » INSTITUTE FOR The mission of the Molecular Cardiology Research Institute at Tufts Medical Center is to study the molecular mechanisms underlying cardiovascular function in health and disease; to translate these

MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR fundamental discoveries into new clinical strategies for diagnosis and treatment; and to train and mentor the next generation of cardiovascular researchers. The MCRI is organized into 3 Centers focused on Vascular Biology, Cardiac Biology and Translational Pharmacology and Genomics. Members of the MCRI work collaboratively with clinical cardiologists and cardiovascular surgeons, biochemists, neuroscientists, pharmacologists, geneticists, immunologists, and epidemiologists to further research in all facets of cardiovascular diseases. Pre-doctoral, graduate, and post-graduate training are high priorities of the Institute, with numerous trainees, including students from the Sackler School of Graduate Biomedical Sciences at Tufts and post-doctoral fellows from all over the world conducting their research in MCRI labs. Investigators are engaged in basic exploration of mechanisms of cardiovascular function in health and disease, identifying novel targets for treatment and pursuing translational studies that explore those targets. Particular areas of interest and expertise include models of hypertension, atherosclerosis and heart failure; autonomic dysfunction and arrhythmia; and genetics, genomics and pharmacokinetics. The intellectual and collaborative environment within the MCRI is highly regarded with ongoing studies underway with members of the Divisions of Cardiology, Nephrology and Pulmonary within the Department of Medicine.

Highlights of 2016

»» Dr. Iris Jaffe was named the Executive Director of »» The Jaffe Lab determined that microRNA (miR- the MCRI in October 2016 155) may be a biomarker for hypertension and a therapeutic target for age-related hypertension »» Dr. Gordon Huggins was named Director, Cardiovascular Fellowship Training Program in »» Drs. Navin Kapur and Richard Karas were July 2016 awarded US Pat. No. 9,393,384 entitled “Systems and methods for treating acute and chronic heart failure”

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » Faculty INSTITUTE FOR

Name Academic Rank Title and Special Responsibility Executive Director, MCRI (to 10/2016) Elisa Kent Mendelsohn Professor of Chief Scientific Officer, Tufts Medical Center (to 10/2016)

Richard Karas, MD, PhD (MCRI) RESEARCH CARDIOLOGY MOLECULAR Molecular Cardiology and Medicine Vice-Chairman of Research, Department of Medicine (to 10/2016) Maria Pilar AlcaideAlonso, PhD Assistant Professor Martin Beinborn, MD Assistant Professor Assistant Program Director, Cardiology Fellowship Robert Blanton, MD Assistant Professor Scientific Director, Mouse Physiology Core Laboratory Tinatin Chabrashvili, MD, PhD Associate Professor (Neurology) Isabelle Draper, PhD Assistant Professor Director, Drosophila Lab Jonas Galper, MD, PhD Professor Director, Center for Translational Pharmacology and Genomics Gordon Huggins, MD Associate Professor Vice-Chair, IRB; Chair, SRC Co-Director, MD PhD Program, Tufts University School of Medicine Associate Director, MCRI (to 10/2016) Executive Director, MCRI (from 10/2016) Iris Jaffe, MD, PhD Associate Professor irector, Vascular Biology Research Center Director, Vascular Function Core Laboratory Director, Interventional Research Division of the Surgical Research Laboratories Navin Kapur, MD Associate Professor Director, Acute Circulatory Support Director, Cardiac Biology Research Center Alan Kopin, MD Professor Associate Research Professor Janis Lem, PhD (Ophthalmology) Ho-Jin Park, PhD Assistant Professor Gavin Schnitzler, PhD Assistant Professor

139 Major Clinical Programs Research Activities The Molecular Cardiology Research Institute has a close Research in the MCRI is funded by the NIH (primarily relationship with the Division of Cardiology. Five members of through the NHLBI), the American Heart Association, the MCRI are practicing clinicians within the Division of the Juvenile Diabetes Research Foundation, the Michael Cardiology and several serve in leadership roles in the General J. Fox Foundation, private philanthropic foundations Cardiology, Heart Failure and Transplant Programs, and the and Industry sponsors including pharmaceutical, Interventional Cardiology Center. Please refer to the Division of biotech and medical device companies. The research Cardiology for specific information regarding major clinical interests of the Molecular Cardiology Research Institute

» programs. faculty are described below. » INSTITUTE FOR Teaching Activities Vascular Biology Research Center MCRI Investigators provide extensive mentoring and Iris Z. Jaffe, MD, PhD Director financial support to students at Tufts University School The Jaffe Laboratory studies the role of hormones in

MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR of Medicine and the Sackler School of Graduate heart attack. Heart attack remains the leading cause of Biomedical Sciences. Currently, four graduate students death in the developed world and high blood pressure is are mentored by MCRI faculty and many of the MCRI a significant risk factor for heart attack. Aldosterone is a investigators supervise and lecture in graduate courses. hormone that regulates blood pressure and may have a The clinician- scientists within the MCRI participate in role in the development of hardening of the arteries. the teaching of medical students through the Patient- Drugs that block aldosterone decrease mortality and Doctor II, Cardiovascular Pathophysiology and prevent heart attacks. However, the mechanism of Integrating Biomedical Research and Clinical Medicine protection from heart attack by these drugs is not known. courses, as well as teaching students, house officers and The Jaffe lab has demonstrated that aldosterone controls clinical cardiology fellows while attending in the the pattern of genes turned on in the vessel. Members of ambulatory clinics and on the inpatient services. the laboratory discovered that aldosterone promotes hardening of the arteries by activating the immune Recognized nationally and internationally as a leader in system resulting in inflamed arteries. It also plays a cardiovascular research, the Molecular Cardiology direct role in aging-associated high blood pressure, a Research Institute is training a new generation of condition which affects over 60% of people over 60 years investigators in the state-of-the-art technologies of age and 80% of octogenarians. Recently, the laboratory necessary to translate bench findings to the bedside and discovered that the hormone aldosterone interacts with to develop new diagnostic and therapeutic strategies to the sex hormone estrogen which may explain why fight cardiovascular disease. Fellows are engaged in pre-menopausal women are protected; the team is also basic, translational and clinical research throughout the exploring why women experiencing high blood pressure Institute and the Cardiology Division. during pregnancy have a much higher risk of heart Graduates of the MCRI fellowship program typically disease later in life. Lab members are now also exploring pursue careers in academic medicine (MD graduates) or mechanisms for blood vessel changes with aging to research departments (PhDs) as independent identify new therapies to slow or reverse the aging investigators, with the occasional fellow pursuing an process. These studies will continue provide new insights opportunity in industry. into the causes of common cardiovascular diseases and identify new drug targets for prevention and treatment of heart attacks, strokes, and high blood pressure

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » INSTITUTE FOR MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR

Tinatin Chabrashvili, MD, PhD in postmenopausal women can alter the risk of heart and Dr. Chabrashvili is a clinician-scientist in the blood vessel diseases. The work of the laboratory is Department of Neurology who specializes in movement aimed at understanding how estrogen and nitric oxide disorders. The Chabrashvili laboratory is located in the regulates the development of heart and blood vessel MCRI and studies cerebral microvascular inflammation diseases. The laboratory also has an active research and blood-brain barrier permeability. program in studying the adverse events that can result from the use of cholesterol altering medications. Richard H. Karas, MD, PhD The Karas Laboratory is focused in four primary areas: Cardiac Biology Research Center exploring the effects of estrogen on the cardiovascular Navin Kapur, MD Director system; investigating the extent to which abnormalities The Kapur Laboratory’s translational research focuses of blood vessel function contribute to both on large animal models of acute and chronic heart failure, atherosclerosis and high blood pressure, examining the circulatory support device development, and importance of low levels of the “good cholesterol” HDL in cardioprotective mechanisms in the setting of acute contributing to heart disease and stroke, and studying myocardial infarction. This laboratory was the first to the role of protein kinase G (the main effector of nitric identify that acute mechanical unloading of the left oxide) on vascular health. The laboratory studies the ventricle activates a cardioprotective signaling program molecular pathways within cells of the heart and blood in the setting of acute myocardial infarction. This basic vessels that mediate responses to estrogen. Heart and science laboratory focuses on molecular mechanisms blood vessel diseases are by far the leading causes of governing maladaptive cardiac remodeling in heart death for women in this country, and patient-based failure. Its particular expertise involves signaling via the studies have shown that hormone replacement therapies

141 transforming growth factor beta (TGFb) system. Over the Jonas Galper, MD, PhD past 6 years, the laboratory has published several critical The Galper Laboratory studies autonomic neuropathy, a papers focused on a TGFb co-receptor known as endoglin major complication of diabetes that has been associated and was the first to establish that reduced endoglin activity with a marked increase in the incidence of sudden death improves survival and limits maladaptive cardiac in the diabetic population. The Laboratory has remodeling in heart failure. More recently, the laboratory demonstrated a new relationship between the has demonstrated that targeting endoglin using an development of this complication of diabetes and the antibody-mediated approach not only limits the regulation of cholesterol. The studies have identified development of cardiac fibrosis, but can reverse established several new candidate molecules that might be involved »

» cardiac fibrosis in preclinical models of heart failure.

INSTITUTE FOR in this process and might serve as targets in the treatment and prevention of this complication of Pilar Alcaide, PhD diabetes and the associated abnormal heart beats and The Alcaide Laboratory aims to find specific ways to sudden death. Dr. Galper also studies abdominal aortic prevent and/or treat inflammation, a condition aneurysm, a disease that affects more than 10% of men

MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR negatively affecting health in a variety of diseases above the age 65. Currently, its life threatening ranging from autoimmune disease to cardiovascular complications can only be treated surgically. Using a disease. Inflammation is in part mediated by infiltration mouse model for this disease, the Galper Laboratory has of immune cells such us T cells into tissues and organs. elicited data which suggest that a new drug that was These research studies combine in vitro and in vivo developed for the treatment of life threatening infections vascular immunology and cardiac physiology might be used to decrease the incidence and severity of approaches to identify basic mechanisms that mediate T aneurysms. The laboratory is also testing the possibility cell infiltration in tissues, with a focus in the heart in that a low dose of a drug that causes inflammation might heart failure. A better understanding of these basic actually protect the aorta from the development of this mechanisms may result in the developing of new disease. These experiments may support the use of these therapeutic interventions that target T cell infiltration in agents as a kind of immunization against this the heart as a way to reduce inflammation and devastating disease. potentially heart failure, a syndrome affecting nearly 25 million people worldwide. Recently the Galper laboratory has extended its work on abnormal heart rhythm to similar mechanisms that Robert Blanton, MD might lead to death of nerve cells that cause Parkinson’s The Blanton Laboratory studies the process of cardiac disease. A protein that is produced in excess in the remodeling, which leads to the syndrome of heart failure. diabetic mouse and in the diabetic patient is also present Its members investigate signals within heart muscle in excess in patients with Parkinson’s disease. The lab which slow down or even reverse remodeling in order to has established data supporting the conclusion that this exploit these as new drug targets for heart failure. The excess protein maybe involved in accelerating the death laboratory currently focuses on understanding how a of nerve cells in the brain that cause Parkinson’s disease signaling system called the “cGMP-PKG” pathway slows down remodeling and has discovered a number of new molecules that cooperate with this system in heart muscle. The research involves studies ranging from test tube studies, to animal pre-clinical studies, to studies of humans with heart failure.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » INSTITUTE FOR MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR

Center for Translational Alan Kopin, MD Pharmacology and Genomics The Kopin Laboratory is focused on G protein-coupled receptors (GPCRs), a family of more than 300 proteins Gordon Huggins, MD, Director which modulate a wide variety of physiological Research in the Huggins Laboratory is focused on functions. These receptors are among the most understanding how genetic factors contribute to diseases important targets for drug discovery. Members are involving the heart muscle, heart valves as well as risk developing tools to modulate selected receptors (e.g. factors for heart diseases including obesity and adult- FPR2, CMKLR1) which play a significant role in causing onset diabetes. The goals of the CTG include identifying inflammation (e.g. atherosclerosis, asthma). The disease-causing genes and mutations, developing modulators identified will provide novel tools to enable diagnostic and prognostic markers and drug targets, and better understanding of disease mechanisms as well as creating new therapeutic strategies for those most likely provide a first step toward developing a new class of to develop disease. Through a predictive and therapeutics. The laboratory is also studying how genetic personalized approach, treatments can be tailored for variation in GPCRs influences receptor and/or drug those predisposed to disease based upon the anticipated activity. These investigations may provide hints severity of the disease. The Center is currently studying regarding the role of receptors in health and in disease the genetics of common diseases such as hypertension as well as preview how inter-individual differences may and obesity, as well as hypertrophic cardiomyopathy, alter drug response. bicuspid aortic valve and aortic aneurysm.

143 Isabelle Draper, PhD The Draper Laboratory is a Drosophila laboratory which focuses on expediting the characterization of genes elevant to human physiology. Dr. Draper pioneered the introduction of mammalian genes in the fly system as a means to expedite the exploration of conserved protein function in vivo. Her current research focuses on the investigation of muscle physiology and disease, motor function and RNA processing. Collaborative efforts led » »

INSTITUTE FOR to the establishment of a research pipeline, enabling rapid translation of findings from Drosophila melanogaster to human myoblast cell lines (healthy and diseased; differentiated from primary cultures or from iPSCs). Conversely, the functional characterization of

MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR novel modifiers of muscle disease that are identified in mammalian systems can be expedited in the Drosophila model organism. Using proprietary technology in conjunction with this multisystem approach, the Draper Laboratory is assessing the effects of candidate drugs as potential therapeutics for human muscle/heart disease.

Janis Lem, PhD The Lem Laboratory studies neurodegeneration in blinding diseases such as retinitis pigmentosa, which affect nearly 2 million people worldwide. Currently there are no effective therapies. The laboratory investigates the role of a protein kinase that is activated in retinas by light Martin Beinborn, MD exposure and reversibly inactivated when light is The Beinborn Laboratory focuses primarily on terminated. Members are investigating neuroprotective receptors that are relevant for the treatment of diabetes, properties of this protein as a potential therapeutic target. obesity, and bone disease. Recently, the laboratory’s Gavin Schnitzler, PhD efforts have helped to launch approaches for discovering two new types of diabetes drugs that may be superior to The Schnitzler Laboratory is studying the roles of currently available medications. A major drug screening chromatin changes in the regulation of transcription by program based on some of these findings, carried out in nuclear hormone receptors, including estrogen receptor collaboration with the National Institutes of Health, is and glucocorticoid receptor. The laboratory uses a currently underway. In a second initiative, also in combination of standard and high-throughput collaboration with the NIH, the laboratory has begun to techniques to understand how the genetic and epigenetic identify novel blockers of the parathyroid hormone factors that modulate chromatin structure give rise to receptor. Such compounds areanticipated to be useful tissue-specific transcriptional responses to for the treatment of a rare form of hereditary bone glucocorticoids or estrogen disease, but may also provide future therapies for much more prevalent conditions including life-threatening forms of hypercalcemia and the formation of cancer metastases in bone.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Research Support In 2016, the Institute was engaged in the following research projects:

PI Funding Source Title of Project T Cell Mediated Immune Responses as a Regulator of Heart Pilar Alcaide Alonso NIH Failure Molecular Approaches to Therapeutics Against Diabetes Martin Beinborn Tufts University Collaborates Award and Obesity

NIH CTSI KL2 Scholar » » Cardiac Cell Entry-Inhibition and Protection Therapy for INSTITUTE FOR Tufts University Chronic Chagas Disease Robert Blanton Novel Protein Kinase GI Substrates in Cardiac Remodeling NIH and Blood Pressure Control

Cardurion PDE9 Inhibitor (MCRI) RESEARCH CARDIOLOGY MOLECULAR U of Florida Gene Discovery in Muscular Dystrophy Isabelle Draper U of Florida Novel Therapies for Inherited Muscle Diseases American Heart Association Post-Doctoral Fellowship Jennifer DuPont Tufts University Natalie Zucker Research The Role of Sex Differences in Vascular Aging Center for Women Scholars A Novel Method to Diagnose and Monitor Hemolysis Michelle Esposito Heart Failure Society of America in Patients with Cardiogenic Shock Supported by Percutaneous Mechanical Circulatory Support Novel Mechanism for Death of Dopaminergic Neurons in a Jonas Galper Michael J. Fox Foundation Mouse Model of Parkinson’s Disease Heart Failure Network: New England, New York and Quebec NIH Regional Clinical Center NIH Basic Mechanisms of Human Calcific Aortic Valve Disease Gordon Huggins Salivary Amylase Gene (AMY 1) as Predictor of Weight and Miriam Hospital Diet in LookAhead & DPP Precision Medicine for Dilated Cardiomyopathy in European Ohio State University and African Ancestry American Heart Association Extra-Renal Mineralocorticoid Receptors in Hypertension The Role of Vascular MR-Regulated Genes in Vascular NIH Iris Jaffe Function and Disease Smooth Muscle Mineralocorticoid Receptors in Vascular NIH Aging and Hypertension Testing efficacy of KPT compounds on inhibiting Karyopharm Therapeutics phenylephrine-induced cardiac myocyte hypertrophy Iris Jaffe/Robert Blanton Acute and Sustained Cardiac and Vascular Effects of Novartis Serelaxin in the Angiotensin II/L-NAME Heart Failure Model A new animal model for the study of the mechanism of Hongwei Jin American Heart Association ventricular arrhythmias in type I diabetes

145 Research Support (continued)

PI Funding Source Title of Project Changing the Paradigm of AMI Therapy: The Bench to Abiomed Bedside Approach Abiomed CVAD Registry Protocol Agreement The hemodynamic effects of the (circulatory) device in Boston Scientific animal models of heart failure Navin Kapur Maquet Clinical Hemodynamic Study of MEGA-IABP Function » » INSTITUTE FOR NIH Endoglin: A Novel Target of Therapy for Right Heart Failure NIH Endoglin: A New Target of Therapy for Heart Failure The Hemodynamic Effects of (circulatory devices) on Thoratec Myocardial Oxygen Supply and Demand in a Swine Model of

MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR Ischemia Cardiogenic Shock Richard Karas NIH Training Program in Cardiovascular Research (T32) The Role of PKG-1a in cGMP Signaling Mechanisms through Merck the Evaluation of the Effects of cGMP Modulations in Richard Karas/Robert Blanton Normal and Disease Studies in the PKG1-LZM Mouse Merck TAC LKR140269 Lipidated Stable BAM8-22 Offers a Promising Therapeutic Alan Kopin On Target Therapeutics for Neuropathic Pain Gavin Schnitzler American Heart Association Vascular Pro-Inflammatory Effects of Unliganded Estrogen Development of Novel Lipidated Membrane-Tethered Gavin Schnitzler/Richard Tufts University Russo Award Ligands to Selectively Activate Estrogen Receptor Karas/Alan Kopin Rapid Signaling Pathways

Honors and Awards

Martin Beinborn, MD »» Charter Member NIH Study Section: Vascular Cell »» Core Member and Chair, NIH Special Emphasis and Molecular Biology Panel on Pharmacological Validation of Novel »» Scientific Committee, Mechanism of Vasodilation Targets of interest to the NIDDK 12th International Symposium

Robert Blanton, MD Navin Kapur, MD »» Early Stage Investigator R01 “Novel Protein Kinase »» Early Stage Investigator R01 “Endoglin: A New GI Substrates in Cardiac Remodeling and Blood Target of Therapy for Heart Failure” Pressure Control” »» Best of Basic Science Posters award for poster Gordon Huggins, MD entitled “Gene Expression Profiles Underlying the Cardioprotective Effects of Mechanical Primary »» Named Director, Cardiovascular Fellowship Unloading of the Left Ventricle before Reperfusion Training Program in Acute Myocardial Infarction”, 2016 AHA Iris Jaffe, MD, PhD Scientific Sessions »» Honored with Notable Teaching Recognition in the »» Chair, American Heart Association, Interventional Medicine Clerkship, Tufts University School of Cardiology Committee, CLCD Medicine

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » INSTITUTE FOR MOLECULAR CARDIOLOGY RESEARCH (MCRI) RESEARCH CARDIOLOGY MOLECULAR

Richard Karas, MD, PhD »» Chair, Policy and Evaluation Subcommittee, American Heart Association National Research Committee »» University of Pittsburgh Medical Center, Clinical Translational Science Institute; External Advisory Board

Alan Kopin, MD »» Scientific Advisory Board, Raphael Recanati Genetic Institute, Rabin Medical Center, Israel

147 INSTITUTE FOR MOLECULAR ONCOLOGY RESEARCH (MORI) » » INSTITUTE FOR The Molecular Oncology Research Institute (MORI), a core component of the Tufts Medical Center Cancer Center, has 16 faculty members and occupies over 44,000 square feet in the 75 Kneeland Street MOLECULAR ONCOLOGY RESEARCH (MORI) RESEARCH ONCOLOGY MOLECULAR research building. Its mission is to explore the molecular mechanisms of neoplastic transformation and to promote the translation of basic research findings into the clinic. To achieve this goal, MORI scientists carry out research that spans the spectrum from gene discovery to target validation for drug development. MORI functions independently of the Department of Medicine and reports to a Board of Advisors comprised of senior Tufts Medical Center and TUSM executives and the Chairman of the Department of Medicine.

Highlights of 2016

»» Institute investigators delivered 39 Invited Lectures

»» MORI faculty produced 50 publications

»» Faculty received new research awards totaling 1.58 million

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 » » INSTITUTE FOR Faculty

Name Academic Rank Executive Director, MORI Philip Tsichlis, MD Jane F. Desforges Professor (MORI) RESEARCH ONCOLOGY MOLECULAR Anika Agarwal, MD, MPhil* Assistant Professor Rachel Buchsbaum, MD Associate Professor Alain Charest, PhD* Associate Professor Lidija Covic, PhD Assistant Professor Keyong Du, PhD Assistant Professor Andrew Evens, DO Professor Mark Ewen, PhD* Associate Professor Philip Hinds, PhD Professor Miaofen Hu, PhD Assistant Professor Athan Kuliopulos, MD, PhD Professor Paul Mathew, MD Associate Professor Cheryl London** Research Professor Elizabeth McNiel, DVM, PhD Assistant Professor

Teaching Activities Seminars The Institute has a biweekly seminar program for The Institute sponsors a campus-wide seminar series in intramural research at MORI at which graduate students which invited speakers from other institutions present and postdoctoral fellows present their work. MORI holds their research to Tufts Medical Center and Tufts a monthly faculty seminar program where principal University School of Medicine faculty. Like the monthly investigators present their work to the MORI faculty. faculty seminars, these seminars facilitate inter- These seminars encourage the sharing of ideas and institutional collaboration. prompt collaborations between laboratories

149 Research Support In 2016, the Institute received new, peer-reviewed research awards in the amount of $1.58 million.

PI Funding Source Title of Project Development of PAR2 Pepducins for the Treatment NIH of Atopic Dermatitis Andrew Evens, DO, MS Pitfalls, opportunities and implications of dietary fat in targeting Nutrition & Cancer Pilot Project fatty acid metabolism in

» Zaniboni Scholar Award in Breast Targeting Angiogenin/PlexinB2 to chemosensitize breast cancer » INSTITUTE FOR Cancer Research stem cells and prevent bone metastasis Guo-fu Hu, PhD Sponsored Research Agreement with Karma Pharmaceuticals Karma Pharmaceuticals Limited Limited Rajashree Rana, PhD AHA Targeting Metalloprptease-PAR1 signaling in Atherosclerosis

MOLECULAR ONCOLOGY RESEARCH (MORI) RESEARCH ONCOLOGY MOLECULAR Cancer Center Grant Support: Canine Immunotherapy NIH/NCI Cheryl London, DMV, PhD Administrative Supplement NIH/NCI Studies of Childhood Sarcomas (Project 2 and Core C) FY 16/17 Moore/Moreau Using GSK3 Inhibitors to Target Cancer Stem Cells in Triple- Elia Aguado-Fraile, PhD CancerResearch Negative Breast Cancer

Honors and Awards

Dr. Rachel Buchsbaum »» 13th International Ultmann Chicago Lymphoma »» Tufts University School of Medicine Outstanding Lecturer Symposium; Chicago. 5/7/16 »» Tufts University School of Medicine Notable Teaching »» Understanding Lymphoma (Plenary Session); Lymphoma »» Castle Connolly, Top Doctor, Medical Oncology Research Foundation (LRF) New England Lymphoma Annual Workshop,; Needham, MA. 5/21/16 Dr. Lidija Covic »» Aggressive B-Cell Non-Hodgkin Lymphoma (Disease Invited Speaker Specific Breakout Sessions); Lymphoma Research »» “Dysregulated protease activated receptor 1 (PAR1) Foundation (LRF) New England Lymphoma Annual promotes metastatic phenotype in breast cancer through Workshop, Needham, MA. 5/21/16 HMGA2”Breast Cancer Summit 1016, London, UK, 10/5/16 »» Lymphoma Overview; Best of ASCO (Sponsor: ASCO); »» "Pepducins as Mechanistic Probes and Therapeutics" Washington DC. 7/16/16 »» Annual Meeting of the GDR3545, Tours, France 11/23/16 »» PET Directed Therapy for Early Stage Hodgkin Lympho ma. Dr. Andrew Evens Pan Pacific Lymphoma Conference (Sponsor: University of Nebraska); Kauai, Hawaii. 7/19/ Invited Speaker »» Henderson T and AM Evens. Outcomes in Adolescents and »» Non-LP CD20+ Hodgkin Lymphoma (ie, Gray Zone Young Adults (AYA) with Hodgkin Lymphoma (HL) Treated Lymphoma). Pan Pacific Lymphoma Conference (Sponsor: on US Cooperative Group Protocols: An Adult Intergroup University of Nebraska); Kauai, Hawaii 7/20/16 (E2496) and Children’s Oncology Group (COG AHOD0031) »» Optimizing (NK-Cell) Immunotherapy for the Treatment of »» Comparative Analysis 10th International Symposium on Lymphoma The Immuno-Oncology Summit (Cambridge Hodgkin Lymphoma (ISHL10),; Cologne, Germany. Healthtech Institute); 8/3/16 10/25/16 »» Lymphoma During Pregnancy; Mother Infant Research Other Invited Presentations: Institute (MIRI) Scientific Seminar; Tufts MC, Boston, MA. »» What’s new in the initial management of Hodgkin 9/16/16 Lymphoma? Great Debates and Updates in Hematologic »» Double Hit Lymphoma: How to Approach in the Malignances. New York. 4/1-2/16 Contemporary Era. The New England Lymphoma Rounds »» Low-grade Non-Hodgkin’s Lymphoma: follicular and (Sponsor: LRF);; Boston, MA. 9/20/16 marginal zone lymphoma. Mexican Society of Hematology (AMEH) and ASH; Merida, Mexico; 4/29/16

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 »» Treatment of Limited Stage Hodgkin Lymphoma: Is RT »» Angiogenin promotes hematopoietic regeneration by Necessary? The Inaugural Lymphoma Rounds (Sponsor: dichotomously regulating quiescence of stem and Imedex, LLC and LRF); NY, NY.10/16/16 progenitor cells. »» Hodgkin Lymphoma in Elderly Patients: The US Experience. »» Tufts 1st annual precision medicine in hematology Scientific Workshop at the 10th International Symposium symposium. Boston. 2016 on Hodgkin Lymphoma (ISHL10), Cologne, Germany. Dr. Miaofen Hu 10/22/16 Invited Speaker »» Grey Zone Lymphoma. Scientific Workshop at the 10th »» China, Zhenjiang University School of Medicine, International Symposium on Hodgkin Lymphoma »

»» Host: ZhenPing Xu, Dean for Research 4/12/16 »

(ISHL10); Cologne, Germany. 10/22/16 INSTITUTE FOR »» Hodgkin Lymphoma: Disease-specific Breakout Session I Dr. Athan Kuliopulos for the Annual LRF Lymphoma Educational Forum; 2016; »» 2016 Invited Lecture at the NHLBI Innovator Meeting: Best Chicago, IL.10/29/16 practices for supporting and transitioning discoveries into »» Immunotherapy for the Treatment of Lymphoma: Shooting Health, NIH, Bethesda, MD (October 25-26, 2016) MOLECULAR ONCOLOGY RESEARCH (MORI) RESEARCH ONCOLOGY MOLECULAR for the Moon. Massachusetts Society of Clinical »» Clinical Site Initiation Visit for TRIP-PCI PZ-128, Inova Oncologists (MSCO) Annual Meeting: Key Note Speaker; Center for Thrombosis Research and Drug Development, Boston, MA. 11/3/16 »» Inova Heart and Vascular Institute, Falls Church, VA 3/1/16 »» ASCO Educational Session: PET-Directed Therapy for »» Clinical Site Initiation Visit for TRIP-PCI PZ-128, Early-Stage Hodgkin Lymphoma; American Society of Cardiovascular Medicine, Clinical Oncology (ASCO) Annual Meeting, 6/16 »» University of Massachusetts Medical School, Worcester, »» Named the Chan Soon-Shiong Endowed Scholar in MA, 3/8/16 Precision Medicine at Tufts Medical Center, Boston, MA »» University of Michigan, Department of Pharmacology, Dr. Philip Hinds 4/27/16 Invited Speaker »» University of Cambridge, UK, Department of »» Biomedical Graduate Education in the 21st Century Gastroenterology, 7/4/16

»» Talca Universidad Chile, 8/25/16 Dr. Philip Tsichlis »» Caner a Disease of Development: Therapeutic Invited Speaker Opportunities and Risks »» “The histone demethylase KDM2B and its role in human »» Talca Universidad Chile. 8/26/16 cancer”

Dr. Guofu Hu »» Brandeis University, February 24, 2016, Invited Speaker »» “Akt, Epigenetics and GSK3 regulation” »» Inhibitors of angiogenin-plexinB2 as a novel class of anti- »» Broad Institute, 6/14/16 cancer therapeutics. »» “Non-Redundant Functions of the Three Akt Isoforms and »» Starry Pharmaceuticals, Inc. Xianju, China, 2016 Their Role in the biology of Cancer” »» Targeting angiogenin-plexinB2 for treatment of solid and »» University of Kansas Medical Center, Department of hematopoietic cancers. Microbiology, »» BFC Medicine and Health Forum 2016, Shanghai, China, »» Molecular Genetics and Immunology 10/27/16 2016 »» “Celebrating 25 years of Akt” »» Inhibition of angiogenin-plexinB2 chemosensitize cancer »» Philadelphia, PA, Co-organizer of Meeting and speaker, stem cells. 11/29/16 »» Zhejiang University, China, 2016 »» Akt and regulatory T cells” »» Synergy between anti-angiogenesis and immunotherapy in »» FASEB Meeting, Snowmass, CO,”6/5-10/16 cancer treatment. »» DMCB Retreat Keynote »» Sanofi Shanghai, China, 2016 »» Tufts University, Grafton, MA, Speaker11/19/16

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PUBLICATIONS

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 153 Abstracts, letters to editor and presentations excluded from listings. Division of Cardiology 8. Bader Y, Katsetos, MC, Kimmelstiel C. Percutaneous coronary intervention. Chapter 1. Aghili N, Bader Y, Vest AR, Kiernan MS, in Cardiology Procedures, A Clinical Primer, Kimmelstiel C, DeNof rio D, Kapur NK. Hendel RC, Kimmelstiel C eds., Springer- Biventricular Circulatory Support Using 2 Verlag, London, UK 2016; pp 263-74. Axial Flow Catheters for Cardiogenic Shock Without the Need for Surgical Vascular Access. 9. Bader Y, Kimmelstiel C. Ablation or surgery for Circulation: Cardiovascular Interventions. medically refractory HCM. Updating an imperfect 2016 Jun;9(6). PMID: 27614169. dataset. Catheter Cardivasc Interv. 2016; 88:116-7. » » PUBLICATIONS 2. Aghili N, Daher E, Kimmelstiel C. Central Venous 10. Bader Y, Kimmelstiel C. Bivalirudin is Cannulation. Chapter in Cardiology Procedures, Associated with Improved Clinical and A Clinical Primer, Hendel RC, Kimmelstiel C eds., Economic Outcomes in Heart Failure Patients Springer-Verlag, London, UK 2016; pp 237-48. Undergoing Percutaneous Coronary Intervention: Results from an Observational Database. 3. Alshalash S, Kimmelstiel C. Central Venous Catheter Cardiovasc Interv. 2016 87:374-5. Cannulation. Chapter in Cardiology Procedures, A Clinical Primer, Hendel RC, Kimmelsteil C eds., 11. Barik A, Shah RV, Spahillari A, Murthy VL, Springer-Verlag, London, UK 2016; pp 115-22. Ambale-Venkatesh B, Kumar Rai R, Das K, Santra A, Hembram JR, Bhattacharya D, Freedman 4. Alshalash A, Kimmelstiel C. Pericardiocentesis. JE, Lima J, Das R, Bhattacharyya P, Das S, Chapter in Cardiology Procedures, A Clinical Chowdhury A. Hepatic statosis is associated with Primer, Hendel RC, Kimmesltiel C eds., cariometaboic risk in a rural Indian population: Springer-Verlag, London, UK 2016; pp 133-40. a prospective cohort study. International Journal 5. Amador CA, Bertocchio JP, Andre-Gregoire G, of Cardiology. 2016 Dec 15; 225:161-166. Placier S, Duong Van Huyen JP, El Moghrabi S, 12. Belalcazar LM, Papandonatos GD, Erar B, Peter Berger S, Warnock DG, Chatziantoniou C, Jaffe I, Alkofide H, Balasubramanyam A, Brautbar A, IZ, Rieu P, Jaisser F. Deletion of mineralocorticoid Kahn SE, Knowler WC, Ballantyne CM, McCaffery receptors in smooth muscle cells blunts renal JM, Huggins GS, Genetics Subgroup of the vascular resistance following acute cyclosporine Look AS. Lifestyle Intervention for Weight Loss administrations. Kidney International, and Cardiometabolic Changes in the Setting 2016; 89(2):354-362. PMID: 2642250. of Glucokinase Regulatory Protein Inhibition: 6. Ambrosy AP, Khan H, Udelson JE, Mentz Glucokinase Regulatory Protein-Leu446Pro RJ, Chioncel O, Greene SJ, Vaduganathan Varient in Look AHEAD. Circ Cardiovasc M, Subacuis HP, Konstam MA, Swedberg K, Genet. 2016;9(1):71-8. PMC4758870. Zannand F, Maggioni AP, Gheorghiade M, 13. Beninger P, Boumil M, Salem D, Getz Butler J. Changes in Dyspnea Status During K, Klapholz H, Curfman GD, Jotwani Hospitalization and Postdischarge Health-Related R, Berman H. Bridging the Academia/ Quality of Life in Patients Hospitalized for Heart Industry Chasm: Proposed Solutions. J Clin Failure: Findings From the EVEREST Trial, Pharmacol, 2016 Dec;56(12):1457-1460, Circ Heart Fail. 2016 May;9(5).pii: e002458. doi: 10.1002/jcph.762. Epub 2016 Jun 7. 7. Auseon AJ, O’Gara PT, Klodas E, Holmes DR Jr, 14. Breathett K, Allen LA, Udelson J, Davis G, Jackson MJ, Green JS, Konstam MA, Nishimura Bristow M. Changes in Left Ventricular Ejection RA. The Essential Role of Educator Development: Fraction Predict Survival and Hospitalization 10 Years of the ACC Emerging Faculty Program. in Heart Failure With Reduced Ejection J Am Coll Cardiol. 2016 May 10;67(18):2177-82. Fraction. Circ Heart Fail. 2016 Oct;9(10). Doi: 10.1016/j.jacc.2016.02.052. PMID: 27151350.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 15. Burke SD, Zsengeller ZK, Khankin EV, Agnes Article, “treatment of Arrhythmogenic Right S. Lo AS, Rajakumar A, DuPont JJ, McCurley A, Ventricular Cardiomyopathy/Dysplasia: An Moss MR, Zhang D, Clark CD, Wang A, Seely International Task Force Consensus Statement.” EW, Kang PM, Stillman IE, Jaffee IZ, Karumanchi Circulation. 2016 Mar 15;133(11):e437-8. SA. Soluble fms-like tyrosine kinase 1 promotes 21. Davel AP, Anwar IJ, and Jaffe IZ. The endothelial angiotensin II sensitivity during preeclampsia Mineralocorticoid Receptor: Mediator of the by impairing endothelial nitric oxide fundtion. Switch from Vascular Health to Disease. Current Journal of clinical Investigation 2016;126(7):2561- Opinion in Nephrology and Hypertension 2016 74. PMID: 27270170; PMCID: PMC4922717. Dec 7. [Epub ahead of print] PMID: 27930384. » » PUBLICATIONS 16. Butler J, Hamo CE, Udelson JE, Pitt B, Yancy C, 22. de Denus S, Rouleau JL, Mann DL, Huggins GS, Shah SJ, Desvigne-Nickens P, Bernstein HS, Clark Cappola TP, Shah SH, Keleti J, Zada YF, Provost S, RL, Depre C, Dinh W, Hamer A, Kay-Mugford Bardhadi A, Phillips MS, Normand V, Mongrain P, Kramer F, Lefkowitz M, Lewis K, Maya J, I, Dube MP. A pharmacogenetic investigation of Maybaum S, Patel MJ, Pollack PS, Roessig L, intravenous furosemide in decompensated heart Rotman S, Salsali A, Sims JJ, Senni M, Rosano failure: a meta-analysis of three clinical trials. The G, Dunnmon P, Stockbridge N, Anker SD, Zile pharmacogenomics journal. 2016. PMC5009007. MR, Gheorghiade M. Exploring New Endpoints for Patients With Heart Failure With Preserved 23. DuPont JJ, McCurley A, Davel AP, McCarthy Ejection Fraction. Circ Heart Fail. 2016 Nov;9(11). J, Bender SB, Hong K, Yan Yang, Yoo JK, Aronovitz M, Baur WE, Christou DD, Hill 17. Butler J, Hernandez AF, Anstrom KJ, MA, and Jaffe IZ. Vascular mineralocorticoid Kalogeropoulos A, Redfield MM, Konstam MA, receoptor regulates microRNA-155 to promote Tang WH, Felker GM, Shah MR, Braunwald E. vasoconstriction and rising blood pressure Rationale and Design of the ATHENA-HF Trial: with againg. JCI Insight. 2016;1(14):e88942. Aldosterone Targeted Neurohormonal Combined Doi.10.1172/jci.insight.88942. PMID: 27683672. With Natriuresis Therapy in Heart Failure. JACC Heart Fail. 2016 Sep;4(9):726-35. Doi: 10.1016/j. 24. Esposito M, Kuchibhotla S, Zisa D, O’Kelly R, jchf.2016.07.13. Epub 2016 Sep 7. PMID: 27614938. Annamalai S, Ghuloom A, Lussier L, Breton C, Rheude T, Mullin A, Kimmelstiel C, Kiernan 18. Butler J, Konstam MA. Dilemmas With Race M, Vest A, Kapur N. TCT-114 Comparing and Heart Failure Treatment. Circ Heart Fail. Hemodynamic Profiles and Outcomes in 2016 Oct;9(10). Pii: e003384. PMID: 27707751. Cardiogenic Shock Requiring VA-ECMO 19. Cook TD, Greene SJ, Kalogeropoulos AP, or Impella for Circulatory Support. J Am Fonarow GC, Zea R, Swedberg K, Zannad F, Coll Cardiol. 2016 Nov 1;68(18S):B45-B46. Maggioni AP, Konstam MA, Gheorghiade M, Doi: 10.1016/j.jacc.2016.09.020. Butler J. Temporal Changes in Postdischarge 25. Estes NA 3rd. Clinical Outcomes of Mortality Risk After Hospitalization for Patients Who Received the Subcutaneous Heart Failure (from the EVEREST Trail). Implantable Cardioverter Defibrillator. Am J Cardiol. 2016 Feb 15;117(4):611-6. JAMA Cardiol. 2016 No 1;1(8):965. Doi: 10.1016/j.amjcard.2015.11.050. Epub 2015 Dec 8. PMID: 26742474. 26. Estes NA 3rd. Clinical Outcomes of Patients Who Received the Subcutaneous 20. Corrado D, Wichter T, Link MS, Hauer R, Implantable Cardioverter Defibrillator. Marchlinski F, Anastasakis A, Bauce B, Basso JAMA Cardiol 2016 Nov 1:1(8):965. C, Brunckhorst C, Tsatsopoulou A, Tandri H, Paul M, Schmied C, Pelliccia A, Duru F, 27. Estes NAM EP News Clinical Heart Rhythm Estes NA 3rd, McKenna WJ, Thiene G, Marcus January 2016 – December 2016: Monthly FI, Calkins H. Response to Letter Regarding Literature review (12 publications).

155 28. Ferreira JP, Girerd N, Alshalash S, Konstam MA, 35. Jia G, Habibi J, Aroor AR, Martinez-Lemus LA, Zannad F. Antithrombotic therapy in heart failure DeMarco VG, Ramires-Perez Fl, Sun Z, Hayden patients with and without atrial fibrillation: MR, Meininger GA, Barrett Mueller K, Jaffe IZ update and future challenges. Eur Heart J. 2016 and Sowers JR. Endotherlial mineralocorticoid Aug;37(31):2455-64. Doi: 10.1093/eurheartj/ receptor mediates died induced aortic stiffness ehw213. Epub 2016 Jun 1. PMID: 27252452. in females. Circulation Research, 2016:118:935- 29. Ferres MA, Bianchi DW, Siegel AE, Bronson 943. PMID: 26879229. PMC4798906. RT, Huggins GS, Guedj F. Perinatal Natural 36. Kapur NK, Zisa DC. Veno-arterial extracorporeal

» History of the Ts1Cje Mouse Model of Down membrane oxygenation (VA-ECMO) fails to » PUBLICATIONS Syndrome: Growth Restriction, Early Mortality, solve the haemodynamic support equation Heart Defects, and Delayed Development. PLoS in cardiogenic shock. EuroIntervention. 2016 One. 2016;11(12):e0168009. PMC5145234. Mar;11(12):1337-9. Doi: 10.4244/EIJV11I12A261. 30. Gopal S, Miller K and Jaffe IZ. Molecular 37. Kiernan MS, Sundareswaran KS, Pham DT, Kapur Mechanisms for Vascular Complications NK, Pereira NL, Strueber M, Farrar DJ, DeNofrio of Targeted Cancer Therapies. Clinical D, Rogers JG. Preoperative Determinants of Science. 2016;130(20):1763-1779. Quality of Life and Functional Capacity Response 31. Hawwa N, Vest AR, Kumar R, Lahoud R, Young to Left Ventricular Assist Device Therapy. J Card JB, Wu Y, et al. Comparison between the Fail. 2016 Oct;22(10):797-805. PMID: 26777757. Kansas City Cardiomyopathy Questionnaire 38. Kimmelstiel C. Alcohol Septal Ablation. and NYHA in Assessing Functional Chapter in Cardiology Procedures, A Clinical Capacity and Clinical Outcomes. Journal Primer, Hendel RC, Kimmesltiel C eds., of Cardiac Failure. 2016 Dec 12:1-25. Springer-Verlag, London, UK 2016; pp 275-82. 32. Heidenreich PA, Solis P, Estes NA 3rd, Fonarow 39. Kimmelstiel C, Pinto D, Aronow HD, Weintraub GC, Jurgens CY, Marine JE, McManus DD, A, Dangas G, Fan W, Prats J, Deliargyris EN, McNamara RL. 2016 ACC/AHA Clinical Katzen BT. Bivalirudin is Associated With Performance and Quality Measures of Adults With Improved In-Hospital Outcomes Compared Atrial Fibrillation or Atrial Flutter: A Report of the With Heparin in Percutaneous Vascular American College of Cardiology/American Heart Interventions: An Observational, Propensity- Association Task Force on Performance Measures. Matched Analysis From The Premier Hospital J Am Coll Cardiol. 2016 Aug 2;68(5):525-68. Database. Circ Cardiovasc Interv 2016; 9:1-9. 33. Hwang MH, Yoo JK, Luttrell M, Kim HK, 40. Konstam MA. Angiotensin Receptor-Neprilysin Meade TH, English M, Talcott S, Jaffe Inhibition in Heart Failure With Reduced IZ, and Christou DD. Acute Effect of Ejection Fraction: A Paradigm for All? Mineralocoroticoid Receptor Antagonism on JACC Heart Fail 2016 Oct;4(10):823-5. Doi. Vascular Function in Healthy Older Adults. 10.1016/j.jchf.2016.07.013. Epub 2016.07.013. Experimental Gerentology, 2016;73:86-94. Epub 2016 Sep 7. PMID: 27614938. PMID: 26639352; PMCID: PMC4713256. 41. Konstam MA, Upshaw J. Sisyphus and 30-Day 34. Ibrahim NE, Gaggin HK, Konstam MA, Januzzi Heart Failure Readmissions: Futility in Predicting JL Jr. Established and Emerging Roles of a Flawed Outcome metric. JACC Heart Fail. 2016 Biomarkers in Heart Failure Clinical Trails. Circ Jan;4(1):21-3. Doi: 10.1016/j.jchf.2015.10.002. Heart Fail. 2016 Sep;9(9). Pii: e002528. Doi: Epub 2015 Dec 2. PMID: 26656141. 10.1161/CIRCHEARTFAILURE.115.002528. PMID: 27582282.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 42. Krahn AD, Bashir J, Birnie DH, Brown J, Spencer Cardiovascular Morbidity and Mortality Among JH, Leander C, Estes NA. Impact of gereator Individuals With Type 2 diabetes: The Look replacement on the risk of Fidelis lead fracture. AHEAD Study. Diabetes. 2016;65(1):297-302. Heart Rhythm. 2016 Aug;13(8);1618-23. 50. Lu MLR, Davila CD, Shah M, Wheeler DS, 43. Kubba S, Davila CD, Forfia PR. (2016). Ziccardi MR, Banerji S, Figueredo VM. (2016). Methods for Evaluating Right Ventricular Marital status and living condition as predictors Function and Ventricular-Arterial Coupling. of mortality and readmissions among African Progress in Cardiovascular Diseases. Americans with heart failure. International

Journal of Cardiology, 222, 313-318. » »

44. Kuchibhotla, S, Esposito M, Zisa D, O’Kelly R, PUBLICATIONS Annamalai S, Ghuloom A, Lussier L, Breton C, 51. Lu Q, Schnitzler G, Vallaster CS, Ueda K, Rheude T, Mullin A, Kimmelstiel C, Kiernan M, Erdkamp S, Briggs CE, Lyer LK, Jaffe IZ, Vest A, Kapur N. TCT-132 Utility of the SAVE Karas RH. Unliganded estrogen receptor Score as a Predictor of Survival in Cardiogenic alpha regulates vascular cell function and Shock Requiring VA-ECMO or Impella for gene expression: Molecular and Cellular Acute Mechanical Circulatory Support. J Am Endocrinology 2016 Nov 22. Pii: S0303- Coll Cardiol. 2016 Nov 1;68(18S):B53-B54, 7207(16)30488-9. Doi:10.1016/j.mce.2016.11.019. doi: 10.1016/j.jacc.2016.09.038. [Epub ahead of print] PMID:27888004. 45. Kumar K, Mandleywala SN, Gannon MP, Estes NA 52. Madias C, Kimmelstiel C. Right Heart 3rd, Weinstock J, Link MS. Development of a Chest Catheterization. Chapter in Cardiology Wall Protector Effective in Preventing Sudden Procedures, A Clinical Primer, Hendel Cardiac Death by Chest Wall Impact (Commotio RC, Kimmelstiel C eds., Springer-Verlag, Cordis). Clin J Sport Med. 2016 Mar 24. London, UK 2016; pp 123-32. 46. Kuttab J, Kimmelstiel C. Endomyocardial 53. Manning WJ, Spahillari A. Combined Pulmonary Biopsy. Chapter in Cardiology Procesures, A Vein and LA/LAA Thrombus Assessment: Can Clinical Primer, Hendel RC, Kimmelstiel C eds., CMR Kill Two Birds With One Stone? JACC Springer-Verlag, London, UK 2016; pp 317-24. Cardiovasc Imaging. 2016 Jul; 9(7):819-21. 47. Lekva T, Lyle R, Roland MCP, Friis C, Bianchi DW, 54. Maron BJ, Rowin EJ, Casey SA, Garberich Jaffe IZ, Norwitz ER, Bollerslev J, Henriksen T and RF, Maron MS. “What Do Patients With Ueland T. Gene expression in term placentas is Hypertrophic Cardiomyopathy Die from?” regulated more by spinal or epidural anesthesia Am J Cardiol. 2016 Feb 1;117(3):434-5. than by preeclampsia or gestational diabetes 55. Maron BJ, Rowin EJ, Casey SA, Maron mellitus. Scientific Reports 2016 Jul 11;6:29715. MS. “How Hypertrophic Cardiomyopathy PMID:27405415; PMCID:PMC4942618. Became a Contemporary Treatable 48. Lu MT, Park J, Ghemigian K, Mayrhofer T, Genetic Disease with Low Mortality.” Puchner SB, Liu T, Fleg JL, Udelson JE, Truong JAMA Cardiol. 2016 Apr 1;1(1):98-105. QA, Ferencik M, Hoffmann U. Epicardial 56. Maron MS, Rowin EJ, Olivotto I, Casey SA, and paracardial adipose tissue volume and Arretini A, Tomberli B, Garberich RF, Link MS, attenuation – Association with high-risk Chan RH, Lesser JR, Maron BJ. “Contemporary coronary plaque on computed tomographic Natural History and Management of angiography in the ROMICAT II trial. Nonobstructive Hyptertrophic Cardiomyopathy.” 49. Look AHEAD Research Group (Gordon J Am Coll Cardiol. 2016 Mar 67:1399-409. Huggins Chair of Writing Group). Prospective Associateion of GLUL rs10911021 With

157 57. Marzolla V, Armani A, Mammi C, Moss ME, Ventricular Failure Following Left Ventricular Pagliarini V, Pontecorvo L, Antelmi A, Fabbri A, Assist Device Surgery. Journal of Cardiac Failure Rosano G, Jaffe IZ and Caprio M. Essential role of 2016 Feb 22(2): 110-6. PMID: 26564619. ICAM-1 in aldosterone-induced atherosclerosis. 65. Morine KJ, Paruchuri V, Qiao X, Aronovitz International Journal of Cardiology (In Press). M, Pham DT, Huggins G, DeNofrio D, 58. McCaffery JM, Huggins GS. Response to Kiernan MS, Karas RH, Kapur NK. Endoglin Comment on The Look AHEAD Research Selectively Modulates Transient Receptor Group. Prospective Association of GLUL Potential Channel Expression in Left and

» rs10911021 With Cardiovascular Morbidity Right Heart Failure. Cardovascular Pathology » PUBLICATIONS and Mortality Among Individuals With Type 2016 Aug 25 (6):478-482. PMID: 27614169. 2 Diabetes: The Look AHEAD Study. Diabetes 66. Morine KJ, Paruchuri V, Qiao X, Mohammad 2016;65:297-302. Diabetes. 2016;65(9):e30. N, McGraw A, Yunis A, Jaffe IZ, Kapur NK. 59. Mecklai A, Subacius H, Konstam MA, Circulating Multimarker Profile of Patients Gheorghiade M, Butler J, Ambrosy AP, Katz with Symptomatic Heart Failure Supports SD. In-Hospital Diuretic Agent Use and Enhanced Fibrotic Degradation and Decreased Post-Discharge Clinical Outcomes in Patients Angiogenesis. Biomarkers 2016 Feb 21:91-7. Hospitalized for Worsening Heart Failure: Insights 67. Moss AJAJ Executive Committees of the From the EVEREST Trial. JACC Heart Fail. 2016 Multicenter Research Group (MRG); Multicenter Jul;4(7):580-8. Doi: 10.1016/j.jchf.2016.02.008. Automatic Defibrillator Implantation Trial Epub 2016 Mar 30. PMID: 27039131. (MADIT). Multicenter Cardiovascular 60. Miller VM, Jenkins GD, Biernacka JM, Heit JA, Studies and Trials: Lessons Learned From 35 Huggins GS, Hodis HN, Budoff MJ, Lobo RA, Years of Productive Collaboration J Am Coll Taylor HS, Manson JE, Black DM, Naftolin F, Cadiol. 2016 Nov 15;68(20):2232-2234. Harman SM, de Andrade M. Pharmacogenomics 68. Mukherjee JT, Beshansky JR, Ruthazer R, Alkofide of estrogens on changes in carotid artery H, Ray M, Kent D, Manning WJ, Huggins GS, intima-medial thickness and coronary arterial Selker HP. In-hospital measurement of left calcification: Kronos Early Estrogen Prevention ventricular ejection fraction and one-year Study. Physiol Genomics. 2016;48(1):33-41. outcomes in acute coronary syndromes: 61. Monaco TJ, Davila CD. (2016). Safety, efficacy, results from the IMMEDIATE Trail . Cardiovasc and clinical utility of macitentan in the treatment Ultrasound. 2016;14(1):29. PMC4973066. of pulmonary arterial hypertension. Drug 69. Osgood R, Scanlon C, Jotwani R, Rodkey design, development and therapy, 10, 1675. D, Arshanskiy M, Salem D. Shaken but 62. Morin DP, Bernard ML, Madias C, Rogers prepared: Analysis of disaster response at PA, Thihalolipavan S, Estes NA 3rd. The State an academic medical center following the of the Art: Atrial Fibrillation Espidemiology, Boston Marathon bombings. J Bus Contin Prevention, and Treatment. Mayo Clin Proc. Emer Plan. 2015-2016 Winter;9(2):177-84. 2016 Nov 5. Pii: S0025-6196(16)30538-9. 70. Page RL, Joglar JA, Cladwell MA, Calkins H, Conti 63. Morine KJ, Kapur NK. Percutaneous JB, Deal BJ, Estes NA 3rd, Field ME, Goldberger Mechanical Circulatory Support for ZD, Hammill SC, Indik JH, Lindsay BD, Olshansky Cardiogenic Shock. Current Treatment Options B, Russo AM, Shen WK, Tracy CM, Al-Khatib Cardiovascular Medicine 2016 Jan 18(1):6. SM; Evidence Review Committee Chair. ACC/ 64. Morine KJ, Kiernan MS, Pham DT, Paruchuri AHA/HRS Guideline for the Management V, DeNofrio D, Kapur NK. The Pulmonary of Adult Patients With Supraventricular Artery Pulsatility Index is Associated With Right Tachycardia: Executive Summary: A Report of

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 the American College of Cardiology/American 76. Rybicki FJ, Udelson JE, Peacock WF, Goldhaber Heart Association Task Force on Clinical SZ, Isselbacker EM, Kazerooni E, Kontos MC, Practice Guidelines and the Heart Rhythm Litt H, Woodward PK. 2015 ACR/ACC/AHA/ Society. Circulation. 2016 Apr 5;133(14). AATS/ACEP/ASNC/NASCI/SAEM/SCCT/SCMR/ 71. Page RL, Joglar JA, Caldwell MA, Calkins SCPC/SNMMI/STR/STS Appropriate Utilization H, Conti JB, Deal BJ, Estes NA 3rd, Field of Cardiovascular Imaging in Emergency ME, Goldberger ZD, Hammill SC, Indik JH, Department Patients With Chest Pain: A Joint Lindsay BD, Olshansky B, Russo AM, Shen WK, Document of the American College of Radiology Appropriateness Criteria Committee and the Tracy CM, Al-Khatib SM; Evidence Review » » PUBLICATIONS Committee Chair. ACC/AHA/HRS Guideline American College of Cardiology Appropriate Use for the Management of Adult Patients With Criteria Task Force. Jam Coll Cardiol. 2016 Feb Supraventricular Tachycardia: Executive 23;67(7):853-79. Doi:10.1016/j/jack.2015.09.011. Summary: A Report of the American College Epub 2016 Jan 22. PMID: 26809772. of Cardiology/American Heart Association 77. Salvador AM, Nevers T, Velazquez F, Aronovitz Task Force on Clinical Practice Guidelines and M, Wang B, Molina AA, Jaffe IZ, Karas RH, the Heart Rhythm Society. Circulation. J Am Blanton RM Alcaide P. Intercellular adhesion Coll Cardiol. 2016 Apr 5;67(13):1575-623. molecule 1 regulates left ventricular leukocyte 72. Pagidipati NJ, Hemal K, Coles A, Mark DB, infiltration, cardiac remodeling and function Dolor RJ, Pellikka PA, Hoffmann U, Litwin SE, in pressure overlaod induced heart failure. J Udelson J, Daubert MA, Shah SH, Martinez Am Heart Assoc. 2016 Mar 15;5(3):e003126. B, Lee KL, Douglas PS. Sex Difference in PMID:27068635; PMCID: PMC4943280. Functional Stress Test Versus CT Angiography 78. Slipczuk L, Rafique AM, Davila CD, Beigel in Symptomatic Patients With Suspected CAD: R, Pressman GS, Siegel RJ. (2016). The Role Insights From PRIMISE. J Am Coll Cardiol. of Medical Therapy in Moderate to Severe 2016 Mar 29. Pii: S0735-1097(16)32402-0. Doi: Degenerative Mitral Regurgitation. Reviews 10.1016/j.jacc.2016.03.523. PMID: 27058908. in cardiovascular medicine, 17(1-2), 28. 73. Patnaik S, Davila CD, Lu M, Alhamshari Y, 79. Spahillari A, Makamal KJ, DeFilippi C, Kizer JR, Banerji S, Pressman G. (2016). Correlates of Gottdiener JS, Djousse L, Lyles MF, Bartz TM, Serial Ultrasound Guided Volume Assessments Murthy VL, Shah RV. The association of lean and in Patients with Acute Decompensated fat mass with all-cause mortality in older adults: Heart Failure Using the Vscan System. The Cardiovascular Health Study. Nutr Metab Journal of Cardiac Failure, 22(8), S56. Cardiovasc Dis. 2016 Nov; 26(11):1039-1047. 74. Pursnani A, Celeng C, Schlett CL, Mayrhofer 80. Stillman AE, Gatsonis C, Lima JA, Black T, Zakroysky P, Lee H, Ferencik M, Felg JL, WC, Cormack J, Gareen I, Hoffmann U, Bamberg F, Wiviott SD, Truong QA, Udelson Liu T, Mavromatis K, Schnall MD, Udelson JE, Nagurney JT, Hoffmann U. Use of Coronary JE, Woodard PK. Rationale and design of Computed Tomographic Angiography the Randomized Evaluation of patients Findings to Modify Statin and Aspirin with Stable angina Comparing Utlization Prescription in Patients With Acute Chest of noninvasive Examinations (RESCUE) Pain. Am J Cardiol. 2016 Feb 1;117(3):319- trial. Am Heart J. 2016 Sep;179:19-28. 24. Doi: 10.1016/j.amjcard.2015.10.052. 81. Stone GW, Selker HR, Thiele H, Patel MR, Epub 2015 Nov 18. PMID: 26762723. Udelson JE, Ohman EM, Maehara A, Eitel I, 75. Rowin EJ, Maron MS. The Role of Cardiac Granger CB, Jenkins PL, Nichols M, Ben-Yehuda MRI in the Diagnosis and Risk Stratification O. Relationship Between Infarct Size and of Hypertrophic Cardiomyopathy. Arrhythm Outcomes Following Primary PCI: Patient-Level Electrophysiol Rev. 2016;5(3):197-202.

159 Analysis From 10 Randomized Trials. J Am 89. Udelson JE, Stevenson LW. The Future of Heart Coll Cardiol. 2016 Apr 12;67(14):1674-83. doi: Failure Diagnosis, Therapy, and Management. 10.1016/j.jacc.2016.01.069. PMID: 27056772. Circulation. 2016 Jun 21;133(25):2671-86. 82. Truitt E, Thompson R, Blazey-Martin D, NiSai 90. Vaduganathan M, Marti CN, Mentz RJ, Greene D, Salem D. Effect of the Implementation SJ, Ambrosy AP, Subacius HP, Fonarow GC, of Barcode Technology and an Electronic Chioncel O, Bazari H, Maggioni AP, Zannad Medicantion Administration Record on F, Konstam MA, Sato N, Gheorghiade M, Adverse Drug Events. Hosp Pharm. 2016 Butler J; EVEREST Trial investigators. Serum

» June;51(6):474-83. Doi: 10.1310/hpj5106-474. Osmolality and Postdischarge Outcomes » PUBLICATIONS 83. Truong QA, Schulman-Marcus J, Zakroysky After Hospitalization for Heart Failure. P, Chou ET, Nagurney JT, Fleg JL, Schoenfeld Am J Cardiol. 2016 Apr 1;117(7):1144-50. DA, Udelson JE, Hoffmann U, Woodward Doi: 10.1016/j.amjcard.2015.12.059. PK. “Coronary CT Angiography versus Epub 2016 Jan 14. PMID: 26851146. Standard Emergency Deparment Evaluation 91. Vest AR, Kennel PJ, Maldonado D, Young for Acute Chest Pain and Diabetic Patients: JB, Mountis MM, Naka Y, et al. Recovery of Is There Benefit with Early Coronary CT Serum Cholesterol Predicts Survival After Angiography? Results of the Randomized Left Ventricular Assist Device Implantation. Comparative Effectiveness ROMICAT II Circulation: Heart Failure. 2016 Sep;9(9). Trial.” J Am Heart Assoc, 2016 Mar 22;5(3). Pii: 92. Vest AR, Mistak SM, Hachamovitch R, Mountis e003137. Doi: 10.1161/JAHA.115.003137. MM, Moazami N, Young JB. Outcomes for 84. Turakhia MP, Estes NA 3rd. Stroke Patients With Diabetes After Continuous-Flow Risk Stratification in Atrial Fibrillation: Left Ventricular Assist Devce Implantation. Bridging the Evidence Gaps. J Cardiovasc J Card Fail. 2016 Oct;22(10):789-96. Electrophysiol. 2016 Mar;27(3):271-3. 93. Vest AR, Patel P, Schauer PR, Satava ME, 85. Udelson JE. Editorial Commentary: Can Cavalcante JL, Brethauer S, et al. Clinical noninvasive imaging techniques improve care and Echocardiographic Outcomes After for patients at risk for sudden cardiac death? Bariatric Surgery in Obese Patients With Left Trends Cardiovasc Med. 2016 May;26(4):361-3. Ventricular Systolic Dysfunction. Circulation: 86. Udelson JE. MY APPROACH to outpatients Heart Failure. 2016 Mar;9(3):e002260. with suspected CAD. Trends Cardiovasc 94. Vest AR, Schauer PR, Young JB. Failure and Med. 2016 Oct;26(7):658-9. Fatness: Could Surgical Management of Obesity 87. Upshaw JN, Kiernan MS, Morine KJ, Pham DT, Reduce Heart Failure Hospitalizations? J Kapur NK, DeNofrio D. Incidence, Management Am Coll Cardiol. 2016 Mar 1;67(8):904-6. and Outcomes of Suspected Continuous-Flow 95. Victorio JA, Clerici SP, Palacios R, Alonso MJ, Left Ventricular Assist Device Thrombosis. ASAIO Vassallo DV, Jaffe IZ, Rossoni LV, Davel AP. Journal 2016 Jan-Beb 61(1):33-9. PMID: 26479464. Spironolactone prevents endothelial nitric 88. Upshaw JN, Konstam MA, Klaveren D, Noubary oxide synthase uncoupling and vascular F, Huggins GS, Kent DM. Multistate Model to dysfunction induced by B-adrenergic Predict Heart Failure Hospitalizations and overstimulation: Role of perivascular adipose All-Cause Mortality in Outpatients With Heart tissue. Hypertension 2016 Sep;68(3):726-35. Failure With Reduced Ejection Fraction: Model PMID:27432866; PMCID: PMC4978608. Derivation and External Validation. Circ Heart 96. Wilkoff BL, Fauchier L, Stiles MK, Morillo CA, Fail. 2016;9(8). Pii: e003146. Doi: 10.1161/ Al-Khatib SM, Almendral J, Aguinaga L, Berger CIRCHEArtfailure.116.003146. PMID: 27514751. RD, Cuesta A, Daubert JP, Dubner S, Ellenbogen

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 KA, Estes NA 3rd, Fenelon G, Garcia FC, 103. Leo CG, Mincarone P, Sabina S, Latini G, Gasparini M, Haines DE, Healey JS, Hurtwitz Wong JB. A conceptual framework for JL, Keegan R, Kolb C, Kuck KH, Marinskis G, rationalized and standardized Universal Martinelli M, McGuire M, Molina LG, Okumura Newborn Hearing Screening (UNHS) programs. K, Proclemer A, Russo AM, Singh JP, Swerdlow Italian Journal of Pediatrics 2016;42:15. CD, Teo WS, Uribe W, Viskin S, Wang CC, Zhang 104. Lok AS, McMahon BJ, Brown RS, Jr., Wong S. 2015 HRS/EHRA/APHRS/SOLACE expert JB, Ahmed AT, Farah W, Almasri J, Alahdab consensus statement on optimal implantable F, Benkhadra K, Mouchli MA, Singh S, cardioverter-defibrillator programming and Mohamed EA, Abu Dabrh AM, Prokop LJ, » » PUBLICATIONS testing. J Arrhytm. 2016 Feb;32(1):1-28. Wang Z, Murad MH, Mohammed K. Antiviral Division of Clinical Decision Making therapy for chronic hepatitis B viral infection in adults: A systematic review and meta- 97. Alseiari M, Meyer KB, Wong JB. Evidence analysis. Hepatology 2016;63:284-306. Underlying KDIGO (Kidney Disease: Improving 105. Norbash A, Yucel K, Yuh W, Doros G, Ajam Global Outcomes) Guideline Recommendations: A, Lang E, Pauker S, Mayr N. Effect of team A Systematic Review. American Journal training on improving MRI study completion of Kidney Diseases 2016;67:417-422. rates and no-show rates. Journal of Magnetic 98. Brown RS, Jr., McMahon BJ, Lok AS, Wong Resonance Imaging 2016;44:1040-1047. JB, Ahmed AT, Mouchli MA, Wang Z, Prokop 106. Paul S, Saxena A, Terrin N, Viveiros K, Balk EM, LJ, Murad MH, Mohammed K. Antiviral Wong JB. Hepatitis B Virus Reactivation and therapy in chronic hepatitis B viral infection Prophylaxis During Solid Tumor Chemotherapy: during pregnancy: A systematic review and A Systematic Review and Meta-analysis. meta-analysis. Hepatology 2016;63:319-333. Annals of Internal Medicine 2016;164:30-40. 99. Dahabreh IJ, Trikalinos TA, Balk EM, Wong 107. Schroy PC, 3rd, Duhovic E, Chen CA, JB. Recommendations for the Conduct and Heeren TC, Lopez W, Apodaca DL, Wong Reporting of Modeling and Simulation Studies JB. Risk Stratification and Shared Decision in Health Technology Assessment. Annals Making for Colorectal Cancer Screening: of Internal Medicine 2016;165:575-581. A Randomized Controlled Trial. Medical 100. de Ferranti SD, Rodday AM, Mendelson Decision Making 2016;36:526-535. MM, Wong JB, Leslie LK, Sheldrick RC. 108. Wang C, Schmid CH, Iversen MD, Harvey WF, Prevalence of Familial Hypercholesterolemia Fielding RA, Driban JB, Price LL, Wong JB, in the 1999 to 2012 United States National Reid KF, Rones R, McAlindon T. Comparative Health and Nutrition Examination Surveys Effectiveness of Tai Chi Versus Physical Therapy (NHANES). Circulation 2016;133:1067-1072. for Knee Osteoarthritis: A Randomized Trial. 101. Jonas MM, Lok AS, McMahon BJ, Brown RS, Jr., Annals of Internal Medicine 2016;165:77-86. Wong JB, Ahmed AT, Farah W, Mouchli MA, Singh S, Prokop LJ, Murad MH, Mohammed K. Antiviral therapy in management of chronic hepatitis B viral infection in children: A systematic review and meta-analysis. Hepatology 2016;63:307-318. 102. Kassirer JP. Editorial independence: painful lessons. Lancet 2016;387:1358-1359.

161 Division of Endocrinology, Diabetes 116. Bowman TA, O’Keefe, K, D’Acquila, T, Yan QW, and Metabolism Griffin JD, Killion EA, Salter DM, Mashek DG, Buhman K, Greenberg AS. Acyl CoA synthetase 109. Alzaman N, Dawson-Hughes B, Nelson J, 5 ablation in mice increases energy expenditure D’Alessio, D, Pittas AG. Vitamin D status of and insulin sensitivity and delays fat absorption. black and white Americans and changes Molecular Metabolism, 2016; 5(3): 210-20 in vitamin D metabolites after varied doses of vitamin D supplementation. 117. Ceglia L, Toni R. Vitamin D and muscle Am J Clin Nutrit 2016; 104(1): 205-14 performance in athlets In: Feldman D, Pike

» W, Bouillon R, Giovannucci E, Goltzman » PUBLICATIONS 110. Asztalos IB, Gleason JA, Sever S, Gedik R, Asztalos D, Hewison M (Eds), Vitamin D, Fourth BF, Horvath KV, Dansinger, ML, Lamon-Fava Edition, Elsevier, San Diego, 2016 S. Schaefer EJ. Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular 118. Ceglia L & Toni R. Vitamina D e muscolo striato. disease risk factors: a randomized clinical L’Endocrinologo, 2016 Jun;17(3):136-142. [Italian] trial. Metabolism 2016; 65:1636-45 119. Chung M, Wang DD, Archer A, Higgins J, Kim 111. Binkley N1, Dawson-Hughes B, Durazo- S, Laughlin M, Qi L, Raatz SK, Siegel RD, Slavin Arvizu R, Thamm M, Tian L, Merkel JM, JL, Spahn J, Steffen D, Warshaw H, Tang A, Jones JC, Carter GD, Sempos CT. Vitamin Future Research Needs on Sugars and Health D Measurement Standardization: The Way Outcomes, BMC Nutrition, 2:66, 2016. Out of the Chaos. In: Proceedings of the 120. Darr R, Nambuba J, Del Rivero J, Janssen I, 19th Vitamin D Workshop. Demay M and Merino M, Todorovic M, Balint B, Jochmanova Christakos S (eds). J Steroid Biochem Mol I, Prchal JT, Lechan RM, Tischler AS, Popovic Biol. 2016 Dec 12. pii: S0960-0760(16)30341- V, Miljic D, Adams KT, Prall FR, Ling A, 7. doi: 10.1016/j.jsbmb.2016.12.002. Golomb MR, Ferguson M, Nilubol N, Chen 112. Bischoff-Ferrari HA and Dawson-Hughes B. CC, Chew E, Taieb D, Stratakis CA, Fojo Vitamin D and Fall Prevention – An Update. In: T, Yang C, Kebebew E, Zhuang Z, Pacak Proceedings of the 9th International Symposium K, Novel insights into the polycythemia- on Nutritional Aspects of Osteoporosis, Montreal, paraganglioma-somatostatinoma syndrome, Canada. Weaver C, Daly R, and Bischoff-Ferrari H Endocrine-Related Cancer 23: 899-908, 2016. (eds). 2016: DOI:10.1007/978-3-319-32417-3_19. 121. Dawson-Hughes B and Bischoff-Ferrari H. 113. Bischoff-Ferrari HA, Dawson-Hughes B, Orav Considerations concerning the definition EJ, Stähelin HB, Meyer O, Theiler R, Dick W, of sarcopenia: response to comments. Willett WC, Egli A. Effect of monthly high Osteoporos Int 2016; 27:3147-3148 dose vitamin D on functional decline and 122. Dawson-Hughes B, Bischoff-Ferrari H. falls: a double-blind randomized controlled Considerations concerning the definition of trial. JAMA Int Med 2016; 176:175-183. sarcopenia. Osteoporos Int 2016;27:3139-3144. 114. Bischoff-Ferrari HA, Orav JO, Dawson-Hughes 123. Dawson-Hughes B, Mitchell PJ, Cooper C, Gordon B. Estimating Vitamin D Status and the Choice of CM, and Rizzoli R. Response to Fenton and Supplementation Dose-Reply. JAMA Intern Med Fenton: evidence does not support the alkaline 2016; DOI:10.1001/jamainternmed.2016;1629. diet. Osteoporosis Int 2016:27:2389-2390 115. Bocco BM, Werneck-de-Castro JP, Oliveira KC, et 124. Dawson-Hughes B. Acid-Base Balance of the al. Type 2 Deiodinase Disruption in Astrocytes Diet – Implications for Bone. In: Proceedings of Results in Anxiety-Depressive-Like Behavior in the 9th International Symposium on Nutritional Male Mice. Endocrinology 2016;157:3682-95.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Aspects of Osteoporosis, Montreal, Canada. 131. Liberatore A and Lechan RM, Bilateral Weaver C, Daly R, and Bischoff-Ferrari (eds). carotid-cavernous fistulas: An uncommon 2016: DOI:10.1007/978-3-319-32417-3_9. cause of pituitary enlargement and 125. Dawson-Hughes B and Bischoff-Ferrari H. hypopituitarism, Case Reports in Endocrinology Defining sarcopenia. In: Proceedings of the Vol 2016; Article ID 6364203, 2016 9th International Symposium on Nutritional 132. Martin CK, Bhapkar M, Pittas AG, Pieper CF, Aspects of Osteoporosis, Montreal, Canada. Das SK, Williamson DA, Scott T, Redman LM, Weaver C, Daly R, and Bischoff-Ferrari (eds). Stein R, Gilhooly CH, Steward T, Robinson L and

2016: DOI:10.1007/978-3-319-32417-3_2. Roberts SB for the Comprehensive Assessment of » » PUBLICATIONS 126. Farkas I, Vastagh C, Farkas E, et al. Glucagon- Long-term Effects of Reducing Intake of Energy Like Peptide-1 Excites Firing and Increases (CALERIE) Phase 2 Study Group. Association of GABAergic Miniature Postsynaptic Currents calorie restriction with mood, quality of life, sleep (mPSCs) in Gonadotropin-Releasing Hormone and sexual function in healthy non-obese adults. (GnRH) Neurons of the Male Mice via Activation JAMA Internal Medicine 2016; 176(6):743-52 of Nitric Oxide (NO) and Suppression of 133. Mohacsik P, Fuzesi T, Doleschall M, et al. Endocannabinoid Signaling Pathways. Frontiers Increased Thyroid Hormone Activation in cellular neuroscience 2016;10:214. Accompanies the Formation of Thyroid 127. Fontana L, Villareal DT, Das SK, Smith SR, Hormone-Dependent Negative Feedback Meydani SN, Pittas AG, Klein S, Bhapkar in Developing Chicken Hypothalamus. M, Rochon J, Ravussin E, Holloszy JO and Endocrinology 2016;157:1211-21. the CALERIE Study Group. Effects of 2-year 134. Molnar CS, Sarvari M, Vastagh C, et al. Altered calorie restriction on circulating levels of Gene Expression Profiles of the Hypothalamic IGF-1, IGF-binding proteins and cortisol in Arcuate Nucleus of Male Mice Suggest Profound non-obese men and women: a randomized Developmental Changes in Peptidergic Signaling. clinical trial. Aging Cell 2016;15(1):22-7. Neuroendocrinology 2016;103:369-82. 128. Harshman SG, Fu X, Karl JP, Barger K, 135. Noel SE, Arevalo S, Smith CE, Chao-Qiang L, Lamon-Fava S, Kuliopulos A, Greenberg Dawson-Hughes B, Ordovas JM, Tucker KL. AS, Smith D, Shen X, Booth SL. Tissue Genetic admixture and body composition in concentrations of vitamin K and expression Puerto Rican adults from the Boston Puerto of key enzymes of vitamin K metabolism are Rican Osteoporosis Study. J Bone Miner Res influence by sex and diet but not housing in 2016: DOI: 10.1007/s00774-016-0775-6. C57BL6J mice. J Nutr. 2016;146 (2): 1521-7. 136. Rubin BS, Paranjpe M, DaFonte T, Schaeberle 129. Javeed I, Chandhok N, Lechan RM, Tischler AS, C. Soto AM, Obin M, Greenberg AS. Perinatal Siegel R, Kung J, The Art of Neuroendocrinology: BPA exposure alters body weight and A Case-Based Approach to Medical Decision composition in a dose specific and sex specific Making, Challenges in the Management of manner. The addition of peripubertal exposure Ectopic Cushing’s Syndrome, L. Blevins, exacerbates adverse effects in female mice. Ed, Nova Science Pub, Inc., 2016. Reprod Toxicol 2016; S0890-6238(16)30307-0 130. Lechan RM, Toni R. Functional anatomy of 137. Shahraz S, Pittas AG, Lundquist CM, Danaei G the hypothalamus and pituitary. In: Grossman and Kent D. Do Patient Characteristics Impact A, Karbonitis M (Eds), Pituitary disease and Decisions by Clinicians on Hemoglobin A1c neuroendocrinology. Endotext.org, 2016 Targets? Diabetes Care 2016; 39(9):e145-6.

163 138. Shea MK, Gilhooly CH, Dawson-Hughes his masks: and anatomical-clinical collection B. Food groups associated with measured of the late 19th century at the Universities of net acid excretion in community-swelling Parma and Turin. Skyra, Milan, 2016; pp.21-27. older adults. European J Clinical Nutr 145. Toni R & Ceglia L. La malattia ossea di Paget. 2016; DOI: 10.1038/ejcn.2016.195 L’Endocrinologo, 2016; Sept; 17(6) [Italian] 139. Singh U, Kumar S, Shelkar GP, Yadhav M, Kokare 146. Weaver CM, Dawson-Hughes B, Lappe JM, DM, Goswami C, Lechan RM, Singru PS, TRPV3 Wallace TC. Response to Bolland letter Re: in the ventral tegmental area of rat: role in Errors in the NOF meta-analysis of calcium

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PUBLICATIONS and vitamin D supplements. Osteoporosis pathway, Neuropharmacology 2016; 110: 198-210. Int 2016; DOI 10.1007/s00198-016-3525-7. 140. Singh O, Kumar S, Singh U, Kumar V, Lechan 147. Weaver CM, Alexander DD, Boushey CJ, RM, Singru PS, Cocaine-and amphetamine Dawson-Hughes B, Lappe JM, LeBoff MS, regulated transcript peptide (CART) in the Looker AC, Wallace TC. Calcium plus brain of zebra finch, Taeniopygia guttata: Vitamin D Supplementation and Risk of organization, interaction with neuropeptide Fractures: An Updated Meta-Analysis from Y, and response to changes in energy status, the National Osteoporosis Foundation. J Compr Neurol 2016; 524: 3014-3041. Osteoporosis Int 2016; 27: 367-376. 141. Stice CP, Hussain S, Liu C, Ausman LM, 148. Weaver CM, Dawson-Hughes B, Lappe JM, Xang WD, Greenberg AS. Deletion of Wallace TC. Erratum and Additional Analyses tumor progression locus 2 attenuates Re: the NOF Meta-analysis of Calcium and alcohol-induced hepatic inflammation. Vitamin D Supplements. Osteoporosis Int Hepatobiliary Surg Nutr. 2016; 5(1): 29-37. 2016: DOI:10.1007/s00198-016-3699-z. 142. Toni R, E. Bassi, F. Barbaro, N. Zini, A. Zamparelli, 149. Wright NC, Saag KG, Dawson-Hughes B, M. Alfieri, D. Dallatana, S. Mosca,C. Della Casa, Khosla S, Siris, ES. The Impact of the New C. Gnocchi, G. Lippi, G. Spaletta, E. Bassoli, NBHA Diagnostic Criteria on the Prevalence of L. Denti, A. Gatto, F. Ricci, P.L. Tazzari, A. Osteoporosis in the United States. Osteoporosis Parrilli, M. Fini, M. Sandri, S. Sprio, A. Tampieri. Int 2016: DOI 10.1007/s00198-016-3865-3. Bioartificial endocrine glands: at the cutting edge of translational research in endocrinology. 150. Yavari A, Stocker CJ, Ghaffari S, et al. Chronic In: Sprio S. Tampieri A (Eds). Bio-inspired Activation of gamma2 AMPK Induces regenerative medicine: material, processes, Obesity and Reduces beta Cell Function. and clinical applications. Pan Standford Cell metabolism 2016;23:821-36. Publishing, Singapore, 2016, pp. 357-387 151. Zseli G, Vida B, Martinez A, Lechan RM, Khan 143. Toni R, E. Bassi, S. Montaldo, A. Porro. Lorenzo AM, Fekete C. Elucidation of the anatomy of a Tenchini and his masks. An anatomical satiety network: Focus on connectivity of the clinical collection of the late 19th century at parabrachial nucleus in the adult rat. The Journal the Universities of Parma and Turin Skyra. of comparative neurology 2016;524:2803-27. Milan, 2016, pp. 1- 230, ISBN 978857230597. Division of Gastroenterology 144. Toni R, E. Bassi, M. Alfieri F. Barbaro, D. Dallatana, 152. Guelrud M., Jouhourian C, Bonis PA, Abdominal N. Zini, S. Mosca C. Della Casa, F.Simonacci, E. compression during endoscopy (the Bolster Raposio, A. Porro. Lorenzo Tenchini, clinical technique) demonstrates hidden Schatzki anatomist in Parma and forerunner of the rings (with videos). Gastrointest Endosc simulated face transplant In: R. Toni, E. Bassi, S. 2016;83:1024Guelrud M, Fitzgerald E, Chen L, Montaldo, A. Porro (Eds). Lorenzo Tenchini and

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Allison H, Zuo T, Suarez Y, Yoo J., Appendiceal 159. Mason JB, Romano FR, Heinze CR, Barber Adenocarcinoma Presenting as a Rectal Polyp. LG, Freeman LM. Association between body Case Rep Gastroenterol 2016;10:38-43 condition score and cancer prognosis in 153. Leung, J., Dellon ES, Collins MH, Bonis PA, dogs with lymphoma and osteosarcoma. Capocelli KE, Dohil R, Falk GW, Furuta GT, J Vet Intern Med 2016; 30: 1179-86. Menard-Katcher C, Gupta SK, Hirano I, 160. Mason JB Liu W, Crott J, Lyu L, Pfalzer A, Li J, Hiremath GS, Kagalwalla AF, Wershil BK, Choi SW, Yang Y, , Liu Z. Diet- and genetically- Liacouras CA, Muir AB, Mukkada VA, Putnam induced obesity produces alterations in the

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PUBLICATIONS LJ, Kahl BS, Evens AM, Hamlin PA, Lazarus HM, Petersdorf E, Bredeson C.Allogeneic 231. Jiang Z, Butler-Bowen H, Rodriguez T, Garcon Hematopoietic Cell Transplantation as Curative MC, Smith MH, Relias V, Saif MW. Role of Therapy for Patients with Non-Hodgkin methylphenidate in the treatment of fatigue in Lymphoma: Increasingly Successful Application advanced pancreatic cancer population. Ann to Older Patients. Biol Blood Marrow Transplant. Gastroenterol. 2016 Oct-Dec;29(4):536-543. 2016; 22(9):1543-51. PMID: 27131863 232. Joshi R, Goihberg E, Ren W, Pilichowska M, 225. Ferrara F, Staquicini DI, Driessen WH, D’Angelo Mathew P. Proteolytic fragments of fibronectin S, Dobroff AS, Barry M, Lomo LC, Staquicini FI, function as matrikines driving the chemotactic Cardo-Vila M, Soghomonyan S, Alauddin MM, affinity of prostate cancer cells to human bone Flores LG 2nd, Arap MA, Lauer RC, Mathew P, marrow mesenchymal stromal cells via the a5b1 Efstathiou E, Aparicio AM, Troncoso P, Navone integrin. Cell Adhesion and Migration 2016. Aug NM, Logothetis CJ, Marchio S, Gelovani JG, 11:1-11.DOI:10:1080/19336918.2016.1212139 Sidman RL, Pasqualini R, Arap W. Targeted 233. Kritharis A, Pilichowska M, Evens AM. molecular-genetic imaging and ligand-directed How I manage patients with grey zone therapy in aggressive variant prostate cancer. Proc lymphoma. British Journal of Haematology. Natl Acad Sci USA 2016 Oct 24. Pii:201615400 2016; 174:345-50. PMID: 27301470 226. Fotopoulos G, Syrigos K, Saif MW. Genetic 234. Landau H, Smith M, Landry C, Chou JF, Devlin factors affecting patient responses SM, Hassoun H, Bello C, Giralt S, Comenzo RL. to pancreatic cancer treatment. Ann Long-term event-free and overall survival after Gastroenterol. 2016 Oct-Dec;29(4):466-476 risk-adapted melphalan and SCT for systemic 227. Gertz MA, Landau H, Comenzo RL, Seldin light chain amyloidosis. Leukemia. 2016 Aug 18. D, Weiss B, Zonder J, Merlini G, Schönland doi: 10.1038/leu.2016.229. [Epub ahead of print] S, Walling J, Kinney GG, Koller M, Schenk 235. Li J, Kluger H, Devine L, Lee JJ, Kelly WK, Rink L, DB, Guthrie SD, Liedtke M. First-in-Human Saif MW. Phase I study of safety and tolerability Phase I/II Study of NEOD001 in Patients With of sunitinib in combination with sirolimus in Light Chain Amyloidosis and Persistent Organ patients with refractory solid malignancies Dysfunction. J Clin Oncol 2016;34:1097-103 and determination of VEGF (VEGF-A) and 228. Goodman MD, McPartland S, Detelich soluble VEGF-R2 (sVEGFR2) in plasma. Cancer D, Saif MW . Chemotherapy for Chemother Pharmacol. 2016 Jun;77(6):1193- intraperitoneal use: a review of hyperthermic 200. doi: 10.1007/s00280-016-3033-7 intraperitoneal chemotherapy and early 236. Linendoll N, Saunders T, Burns R, Nyce JD, post-operative intraperitoneal chemotherapy. Wendell KB, Evens AM, Parsons SK. Health- J Gastrointest Oncol. 2016 Feb;7(1):45-57. related quality of life in Hodgkin lymphoma: doi: 10.3978/j.issn.2078-6891.2015.111 a systematic review. Health Qual Life Outcomes. 2016; 14(1):114. PMID: 27473596

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 237. Lishner M, Avivi I, Apperley JF, Dierickx D, Sezer O, Terpos E, Turesson I, Usmani S, Weiss Evens AM, Fumagalli M, Nulman I, Oduncu BM, Palumbo A; International Myeloma Working FS, Peccatori FA, Robinson S, Van Calsteren K, Group. Second primary malignancies in multiple Vandenbroucke T, Van den Heuvel F, Amant myeloma: an overview and IMWG consensus. F. Hematologic Malignancies in Pregnancy: Ann Oncol. 2016 Nov 17. pii: mdw606. doi: Management Guidelines From an International 10.1093/annonc/mdw606. [Epub ahead of print] Consensus Meeting. Journal of Clinical Oncology. 243. Niazi A, Saif MW. Colon Mass as a Secondary 2016 Feb 10;34(5):501-8. PMID: 26628463 Metastasis from Cholangiocarcinoma: A

238. Ma WW, Saif MW, El-Rayes BF, Fakih MG, Diagnostic and Therapeutic Dilemma. Cureus. » » PUBLICATIONS Cartwright TH, Posey JA, King TR, von 2016 Jul 22;8(7):e707. doi: 10.7759/cureus.707 Borstel RW, Bamat MK. Emergency use of 244. Nikolaou V, Syrigos K, Saif MW. Incidence uridine triacetate for the prevention and and implications of chemotherapy related treatment of life-threatening 5-fluorouracil hand-foot syndrome. Expert Opin Drug and capecitabine toxicity. Cancer. 2016 Saf. 2016 Dec;15(12):1625-1633. Sep 13. doi: 10.1002/cncr.30321 245. Papaxoinis G, Syrigos K, Saif MW . Novel 239. Ma X, Zhou P, Wong SW, Warner M, Chaulagain therapeutic approaches and mechanisms in C, Comenzo RL. siRNA targeting the κ light neuroendocrine tumors: the role of targeted chain constant region: preclinical testing of an agents. Discov Med. 2016 May;21(117):391-402 approach to nonfibrillar and fibrillar light chain deposition diseases. Gene Ther. 2016 Jul 7. doi: 246. Papaxoinis G, Syrigos K, Saif MW.New 10.1038/gt.2016.50. [Epub ahead of print] concepts in the treatment strategy of neuroendocrine tumors: the role of biotherapy. 240. Mato AR, Nabhan C, Barr PM, Ujjani CS, Hill BT, Discov Med. 2016 May;21(117):381-9 Lamanna N, Skarbnik AP, Howlett C, Pu JJ, Sehgal AR, Strelec LE, Vandegrift A, Fitzpatrick DM, Zent 247. Parsons S, Fineberg I, Lin M, Singer M, CS, Feldman T, Goy A, Claxton DF, Bachow SH, Tang M, Erban J. Special Series: NCI-ASCO Kaur G, Svoboda J, Nasta SD, Porter D, Landsburg Teams - Original Contribution Promoting DJ, Schuster SJ, Cheson BD, Kiselev P, Evens AM. High-Quality Cancer Care and Equity Outcomes of CLL patients treated with sequential Through Disciplinary Diversity in Team kinase inhibitor therapy: a real world experience. Composition Journal of Oncology Practice. Blood. 2016; 28(18):2199-2205. PMID: 27601462 JOP DOI 10.1200/JOP.2016.013920 241. Merlini G, Lousada I, Ando Y, Dispenzieri A, 248. Passero FC Jr, Grapsa D, Syrigos KN, Saif Gertz MA, Grogan M, Maurer MS, Sanchorawala MW. The safety and efficacy of Onivyde V, Wechalekar A, Palladini G, Comenzo RL. (irinotecan liposome injection) for the Rationale, application, and clinical qualification treatment of metastatic pancreatic cancer for NT-proBNP as a surrogate end point in following gemcitabine-based therapy. Expert pivotal clinical trials in patients with AL Rev Anticancer Ther. 2016 Jul;16(7):697-703. amyloidosis. Leukemia. 2016 Jul 15. doi: doi: 10.1080/14737140.2016.1192471 10.1038/leu.2016.191. [Epub ahead of print] 249. Paulus JK, Switkowski KM, Allison GM, Connors 242. Musto P, Anderson KC, Attal M, Richardson PG, M, Buchsbaum RJ, Freund KM, and Blazey-Martin Badros A, Hou J, Comenzo R, Du J, Durie BG, D. Where is the leak in the pipeline? Investigating San Miguel J, Einsele H, Chen WM, Garderet L, gender differences in academic promotion at an Pietrantuono G, Hillengass J, Kyle RA, Moreau P, academic medical center. Perspectives in Medical Lahuerta JJ, Landgren O, Ludwig H, Larocca A, Education, 2016. DOI 10.1007/s40037-016-0263-7 Mahindra A, Cavo M, Mazumder A, McCarthy PL, Nouel A, Rajkumar SV, Reiman A, Serra ER,

171 250. Press OW, Li H, Schöder H, Straus DJ, Moskowitz 256. Russo S, Saif MW. Neoadjuvant therapy for CH, LeBlanc M, Rimsza LM, Bartlett NL,Evens pancreatic cancer: an ongoing debate. Therap AM, Mittra ES, LaCasce AS, Sweetenham JW, Adv Gastroenterol. 2016 Jul;9(4):429-36. doi: Barr PM, Fanale MA, Knopp MV, Noy A, Hsi ED, 10.1177/1756283X16646524. No abstract available Cook JR, Lechowicz MJ, Gascoyne RD, Leonard 257. Saif MW, Diasio RB. Benefit of uridine triacetate JP, Kahl BS, Cheson BD, Fisher RI, Friedberg JW. (Vistogard) in rescuing severe 5-fluorouracil US Intergroup Trial of Response-Adapted Therapy toxicity in patients with dihydropyrimidine for Stage III to IV Hodgkin Lymphoma Using Early dehydrogenase (DPYD) deficiency. Cancer Interim Fluorodeoxyglucose-Positron Emission » Chemother Pharmacol. 2016 Jul;78(1):151- » PUBLICATIONS Tomography Imaging: Southwest Oncology 6. doi: 10.1007/s00280-016-3063-1 Group S0816. Journal of Clinical Oncology. 2016 Jun 10;34(17):2020-7. PMID: 27069074 258. Saif MW, Smith MH, Maloney A, Diasio RB. Imatinib-induced hyperbilirubinemia with 251. Ravi D, Beheshti A, Abermil N, Passero F, Sharma UGT1A1 (*28) promoter polymorphism: first J, Coyle M, Kritharis A, Kandela I, Hlatky L, case series in patients with gastrointestinal Sitkovsky MV, Mazar A, Gartenhaus RB, Evens stromal tumor. Ann Gastroenterol. AM. Proteasomal Inhibition by Ixazomib Induces 2016 Oct-Dec;29(4):551-556 CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma. Cancer Research. 259. Saif MW. Lanreotide for the treatment of 2016; 76 (11):3319-31. PMID: 26988986 gastroenteropancreatic neuroendocrine tumors. Expert Opin Pharmacother. 2016;17(3):443-56. 252. Ren W, Joshi R, Mathew P. Synthetic lethality doi: 10.1517/14656566.2016.1127914 in PTEN-mutant prostate cancer is induced by combinatorial P13K/AKT and BCL-X1 260. Saif MW, Vethody C. Poorly Differentiated inhibition. Molecular Cancer Research Neuroendocrine Tumor of the Esophagus with 2016 14:1176-1181. Epub 2016 Sep2 Hypertrophic Osteoarthropathy and Brain Metastasis: A Success Story. Cureus. 2016 253. Rosenberg AS, Klein AK, Ruthazer R, Evens Jun 19;8(6):e646. doi: 10.7759/cureus.646 AM. Hodgkin lymphoma post-transplant lymphoproliferative disorder: A comparative 261. Saif MW, Knost JA, Chiorean EG, Kambhampati analysis of clinical characteristics, prognosis, SR, Yu D, Pytowski B, Qin A, Kauh JS, O'Neil and survival. American Journal of Hematology. BH . Phase 1 study of the anti-vascular 2016; 91(6):560-5. PMID:26928381 endothelial growth factor receptor 3 monoclonal antibody LY3022856/IMC-3C5 in patients 254. Rosenberg AS, Ruthazer R, Paulus JK, with advanced and refractory solid tumors Kent DM, Evens AM, Klein AK. Survival and advanced colorectal cancer. Cancer Analyses and Prognosis of Plasma-Cell Chemother Pharmacol. 2016 Oct;78(4):815- Myeloma and Plasmacytoma-Like 24. doi: 10.1007/s00280-016-3134-3 Posttransplantation Lymphoproliferative Disorders. Clin Lymphoma Myeloma Leuk. 262. Sanchorawala V, Shelton AC, Lo S, Varga 2016; 16(12):684-692.e3. PMID: 27771291 C, Sloan JM, Seldin DC. Pomalidomide and dexamethasone in the treatment of 255. Saif MW, Wasif K, Butler-Bowen H, Miller AL amyloidosis: results of a phase 1 and 2 K, Diasio RB . Acquired factor VII deficiency trial.Blood. 2016 Aug 25;128(8):1059-62. following FOLFOX in a patient with colorectal doi: 10.1182/blood-2016-04-710822 cancer who was also DPD deficient. Therap Adv Gastroenterol. 2016 Jan;9(1):121-7. doi: 263. Shah GL, Winn A, Lin PJ, Klein A, Sprague KA, 10.1177/1756283X15604115. No abstract available Smith H, Cohen JT, Miller KB, Comenzo RL, Parsons SK. Cost Implications of Comorbidity in Autologous Stem Cell Transplant in

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Elderly Patients with Multiple Myeloma using Follow-up to the National Faculty Survey SEER-Medicare. Bone Marrow Research, Cohort. Acad Med. 2016 Aug;91(8):1068-1073. 2016. 2016:3645623.PMID: 27830092 PMID: 27276007; PMCID: PMC4965349. 264. Wasif K, Wasif N, Saif MW. Imatinib- 272. Gandhi TK, Abookire SA, Kachalia A, Sands induced Ototoxicity in a Patient with K, Mort E, Bommarito G, Gagne J, Sato L, Gastrointestinal Stromal Tumor (GIST). Weingart SN. Design and implementation Cureus. 2016 Oct 26;8(10):e848 of the Harvard fellowship in patient safety 265. Weiss BM, Wong SW, Comenzo RL. and quality. Am J Med Qual 2016;31:22-6. » »

Beyond the plasma cell: emerging 273. Huang KT, Lu TJ, Alizadeh F, Mostaghimi PUBLICATIONS therapies for immunoglobulin light chain A. Homebound Patients’ Perspectives amyloidosis. Blood 2016;127:2275-80 on Technology and Telemedicine: A 266. Xing W, Dresser K, Zhang R, Evens AM, Yu Qualitative Analysis. Home Health Care H, Woda BA, Chen BJ. PD-L1 expression Serv Q. 2016 Nov; [Epub ahead of print]. in EBV-negative diffuse large B-cell 274. Jean-Pierre P, Cheng Y, Wells K, Freund K, lymphoma: clinicopathologic features and Snyder F, Fiscella K, Holden A, Paskett E, Dudley prognostic implications. Oncotarget. 2016; D, Simmons MA, Valverde P. Satisfaction With 7(37):59976-59986. PMID: 27527850 Cancer Care Among Underserved Racial-Ethnic 267. Xu K, Tian X, Oh S, Movassaghi M, Naber SP, Minorities And Lower Income Patients Receiving Kuperwasser C, Buchsbaum RJ. The fibroblast Patient Navigation. Cancer. 2016 Apr;122(7):1060- Tiam-Osteopontin pathway modulates 7. PMID: 26849163; PMCID: PMC4803516. breast cancer invasion and metastasis. Breast 275. Joseph NP, Bernstein J, Pelton S, Belizaire Cancer Research.2016, 18:14; doi: 10.1186/ M, Goff G, Horanieh N, Freund KM. Brief s13058-016-0674-8 Division of Internal Client-Centered Motivational and Behavioral Medicine and Adult Primary Care Intervention to Promote HPV Vaccination in a Hard-to-Reach Population: A Pilot Division of Internal Medicine and Randomized Controlled Trial. Clin Pediatr Adult Primary Care (Phila). 2016 Aug;55(9):851-9. PMID: 26968631. 268. Abookire SA, Gandhi TK, Kachalia A, Sands K, 276. Kent DM, Dahabreh IJ, Ruthazer R, Furlan Mort E, Bommarito G, Gagne J, Sato L, Weingart AJ, Reisman M, Carroll JD, Saver JL, Smalling SN. Creating a fellowship curriculum in patient RW, Jüni P, Mattle HP, Meier B, Thaler DE. safety and quality. Am J Med Qual 2016;31:27-30. Device Closure of Patent Foramen Ovale 269. Carbo AR, Goodman EB, Totte C, Clardy P, after Stroke: Pooled Analysis of Completed Feinbloom D, Kim H, Kriegel G, Dierks M, Randomized Trials. Journal of American Weingart SN, Sands K, Aronson M, Tess A. College of Cardiology. 2016; 67(8):907-17. Resident case review at the departmental level: A 277. Kent DM, Nelson J, Dahabreh IJ, Rothwell PM, win-win scenario. Am J Med; 2016;129:448-52. Altman DG, Hayward RA. Risk and treatment 270. Freund KM. Implementation of evidence-based effect heterogeneity: re-analysis of individual patient navigation programs. Acta Oncol. 2016 participant data from 32 large clinical trials. Dec 29:1-5. doi: 10.1080/0284186X.2016.1266078. International Journal of Epidemiology. 2016 [Epub ahead of print]. PMID: 28033027. Jul 3. pii: dyw118. [Epub ahead of print] 271. Freund KM, Raj A, Kaplan SE, Terrin N, Breeze JL, Urech TH, Carr PL. Inequities in Academic Compensation by Gender: A

173 278. Ko NY, Snyder FR, Raich PC, Paskett ED, Dudley 285. Paulus JK, Lai LY, Lundquist C, Daneshmand D, Lee JH, Levine P, Freund KM. Racial and Ethnic A, Buettner H, Lutz JS, Raman G, Wessler BS, Differences in Patient Navigation: Results from Kent DM. Field Synopsis of the Role of Sex the Patient Navigation Research Program. Cancer in Stroke Prediction Models. Journal of the 2016 Sep 1;122(17):2715-22. PMID: 27227342. American Heart Association. 2016 May 5;5(5). 279. Lavelle TA, Kent DM, Lundquist C, Thorat T, 286. Paulus JK, Switkowski KM, Allison GM, Cohen JT, Wong JB, Olchanski N, Neumann Connors M, Buchsbaum RJ, Freund KM, PJ. How often do cost-effectiveness analyses Blazey-Martin D. Where is the leak in the

» incorporate patient-level heterogeneity? A pipeline? Investigating gender differences in » PUBLICATIONS review of the literature. Abstract presentation academic promotion at an academic medical at the 2016 conference of the Society for centre. Perspect Med Educ. 2016 Apr;5(2):125-8. Medical Decision Making (SMDM). October PMID: 27001528; PMCID: PMC4839010. 23-26, 2016. Vancouver, BC, Canada. 287. Paulus JK, Wessler BS, Lundquist C, Lai L, 280. Lipitz-Snyderman A, Weingart S, Anderson B, Raman G, Lutz JS, Kent DM. A field synopsis of Epstein AS, Killen A, Classen D, Sima CS, Fortier gender effects in clinical prediction models for E, Atoria CL, Pfister DG. Detection of potentially cardiovascular disease. Poster Presentation, avoidable harm in oncology from patient Quality of Care and Outcomes Research (QCOR) medical records. J Oncol Pract 2016;12:178-9. Scientific Sessions, Phoenix, AZ, February 2016. 281. Messé SR, Gronseth G, Kent DM, Kizer JR, 288. Paulus JK, Wessler BS, Lundquist C, Lai LL, Homma S, Rosterman L, Kasner SE. Practice Raman G, Lutz JS, Kent DM. Field Synopsis of Sex advisory: Recurrent stroke with patent foramen in Clinical Prediction Models for Cardiovascular ovale (update of practice parameter): Report Disease. Circulation: Cardiovascular of the Guideline Development, Dissemination, Quality and Outcomes. 2016;9:S8-S15. and Implementation Subcommittee of 289. Raj A, Carr PL, Kaplan SE, Terrin N, Breeze the American Academy of Neurology. JL, Freund KM. Longitudinal Analysis of Neurology. 2016 Aug 23;87(8):815-21. Gender Differences in Academic Productivity 282. Mukherjee JT, Beshansky JR, Ruthazer R, Alkofide Among Medical Faculty Across 24 Medical H, Ray M, Kent D, Manning WJ, Huggins GS, Schools in the United States. Acad Med. 2016 Selker HP. In-hospital measurement of left Aug;91(8):1074-1079. PMID: 27276002. ventricular ejection fraction and one-year 290. Rosenberg AS, Ruthazer R, Paulus JK, Kent outcomes in acute coronary syndromes: results DM, Evens AM, Klein AK. Survival analyses from the IMMEDIATE Trial. Cardiovascular and prognosis of plasma-cell myeloma and Ultrasound. 2016 Aug 3;14(1):29. plasmacytoma-like posttransplantation 283. Pack QR, Priya A, Lagu T, Pekow PS, Engelman lymphoproliferative disorders. Clinical R, Kent DM, Lindenauer PK. Development Lymphoma, Melanoma, & Leukemia. and validation of a predictive model for 2016 Sep 17. [Epub ahead of print] short- and medium-term hospital readmission 291. Shahraz S, Pittas AG, Kent DM. Prediabetes following heart valve surgery. Journal of the risk in adult Americans according to American Heart Association. 2016;5(9). a risk test. JAMA Internal Medicine. 284. Paulus JK, Kent DM. Sex versus gender in 2016 Oct 3. [Epub ahead of print] recurrent events following acute coronary 292. Shahraz S, Pittas AG, Lundquist CM, Danaei syndrome: a “femininity paradox”? G, Kent DM. Do Patient Characteristics Impact Journal of the American College of Decisions by Clinicians on Hemoglobin A1c Cardiology. 2016;68(12):1371-1372. Targets? Diabetes Care. 2016 Sep;39(9);e145-6.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 293. Stefan MS, Nathanson BH, Lagu T, Priya A, Pekow 301. Wetherell M, Sweeney M, Weingart SN. Can PS, Steingrub JS, Hill NS, Goldberg RJ, Kent DM, clinicians predict readmissions? A prospective Lindenauer PK. Ouotcomes of Noninvasive and cohort study. J Healthc Qual, 2016 Sep 13. Invasive Ventilation in Patients Hospitalized with 302. Zamore R, Harubin B, Sweeney M, Weingart Asthma Exacerbation. Annals of the American SN. Follow up of abnormal metanephrine Thoracic Society. 2016 Jul;13(7):1096-104. and catecholamine testing: chasing 294. Tangri N, Inker LA, Hiebert B, Wong J, Naimark missed neuroendocrine tumors. J Clin D, Kent D, Levey AS. A Dynamic Predictive Outcomes Manage 2016; 23:353-8.

Model for Progression of CKD. American » » PUBLICATIONS Journal of Kidney Diseases. 2016 Sep 29. Division of Nephrology pii: S0272-6386(16)30417-6. doi: 10.1053/j. 303. Alseiari M, Meyer KB, Wong JB. Evidence ajkd.2016.07.030. [Epub ahead of print] underlying KDIGO (Kidney Disease: Improving 295. Tangri N, Inker LA, Hiebert B, Wong J, Naimark D, Global Outcomes) guideline recommendations: a Kent D, Levey AS. A Dynamic Predictive Model for systematic review. Am J Kidney Dis 2016;67:417- Progression of CKD. American Journal of Kidney 22. Epub 2015 Oct 29. PubMed PMID: 26526035. Diseases. 2016 Sep 29; pii: S0272-6386(16)30417-6. 304. Amro OW, Paulus JK, Noubary F, Perrone 296. Upshaw JN, Konstam MA, Klaveren Dv, Noubary F, RD. Low-osmolar diet and adjusted water Huggins GS, Kent DM. Multistate Model to Predict intake for vasopressin reduction in autosomal Heart Failure Hospitalizations and All-Cause dominant polycystic kidney disease: a pilot Mortality in Outpatients With Heart Failure With randomized controlled trial. Am J Kidney Dis Reduced Ejection Fraction: Model Derivation and 2016;68:882-91. PubMed PMID: 27663039. External Validation. Circulation: Heart Failure. 305. Amro OW, Ramasamy M, Strom JA, Weiner 2016 Aug;9(8). pii: e003146. [Epub ahead of print] DE, Jaber BL. Nephrologist-facilitated advance 297. Weingart SN, Stoffel EM, Chung DC, Sequist care planning for hemodialysis patients: a TD, Lederman RI, Pelletier SR, Shields HM. quality improvement project. Am J Kidney Dis Delayed workup of rectal bleeding in adult 2016;68:103-9. PubMed PMID: 26806003. primary care: examining process-of-care failures. 306. Androgué HJ, Madias NE. Assessing acid-base Jt Comm J Qual Patient Saf 2016; 42: 32-40. status: physiologic versus physicochemical 298. Weingart SN, Stoffel EM, Chung DC, Sequist approach. Am J Kidney Dis 2016;68:793-802. TD, Lederman RI, Pelletier SR, Shields 307. Bansal N, Carpenter MA, Weiner DE, Levey AS, HM. Working up rectal bleeding in adult Pfeffer M, Kusek JW, Cai J, Hunsicker LG, Park primary care practices. J Eval Clin Pract, M, Bennett M, Liu KD, Hsu CY. Urine injury 2016 Jul 20. doi: 10.1111/jep.12596. biomarkers and risk of adverse outcomes in 299. Wells KJ, Winters PC, Jean-Pierre P, Warren-Mears un recipients of prevalent kidney transplants: V, Post D, Van Duyn MA, Fiscella K, Darnell the Folic Acid for Vascular Outcome Reduction J, Freund KM; Patient Navigation Research in Transplantation Trial. J Am Soc Nephrol Program Investigators. Effect of patient navigation 2016;27:2109-21. PubMed PMID: 26538631. on satisfaction with cancer-related care. 308. Bansal N, Katz R, Seliger S, DeFilippi C, Sarnak Support Care Cancer. 2016 Apr;24(4):1729-53. MJ, Delaney JA, Christenson R, de Boer IH, PMID: 26438146; PMCID: PMC4767607. Kestenbaum B, Robinson-Cohen C, Ix JH, 300. Wessler BS, Paulus JK, Lundquist C, Raman G, Shlipak MG. Galectin-3 and soluble ST2 and Lutz JS, Kent DM. Non-cardiac comorbidities kidney function decline in older adults: The in predictive models for valvular heart disease Cardiovascular Health Study (CHS). Am J Kidney interventions. Poster Presentation, Quality of Dis 2016;67:994-96. PubMed PMID: 26830253. Care and Outcomes Research (QCOR) Scientific Sessions, Phoenix, AZ, February 2016.

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SB, Parikh CR, Ix JH, Fried LF, Newman AB, PUBLICATIONS Shlipak MG, Harris TB, Sarnak MJ; Health ABC A, Carroll KJ, Schmid CH, Levey AS. Early Study. Association of serum erythropoietin change in urine protein as a surrogate end with cardiovascular events, kidney function point in studies of IgA nephropathy: an decline, and mortality: The Health Aging and individual-patient meta-analysis. Am J Kidney Body Composition Study. Circ Heart Fail Dis 2016; 68:392-401; PMID:27032886. 2016;9:E002124. PubMed PMID: 26721912. 332. Inker LA, Shafi T, Okparavero A, Tighiouart H, 326. Grams ME, Sang Y, Coresh J, Ballew SH, Eckfeldt JH, Katz R, Johnson WC, Dermond Matsushita K, Levey AS, Greene TH, N, Tariq Z, Benayacje I, Post WS, Coresh J, Moinar MZ, Szabo Z, Kalantar-Zadeh K, Levey AS, Shlipak MG. Effects of race and Kovesdy CP. Candidate surrogate end sex on measured GFR: The Multi-Ethnic points for ESRD after AKI. J Am Soc Nephrol Study of Atherosclerosis. Am J Kidney Dis 2016;27:2851-9. PubMed PMID: 26857682. 2016;68:743-51. PubMed PMID: 27555103. 327. Grams ME, Sang Y, Levey AS, Matsushita K, 333. Inker LA, Tighiouart H, Coresh J, Foster MC, Ballew S, Chang AR, Chow EK, Kasiske BL, Anderson AH, Beck GJ, Contreras G, Greene Kovesdy CP, Nadkami GN, Shalev V, Segev DL, T, Karger AB, Kusek JW, Lash J, Lewis J, Coresh J, Lentine KL, Garg AX; Chronic Kidney Schelling JR, Navaneethan SD, Sondheimer Disease Prognosis Consortium. Kidney-failure J, Shafi T, Levey AS. GFR estimation using risk projection for the living kidney-donor β-trace protein and β2-microglobulin in candidate. N Engl J Med 2016;374:411-21. CKD. Am J Kidney Dis 2016;67:40-8. Epub Epub 2015 Nov 6. PubMed PMID: 26544982. 2015 Sep 9. PubMed PMID: 26362696. 328. Gul A, Miskulin DC, Paine SS, Narsipur SS, 334. Isakova T, Cai X, Lee J, Katz R, Cauley JA, Fried Arbeit LA, Harford AM, Weiner DE, Schrader LA, Hoofnagle AN, Satterfield S, Harris TB, R, Horowitz BL, Zager PG. Comparison of Shlipak MG, Sarnak MJ, Ix JH; Health ABC prescribed and measured dialysate sodium: a Study. Associations of FGF23 with change in quality improvement project. Am J Kidney Dis bone mineral density and fracture risk in older 2016;67:439-45. PubMed PMID: 26776538. individuals. J Bone Miner Res 2016;31:742-8. Epub 2015 Nov 21. PubMed PMID: 26590361. 329. Heyer CM, Sundsbak JL, Abebe KZ, Chapman AB, Torres VE, Grantham JJ, Bae KT, Schrier 335. Kim DH, Grodstein F, Newman AB, Chaves RW, Perrone RD, Braun WE, Steinman TI, PH, Odden MC, Klein R, Sarnak MJ, Lipsitz Mrug M, Yu AS, Brosnahan G, Hopp K, Irazabal LA. Microvascular and macrovascular MV, Bennett WM, Flessner MF, Moore CG, abnormalities and cognitive and physical Landsittel D, Harris PC; HALT PKD and CRISP function in older adults: Cardiovascular Health Investigators. Predicted mutation strength of Study. J Am Geriatr Soc 2016;63:1886-93. nontruncating PKD1 mutations aids genotype- Epub 2015 Sep 4. PubMed PMID: 26338279. phenotype correlations in autosomal dominant 336. Kovesdy CP, Coresh J, Ballew SH, Woodward M, polycystic kidney disease. J Am Soc Nephrol Levin A, Naimark DM, Nally J, Rothenbacher 2016;27:2872-82. PubMed PMID: 26823553. D, Stengel B, Iseki K, Matsushita K, Levey AS: CKD Prognosis Consortium.

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» Am J Kidney Dis 2016;68:522-32. MR, Inker LA, Levey AS; CRIC (Chronic Renal » PUBLICATIONS 338. Kraut JA, Madias NE. Metabolic acidosis of CKD: Insufficiency Cohort) Study Investigators. Non- an update. Am J Kidney Dis 2016;67:307-17. GFR determinants of low-molecular-weight serum Epub 2015 Oct 15. PubMed PMID: 26477665. protein filtration markers in CKD. Am J Kidney Dis 2016;68:892-900. PubMed PMID: 27663040. 339. Kraut JA, Madias NE. Lactic acidosis: current treatments and future directions. 348. Marn Pernat A, Peršic V, Usvyat L, Saunders L, Am J Kidney Dis 2016;68:473-82. Rogus J, Maddux FW, Lacson E Jr, Kotanko P. Implementation of routine foot check in patients 340. Kupferman J, Amador JJ, Lynch KE, Laws with diabetes on hemodialysis: associations RL, López-Pilarte D, Ramirez-Rubio O, with outcomes. BMJ Open Diabetes Res Care Kaufman JS, Lau JL, Weiner DE, Robles NVB, 2016;4:e000158. PubMed PMID: 26958348. Verma KP, Scammell MK, McClean MD, Brooks DR, Friedman DJ. Characterization 349. McCausland FR, Claggett B, Burdmann of Mesoamerican nephropathy in a kidney EA, Eckardt KU, Kewalramani R, Levey AS, failure hotspot in Nicaragua. Am J Kidney Dis McMurray JJ, Parfrey P, Remuzzi G, Singh AK, 2016;68:716-25. PubMed PMID: 27575010. Solomon SD, Toto RD, Pfeffer MA. C-reactive protein and risk of ESRD: results from the 341. Laws RL, Brooks DR, Amador JJ, Weiner DE, Trial to Reduce Cardiovascular Events with Kaufman JS, Ramirez-Rubio O, Riefkohl A, Aranesp Therapy (TREAT). Am J Kidney Dis Scammell MK, Lopez-Pilarte D, Sanchez 2016;68:873-81. PubMed PMID: 27646425. JM, Parikh CR, McClean MD. Biomarkers of kidney injury among Nicaraguan sugarcane 350. McGill RL, Ruthazer R, Meyer KB, Miskulin workers. Am J Kidney Dis 2016;67:209-17. DC, Weiner DE. Peripherally inserted central Epub 2015 Oct 6. PubMed PMID: 26454687. catheters and hemodialysis outcomes. Clin J Am Soc Nephrol 2016;11:1430-40. 342. Levey AS, Bilous R, Shlipak MG. CKD and diabetes: what we can learn from their 351. Miskulin DC, Majchrzak K, Tighiouart H, similarities and differences. Am J Kidney Dis Muther RS, Kapoian T, Johnson DS, Weiner 2016;67:360-4. PubMed PMID: 26916373. DE. Ergocalciferol supplementation in hemodialysis patients with vitamin D deficiency: 343. Levey AS, Inker LA. GFR as the “gold standard”: a randomized clinical trial. J Am Soc Nephrol estimated, measured and true. Am J Kidney 2016;27:1801-10. PubMed PMID: 26677862. Dis 2016;67:9-12. PubMed PMID: 26708193. 352. Naimark D, Grams ME, Matsushita K, Balck 344. Levey AS, Inker LA, Coresh J. Reply: Managing C, Drion I, Fox CS, Inker LA, Ishani A, Jee chronic kidney disease in older people. JAMA SH, Kitamura A, Lea JP, Nally J, Peralta CA, 2016;315:307. PubMed PMID: 26784787. Rothenbacher D, Ryu S, Tonelli M, Yatsuya 345. Levey AS, Weiner DE, Gilbert SJ, Dorman H, Coresh J, Gansevoort RT, Warnock DG, NM. Editorial: Ten years atop the Woodward M, de Jong PE; CKD Prognosis masthead. Am J Kidney Dis 2016;68:825- 7. PubMed PMID: 27884276.

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elderly population in Iceland. Nephrol RP, Suhre K, KastenmÜller G, Köttgen A. A » » PUBLICATIONS Dial Transpl 2016;31:439-47. Epub 2015 metabolome-wide association study of kidney Oct 31. PubMed PMID: 26519958. function and disease in the general population. 354. Ramirez-Rubio O, Amador JJ, Kaufman JS, J Am Soc Nephrol 2016;27:1175-88. Epub Weiner DE, Parikh CR, Khan U, McClean 2015 Oct 8. PubMed PMID: 26449609. MD, Laws RL, Lopez-Pilarte D, Friedman DJ, 361. Selamet U, Tighiouart H, Sarnak MJ, Beck G, Kupferman J, Brooks DR. Urine biomarkers Levey AS, Block G, Ix JH. Relationship of dietary of kidney injury among adolescents in phosphate intake with risk of end-stage renal Nicaragua, a region affected by an epidemic of disease and mortality in chronic kidney disease chronic kidney disease of unknown etiology. stages 3-5: The Modification of Diet in Renal Nephrol Dial Transpl 2016;31:424-32. Epub Disease Study. Kidney Int 2016;89:176-84. 2015 Aug 25. PubMed PMID: 26311057. Epub 2015 Sep 30. PubMed PMID: 26422502. 355. Raphael KL, Murphy RA, Shlipak MG, 362. Shafi T, Levey AS, Coresh J. In reply to ‘Plasma Satterfield S, Huston HK, Sebastian A, clearance of iohexol in hemodialysis patients Sellmeyer DE, Patel KV, Newman AB, Sarnak requires prolonged blood sampling.’ Am J Kidney MJ, Ix JH, Fried LF; Health ABC Study. Dis 2016;67:811-12. PubMed PMID: 27091016. Bicarbonate concentration, acid-base status, 363. Shafi T, Michels WM, Levey AS, Inker LA, and mortality in the Health, Aging, and Body Dekker FW, Krediet RT, Hoekstra T, Schwartz Composition Study. Clin J Am Soc Nephrol GJ, Eckfeldt JH, Coresh J. Estimating residual 2016;11:308-16. PubMed PMID: 26769766. kidney function in dialysis patients without 356. Rebholz CM, Crews DC, Grams ME, urine collection. Kidney Int 2016;89:1099-110. Steffen LM, Levey AS, Miller ER III, Appel Epub 2016 Jan 21. PubMed PMID: 26924062. LJ, Coresh J. DASH (Dietary Approaches 364. Shrestha D, Liu S, Hammond SK, LaValley to Stop Hypertension) diet and risk of MP, Weiner DE, Eisen EA, Applebaum subsequent kidney disease. Am J Kidney Dis KM. Risk of renal cell carcinoma following 2016;68:853-61. PubMed PMID: 27519166. exposure to metalworking fluids among 357. Rebholz CM, Grams ME, Lutsey PL, Hoofnagle autoworkers. Occup Environ Med AN, Misialek JR, Inker LA, Levey AS, Selvin E, 2016;73:656-62. PubMed PMID: 27484955. Hsu CY, Kimmel PL, Vasan RS, Eckfeldt JH, 365. Sud M, Tangri N, Pintilie M, Levey AS, Coresh J; Chronic Kidney Disease Biomarkers Naimark DM. Progression to stage 4 chronic Consortium. Biomarkers of vitamin D status and kidney disease and death, acute kidney injury risk of ESRD. Am J Kidney Dis 2016;67:235-242. and hospitalization risk: a retrospective Epub 2015 Oct 13. PubMed PMID: 26475393. cohort study. Nephrol Dial Transplant 358. Sarnak MJ, Roberts KE. Pulmonary hypertension 2016;31:1122-30. PubMed PMID: 26590389. in CKD: some answers, yet more questions. J Am Soc Nephrol 2016;27:661-3. Epub 2015 Sep 18. PubMed PMID: 26386071.

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181 on survival of patients with pulmonary arterial 407. Higher estradiol and lower hypertension (PAH) in the registry to evaluate dehydroepiandrosterone-sulfate levels early and long-term PAH disease management are associated with pulmonary arterial (REVEAL). Circulation 2016;133(7):1096-104. hypertension in men. Am J Respir Crit 399. Richter SE, Roberts KE, Preston IR, Hill NS. Care Med 2016;193:1168-75. A simple derived prediction score for the 408. Wilson JL, Rupasinghe C, Usheva A, Warburton identification of an elevated pulmonary artery R, Kaplan C, Taylor L, Hill N, Mierke DF, Polgar wedge pressure using precatheterization P. Modulating the dysregulated migration of

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187 485. Gooding HC, Sheldrick RC, Leslie LK, Shah S, de and Outflow Cannulae. J Cardiothorac Vasc Ferranti SD, Mackie TI. Adolescent perceptions of Anesth. 2016 Nov 24. pii: S1053-0770(16)30643-7. cholesterol screening results: "young invincibles" doi: 10.1053/j.jvca.2016.11.038. PMID: 28216204. or developing adults? J Adolesc Health. 2016 493. Jean-Pierre P, Cheng Y, Wells KJ, Freund KM, May; doi: 10.1016/j.jadohealth.2016.03.027. Snyder FR, Fiscella K, Holden AE, Paskett ED, 486. Graham RJ, Rodday AM, Weidner RA, Parsons Dudley DJ, Simon MA, Valverde PA. Patient SK. The Impact on Family of Pediatric navigation research program. Satisfaction Chronic Respiratory Failure in the Home. J with cancer care among underserved

» Pediatr. 2016 Aug; 175:40-6. Doi: 10.1016/j. racial-ethnic minorities and lower-income » PUBLICATIONS jpeds.2016.05.009. Epub 2016 Jun 8. patients receiving patient navigation. Cancer. 487. Greenberg D, Neumann PJ. Cost-Effectiveness Epub 2016 Feb 5. PMID: 26849163. Analysis Expands its Reach Worldwide. 494. John-Baptiste A, Schapira MM, Cravens Value Health Reg Issues. 2016 Sep;10:101- C, Chambers JD, Neumann PJ, Siegel J, 102. PubMed PMID: 27881271. Lawrence W. The Role of Decision Models 488. Hyde J, Mackie TI, Palinkas LA, Niemi E, Leslie in Health Care Policy: A Case Study. Med LK. Evidence use in mental health policy Decis Making. 2016 Jul;36(5):666-79 making for children in foster care. Adm Policy 495. Joseph NP, Bernstein J, Pelton S, Belizaire Ment Hlth. 2016 January; 43(1): 52-66 doi: M, Goff G, Horanieh N, Freund KM. Brief 10.1007/s10488-015-0633-1. PMID: 25711392. Client-Centered Motivational and Behavioral 489. Inker LA, Shafi T, Okparavero A, Tighiouart H, Intervention to Promote HPV Vaccination Eckfeldt JH, Katz R, Johnson WC, Dermond in a Hard-to-Reach Population: A Pilot N, Tariq Z, Benayache I, Post WS, Coresh J, Randomized Controlled Trial. Clin Pediatr Levey AS, Shlipak MG. Effects of Race and (Phila). 2016 Mar 10. PMID: 26968631. Sex on Measured GFR: The Multi-Ethnic 496. Kent DM, Dahabreh IJ, Ruthazer R, Furlan Study of Atherosclerosis. Am J Kidney Dis. AJ, Reisman M, Carroll JD, Saver JL, Smalling Epub 2016 Aug 20. PMID: 27555103. RW, Jüni P, Mattle HP, Meier B, Thaler DE. 490. Inker LA, Tighiouart H, Coresh J, Foster MC, Device closure of patent foramen ovale Anderson AH, Beck GJ, Contreras G, Greene T, after stroke: Pooled analysis of completed Karger AB, Kusek JW, Lash J, Lewis J, Schelling randomized trials. J Am Coll Cardiol. 2016 JR, Navaneethan SD, Sondheimer J, Shafi Mar 1;67(8):907-17. PMID: 26916479. T, Levey AS. GFR Estimation Using β-Trace 497. Kent DM, Nelson J, Dahabreh IJ, Rothwell PM, Protein and β2-Microglobulin in CKD. Am J Altman DG, Hayward RA. Risk and treatment Kidney Dis. 2016. PubMed PMID: 26362696; effect heterogeneity: re-analysis of individual PubMed Central PMCID: PMC4695294. participant data from 32 large clinical trials. 491. Iversen MD, Price LL, von Heideken J, Harvey Int J Epidemiol. 2016 Jul 3. pii: dyw118. PMID: WF, Wang C. Physical examination findings 27375287. [PMC Journal In Process] and their relationship with performance-based 498. Ko NY, Snyder FR, Raich PC, Paskett ED, Dudley function in adults with knee osteoarthritis. DJ, Lee JH, Levine PH, Freund KM. Racial and BMC Musculoskelet Disord. 2016 Jul 12;17:273. ethnic differences in patient navigation: Results PMID: 27405996. PMCID: PMC4941016. from the Patient Navigation Research Program. 492. Jain A, Rohrer B, Gebhardt B, Breeze JL, Quick Cancer. Epub 2016 May 26. PMID: 27227342. JD, Couper G, Kiernan MS, Lawrence M, Cobey 499. Koopmans L, Bernaards CM, Hildebrandt FC. Left Ventricular Assist Device Thrombosis is VH, Lerner D, de Vet HC, van der Beek AJ. Associated With an Increase in the Systolic-to- Cross-cultural adaptation of the individual Diastolic Velocity Ratio Measured at the Inflow work performance questionnaire. Work. Epub 2016 Jan 25. PMID: 26835864.

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 500. Lee AC, Harvey WF, Price LL, Morgan LP, 508. Lin PJ, Saret CJ, Neumann PJ, Sandberg EA, Morgan NL, Wang C. Mindfulness is associated Cohen JT. Assessing the Value of Treatment to with psychological health and moderates Address Various Symptoms Associated with pain in knee osteoarthritis. Osteoarthritis Multiple Sclerosis: Results from a Contingent Cartilage. Epub 2016 Jun 24. PMID: 2734946. Valuation Study. Pharmacoeconomics. 2016 501. Lee B, Tam I, Weigel B, Breeze JL, Paulus Dec; 34(2):1255-1265. PMID: 27461538 JK, Nelson J, Allison GM. Comparative 509. Lin PJ, Yeh WS, Neumann PJ. Willingness to Outcomes of Beta-lactam Antibiotics in Pay for a Newborn Screening Test for Spinal

Outpatient Parenteral Antibiotic Therapy Muscular Atrophy. Pediatr Neurol. 2016 Sep 15. » » PUBLICATIONS (OPAT): Readmissions, Antibiotic Switches [Epub ahead of print] PubMed PMID: 27769729 and Value of OPAT. J Antimicrob Chemother. 510. Linendoll N, Saunders T, Burns R, Nyce JD, 2015;70:2389-96. PMID: 26024869. Wendell KB, Evens AM, Parsons SK. Health- 502. Leo CG, Mincarone P, Sabina S, Latini G, Wong related quality of life in Hodgkin lymphoma: a JB. A conceptual framework for rationalized systematic review. Health Qual Life Outcomes. and standardized Universal Newborn 2016 Jul 29;14(1):114. PMID: 27473596. Hearing Screening (UNHS) programs. Ital 511. Liu X, Foster MC, Tighiouart H, Anderson AH, J Pediatr. 2016 Feb 12;42:15. doi: 10.1186/ Beck GJ, Contreras G, Coresh J, Eckfeldt JH, s13052-016-0223-1. PMID: 26872853. Feldman HI, Greene T, Hamm LL, He J, Horwitz 503. Leonberg-Yoo AK, Tighiouart H, Levey AS, Beck E, Lewis J, Ricardo AC, Shou H, Townsend RR, GJ, Sarnak MJ. Urine Potassium Excretion, Kidney Weir MR, Inker LA, Levey AS; CRIC (Chronic Failure, and Mortality in CKD. Am J Kidney Renal Insufficiency Cohort) Study Investigators. Dis. Epub 2016 May 24. PMID: 27233381. Non-GFR Determinants of Low-Molecular-Weight 504. Leopold C, Chambers JD, Wagner AK. 30 Serum Protein Filtration Markers in CKD. Am J years of media coverage on high drug prices Kidney Dis. Epub 2016 Sep 20. PMID: 27663042. in the US – a never-ending story or a time for 512. Lo GH, McAlindon TE, Hawker GA, Driban JB, change? Value Health. 2016 Jan;19(1):14-16. Price LL, Song J, Eaton CB, Hochberg MC, Jackson 505. Leslie LK, Mehus CJ, Hawkins JD, Boat T, McCabe RD, Kwoh CK, Nevitt MC, Dunlop DD. Addressing MA, Barkin S, Perrin EC, Metzler CW, Prado G, concerns regarding a newly proposed knee Tait VF, Brown R, Beardslee W. Primary Health osteoarthritis composite symptom score. Arthritis Care: Potential Home for Family-Focused Rheumatol. 2016 Jan 27. PMID: 26814833. Preventive Interventions. Am J Prev Med. 2016 513. Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Oct;51(4 Suppl 2):S106-18. doi: 10.1016/j. Ahmed AT, Farah W, Almasri J, Alahdab F, amepre.2016.05.014. PubMed PMID: 27498167. Benkhadra K, Mouchli MA, Singh S, Mohamed 506. Lin PJ, Zhong Y, Fillit HM, Chen E, Neumann EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad PJ. Medicare Expenditures of Individuals MH, Mohammed K. Antiviral therapy for with Alzheimer's Disease and Related chronic hepatitis B viral infection in adults: Dementias or Mild Cognitive Impairment A systematic review and meta-analysis. Before and After Diagnosis. J Am Geriatr Hepatology. 2016 Jan;63(1):284-306. doi: Soc. Epub 2016 Jun 13. PMID: 27295430. 10.1002/hep.28280. Review. PMID: 26566246. 507. Lin PJ, Winn AN, Parsons SK, Neumann 514. Malone DC, Berg NS, Claxton K, Garrison LP Jr, PJ, Weiss ES, Cohen JT. Linking Costs and IJzerman M, Marsh K, Neumann PJ, Sculpher Survival in the Treatment of Older Adults With M, Towse A, Uyl-de Groot C, Weinstein MC. Chronic Myeloid Leukemia: An Analysis of International Society for Pharmacoeconomics and SEER-Medicare Data From 1995 to 2007. Med Care. 2016 Apr;54(4):380-5. PMID: 26759984.

189 Outcomes Research Comments on the American 522. Messé SR, Gronseth G, Kent DM, Kizer JR, Society of Clinical Oncology Value Framework. J Homma S, Rosterman L, Kasner SE. Practice Clin Oncol. Epub 2016 Jun 13. PMID: 27298420. advisory: Recurrent stroke with patent foramen 515. Marceau LD, Welch LC, Pemberton VL, ovale (update of practice parameter): Report Pearson GD. 2016. Educating Parents about of the Guideline Development, Dissemination, Pediatric Research: Children and Clinical and Implementation Subcommittee of the Studies Website Qualitative Evaluation. American Academy of Neurology. Neurology. Qual Health Res, Jul;26(8):1114-22. doi: Epub 2016 Jul 27. PMID: 27466464.

» 10.1177/1049732315616620. PMCID: In Process. 523. Miskulin DC, Majchrzak K, Tighiouart H, » PUBLICATIONS 516. Marszalek J, Price LL, Harvey WF, Driban JB, Wang Muther RS, Kapoian T, Johnson DS, Weiner DE. C. Outcome Expectations and Osteoarthritis: Ergocalciferol Supplementation in Hemodialysis Perceived Benefits of Exercise Are Associated with Patients With Vitamin D Deficiency: A Self-Efficacy and Depression. Arthritis Care Res. Randomized Clinical Trial. J Am Soc Nephrol. 2016 Jul 7. [Epub ahead of print].PMID: 27390257 2016. Jun;27(6):1801-10.. PubMed PMID: 26677862; PubMed Central PMCID: PMC4884115. 517. Mathai SC, Minai O, Sullivan SD, Lerner D, Levine D. Rationale and study design of MOTION: A 524. Morain SR, Concannon TW, Wittenberg E. HIV, phase 4, prospective, single-arm, open-label breast cancer and vaccines: what do high-profile study to measure outcomes in patients with cases reveal about stakeholder engagement in pulmonary arterial hypertension not on active research? J Comp Eff Res. 2016 Sep 2:0. [Epub treatment. Respir Med 2017 Jan; 122 Suppl: ahead of print] PubMed PMID: 27586693. S23-S27. Epub 2016 Nov 2. PMID: 27890471 525. Mukherjee JT, Beshansky JR, Ruthazer R, Alkofide 518. Matthan NR, Ausman LM, Meng H, H, Ray M, Kent D, Manning WJ, Huggins GS, Tighiouart H, Lichtenstein AH. Estimating Selker HP. In-hospital measurement of left the reliability of glycemic index values and ventricular ejection fraction and one-year potential sources of methodological and outcomes in acute coronary syndromes: biological variability. Am J Clin Nutr. 2016 results from the IMMEDIATE Trial. Cardiovasc Oct;104(4):1004-1013. PubMed PMID: 27604773; Ultrasound. 2016 Aug 3;14(1):29. PMID: 27488569. PubMed Central PMCID: PMC5039811. 526. Neumann PJ, Farquhar M, Wilkinson CL, 519. Mayne SL, Ross ME, Song L, McCarn B, Lowry M, Gold M. Lack of Cost-Effectiveness Steffes J, Liu W, Margolis B, Azuine R, Gotlieb Analyses to Address Healthy People 2020 E, Grundmeier RW, Leslie LK, Localio R, Priority Areas. Am J Public Health. 2016 Wasserman R, Fiks AG. Variations in Mental Dec;106(12):2205-2207. PubMed PMID: 27631752. Health Diagnosis and Prescribing Across 527. Neumann PJ, Thorat T, Zhong Y, Anderson J, Pediatric Primary Care Practices. Pediatrics. Farquhar M, Salem M, Sandberg E, Saret CJ, 2016 May;137(5). PMID: 2724479. Wilkinson C, Cohen JT. A Systematic Review 520. McGill RL, Ruthazer R, Meyer KB, Miskulin of Cost-Effectiveness Studies Reporting DC, Weiner DE. Peripherally Inserted Central Cost-per-DALY Averted. PLoS One. 2016 Catheters and Hemodialysis Outcomes. Dec 22;11(12):e0168512. doi: 10.1371/ Clin J Am Soc Nephrol. 11(8):1434-40, 2016. journal.pone.0168512. PMID: 28005986. [PMID: 27340280] [PMCID: PMC4974875] 528. Nigoghossian CD, Dzierba AL, Etheridge 521. McGill RL, Ruthazer R, Lacson E Jr, Meyer KB, J, Roberts R, Muir J, Brodie D, Schumaker Miskulin DC, Weiner DE. Vascular imaging for G, Bacchetta M, Ruthazer R, Devlin JW. hemodialysis vascular access planning. Hemodial Effect of Extracorporeal Membrane Int. 2016 Nov 20. doi: 10.1111/hdi.12513. Oxygenation Use on Sedative Requirements [Epub ahead of print] PMID: 27868336. in Patients with Severe Acute Respiratory Distress Syndrome, Pharmacotherapy. 36(6):607-16. 2016. PMID: 27130442

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 529. O'Connor KL, Scisco JL, Smith TJ, Young 535. Pantel HJ, Stensland KD, Nelson J, Francone AJ, Montain SJ, Price LL, Lieberman TD, Roberts PL, Marcello PW, Read T, Ricciardi HR, Karl JP. Altered Appetite-Mediating R. Should We Use the Model for End-Stage Hormone Concentrations Precede Liver Disease (MELD) to Predict Mortality Compensatory Overeating After Severe, After Colorectal Surgery? J Gastrointest Surg. Short-Term Energy Deprivation in Healthy 2016 Aug;20(8):1511-6. doi: 10.1007/s11605- Adults. J Nutr. 2016 Feb;146(2):209-17. 016-3167-2. PubMed PMID: 27216407. Epub 2016 Jan 6. PMID: 26740683. 536. Parsons SK, Fineberg IC, Lin M, Singer M,

530. O'Hagan JB, Khazova M, Price LL. Low-energy Tang M, Erban JK. Promoting High-Quality » » PUBLICATIONS light bulbs, computers, tablets and the blue Cancer Care and Equity Through Disciplinary light hazard. Eye (Lond). 2016 Feb;30(2):230-3. Diversity in Team Composition. J Oncol doi: 10.1038/eye.2015.261. PMID: 26768920. Pract. Epub 2016 Aug 30. PMID: 27577618. 531. Okparavero A, Foster MC, Tighiouart H, 537. Paterakis K, Koutsias S, Doxani C, Xanthopoulou Gudnason V, Indridason O, Gudmundsdottir P, Kokkali C, Mpoulimari I, Tziastoudi M, H, Eiriksdottir G, Gudmundsson EF, Inker LA, Karampelas I, Dardiotis E, Hadjigeorgiou G, Brotis Levey AS. Prevalence and complications of AG, Zintzaras E. Variants of the elastin (ELN) chronic kidney disease in a representative elderly gene and susceptibility to intracranial aneurysm: population in Iceland. Nephrol Dial Transplant. a synthesis of genetic association studies using 2016 Mar;31(3):439-47. PubMed PMID: 26519958; a genetic model-free approach. Int J Neurosci. PubMed Central PMCID: PMC4762399. 2016 Aug 14:1-6. [Epub ahead of print] PubMed 532. Pack QR, Priya A, Lagu T, Pekow PS, Engelman PMID: 27687579.Paul S, Saxena A, Terrin N, R, Kent DM, Lindenauer PK. Development Viveiros K, Balk EM, Wong JB. Hepatitis B Virus and Validation of a Predictive Model for Reactivation and Prophylaxis During Solid Tumor Short- and Medium-Term Hospital Readmission Chemotherapy: A Systematic Review and Meta- Following Heart Valve Surgery. J Am Heart analysis. Ann Intern Med. 2016 Jan 5;164(1):30-40. Assoc. 2016 Aug 31;5(9). PMID: 27581171. doi: 10.7326/M15-1121. PMID: 26595058. 533. Palinkas LA, Garcia AR, Aarons GA, Finno- 538. Paulus JK, Kent DM. Sex Versus Gender in Velasquez M, Holloway IW, Mackie TI, Recurrent Events Following Acute Coronary Leslie LK, Chamberlain P. Measuring Use of Syndrome: A "Femininity Paradox?" J Am Coll Research Evidence: The Structured Interview Cardiol. 2016 Sep 20;68(12):1371-2. PMID: for Evidence Use. Res Soc Work Pract. 2016 27634130Paulus JK, Lai LY, Lundquist C, Sep;26(5):550-564. PubMed PMID: 27616869; Daneshmand A, Buettner H, Lutz JS, Raman PubMed Central PMCID: PMC5014436. G, Wessler BS, Kent DM. Field Synopsis of the Role of Sex in Stroke Prediction Models. J Am 534. Panagioti M, Bower P, Kontopantelis E, Lovell Heart Assoc. 2016 May 5;5(5). PMID: 27151514. K, Gilbody S, Waheed W, Dickens C, Archer J, Simon G, Ell K, Huffman JC, Richards DA, van der 539. Paulus JK, Rosenberg AS. Breast cancer and Feltz-Cornelis C, Adler DA, Bruce M, Buszewicz venous thromboembolism (VTE): timing matters. M, Cole MG, Davidson KW, de Jonge P, Gensichen Blood. 2016 Feb 18;127(7):793-4. PMID: 26893393 J, Huijbregts K, Menchetti M, Patel V, Rollman 540. Paulus JK, Switkowski KM, Allison GM, Connors B, Shaffer J, Zijlstra-Vlasveld MC, Coventry PA. M, Buchsbaum RJ, Freund KM, Blazey-Martin D. Association Between Chronic Physical Conditions Where is the leak in the pipeline? Investigating and the Effectiveness of Collaborative Care for gender differences in academic promotion Depression: An Individual Participant Data Meta- at an academic medical centre. Perspect analysis. JAMA Psychiatry. 2016 Sep 1;73(9):978- MedEduc. 2016 Apr;5(2):125-8. doi: 10.1007/ 89. doi: 10.1001/jamapsychiatry.2016.1794. s40037-016-0263-7. PubMed PMID: 27001528; PubMed PMID: 27602561. PubMed Central PMCID: PMC4839010.

191 541. Paulus JK, Thaler DE. Does case misclassification school-aged children in a rural district of India. threaten the validity of studies investigating the Indian Heart J. 2016 Jan-Feb;68(1):43-7. doi: relationship between neck manipulation and 10.1016/j.ihj.2015.10.302. Epub 2016 Jan 11. vertebral artery dissection stroke? Yes. Chiropr 549. Raman G, Adam GP, Halladay CW, Langberg VN, Man Therap. 2016 Nov 5;24:42. PubMed PMID: Azodo IA, Balk EM. Comparative Effectiveness 27822362; PubMed Central PMCID: PMC5097396. of Management Strategies for Renal Artery 542. Paulus JK, Wessler BS, Lundquist C, Lai LL, Stenosis: An Updated Systematic Review. Ann Raman G, Lutz JS, Kent DM. Field Synopsis Intern Med. 2016 Aug 16. doi: 10.7326/M16-

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» by sex and diet, but not housing in C57Bl6 mice. Sci Technolog Med Sci. 2016; 36: 82-87, » PUBLICATIONS The Journal of Nutrition. 2016; Aug;146(8):1521-7. 639. London C, Gardner HL, Rippy S, et al. KTN0158, 630. Hinds, P.W. Commentary on Alfred a humanized anti-KIT monoclonal antibody, G. Knudson, Jr.: “Hereditary Cancer, demonstrates biologic activity against both Oncogenes, and Antioncogenes. Cancer normal and malignant canine mast cells. Clinical Res. 2016; May 15;76(10):2851-3 cancer research : an official journal of the 631. Jena N, Sheng J, Hu JK, et al. CDK6- American Association for Cancer Research. 2016 mediated repression of CD25 is required 640. Lundberg AP, Francis JM, Pajak M, et al. for induction and maintenance of Pharmacokinetics and derivation of an anticancer Notch1-induced T-cell acute lymphoblastic dosing regimen for the novel anti-cancer agent leukemia. Leukemia 2016; 30: 1033-43 isobutyl-deoxynyboquinone (IB-DNQ), a NQO1 632. Joshi R, Goihberg E, Ren W, Pilichowska bioactivatable molecule, in the domestic felid M, Mathew P. Proteolytic fragments of species. Investigational new drugs. 2016; fibronectin function as matrikines driving the 641. Mami I, Bouvier N, El Karoui K, et al. chemotactic affinity of prostate cancer cells to Angiogenin Mediates Cell-Autonomous human bone marrow mesenchymal stromal Translational Control under Endoplasmic cells via the α5β1 integrin. Cell Adh Migr Reticulum Stress and Attenuates Kidney 2016; Aug 11:1-11 [Epub, ahead of print] Injury. J Am Soc Nephrol. 2016; 27: 863-76, 633. Kilpatrick CL, Murakami S, Feng M, et al. 642. Mani R, Yan R, Mo X, et al. Non- Dissociation of Golgi-associated DHHC-type immunosuppressive FTY720-derivative Zinc Finger Protein (GODZ)- and Sertoli OSU-2S mediates reactive oxygen species- Cell Gene with a Zinc Finger Domain-β mediated cytotoxicity in canine B-cell (SERZ-β)-mediated Palmitoylation by Loss of lymphoma. Veterinary and comparative Function Analyses in Knock-out Mice. J Biol oncology. 2016; NIHMSID: NIHMS754518 Chem. 2016; Dec 30;291(53):27371-27386. 643. Mato AR, Nabhan C, Barr PM, et al. Outcomes 634. Kritharis A, Pilichowska M, Evens AM. How I of CLL patients treated with sequential manage patients with grey zone lymphoma. kinase inhibitor therapy: a real world British Journal of Haematology. 2016; 174:345-50. experience. Blood. 2016; 28(18):2199-2205. 635. LeBlanc AK, Breen M, Choyke P, et al. 644. Paulus JK, Switkowski KM, Allison GM, et al. Perspectives from man's best friend: National Where is the leak in the pipeline? Investigating Academy of Medicine's Workshop on gender differences in academic promotion at Comparative Oncology. Science translational an academic medical center. Perspectives in medicine. 2016; 8(324):324ps5. Medical Education, 2016; DOI 10.1007/s40037- 636. Linendoll N, Saunders T, Burns R, et al. 016-0263-7 Press OW, Li H, Schöder H, et al. US Health-related quality of life in Hodgkin Intergroup Trial of Response-Adapted Therapy lymphoma: a systematic review. Health for Stage III to IV Hodgkin Lymphoma Using Qual Life Outcomes. 2016; 14(1):114. Early Interim Fluorodeoxyglucose-Positron

TUFTS MEDICAL CENTER DEPARTMENT OF MEDICINE — ANNUAL REPORT 2016 Emission Tomography Imaging: Southwest 654. Sun Y, Côté JF, Du K, Elmo2 is a regulator Oncology Group S0816. Journal of Clinical of insulin dependent Glut4 membrane Oncology. 2016; Jun 10;34(17):2020-7. translocation. J Biol Chem. 2016 May 20. pii: 645. Ravi D, Beheshti A, Abermil N, et al. jbc.M116.731521. [Epub ahead of print] Proteasomal Inhibition by Ixazomib 655. Voulgarelis M, Tsichlis PN. Proline hydroxylation Induces CHK1 and MYC-Dependent Cell linked to Akt activation. Science. 2016; Aug Death in T-cell and Hodgkin Lymphoma. 26;353(6302):870-1. doi: 10.1126/science.aah6254. Cancer Research. 2016; 76 (11): 3319-31. 656. Vyrla D, Nikolaidis G, Oakley F, et al. TPL2 » »

646. Ren W, Joshi R, Mathew P. Synthetic Kinase Is a Crucial Signaling Factor and PUBLICATIONS Lethality in PTEN-mutant prostate cancer Mediator of NKT Effector Cytokine Expression is induced by combinatorial PI3K/Akt in Immune-Mediated Liver Injury. J and BCL-XL inhibition. Mol Cancer Res Immunol. 2016; May 15;196(10):4298-310. 2016; 14:1176-1181 (Rapid Impact) doi: 10.4049/jimmunol.1501609. 647. Rippy SB, Gardner HL, Nguyen SM, et al. A 657. Wieser, V., Adolph, T.E., Enrich, B., et al. pilot study of toceranib/vinblastine therapy Reversal of murine alcoholic steatohepatitis for canine transitional cell carcinoma. BMC by pepducin-based functional blockade veterinary research. 2016; 12(1):257. of interleukin-8 receptors.2016 648. Rosenberg AS, Klein AK, Ruthazer R, Evens 658. Xing W, Dresser K, Zhang R, et al. PD-L1 AM. Hodgkin lymphoma post-transplant expression in EBV-negative diffuse large lymphoproliferative disorder: A comparative B-cell lymphoma: clinicopathologic analysis of clinical characteristics, features and prognostic implications. prognosis, and survival. American Journal Oncotarget. 2016; 7(37):59976-59986. of Hematology. 2016; 91(6):560-5. 659. Xu K1, Tian X2, Oh SY, et al. The fibroblast 649. Rosenberg AS, Ruthazer R, Paulus JK, Kent Tiam1-osteopontin pathway modulates DM, Evens AM, Klein AK. Survival Analyses breast cancer invasion and metastasis. and Prognosis of Plasma-Cell Myeloma and Breast Cancer Res. 2016; Jan 28;18(1):14 Plasmacytoma-Like Posttransplantation 660. Yang, E., Cospwski, J. Nguyen, N., et al. Lymphoproliferative Disorders. Clin Lymphoma Dysregulated Protease activated receptor Myeloma Leuk. 2016; 16(12):684-692.e3. 1 (PAR1) promotes metastatic phenotype 650. Shah G, Winn A, Lin P-J, et al. Cost implications in breast cancer through HMGA2. of comorbidity for autologous stem cell PMID; Oncogene. 2016; 35:1529-40 transplantation in elderly patients with multiple myeloma using SEER-Medicare. Bone Marrow Research, 2016; Vol 2016: Article ID 3645623, 651. Shearer, A.M., Rana, R., Austin, K., et al. Targeting Liver Fibrosis with a Cell- Penetrating PAR2 Pepducin J Biol Chem. 2016; Oct 28;291(44):23188-23198 652. Shibata A, Ibaragi S, Mandai H, et al. Synthetic Terrein Inhibits Progression of Head and Neck Cancer by Suppressing Angiogenin Production. Anticancer Res. 2016; 36: 2161-2168 653. Silberstein L, Goncalves KA, Kharchenko PV, et al. Proximity-based differential single cell analysis of the niche to identify stem/progenitor cell regulators. Cell Stem Cell. 2016; 19: 530-543,

199 DEPARTMENT OF MEDICINE 2016 Annual Report

Tufts Medical Center Department of Medicine 800 Washington Street Boston, MA 02111

Published June 2017