Patient-Centered Research ANNUAL REPORT 2015 Annual Report Table of contents 2015

The annual report is presented President’s welcome...... 2 by the office of the president of Leadership team...... 3 Aurora Research Institute, which Aurora’s Way Forward...... 4 oversees the patient-centered research conducted throughout Discovery Laboratory ...... 5 Aurora Health Care. Journal of Patient-Centered Research and Reviews...... 7 Research recognition events...... 8 Randall Lambrecht, PhD Academic relations...... 9 Senior Vice President, Philanthropy...... 11 Aurora Health Care President, Aurora Research Institute Cardiovascular research ...... 12 414-219-7838 CIRCA...... 13 [email protected] Research highlights...... 15 Cardiovascular research committees...... 21 Editorial Staff Cardiovascular volumes...... 21 Cardiovascular publications...... 22 Katie Klein Manager, Research Publications 414-219-3428 Oncology research ...... 24 [email protected] TORQUE...... 25 Early Phase Cancer Research Program...... 27 Julie Walters Multimedia Designer Research highlights...... 28 414-219-7825 Oncology volumes...... 32 [email protected] Oncology research committees...... 33

Joe Grundle Oncology publications...... 33 Senior Scientific Writer & Editor 414-219-7323 Neurosciences research ...... 34 [email protected] ANII...... 35 Research highlights...... 36 Neurosciences research committees...... 40 Neurosciences volumes...... 41 Neurosciences publications...... 41

Additional strategic research ...... 42 Women’s Health research and volumes...... 43 Orthopedic research and volumes...... 44 Aurora UW Medical Group research...... 45 Center for Urban Population Health...... 47 Research highlights...... 48 Additional strategic publications...... 49

About Aurora Research Institute ...... 52 Research Business Services...... 53 The information presented in Sponsored Programs Office...... 54 this annual report is intended for general information and educational Clinical Trials Department...... 54 purposes. It is not intended to replace Translational Research...... 55 the advice of your own physician. Contact your physician if you believe Biorepository and Specimen Resource Center...... 56 you have a health problem. Interdepartmental collaborations...... 57 President’s welcome Board of Directors

Aurora Research Institute is governed by a board of directors consisting of Aurora Health Care leaders who oversee the strategic and financial decisions that shape the institute’s future.

Bob Stoltz, MBA, Vani Nilakantan, PhD, and Nina Garlie, PhD, watch as Carolynn Glocka, MBA, BSN, and Randall Lambrecht, PhD, cut a ribbon, symbolizing the opening of Discovery Laboratory. CHAIR Ruric (Andy) Anderson, MD Chief Medical Officer Aurora Research Institute unifies the innovative research efforts throughout Aurora Health Care, aiding the health system in its mission to help people live Gerard Colman, PhD well by providing investigational options for patients. Chief Operating Officer Best Brand Transforming over 14,000 square feet at Aurora Sinai Medical Center as part Patrick Falvey, PhD of a more than $5 million capital investment, the institute created a unique Executive Vice President of research environment known as Discovery Laboratory. Opened in October 2015, Integration researchers are working on discoveries for cancer and cardiovascular diseases.

The neuroanatomical laboratory that opened in May 2015 at Aurora St. Luke’s TREASURER Medical Center has served as a useful research resource and an educational tool Gail Hanson for visiting students, drawing local media attention. Chief Financial Officer Advancing scientific breakthroughs, Aurora’s Journal of Patient-Centered Research and Reviews continues to expand its global reach with more than 11,500 article downloads in more than 100 countries in 2015 alone. ASSISTANT SECRETARY Rachelle (Shelly) Hart Best Value General Counsel Providing an environment of innovation, the institute participated in the studies necessary for APN Health LLC to receive Food and Drug Administration PRESIDENT clearance for its Navik 3D heart imaging system. Randall Lambrecht, PhD Collaborations with industry and other research partners allow Aurora to bring Senior Vice President neurosurgical innovations and the latest cancer therapies to patients.

Best People SECRETARY Aurora has emerged as a national destination for research as evidenced by Mike Lappin recruitment of leading scientists and clinicians focused on new breakthroughs Chief Administrative Officer and dedicated caregivers who give of their time and resources.

Counting them among our numbers – this work to help people live well would Dennis Potts not be possible without the thousands of patients who participate in clinical trials Executive Vice President of or donate tissue and the donors who drive innovation with their generous gifts. the South Region On behalf of Aurora Research Institute and its board of directors, I am pleased to provide this highlight of our 2015 outcomes. As always, I welcome your feedback. Preston Simons Chief Information Officer

Randall Lambrecht, PhD Senior Vice President, Aurora Health Care/President, Aurora Research Institute

aurora.org/research 2 Leadership team

Vice President Program Directors

Kurt Waldhuetter, MS Nina Garlie, PhD Vani Sara Planton, BSN Research Business Regenerative Nilakantan, PhD Clinical Trials Services Medicine Investigator-Initiated Research & Sponsored Programs Office

Medical Research Directors Randall Lambrecht, PhD Senior Vice President, Aurora Health Care President, Aurora Research Institute

Vicki Soerens Dennis Arshad Jahangir, MD Michael Judy Tjoe, MD Executive Assistant Baumgardner, MD Sheikh Khalifa bin Thompson, MD, PhD Translational Oncology Aurora UW Medical Hamad Al Thani Center Early Phase Cancer Research: Quest for Group Research Core for Integrative Research Research Program Understanding and on Cardiovascular Aging Exploration (TORQUE) (CIRCA) Randall Lambrecht, PhD, president of Aurora Research Institute, oversees all clinical research at Aurora Health Managers Care, one of the largest integrated health care systems in the country.

Under Dr. Lambrecht’s leadership, hundreds of clinical trials and investigator-initiated research studies are being conducted across Aurora’s 15 hospitals and more than 150 clinics. Jan DeBartolo, MSN Katie Klein David Krum, MS Andy Marek He also facilitates the advancement of Clinical Trials Research Publications Cardiovascular Research Analytics innovative health care technologies. Research

Dr. Lambrecht has spent nearly 30 years as a researcher and professor. He has secured numerous federal research grants to study molecular and cellular mechanisms of infectious disease, authored more than 60 publications, presented over 110 lectures/seminars and developed Annette Paul, MAT Natalie Polinske, MS Katie Richter Wendy Schmidt, RN Clinical Trials Biorepository and Clinical Trial Clinical Trials molecular-based diagnostic tests that Specimen Resource Business Services were subsequently commercialized. Center

Dr. Lambrecht holds certification by the American Society of Clinical Pathologists and is a fellow for the Association of Schools of Allied Health Professions. He serves as a scientific reviewer for several journals and on numerous professional and community boards. Bob Stoltz, MBA, MT Carol Tutino, BSN, MS Mindy Waite, PhD Research Lab Clinical Trials Research Grants and Projects

3 Aurora Research Institute | Annual Report 2015 CONTRIBUTING TO AURORA’S WAY FORWARD

2016 AND BEYOND

BEST BRAND BEST VALUE

• A urora Research Institute completed its first year as a separate legal • The Aurora Neuroscience Innovation entity from Aurora Health Care. Institute received a $1 million award to develop a neuro-oncology research • The institute unveiled its new Discovery Laboratory on the Aurora Sinai program. Medical Center campus. The state-of the-art facility houses a number of research laboratories that support cellular, molecular, proteomic, imaging • A tribute to Sheikh Khalifa bin Hamad and stem cell research in cancer, cardiovascular and neurosciences. Al Thani was unveiled on a wall outside Center for Integrative Research on • Journal of Patient-Centered-Research and Reviews experienced huge Cardiovascular Aging at Aurora St. increases in readership and worldwide downloads allowing the editorial Luke’s Medical Center, recognizing his team to apply for elite indexing status after only two years. $2 million gift. • T he Sponsored Programs Office in conjunction with the Investigator- • The Biorepository and Specimen Initiated Research Department tracked a number of major research grants Resource Center was awarded a grant to and collaborations including Michael Michalkiewicz, PhD, and his National help establish itself as valuable resource Institutes of Health award from Vanderbilt University for precision medicine. for biomedical and clinical research. • The Clinical Trials Department participated in major multicenter trials for • T he institute received approval to make a devices – CoreValve, WATCHMAN and Evera MRI SureScan ICD System – significant investment with the purchase that received Food and Drug Administration approval in 2015. of a clinical trial management system, and • During a site visit, National Institutes of Health auditors applauded Aurora opening of a grant management position NCORP (National Cancer Institute Community Research Oncology Program) to help support the growing number of for its first successful year of the grant under the direction of principal sponsored research projects. investigators Thomas Saphner, MD, and Michael Thompson, MD, PhD. • A much needed review and internal • A major study on the risk of testosterone therapy and heart disease helped audit of research was conducted to help change the course and recommendations of pending federal guidelines. shape policies and procedures. Policies developed or revised included conflict of • W isconsin Lt. Gov. Rebecca Kleefisch visited Aurora St. Luke’s Medical interest, clinical trial billing and research Center and toured research areas and neurosciences facilities. misconduct.

BEST PEOPLE By working with internal and external parties, I help put into place the required study and other underlying agreements that enable • T hrough annual research recognition collaborative studies to be conducted. events at Aurora St. Luke’s and Aurora BayCare Medical Centers and at Aurora – Lee Banfi, MBA, CPA Sponsored Programs Specialist, Sr. Scientific Day, outstanding researchers received recognition for their efforts. I contribute to patient-centered I contribute to patient-centered research • A total of 18 college students spent research by helping investigators on a daily basis by developing a rapport time conducting research during the submit their research to the with patients leading to the screening, summer either in research laboratories Institutional Review Board. consenting and enrolling of patients in or supporting other research activities one of the several clinical trials I oversee. as part of the institute’s summer student – Noreen Wynn, MS, MS Research Regulatory Specialist, Sr. – Jennifer Cooper, BSN research programs. Research Nurse Coordinator, Sr. • Caregivers gave of themselves to support charitable events and organizations Aurora Research Institute’s administrative including Vince Lombardi Cancer assistant team works together to ensure communication among our multidisciplinary Foundation, American Heart Association, researchers is effective and efficient. Aurora Health Care Foundation and the X49140 (11/14) ©AHC students of Hawthorne Elementary School. – Diane Gentilini Administrative Assistant, Sr.

aurora.org/research 4 Discovery Laboratory

Where revolutionary research is happening

On display behind glass walls, Aurora Health Efficient, artistic Care researchers work from the molecular to cellular levels to gain a better understanding The space-saving layout of Discovery of genes and proteins and how they react to Laboratory features shared work stations new and existing therapies. and communal core equipment. This efficient design avoids duplication found in traditional In Aurora Research Institute’s Discovery pod-like laboratories and enhances Laboratory, the goal is to find innovative communication among researchers. ways to improve patient outcomes for cancer, cardiovascular diseases and The tissue processing and microscopy area neurological disorders. More simply put, is equipped for preparation, staining and the goal is to discover cures. analysis of slides. Typically this service is outsourced, which would add cost and time To facilitate this research, the institute to research projects. transformed over 14,000 square feet on the Aurora Sinai Medical Center campus An enclosed area at biosafety level 2 allows as part of a more than $5 million capital for genetic manipulation using viruses investment. The innovative transformation and other microorganisms to develop new includes a unique laboratory environment, immunotherapies. small animal facility and offices. A refrigerated room allows for cold- temperature experiments. A separate room houses deep freeze cryogenic equipment for storage of tissues, cells and supplies at -20, -80 and -150 degrees.

Rounding out the laboratory are traditional human and animal cell and tissue preparation and culture spaces.

And don’t forget to look up. A barrel vault ceiling features an artistic DNA sequence design.

Learn more about how Aurora researchers are trying to cure heart disease (see story on page 14) and cancer (see story on page 37). Labs within the lab Grand opening celebrations • Imaging Laboratory • Experimental Optics Laboratory Oct. 27 • Microscopy/Histology Laboratory Ribbon-cutting ceremony • Cell Biology Laboratory • Flo w Cytometry Laboratory Oct. 28 • V irology Laboratory Open house • Pr otein and Molecular Laboratory

Recognized leaders Areas of study and centers • Nina Garlie, PhD • Neurosciences • Vani Nilakantan, PhD Aurora Neuroscience Innovation • Bob Stoltz, MBA, MT Institute (ANII) • David Krum, MS • Br east and other cancers Translational Oncology Research: Quest for Understanding and Featured scientists Exploration (TORQUE) • Santhi Konduri, PhD • Cardiovascular diseases and aging • Sanjay Kansra, PhD Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on • Amber LaCrosse, PhD Cardiovascular Aging (CIRCA) • Scarlet Shi, PhD • Larisa Emelyanova, PhD • Acute kidney injury • Precision medicine

Discovery Laboratory was possible because of the commitment of many bright and talented researchers, physicians and caregivers along with the hope and generosity ‘‘ of friends and donors.

Aurora Health Care, Aurora Sinai Medical Center and Aurora Health Care Foundation provided the administrative fortitude and support that allowed ‘‘the unique laboratory environment to be created. But, most importantly, discoveries can only be translated into innovative patient care with the courage and involvement of

patients and their families. Bob Stoltz, MBA (top), David Krum, MS (middle), and Vani Nilankantan, PhD (bottom), lead tours through the – Randall Lambrecht, PhD Discovery Laboratory.

aurora.org/research 6 JPCRR year in review 2015 highlights • Surpassed 16,000 article downloads • Expanded reach to 115 countries • Indexed in Directory of Open Access Journals, search engine Google Scholar • Selected to publish scientific abstracts presented at Health Care Systems Research Network’s annual conference • Applied to PubMed Central

Popularity of Aurora Health Care’s Journal Most read of Patient-Centered Research and Reviews soared in its second year of publication. Such rapid growth inspired the journal’s editorial board to create the JPCRR The articles published quarterly by JPCRR Article of the Year award. reached more than 100 countries, forging a global footprint that spans the United States, At Aurora Research Institute’s Japan, Chile, Kenya, Germany, Australia and Greater Milwaukee Clinical Research everywhere in between. Recognition Event in September, author Leslie Waltke, DPT, became the first Moreover, article downloads from JPCRR recipient of the award for her article online exceeded 11,500 in 2015, doubling the on exercise rehabilitation in cancer web traffic of the journal’s inaugural year. patients, which has been downloaded 4,500 times to date.

Special issues With the help of guest editors, JPCRR published two specialty theme issues.

Guest edited by Mark Mewissen, MD, an interventional radiologist at Aurora St. Luke’s Medical Center, Volume 2, Issue 3 featured recent breakthroughs in vascular disease treatment.

JPCRR closed the year with an issue dedicated to the underrecognized field of integrative medicine. Guest edited by family physician Tiffany Mullen, DO, the issue shed light on the clinical roles of healthy diet, herbal supplements, acupuncture, tai chi and sleep patterns, among other holistic practices.

Sponsored by Robyn Temkin Memorial Fund, JPCRR is a multispecialty medical journal overseen by Editor-in-Chief Leslie Waltke, DPT, receives the 2015 JPCRR Dennis Baumgardner, MD, managing Article of the Year Award from Aurora Research editor Joe Grundle and production Institute President Randall Lambrecht, PhD. manager Julie Walters.

7 Aurora Research Institute | Annual Report 2015 Recognizing our best people Awardees Sixth Annual Greater Milwaukee Clinical Research Recognition Event 2015 Greater Milwaukee Held September 30 at Aurora St. Luke’s Medical Center, Aurora Research Award Recipients Institute recognized achievements in research by Aurora Health Care Subject Hero Award caregivers in the Greater Milwaukee area. Craig Hummer (see page 19)

Focus on Innovation Clinical Trials Research Award Elizabeth Marriott, MD Daniel O’Hair, MD, shared the successes Richard Rovin, MD, of Aurora’s Transcatheter Aortic Valve shared robotic optical Investigator-Initiated Research Award Replacement Program, which has grown imaging advances for Michael Michalkiewicz, PhD from involvement in clinical trials to a the care of patients with Senior Investigator Award destination for patients with aortic stenosis neurological disorders that Joseph Davies, MD throughout the United States and abroad. Aurora is leading. New Investigator Award Ulugbek Negmadjanov, MD

Research Champion Award Michael Mullane, MD

Research Team Award Biorepository and Specimen Resource Center (Natalie Polinske, MS, Anne-Marie McAnelly, Kujana Clayton, Brittany Last)

Research Service Award Ashley Gehrand, MS Whitney Jacobson, BSN Robyn Shearer, MS

JPCRR Article of the Year Award Leslie Waltke, DPT

2015 Green Bay Award Recipients

Medical Educator of the Year Award Ashwani Bhatia, MD

Medical Education Department of the Year Award Fall Research and Medical Education Reception Obstetrics and Gynecology Held October 1 at Aurora BayCare Orthopedic and Sports Medicine Center, Aurora Principal Investigator Award BayCare Medical Center recognized achievements in research and education by Brandon Scharer, DPM Aurora Health Care and BayCare Clinic caregivers in the Green Bay area. Jason DeVries, DPM Innovation Award Focus on Innovation Danzhu Guo, MD Danqing Guo, MD Danzhu Guo, MD, and Danqing Guo, MD, shared their innovative way to treat carpal tunnel. Lifetime Achievement Award Paul Summerside, MD

Paul Summerside, MD, former chief medical officer at BayCare Clinic, retired at the end of 2015, closing the book on an 18-year career with the Green Bay-based health organization. Summerside, emergency medicine physician and research champion, most recently served as president of BayCare Joint Ventures, where he oversaw the organization’s external partnerships and related strategies.

aurora.org/research 8 Academic relations

Cultivating future researchers Through different internship opportunities this past summer, 18 students gained valuable insights about research and, in turn, supported a variety of initiatives.

Mentors from Aurora Research Institute, Aurora UW Medical Group, Aurora Health Care Metro and Aurora BayCare Medical Center provided promising future researchers opportunities that will give them an edge as they pursue careers in medicine and other health care professions.

Aurora Research Institute Aurora Health Care Metro Medical Staff Summer Student Internship Program Summer Research Fellowship Program

Led by: Randall Lambrecht, PhD, and Vani Nilakantan, PhD Led by: Neil Guenther, MD, and Hershel Raff, PhD

Supported by: physicians who donate to Aurora Health Care Foundation’s Medical Staff Endowment Fund MAX ALBIERO Year/University: senior/University of Wisconsin-Madison Project: MGMT inhibition leads to CDK4/6 inhibition and enhances palbociclib’s activity in breast cancer TANVIR BAJWA JR. Mentors: George Bobustuc, MD, Santhi Konduri, PhD Year/University: junior/Loyola University, Chicago Project: Studies on Ca2+ mobilization capacity in cardiac fibroblasts DANIEL BAKER from failing hearts Year/University: senior/University of Wisconsin-Madison Mentor: Gracious Ross, PhD Project: Muriel and Jack Winter Family Research Institute and the Milwaukee Heart Project exhibit CATIE DOWNEY Mentor: Kurt Waldhuetter, MS Year/University: senior/Amherst College, Amherst, Mass. Project: To elucidate mechanism(s) of progressive fibrosis through MEGAN HUBER inhibition of programmed cell death in fibroblasts from human heart Year/University: junior/Oregon State University, Corvallis Mentors: Arshad Jahangir, MD, and colleagues Project: Epidemiology study of blastomycosis in eastern Wisconsin and laboratory study of chemically resistant soil fungi MACIEJ GRACZ Mentors: Dennis Baumgardner, MD, Jessica Kram, MPH Year/University: senior/Marquette University, Milwaukee Project: Blocking of prostaglandin E2 receptor EP2 may be involved MELISSA KERHIN in modifying immune response Year/University: senior/University of Wisconsin-Madison Mentor: John Richards, PhD Project: Effect of teriflunomide on breast carcinogenesis Mentors: Sanjay Kansra, PhD COLE LEONOVICZ Year/University: junior/University of Miami, Florida COURTNEY POKRZYWA* Project: Epigenetic programming of the adult rat phenotype by Year/University: second-year medical resident/University of neonatal hypoxia and hypothermia Wisconsin School of Medicine and Public Health Mentor: Hershel Raff, PhD Project: Use of opioids in chronic, noncancer pain management Mentors: Dennis Baumgardner, MD, Fabiana Kotovicz, MD, Jessica ELIZABETH STOECKL Kram, MPH Year/University: junior/University of Notre Dame, Indiana Project: Ranolazine protects failing human cardiac fibroblasts ALEX REDDY against dronedarone-induced mitochondrial dysfunction and Year/University: junior/University of Wisconsin-Milwaukee oxidative stress Project: RAPID Withdrawal Mentors: Arshad Jahangir, MD, Larisa Emelyanova, PhD, and Mentors: Andy Marek, Jon Cook colleagues

JUSTIN ROUNTREE MIKE WALLACE Year/University: senior/Carroll University, Waukesha, Wis. Year/University: senior/College of Charleston, South Carolina Project: Implications of resting outpatient clinic heart rate among Project: Chemosensitization of malignant gliomas by a natural patients with left ventricular ejection fraction <35% compound Mentor: Scarlet Shi, PhD Mentor: Chang-Hyuk Kwon, PhD

PAYDEN WHITE MEGAN WAPLES Year/University: junior/University of Wisconsin-Madison Year/University: sophomore/Emory University, Atlanta Project: Aurora’s Biorepository and Specimen Resource Center Project: Effects of intravenous immunoglobulin and its glycoforms Mentor: Natalie Polinske, MS, Anne-Marie McAnelly on secretion of antibodies by plasma cells Mentor: Martin Oaks, PhD * Aurora UW Medical Group Department of Family Medicine Summer Student Research and Clinical Assistantship

9 Aurora Research Institute | Annual Report 2015 Aurora BayCare Medical Center interns Shadow Led by: Annette Paul, MAT opportunities

From summer campers to college students, ALEX CHRISTENSEN Aurora Research Institute provides research Year/University: junior/University of Wisconsin-La Crosse training and educational opportunities to create Project: Various oncology database research studies a pipeline of future health care professionals. Mentor: Dhimant Patel, MD Middle-schoolers attending a Discovery World MARK (MAC) GARDON Year/University: postgraduate/Xavier University, Cincinnati summer camp viewed a neurosurgery and Project: Comparing abdominal, laparoscopic and vaginal toured the anatomy lab and Regenerative hysterectomy techniques across the Aurora Health Care system to Medicine Center during a field trip to Aurora determine best practice goals St. Luke’s Medical Center on Aug. 5. Mentor: Brian Dobbins, MD Local media outlet CBS 58 interviewed ASHLEY HEESACKER Nina Garlie, PhD, and some of the students Year/University: postgraduate/University of Wisconsin-Milwaukee for its newscast. Project: Procalcitonin sepsis Mentor: Darren Heesacker, MD

Students from Cardinal Stritch University toured the Regenerative Medicine Center and Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging (CIRCA) at Aurora St. Luke’s on Nov. 19.

The opportunity provided the students with real-world applications for the skills they are learning in school and how they can be translated into careers that involve a variety of laboratory techniques in the future.

aurora.org/research 10 Caregivers who care

In a variety of ways, Aurora Research Institute caregivers support organizations with missions to change lives for the better.

Aurora Health Care Foundation Through Aurora Health Care Foundation’s 2015 Aurora Partnership Campaign, institute caregivers embraced the giving spirit, contributing more than $17,500 to a variety of public agencies, including about $11,350 to Aurora-specific funds. Available during October and November, the campaign provides a way for Aurora caregivers to support internal and external charitable funds.

The institute’s ongoing partnership We help the with Aurora’s foundation also Adopt-a-student program benefitted the neonatal intensive causes we Participating in Aurora Sinai Medical Center’s Adopt-A-Student care unit at Aurora Sinai Medical program, institute caregivers in December fulfilled holiday believe in. Center with a Tradition of Caring wishes of warm clothes, action figures, dolls and more for 16 event sponsorship and raised students who attend Hawthorne Elementary School. In total, Because caring awareness about the translational Aurora adopted 266 students in 2015, donating more than is what we do. research being conducted in the 2,000 gifts for economically disadvantaged students. newly opened Discovery Laboratory.

Taking strides to fight disease Tackling cancer in Milwaukee and Green Bay, institute caregivers, family and friends raised $950 for the Vince Lombardi Cancer Foundation through its Lombardi Walks/ Runs in June. A beneficiary of the Lombardi foundation, the institute also helped sponsor the Vince Lombardi Award of Excellence Dinner Ball in April.

Institute caregivers, family and friends raised $544 for the American Heart Association through its 2015 Milwaukee Heart and Stroke Walk/Fun Run on Sept. 20 at Veterans organized a booth at the AHA event with people donning Park, Milwaukee. Fundraising activities included an inaugural gloves to learn about anatomy with animal hearts and getting basket raffle. Providing a community benefit, the institute a printout of their heart rhythm with portable technology.

11 Aurora Research Institute | Annual Report 2015 Daniel O’Hair, MD Jasbir Sra, MD Co-Vice President, Aurora Cardiovascular Services Co-Vice President, Aurora Cardiovascular Services

Through Dr. O’Hair’s leadership in robotic- One of the leading cardiac assisted surgery, Aurora St. Luke’s Medical electrophysiologists in the country, Dr. Sra Center has become the seventh largest is dedicated to cutting-edge research robotic heart center in the world, a and leads development of advanced ranking that has held since 2001. technologies through his startup company APN Health LLC. Cardiovascular research

79 589 cardiovascular clinical trials open to total cardiovascular clinical trial accrual and follow-up as of Dec. 31, 2015 enrollments in 2015

Electrophysiology (19) 24% Translational (156) 26%

Peripheral Interventional/ Vascular Interventional/ Medical (15) 19% Medical (132) 22% (20) 25% Electrophysiology (179) 30% Congestive Congestive Heart Failure Heart Failure (10) 13% (88) 15%

Translational (2) 3% Peripheral Surgery Surgery Vascular (24) 4% Pulmonary (4) 5% (5) 1% Pulmonary Hypertension Hypertension (9) 11% (5) 1%

>$600,000 in external grant funding awarded for investigator-initiated cardiovascular research studies 35% of Aurora’s research is cardiovascular-related 55% of Aurora’s cardiovascular research is investigator-initiated Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging

Led by medical research director Arshad Jahangir, MD, the Sheikh Khalifa bin Hamad Al Thani Center for Integrative Research on Cardiovascular Aging (CIRCA) is one of a few research centers in the world devoted entirely to study the effect of aging on the cardiovascular system. CIRCA wellness and improve the quality of team of scientists, associates and With the support of a generous life of older people. assistants are studying the molecular $2 million donation from His Highness in basis for the aging heart’s decreased 2014, CIRCA’s mission is to conduct basic, In the Discovery Laboratory at ability to tolerate stress and increased translational and clinical research on the Aurora Sinai Medical Center and the susceptibility to injury and heart biology of aging, and to develop new ways cardiovascular research laboratory rhythm disorders. to predict, diagnose and treat age-related at Aurora St. Luke’s Medical Center, cardiovascular dysfunction to preserve Dr. Jahangir and the CIRCA research

Publications/presentations CIRCA in the news In 2015, the CIRCA team shared its research findings through manuscript 10 CBS 58: TMJ4: publication in peer-reviewed journals published Is your heart Ask the Expert: and abstract presentation at national manuscripts older than What factors affect and international meetings, advancing your age? cardiovascular aging? the collective understanding of the aging heart. 11 Some of the prestigious scientific journals include JACC: Cardiovascular published Imaging, PLoS One, Circulation abstracts Research, Expert Review of Cardiovascular Therapy, Expert Review of Clinical Pharmacology and Cardiology in Review, and esteemed society meetings of the American College of Cardiology, American Heart Association and American Society of Chest Physicians.

(Left) Research associate Kelsey Kraft works in the newly opened Discovery Laboratory on the Aurora Sinai Medical Center campus.

(Below) Senior research scientist Scarlet Shi, PhD, presents some of her cardiovascular research findings during the open house celebration of Discovery Laboratory.

National Institutes of Health To receive grant funding from the National Institutes of Health (NIH), applications are reviewed by members of various scientific study sections. The NIH appoints “the most accomplished, broad-thinking and creative scientists and experts to serve as peer reviewers.”

Dr. Jahangir continued as a peer reviewer for the Myocardial Ischemia and Metabolism study section in 2015. The study section reviews applications for research of myocardial ischemia/reperfusion, coronary circulation and myocardial metabolism.

13 Aurora Research Institute | Annual Report 2015 Intramural funding Through new and continued projects, CIRCA researchers were awarded $230,000 in intramural funding through the Cardiac and Cardiovascular Surgery research award programs.

Research scientist Larisa Emelyanova, PhD, hopes to determine why a drug that helps people with atrial fibrillation can be harmful in patients with heart failure and how this detrimental effect can be avoided by pretreatment with another drug. The study is supported by a new 2015 Cardiac Research Award.

With a new 2015 Cardiovascular Surgery Research Award, research scientist Gracious Ross, PhD, is studying a targeted approach to reducing calcium loading in Research associate Ulugbek Negmadjanov, MD, cardiac fibroblast received the New Investigator Award at the annual Clinical Research Recognition Event. The award cells obtained from recognizes new researchers with less than two patients undergoing years of service at Aurora who show success with open heart surgery. a research project and potential for growth in the research community. The goal of this research is to find a way to slow the progression of heart failure. Study highlight CIRCA launches new induced pluripotent stem cell program

Effective ways to prevent cardiovascular grown from iPS cells. Initially, Dr. Joshi- dysfunction are not available. Results Mukherjee will focus on hypertrophic of animal testing cannot always be cardiomyopathy, a condition in which the translated to patient care as those heart muscle becomes abnormally thick and methods do not completely reproduce affects how the heart functions. the human condition. A lack of cardiac In patients with particular genetic tissue from patients for research abnormalities, this precision medicine purposes is another barrier. initiative may help reduce progression of their A new approach to studying the biology heart condition and prevent development of of cardiovascular disease involves the disease in affected family members. reengineering, or inducing, cells from tissue donated by adult patients into (Above) Research associate Stacie Edwards uses a centrifuge while studying stem cells. pluripotent stem cells, which is an (Below) Research scientist Rosy Joshi-Mukherjee, PhD, obtains stem cells from a freezer. embryonic-like state. From these iPS cells, researchers can grow cardiac cells that contain genetic information, including the mutation that causes disease.

This “disease-in-a-dish” approach allows researchers to study cardiovascular disease biology and different therapies to correct abnormalities that cause cellular dysfunction.

Rosy Joshi-Mukherjee, PhD, a new CIRCA research scientist, has launched an innovative research program to define the underlying causes of abnormal heart function and test therapies in miniature beating hearts

aurora.org/research 14 Funded projects

Institute gives nearly $500,000 in start-up boosts for cardiac-related studies

Researchers are like gardeners. Their In 2015, the institute awarded $498,239 Aurora Health Care Foundation. The hypothesis is the seed. through the Sullivan Cardiac Research Sullivan research award is possible Award for Residents and Fellows, Cardiac thanks to the generosity of Tim And Aurora Research Institute’s Research Award and Cardiovascular Sullivan, a member of Aurora Health internal grant program is like a starter Surgery Research Award to 10 Aurora Care’s board of directors, and his wife pot. Funding from the program gives Health Care investigators to conduct Vivian Sullivan. They donated $1 million researchers an initial boost that cardiac-related research. to support the cardiovascular research spurs future, larger projects with the of interventional cardiologist Tanvir goal of benefitting patients and the The awards are possible because Bajwa, MD, via the fellowship program. community. of the generosity of donors to the

Award highlight 2015 INTRAMURAL AWARD RECIPIENTS Sullivan Cardiac Cardiovascular Surgery Complication prediction model Research Award for Research Awards Transcatheter aortic valve replacement has Residents and Fellows Up to $50,000 each emerged as a minimally invasive approach to Up to $30,000 each treat heart valve disease. Aurora engaged in Vinay Thohan, MD early clinical trials to test the approach using Setu Trivedi, DO Implications of absolute and Medtronic Inc.’s CoreValve – the only health Evaluation and prediction of relative ratio of omega-3 and -6 system in Wisconsin to do so – and was the first complications after transcatheter in physiologic fat reservoirs and in the state to implant the prosthetic valve after it aortic valve replacement using patterns of coronary heart disease in humans (new) received Food and Drug Administration approval. computational methods

CoreValve has since gained FDA approval for use The association between novel Imaad Razzaque, MD clinical factors and gastrointestinal in patients who have previously received a tissue Increased mortality in patients bleeding among patients valve and are in need of a second one. undergoing aortic valve supported with continuous flow replacement: Does undiagnosed Despite its success, complications persist. In left ventricular assist device therapy cardiac amyloidosis play a role? (second-year continuation) collaboration with Marquette University, Setu A research-driven protocol to Trivedi, DO, is laying the groundwork for a detect cardiac amyloidosis with predictive model based on anatomical variations technetium pyrophosphate imaging Gracious Ross, PhD to determine which patients will have the best Store-operated Ca2+ channels in outcomes with the procedure. ventricular fibroblasts as a potential target to prevent progression of Dr. Trivedi received a nearly $30,000 grant Cardiac Research Awards heart failure (new) from the Sullivan Cardiac Research Award for Up to $40,000 each A novel calcium entry mechanism Residents and Fellows for this work. Tanvir Bajwa, MD, and Arshad Jahangir, MD, are serving in myofibroblast as a therapeutic Larisa Emelyanova, PhD target for prevention of cardiac as mentors to Dr. Trivedi. A novel strategy to protect against fibrosis (second-year continuation) dronedarone-induced myocardial dysfunction in the failing heart (new) (From left) Daniel O’Hair, MD, Tanvir Bajwa, MD, and Setu Kourosh Ravvaz, MD, PhD Trivedi, MD, collaborate during a transcatheter aortic valve replacement procedure at Aurora St. Luke’s Medical Center. Predicting the quality of Modulation of mitochondrial postoperative anticoagulation function as a novel approach to therapy following heart valve prevent myocardium injury in replacement surgery the diabetic heart (second-year continuation) Ulugbek Negmadjanov, MD Cytokine-mediated fibroblast Ryan Cooley, MD activation increases resistance A novel pathophysiology-based toward cell death: mechanistic approach to the management of insights and therapeutic postural orthostatic tachycardia complications (second-year syndrome continuation)

Ehkson Holmuhamedov, PhD Martin Oaks, PhD Mitochondrial voltage-dependent Analysis of the Fc glycans of anion channels in pathogenesis of antibodies to HLA antigens in alcoholic cardiomyopathy cardiac and renal transplant candidates (second-year continuation)

15 Aurora Research Institute | Annual Report 2015 2015 EXTRAMURAL Researcher focus AWARD RECIPIENTS Intramural, extramural funding support Since starting with Aurora Health funds, Dr. Thohan is working Michael Michalkiewicz, PhD Care as director of the Advanced to identify clinical factors that National Institutes of Health subaward Heart Failure Therapies program may predict the development of from Vanderbilt University in 2013, Vinay Thohan, MD, has gastrointestinal bleeding in patients $435,127 launched several investigator- with left ventricular assist devices initiated projects with funding – (LVADs). The purpose of the study Integrated, individualized, intelligent totaling nearly $150,000 – from is to improve the selection criteria prescribing (I3P) both internal and external sources. for patients and develop a better understanding of the risks for A nearly $50,000 grant from a Kourosh Ravvaz, MD, PhD patients who receive an LVAD as Cardiovascular Surgery Research National Institutes of Health subaward lifesaving therapy. from Harvard Medical School Award will support collaborative efforts to understand how the ratio A third project supported by the $120,000 of omega-3 and -6 fatty acids in Greater Milwaukee Foundation with Anticlotting simulations to predict tissue and fat stores on the outer a nearly $50,000 grant is targeting optimal treatment for subpopulations layer of the heart may contribute to how best to stratify the risk among coronary heart disease. This work patients with heart disease who Vinay Thohan, MD could lead to greater understanding undergo noncardiac surgery. This Greater Milwaukee Foundation of coronary heart disease changes study may lead to a readily available $48,414 to dietary recommendations to risk-stratifying tool and interventions prevent this disease. that lower risk so patients can The association between Doppler undergo surgeries safely. measures of cardiac diastolic dysfunction Completing work started for a and outcomes among patients separate Cardiovascular Surgery Senior research scientist Scarlet undergoing noncardiovascular surgeries Research Award received in 2014 Shi, PhD, is collaborating on these with nearly $50,000 in additional projects. Growth areas Precision medicine and population health

People who receive a new heart samples stored in the Biorepository comparing the effectiveness of multiple valve are more susceptible to heart and Specimen Resource Center. protocols across different populations. attack and stroke because of the Working with investigators at Through this collaboration, Dr. Ravvaz increased risk of clot formation in Harvard Medical School and received $120,000 from Harvard’s the bloodstream after surgery. The University of Minnesota, Dr. Ravvaz is National Institutes of Health grant to anticoagulation medication warfarin simultaneously trying to further efforts serve as principal investigator of this is the only drug approved by the to personalize warfarin therapy while multiyear study at Aurora Health Care. Food and Drug Administration to prevent strokes and heart attacks in patients with new heart valves. Kourosh Ravvaz, MD, PhD, presents However, warfarin is challenging to the goals of a prescribe as it works well for some collaborative study people, but causes harm in others. with Harvard Medical School With $50,000 support from a and University of Minnesota that will Cardiovascular Surgery Research personalize warfarin Award grant, senior research scientist therapy across Kourosh Ravvaz, MD, PhD, is leading different populations. Dr. Ravvaz received an investigator-initiated precision $120,000 to conduct medicine study to develop a model this research at that will help physicians predict the Aurora Health Care. quality of warfarin therapy in patients undergoing heart valve surgery.

To create and test the prediction model, Dr. Ravvaz and his research team are combining data from Aurora’s electronic health record system with genetic data from blood

aurora.org/research 16 The only recruiting site in Wisconsin

Physician leads nationwide trial on same-day discharge

Does implantation of an implantable cardioverter- Nearly 30 sites enrolled more Image defibrillator require an overnight stay or is it safe to go than 260 subjects receiving courtesy of home the same day? an ICD for primary prevention St. Jude Medical Inc. against sudden cardiac This is a question Indrajit Choudhuri, MD, wanted to answer death. Aurora St. Luke’s so he partnered with Ranjit Suri, MD, of Heart Rhythm Medical Center was the only Associates of New York as national principal investigators recruitment site in Wisconsin. and secured St. Jude Medical Inc. as the sponsor (SDD for ICD, clinicaltrials.gov identifier: NCT01993862). This trial was the first of its kind to clarify that there are no significant differences in complications with either discharge strategy, be it same or next day. Patients readily accepted being discharged on the same day as their procedure. The findings will be presented at the Heart Rhythm Society annual scientific session.

Data collection on patient outcomes continues.

Phyllis Runningen, BSN, is serving as site coordinator.

Registry tracks outcomes of rejection monitoring test

Patients who receive a transplanted St. Luke’s Medical Center is the only This registry trial builds on a previous heart, or an allograft, require long-term recruitment site in the state. trial that found the AlloMap test to be monitoring for possible organ rejection. comparable to biopsy. The goal is to Subjects provide a blood sample The current standard of care calls for enroll about 2,000 subjects and assess at the same intervals as for the invasive biopsies every month or every them for five years. biopsy procedure. Gene expression other month during the first year and of immune system cells are profiled Marilyn Miller, RN, is serving as site biannually thereafter to monitor for using the AlloMap method, which has coordinator. organ rejection. been cleared by the Food and Drug Principal investigator Nasir Sulemanjee, Administration. MD, is tracking short- and long-term outcomes for CareDx Inc.’s AlloMap test, a noninvasive option to avoid the risks and discomforts associated with the biopsy procedure (OAR, clinicaltrials. gov identifier: NCT01833195). Aurora

The goal is to enroll about 2,000 subjects and assess them for five years.

Clinical trial coordinator Marilyn Miller, RN, explains the registry trial that will track short- and long-term outcomes of the noninvasive AlloMap test to a potential subject during the informed consent process.

17 Aurora Research Institute | Annual Report 2015 FDA approvals The only recruiting site in Wisconsin Aurora Research Institute was instrumental in bringing these innovations to market through participation in clinical trials. Physician leads nationwide trial on same-day discharge Trial tests whether CoreValve® Transcatheter Aortic Valve investigational drug System (Medtronic) Expanding the uses for CoreValve, the Food and reduces adverse events Drug Administration in March 2015 approved the valve-in-valve indication for patients who When a person’s heart is unable The purpose of this Phase III previously had their aortic valve surgically replaced to contract normally, it can’t clinical trial is to validate the and need a replacement. CoreValve, implanted via pump with enough force to drug’s safety and effectiveness a minimally invasive transcatheter approach, also circulate blood adequately. to fulfill this unmet need in the is approved for patients who are not candidates These patients with impaired left United States. for surgery. First in the state to implant the ventricular systolic function face artificial aortic valve through a clinical trial, Aurora Researchers plan to enroll an possible complications or death researchers Tanvir Bajwa, MD, and Daniel O’Hair, estimated 760 patients at about when they undergo surgery to MD, continue to study additional uses at Aurora 60 sites in the U.S. and Canada. repair it. St. Luke’s Medical Center, the only recruiting site Jennifer Cooper, BSN, is in Wisconsin for these trials. Michelle Bennett, RN, Frank Downey, MD, is leading serving as site coordinator. Kelly Magee, MSN, Deb Waller, BSN, and Wendy a clinical trial at Aurora St. Schmidt, RN, are part of the team that supports Luke’s Medical Center, the only transcatheter aortic valve replacement trials. recruitment site in Wisconsin, to study the effectiveness (Medtronic) of an investigational drug Evera MRI levosimendan (Tenax Approved by the FDA in September 2015, Therapeutics Inc.) in improving the Evera MRI is the world’s first implantable Registry tracks outcomes of rejection monitoring test outcomes after subjects with cardioverter-defibrillator safe for use with left ventricular systolic magnetic resonance imaging. Atul Bhatia, MD, dysfunction undergo cardiac served as principal investigator at Aurora St. surgery (LEVO-CTS, clinicaltrials. Luke’s, the only recruiting site in Wisconsin for gov identifier: NCT02025621). the international trial. Anthony Chambers, BSN, served as site coordinator.

Praluent (Sanofi U.S.) Researchers study Stephen Welka, MD, is serving as principal investigator at Aurora Memorial Hospital of safety, effectiveness Burlington for a multicenter trial that resulted in FDA approval of Praluent (alirocumab) injection in of bioprosthetic valve July 2015. Praluent is the first cholesterol-lowering treatment approved in a new class of drugs known as PCSK9 inhibitors. Carol Feldhausen, BSN, Not all patients are eligible for investigational valve in the serves as site coordinator minimally invasive transcatheter treatment of subjects with aortic valve replacement. Many moderate or greater aortic WATCHMAN™ (Boston Scientific Corp.) patients still require open heart stenosis, which is narrowing surgery to replace diseased of the valve, or regurgitation, Providing the first-of-its-kind alternative to aortic valves. in which blood flows in the long-term warfarin therapy for stroke reverse direction. risk reduction in patients with David Kress, MD, is leading a nonvalvular atrial fibrillation, clinical trial to study Medtronic No more than 1,300 subjects Boston Scientific Corp. in March Inc.’s Model 400 aortic valve will receive the valve at about 2015 received FDA approval bioprosthesis at Aurora St. 40 sites throughout the United for its WATCHMAN™ Left Atrial Luke’s Medical Center, the only States, Europe and Canada. Appendage Closure Device. recruiting site in Wisconsin Researchers will assess the Jasbir Sra, MD, and Tanvir Bajwa, (PERIGON, clinicaltrials.gov subjects for five years after MD, serve as principal investigators identifier: NCT02088554). implant with regard to valve- at Aurora St. Luke’s for the related adverse events and As part of the Phase III two clinical trials. Anthony Chambers, death. international clinical trial, Dr. BSN, serves as site coordinator. Kress is studying the safety Jennifer Cooper, BSN, is and effectiveness of the serving as site coordinator. Image courtesy of Boston Scientific Corp.

aurora.org/research 18 Patient spotlight Angel or hero? Institute recognizes subject for cardiovascular clinical trial participation

He wrote a story of his experience titled tested,” said Deb Waller, BSN, the Deb Waller, BSN, introduces 2015 Subject “Angels in Our Midst,” and he should research nurse coordinating the trial. Hero Award winner Craig Hummer. count himself among their ranks. “He didn’t know if he would benefit personally and he knew there were When he was 55, Craig Hummer, 57, risks, but he jumped in.” of Muskego suffered a major stroke caused by a hole between the top Implanted in February 2015 by Tanvir two chambers of his heart, otherwise Bajwa, MD, principal investigator known as a patent foramen ovale. of this Phase III trial at Aurora St. Luke’s Medical Center, Hummer was “Apparently I’ve had this condition one of the last subjects randomized since I was born,” Hummer said. to receive the device. Nationwide, To correct it and reduce his chances researchers enrolled 664 subjects, of a future stroke, he decided with testing the device plus stroke support from his wife Kimberly to prevention drugs against the drugs pursue a clinical trial studying the alone for prevention of future strokes. safety and effectiveness of a septal Craig’s Angels Hummer, who remains involved in the occluder device produced by W. L. Kimberly Hummer, wife study for about four more years, said Gore & Associates (clinicaltrial.gov Paul (Layla) Weis Jr., son (daughter-in-law) he is “back to 100 percent, which is identifier: NCT00738894). Jessica Niebuhr, daughter rare for that severe of a stroke.” Kaia, Hadley, Hunter, grandchildren “He took a chance not only for himself, For his willingness to participate in a Anthony Niebuhr, son-in-law but for all of us to try something new, clinical trial – or get his hands dirty as Alvin Kuhn, father-in-law a new treatment that hadn’t been he put it – Aurora Research Institute in Marylyn Kuhn, mother-in-law September recognized Hummer with Scott Kuhn, brother-in-law the 2015 Subject Hero Award. Wade Hummer, brother Roxanne Klejsmits, sister In the news During his acceptance speech, Hummer Donna (Bryan) Neitzel, sister (brother-in-law) thanked the caregivers at Aurora St. Connie (Gary) Lelivelt, sister (brother-in-law) Milwaukee Journal Sentinel: Luke’s from the “top” of his heart. Denise Widenski, sister A close friendship, a quick Mark Hummer, brother Kathy Pluer, sister response, and a tragedy Hummer’s experience should not be used averted to predict outcomes of the clinical trial. Data Eric Hummer, brother collection continues. Scott Stuckart, friend Rory Mulholland, coworker Craig Hummer and grandson Hunter at the Greater Milwaukee Clinical Research Recognition Event. Maurice Parker, foreman (retired) Matt Peters, coworker New Berlin Emergency Medical Services paramedics David Bokerman, MD, emergency medicine physician Umang Shah, MD, neurologist Intensive Care Unit doctors, nurses, nursing aides Deb Waller, BSN, senior research nurse coordinator Tanvir Bajwa, MD, interventional cardiologist Food and Drug Administration clears advanced 3D cardiac mapping system developed at Aurora

Nearly nine years after realizing the need for simpler, cost-effective and innovative techniques, internationally recognized cardiac electrophysiologist Jasbir Sra, MD, received Food and Drug Administration clearance to market a new three-dimensional cardiac mapping system that could transform the treatment of heart rhythm abnormalities such as atrial fibrillation.

Incorporating APN Health LLC, Dr. Sra brought together scientists and engineers from all over the word to work over this unique concept over the last four years. The first product developed by an Aurora Health Care physician to receive FDA clearance, Navik 3DTM can be used to create 3D maps of the cardiac chamber of interest, pinpointing Navik 3D can be used to create three-dimensional maps of the cardiac the exact locations of catheters and guiding them to chamber of interest, pinpointing the exact locations of catheters and guiding them to specific points in the heart to treat arrhythmias. specific points in the heart to treat arrhythmias. It is the first cardiac mapping system that does not require specialized equipment, using existing patient monitoring “Aurora Health Care and the Aurora Research Institute are and fluoroscopic imaging systems in hospital labs. proud to support the work of Dr. Sra and his talented team in the development of this leading-edge technology that “FDA clearance of Navik 3D represents a major milestone,” will ultimately better treat patients with heart irregularities,” said Dr. Sra. “We are proud that we’ve been able to develop said Randall Lambrecht, PhD, president of the institute. a cost-effective and simple technology that will allow “Dr. Sra is a pioneer in his understanding of heart arrhythmias physicians throughout the world to more easily, accurately and we were thrilled to see the FDA clearance of Navik 3D.” and confidently complete their procedures.” APN Health contracted with Aurora to conduct the necessary With backing from Aurora and support from Aurora studies to obtain FDA clearance. The collaboration included Research Institute, the new technology builds on their approval by Aurora’s institutional review board to allow testing commitment to innovation. that helped develop the software. Going forward APN Health has contracted with Aurora to conduct patient studies for further The first product developed improvement before the device sees widespread clinical use. The technology is anchored by a growing portfolio of by an Aurora Health Care patented intellectual property. physician to receive “Our proprietary digital image processing techniques and algorithms provide us with a remarkable platform from which FDA clearance to provide even greater functionality for electrophysiologists,” Dr. Sra said.

Internationally recognized cardiac electrophysiologist Jasbir Sra, MD, works with manager of cardiology research David Krum, MS, to test the Navik 3D cardiac mapping system. The studies necessary to obtain FDA clearance were conducted at Aurora.

aurora.org/research 20 Cardiovascular Research Committees Cardiovascular Research Advisory Committee Cardiovascular Investigator-Initiated Suhail Allaqaband, MD M. Fuad Jan, MD Steven Port, MD Research Committee Khawaja Ammar, MD Bijoy Khandheria, MD Wendy Schmidt, RN Suhail Allaqaband, MD Renuka Jain, MD Vani Nilakantan, PhD Tanvir Bajwa, MD David Kress, MD Mia Stone, MS, BSN Khawaja Ammar, MD (co-chair) Susan Olet, PhD Indrajit Choudhuri, MD Brad Kruger, MAEd, MBA Nasir Sulemanjee, MD Indrajit Choudhuri, MD Jayant Khitha, MD Scarlet Shi, PhD Anthony DeFranco, MD Randall Lambrecht, PhD A. Jamil Tajik, MD Ryan Cooley, MD David Krum, MS Frank Spexarth, RPh Nina Garlie, PhD Mark Mewissen, MD Vinay Thohan, MD Anthony DeFranco, MD Andy Marek Linda Stahovic, MSW, MBA Arshad Jahangir, MD Imran Niazi, MD Kurt Waldhuetter, MS Nina Garlie, PhD Brook Mechelke Nasir Sulemanjee, MD (chair) Vani Nilakantan, PhD Tim Yusk, MS Mary Hook, PhD, RN-BC Tonga Nfor, MD Vinay Thohan, MD Renuka Jain, MD Sara Planton, BSN Arshad Jahangir, MD Imran Niazi, MD Sara Walczak (co-chair)

Cardiovascular Clinical Trials Committee Cardiovascular Research Fellowship Committee Indrajit Choudhuri, MD Jayant Khitha, MD Katie Richter Suhail Allaqaband, MD Renuka Jain, MD Susan Olet, PhD (co-chair) David Kress, MD Wendy Schmidt, RN Khawaja Ammar, MD M. Fuad Jan, MD Robyn Shearer, MS Anthony DeFranco, MD Andy Marek Nasir Sulemanjee, MD (co-chair) (co-chair) Nasir Sulemanjee, MD Nina Garlie, PhD Mark Mewissen, MD (co-chair) Indrajit Choudhuri, MD Jayant Khitha, MD Sara Walczak Arshad Jahangir, MD Tonga Nfor, MD Eric Weiss, MD Nina Garlie, PhD Andy Marek M. Fuad Jan, MD Sara Planton, BSN Arshad Jahangir, MD Tonga Nfor, MD

Cardiovascular volumes – systemwide

Source: Aurora Smart Chart 2013 2014 2015 2013 2014 2015 Cardiovascular surgery Vascular medicine Coronary artery bypass graft Peripheral vascular intervention 1,564 1,710 1,774 882 926 921 (CABG), total With stent 893 954 908 CABG on pump 691 768 792 Without stent 671 756 866 CABG off pump 191 158 129 Endarterectomy 452 504 486 Valve procedures Carotid endarterectomy 282 303 326 Aortic valve replacement 367 446 356 Other endarterectomy 170 201 160 Mitral valve replacement 107 107 104 Abdominal aortic aneurysm repair 153 172 194 Other valve replacement 6 19 19 Endovascular 120 132 166 Aortic valve repair 5 7 8 Open 33 40 28 Mitral valve repair 76 61 69 Thoracic aortic aneurysm repair 92 99 125 Other valve repair 16 8 16 Endovascular 17 22 29 Cardiac ablation-open 100 95 122 Open 75 77 96 Interventional cardiology Lower extremity bypass 157 175 109 Heart catheterization, total 9,449 9,394 8,194 Extracranial intervention 73 34 37 Cardiac catheterization 7,266 7,049 6,057 With stent 67 33 28 Angiogram without pressures 2,183 2,345 2,137 Carotid stent 63 28 24 Coronary intervention 2,590 2,568 2,376 Other extracranial stent 4 5 4 With stent 2,448 2,441 2,228 Without stent 6 1 9 Drug-eluting stent only 2,086 2,129 2,010 Intracranial intervention 13 6 8 Bare-metal stent only 326 300 204 With stent 7 5 0 Both 36 12 14 Without stent 6 1 1 Percutaneous coronary Atherectomy 0 0 7 142 127 148 intervention without stent Electrophysiology Myocardial biopsy 434 343 357 EP study 1,113 1,130 951 Patent foramen ovale/atrial septal 135 135 98 Cardiac mapping 948 839 769 defect closure, total Cardioversion 1,052 1,175 1,161 Open 63 75 58 Ablation – percutaneous 1,021 1,050 884 Closed 72 60 40 Pacemaker 878 1,057 982 Transcatheter aortic valve 112 201 272 Single/dual chamber 777 964 896 replacement (TAVR) Cardiac resynchronization Transcatheter mitral valve 101 93 86 3 17 14 therapy-pacemaker replacement (TMVR) Defibrillator 763 805 747 Balloon valvuloplasty 37 40 34 (percutaneous) Single/dual chamber 424 579 536 Heart failure and transplant Cardiac resynchronization therapy-defibrillator 339 226 211 Ventricular assist device 28 44 50 Lead extraction 48 68 59 Heart transplant 22 22 24

21 Aurora Research Institute | Annual Report 2015 Cardiovascular publications 2015 Aurora-authored, peer-reviewed

Jan MF. A tale of two techniques: demystifying the Ohara T, Iwano H, Thohan V, Kitzman DW, Upadhya B, Journal articles/Book chapters myth. J Patient-Centered Res Rev 2015;2:87-94. Pu M, Little WC. Role of diastolic function in preserved Abudiab MM, Wilansky S, Lester SJ, Yousefzai exercise capacity in patients with reduced ejection Jan MF, Allaqaband S, Ammar KA, Fetke S, R, Tyler R, Tajik AJ. Transient apical thickening fractions. J Am Soc Echocardiogr 2015;28:1184-93. Tajik AJ. Right ventricular free wall hematoma: following apical ballooning syndrome: a case series. contemporary multimodal imaging. JACC O’Leary B, Allaqaband S. Subclavian vein Echocardiography 2015;32:1723-7. Cardiovasc Interv 2015;8:e195-6. stenosis/occlusion following transvenous cardiac Agarwal A, Yousefzai R, Jan MF, Cho C, Shetabi pacemaker and defibrillator implantation: incidence, Jan MF, Mewissen MW. Type II endoleak following K, Bush M, Khandheria BK, Paterick TE, Treiber S, pathophysiology and current management. J Patient endovascular repair of infrarenal abdominal aortic Sra J, Werner P, Allaqaband S, Bajwa T, Tajik AJ. Cent Res Rev 2015;2:112-7. aneurysm: innovative transgraft approach to Clinical application of WHF-MOGE(S) classification contemporary management. J Patient Cent Res Parmar H, Beard R, Mewissen MW, Shaikh A, Bajwa for hypertrophic cardiomyopathy. Glob Heart Rev 2015;2:118-26. T. Use of coronary techniques in celiac and hepatic 2015;10:209-19. artery stenting in post-hepatic transplant patients. Kerl JJ, Spexarth FC, Pedersen R, Stone M, Aggarwal S, Jan MF, Agarwal A, Tajik AJ. J Patient Cent Res Rev 2015;2:127-31. Allaqaband SQ, Schulgit JL, Bajwa TK, Gupta Hypertrophic cardiomyopathy associated with sleep AN, DeFranco AC. Beneficial effects of a point- Ping P, Gustafsson ÅB, Bers DM, Blatter LA, Cai H, apnea: serious implications and cogent management of-care bleeding risk calculator on anticoagulant Jahangir A, Kelly D, Muoio D, O’Rourke B, Rabinovitch strategy. Expert Rev Cardiovasc Ther 2015;13:277-84. selection in the coronary catheterization laboratory. P, Trayanova N, Van Eyk J, Weiss JN, Wong R, Ahmad MN, Yusuf SH, Ullah R, Ahmad MM, Ellis Pharmacother 2015;35:388-95. Schwartz Longacre L. Harnessing the power of MK, Yousaf H, Paterick TE, Ammar KA. Multivariate integrated mitochondrial biology and physiology: Khitha J, Bajwa TK. Left atrial appendage closure criteria most accurately distinguish cardiac from a special report on the NHLBI Mitochondria in Heart with the Watchman device: a review of trial results noncardiac causes of dyspnea. Tex Heart Inst J Diseases Initiative. Circ Res 2015;117:234-8 and clinical application. Cardiac Interventions 2015;42:514-21. Today 2015;9(4):65-70. 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J Patient Cent Res Rev implantation of an entirely intracardiac leadless Lead burden as a factor for higher complication 2015;2:139-46. pacemaker. N Engl J Med 2015;373:1125-35. rate in patients with implantable cardiac devices. Calabrò MP, Carerj S, Russo MS, Luca FL, Onofrio J Patient Cent Res Rev 2015;2:17-24. Sengupta SP, Tajik AJ, Khandheria BK. Fundamentals MT, Antonini-Canterin F, Zito C, Oreto L, Manuri L, and applications of echocardiographic methods Korotkov SM, Brailovskaya IV, Shumakov AR, Khandheria BK, Oreto G. Carotid artery intima-media and systems in the electrophysiology laboratory. In: Emelyanova LV. Closure of mitochondrial potassium thickness and stiffness index changes in normal Saksena S, Damiano RJ Jr, Estes NAM 3rd, Marchlinski β channels favors opening of the Tl(+)-induced children: role of age, height and sex. J Cardiovasc FE (eds). Interventional Cardiac Electrophysiology: permeability transition pore in Ca(2+)-loaded rat liver Med (Hagerstown) [Epub 2015 Sep 24]. A Multidisciplinary Approach. Minneapolis, MN: mitochondria. J Bioenerg Biomembr 2015;47:243-54. Cardiotext Publishing; 2015, pp. 65-70. Choudhuri I, Akhtar M. Ventricular tachycardia and Korotkov SM, Emelyanova LV, Konovalova SA, ventricular fibrillation. In: Saksena S, Damiano RJ Jr, Shahreyar M, Mupiddi V, Choudhuri I, Sra J, Tajik AJ, Brailovskaya IV. Tl+ induces the permeability Estes NAM 3rd, Marchlinski FE (eds). Interventional Jahangir A. Implantable cardioverter defibrillator in transition pore in Ca2+-loaded rat liver mitochondria Cardiac Electrophysiology: A Multidisciplinary diabetics: efficacy and safety in patients at risk of energized by glutamate and malate. Toxicol In Approach. Minneapolis, MN: Cardiotext Publishing, sudden cardiac death. Expert Rev Cardiovasc Ther Vitro 2015;29:1034-41. 2015, pp. 867-90. 2015;13:897-906. Kress DC. Indications for surgical ablation of Cusmà-Piccione M, Zito C, Oreto L, D’Angelo M, Shetabi K, Nfor T, Shen F, Gupta A, Bajwa T, tachyarrhythmias: atrial fibrillation/atrial flutter. In: Tripepi S, Todaro MC, Di Bella G, Oreto G, Khandheria Allaqaband S. Association between body surface Saksena S, Damiano RJ Jr, Estes NAM 3rd, Marchlinski BK, Carerj S. Longitudinal strain by automated area and outcomes after percutaneous coronary FE (eds). Interventional Cardiac Electrophysiology: function imaging detects single-vessel coronary interventions: debunking the obesity paradox. A Multidisciplinary Approach. Minneapolis, MN: artery disease in patients undergoing dipyridamole J Patient Cent Res Rev 2015;2:9-16. Cardiotext Publishing, 2015, pp. 921-8. stress echocardiography. J Am Soc Echocardiogr Sra JS, Saksena S. Catheter ablation of atrial flutter 2015;28:1214-21. Machernis NP, Jain R, Anigbogu M, Ammar KA, and fibrillation. In: Saksena S, Damiano RJ Jr, Estes Brauer E, Khandheria BK. Prosthetic aortic valve Di Bella G, Minutoli F, Piaggi P, Casale M, Mazzeo NAM 3rd, Marchlinski FE (eds). Interventional endocarditis with pseudoaneurysm complicated A, Zito C, Oreto G, Baldari S, Vita G, Pingitore A, Cardiac Electrophysiology: A Multidisciplinary by additional rupture of mitral-aortic intervalvular Khandheria BK, Carerj S. Usefulness of combining Approach. Minneapolis, MN: Cardiotext Publishing, fibrosa. Eur Heart J 2015;36:2741. electrocardiogram and echocardiography findings 2015, pp. 847-66. and brain natriuretic peptide in early detection of Mewissen MW. Vascular medicine: a ‘primary’ Sultan S, Viqar M, Ali R, Tajik AJ, Jahangir A. cardiac amyloidosis in subjects with transthyretin specialty. J Patient Cent Res Rev 2015;2:85-6. Essentials of herb-drug interactions in the elderly gene mutation. Am J Cardiol 2015;116:1122-7. Negmadjanov U, Godic Z, Rizvi F, Emelyanova L, with cardiovascular disease. J Patient Cent Res Rev Gheorghiade M, Greene SJ, Butler J, Filippatos Ross G, Richards J, Holmuhamedov EL, Jahangir 2015;2:174-91. G, Lam CS, Maggioni AP, Ponikowski P, Shah SJ, A. TGF-β1-mediated differentiation of fibroblasts is Sundaram PS, Sra J. Utility of unipolar recordings Solomon SD, Kraigher-Krainer E, Samano ET, Müller associated with increased mitochondrial content and for complex Wolff-Parkinson-White ablation. K, Roessig L, Pieske B; SOCRATES-REDUCED cellular respiration. PLoS One 2015;10(4):e0123046. Indian Pacing Electrophysiol J 2015;15:125-9. Investigators and Coordinators (incl. Zwicke D). Effect of vericiguat, a soluble guanylate cyclase Nemutlu E, Gupta A, Zhang S, Viqar M, Todaro MC, Carerj S, Khandheria B, Cusmà-Piccione stimulator, on natriuretic peptide levels in patients Holmuhamedov E, Terzic A, Jahangir A, Dzeja P. M, La Carrubba S, Antonini-Canterin F, Pugliatti P, Di with worsening chronic heart failure and reduced Decline of phosphotransfer and substrate supply Bello V, Oreto G, Di Bella G, Zito C. Usefulness of atrial ejection fraction: the SOCRATES-REDUCED metabolic circuits hinders ATP cycling in aging function for risk stratification in asymptomatic severe randomized trial. JAMA 2015;314:2251-62. myocardium. PLoS One 2015;10(9):e0136556. aortic stenosis. J Cardiol 2016;67:71-9 [Epub 2015 May 21]. Harwani N, Chukwu E, Alvarez M, Thohan V. Nfor T, Shetabi K, Hassan W, Nfor Q, Khitha J, Gupta Todaro MC, Romano G, Carerj S, Clemenza F, Pilato Comparison of brachial vein versus internal jugular A, Bajwa T, Allaqaband S. Clincial outcomes after M, Khandheria BK. Right ventricular free wall strain: vein approach for access to the right side of the heart drug-eluting stents versus coronary artery bypass a predictor of successful left ventricular assist device with or without myocardial biopsy. Am J Cardiol surgery in high surgical risk patients with left main implantation. Tex Heart Inst J 2015;42:87-9. 2015;116:740-3. or three-vessel coronary artery disease. J Patient Cent Res Rev 2015;2:95-103. Turagam MK, Downey FX, Kress DC, Sra J, Tajik AJ, Jahangir A, Jain R. Strain echocardiography and Jahangir A. Pharmacological strategies for prevention LQTS subtypes: mechanical alterations in an electrical Niazi IK, Sperzel J, Heist EK, Rosenberg SP, Ryu of postoperative atrial fibrillation. Expert Rev Clin disorder. JACC Cardiovasc Imag 2015;8:511-3. K, Yang M, D’Avila A, Singh JP. Three-dimensional Pharmacol 2015;8:233-50. cardiac mapping characterizes ventricular Jain R, Bajwa T, O’Hair D, Khandheria BK. Three- contractile patterns during cardiac resynchronization Turagam MK, Mirza M, Werner PH, Sra J, Kress DC, dimensional echocardiography guidance in case therapy implant: a feasibility study. Pacing Clin Tajik AJ, Jahangir A. Circulating biomarkers predictive of papillary fibroelastoma complicating transaortic Electrophysiol 2015;38:1091-8. of postoperative atrial fibrillation. Cardiol Rev valve implantation. Eur Heart J Cardiovasc Imaging 2016;24:76-87 [Epub 2015 Feb 19]. 2015;16:570.

aurora.org/research 22 Vasu S, Little WC, Morgan TM, Stacey RB, Ntim Blauwet L. McNamara D, Delgado-Montero A, Ryo K, Paulus S, Kallio A, Roberts E, Spexarth F, Zwicke WO, Hamilton C, Thohan V, Chiles C, Hundley WG. Marek JJ, Alharethi R, Mather PJ, Modi K, Sheppard R, D. Transitioning patients with pulmonary arterial Mechanism of decreased sensitivity of dobutamine Thohan V, Pisarcik J, Gorcsan J. Right ventricular size and hypertension from intravenous prostacyclin to associated left ventricular wall motion analyses for function at presentation in peripartum cardiomyopathy oral prostacyclin: single-center experience. Chest appreciating inducible ischemia in older adults. are associated with subsequent left ventricular recovery. 2015;148(4_MeetingAbstracts):935A. J Cardiovasc Magn Reson 2015;17:26. J Am Coll Cardiol 2015;65(10S):A973. Pinninti M, Cho C, Thohan V, Cheema OM, Hastings Vizzari G, Pizzino F, Umland MM, Bajwa T, Cho C, Perez R, Shearer R, Kate RJ, Mazumdar D, TE, Crouch J, Downey FX, Sulemanjee NZ. Multi- Khandheria BK. Right ventricular embolization of Nilakantan V. Predictors of acute kidney injury for disciplinary team management is cost effective laser catheter fragment. Eur Heart J Cardiovasc elderly patients who undergo cardiac procedure. in patients during the index hospitalization of left Imaging 2015;16:1048. J Am Coll Cardiol 2015;65(10S):A1850. ventricular assist device implantation. J Heart Lung Transplant 2015;34:S165-S166. Weiss ES. New paradigms in the treatment of acute Cho CC, Shi Y, Shearer R, Sulemanjee NZ, complicated and uncomplicated type B aortic Zwicke DL, Hastings TE, Cheema OM, Thohan V. Pinninti M, Rivera C, Cho C, Thohan V, Hastings TE, dissection. J Patient Cent Res Rev 2015;2:132-8. Echocardiographic predictors of admission among Cheema O, Downey FX, Crouch J, Weiss E, Sulemanjee patients with heart failure with reduced ejection NZ. The effect of severity of renal dysfunction on Yazdani MF, Wang D, Kay J, Kress DC, Ammar KA. fraction. J Patient Cent Res Rev 2015;2:204. clinical outcomes in patients with continuous-flow left Role of perfusion imaging in diagnosing myxoma ventricular assist device implantation. J Heart Lung mimics. Eur Heart J Cardiovasc Imaging 2016;17:216 Downey FX, Pedersen R, Sulemanjee N, Hastings Transplant 2015;34:S229. [Epub 2015 Nov 17]. TE, Cheema O, Zwicke D, Crouch J, Downey CA, Thohan V. Temporal benefits of continuous flow left Riaz A, Ahmad MN, Husain F, Kazmi SS, Husain Yousaf H, Ammar KA, Tajik AJ. Traumatic pulmonary ventricular assist device therapy assessed with SF- I, Yousaf H, Ammar KA, Gupta A. Prevalence of valve injury following blunt chest trauma. Eur Heart 36. J Heart Lung Transplant 2015;34:S75. errors in fractional flow reserve measurement in a J Cardiovasc Imaging 2015;16:1206. high volume tertiary care center. J Am Coll Cardiol Duarte VE, Yousefzai R, Paterick T, Tajik AJ. Familial 2015;65(10S):A1879. Yousefzai R, Khandheria BK. Prosthetic valve Beals-Hecht syndrome associated with bicuspid endocarditis: multiple complications in one patient. aortic valve and right ventricular apical diverticulum. Ross GR, Bajwa T, Kraft K, Cosic M, Emelyanova Eur Heart J Cardiovasc Imaging 2015;16:881. An unusual combination of congenital defects L, Rizvi F, Holmuhamedov EL, Werner P, Tajik AJ, Yousefzai R, Trivedi S, Jain R, Cheema OM, Crouch diagnosed in adulthood by multimodality imaging. Jahangir A. Ventricular fibroblasts expression of Orai1 JD, Thohan V, Khandheria BK. Expecting the Circulation 2015;132:A18260. and Ca2+-influx through ICRAC is increased in human heart failure. Circulation 2015;132:A14694. unexpected: right atrial mass in a transplant Duarte VE, Yousefzai R, Paterick T, Tajik J. Double- patient. ESC Heart Failure 2015;2:164-7. chambered right ventricle diagnoses in late Shahreyar M, Bhandari S, Malik M, Muppidi V, Dang Zito C, Manganaro R, Khandheria B, Oreto G, adulthood by multi-modality imaging. Report of G, Gupta N, Sulemanjee N, Downey FX, Jahangir Cusmà-Piccione M, Todaro MC, Caprino A, two cases with associated aortopathy. Circulation A. Trends, predictors and outcomes of intracranial Pugliatti P, Di Bella G, Carerj S. Usefulness of left 2015;132:A16827. hemorrhage in patients with left ventricular assist device. Circulation 2015;132:A13573. atrial reservoir size and left ventricular untwisting Emelyanova L, Liu M, Yang G, Stoeckl E, rate for predicting outcome in primary mitral Holmuhamedov E, Rizvi F, Ross GR, Downey FX, Shahreyar M, Mirza M, Shearer R, Choudhuri I, Nangia regurgitation. Am J Cardiol 2015;116:1237-44. Tajik AJ, Jahangir A. Fibroblasts from failing human V, Mortada ME, Dhala A, Niazi I, Bhatia A, Sra J, heart exhibit increased sensitivity to dronedarone- Jahangir A. Implantable cardioverter defibrillator induced oxidative stress and cell death. Circulation patients with COPD are at higher risk of early and Abstracts 2015;132:A15690. long-term mortality. Circulation 2015;132:A13665. Agarwal A, Shetabi K, Yousefzai R, Aggarwal Francaviglia L, Petersen R, Stone M, Mortada ME. Shaikh A, Lopez-Mas A, Allaqaband S, Khandheria BK, S, Jan MF, Cho C, Bush M, Khandheria BK, Score big for decreasing mortality: ICD risk score Getenet A, Umland MM, Singh M, Bajwa T. The effect Paterick TE, Tajik AJ. Elevated troponin as a risk model. J Patient Cent Res Rev 2015;2:205. of percutaneous closure of large atrial septal defects marker for reduced global longitudinal strain in on right ventricular function in adults. J Patient Cent hypertrophic cardiomyopathy. J Am Coll Cardiol Garlie N, Hacker T, Schmuck EG, Koch J, Khitha J, Res Rev 2015;2:216. 2015;65(10S):A988. Raval A, Choudhuri I. Feasibility of atrial delivery and tracking of stem cells in a porcine model. Shaikh A, O’Leary B, Bajwa T. Subclavian steal Ahmad MM, Ammar KA, Ahmad MN, Riaz A, Husain J Patient Cent Res Rev 2015;2:215. syndrome treated with endovascular repair. FA, Kazmi SS, Husain I, Gupta A. Coronary aorta J Am Coll Cardiol 2015;65(10S):A695. systolic and diastolic pressure indices: two novel Hashim H, Jan MF, Singh M, Allaqaband S, Bajwa indicators for predicting significant coronary T, Gupta A. Contemporary usage of intra-arterial Shi Y, Cho C, Garlie L, Perez R, Shearer R, Sulemanjee stenosis –– a validation against fractional flow catheter-directed thrombolytic (CDT) power pulse N, Zwicke D, Hastings T, Cheema O, Thohan reserve. J Patient Cent Res Rev 2015;2:216-7. spray with rheolytic thrombectomy in failed CDT V. Echocardiographic markers of implantable alone for acute limb ischemia. J Patient Cent Res cardioverter-defibrillator therapy. J Am Coll Cardiol Ahmad MN, Yusuf SH, Ullah R, Ellis M, Yousaf H, Rev. 2015;2:217. 2015;65(10S):A913. Paterick TE, Ammar KA. Cardiopulmonary exercise testing-based algorithm and its usefulness in clinical Hashim H, Jan MF, Singh M, Allaqaband S, Bajwa Shi Y, Rappelt M, Yousefzai R, Sulemanjee N, Zwicke cardiology. J Patient Cent Res Rev 2015;2:204-5. T, Gupta A. Tertiary center experience of catheter- D, Hastings T, Cheema O, Downey F, Crouch J, Thohan directed thrombolysis for immediately threatened V. Novel pre-implant characteristics associated with 12 Ali Z, Greer DM, Shearer R, Alemu A, Jahangir A. acute lower limb ischemia of native vessels and month risk of gastrointestinal bleeding among patients Androgen suppression effects on heart failure and bypass graft thrombosis. J Patient Cent Res Rev supported with continuous flow left ventricular assist in patients with prostate cancer. J Am Coll Cardiol 2015;2:210-1. device therapy. Circulation 2015;132:A19925. 2015;65(10S):A887. Honoris L, DeFranco A, Port S, Cho C, Li D, Nasir Shuaib S, Mahlum D, Port S. Comparison of Ali ZS, Greer DM, Shearer RL, Gardezi SA, K, Kronmal R, Barr RG, Budoff M. Correlation measurements of left ventricular wall thickness and Jahangir A. Androgen suppression in patients with of coronary artery calcium scoring on ungated cavity size on SPECT MPI to those obtained with prostate cancer increases incidence of combined computed tomography compared to gated cardiac transthoracic echocardiography. Eur Heart cardiovascular outcomes. Stroke 2015;46:ATMP48. computed tomography scans from the multi- J Cardiovasc Imaging 2015;16:i51-2. Ali Z, Greer DM, Shearer R, Gardezi AS, Chandel ethnic study of atherosclerosis. J Am Coll Cardiol 2015;65(10S):A1063. Sulemanjee N, Prasad P, Wolf T, Thohan V. Gender- A, Jahangir A. Effects of testosterone supplement mismatched heart transplants and gene-expression therapy on cardiovascular outcomes in men with low Honoris L, Thohan V. Clinical diagnoses of cardiac profiling score--lessons from the Outcomes AlloMap® testosterone. J Am Coll Cardiol 2015;65(10S):A1346. sarcoidosis. J Am Coll Cardiol 2015;65(10S):A621. Registry (OAR). J Heart Lung Transplant 2015;34:S302. Ammar KA, Ahmad MM, Ahmad MN, Yousefzai R, Jan MF, Basraon J, Allaqaband S, Singh M, Sulemanjee N, Prasad P, Wolf T, Thohan V, Teuteberg Krishnaswamy J, Khandheria BK, Jain R, Tajik AJ. Walczak S, Bajwa T. Sixty is the new ninety: ten year J. Can gene-expression profiling score help explain the Is hypertrophic cardiomyopathy associated with experience of the in-hospital 24x7 interventional adverse clinical outcomes seen in gender-mismatched aortopathy: an imaging and epidemiologic case cardiology team. Circulation 2015;132:A12775. heart transplants? Am J Transplant 2015;15(suppl 3). control study. Circulation 2015;132:A16188. Available at: http://www.atcmeetingabstracts.com/ Kazmi SS, Riaz A, Ahmad MN, Husain FA, abstract/can-gene-expression-profiling-score-help- Ammar KA, Ahmad MN, Riaz A, Husain FA, Kazmi Husain I, Yousaf H, Shah S, Ammar KA, Gupta A. SS, Yousaf H, Husain I, Gupta A. Coronary aorta explain-the-adverse-clinical-outcomes-seen-in-gender- A baseline Pd/Pa of ≤ 0.86 obviates the need for mismatched-heart-transplants/. diastolic pressure index: a new novel indicator for FFR measurement and adenosine infusion in predicting significant coronary stenosis. A validation intermediate coronary stenoses: a large tertiary care Thandra K, Hussain J, Shahreyar M, Bhandari S, Thakur against fractional flow reserve. J Am Coll Cardiol experience. J Am Coll Cardiol 2015;65(10S):A1738. A, Dang G, Jahangir A. Severe sepsis and cardiac 2015;65(10S):A1942. arrhythmias. Chest 2015;148(4_MeetingAbstracts):47A. Ortiz D, Petterson ME, Singh M, Jahangir A, Ammar KA, Husain FA, Kazmi SS, Riaz A, Ahmad MN, Allaqaban S, Gupta A, Mewissen MW. Outcomes Velagapudi S, Khaled ZN, Omery B, Zahwe F, Yousaf H, Husain I, Gupta A. Coronary aorta systolic after bivalirudin versus unfractionated heparin Anigbogu M, Zukkoor S, Choudhuri I. Real-world pressure index: a novel index of evaluating coronary during peripheral vascular intervention. J Am Coll relevance of manual electrocardiography QT interval artery stenoses based on peak systolic pressure Cardiol 2015;65(10S):A2123. measurement. J Patient Cent Res Rev 2015;2:213. gradients. J Am Coll Cardiol 2015;65(10S):A1886. Paulus S, Kallio A, Roberts E, Spexarth F, Zwicke Zwicke D, Paulus S, Pinninti M, Khandheria B, Ayers AM, Cho CC, Shearer R, Jan MF, Gupta A. Stent D. Transitioning patients with pulmonary arterial Bajwa T, Kramer C, Thohan V. Recognition and thrombosis: regional prevalence, risk factors, and hypertension from inhaled prostacyclin to oral clinical importance of a newly identified interatrial outcomes. J Patient Cent Res Rev 2015;2:208-9. prostacyclin: single-center experience. Chest shunt (tunneled atrial septal defect) in patients 2015;148(4_MeetingAbstracts):936A. with pulmonary hypertension. Chest 2015;148(4_ MeetingAbstracts):926A.

23 Aurora Research Institute | Annual Report 2015 James Weese, MD Vice President, Aurora Cancer Care

Board-certified in surgery, Dr. Weese leads multidisciplinary cancer specialists dedicated to cutting-edge research throughout Aurora Health Care.

Oncology research

172 348 oncology clinical trials open to accrual total oncology clinical trial and follow-up as of Dec. 31, 2015 enrollments in 2015

Breast (50) 29% Breast (192) 55% Gynecology (33) 19% Other (28) 16% Hematology (43) 12% Hemotology (20) 12% Other Renal Cell (10) 3% (5) 3% Gynecology (8) 2% Colorectal Colorectal (32) 9% (11) 6% Lung Prostate (13) 8% Renal Cell Prostate Lung (12) 7% (11) 3% (26) 7% (26) 7%

$225,000 in external grant funding awarded for investigator-initiated oncology research studies 41% of Aurora’s research is oncology-related 17% of Aurora’s oncology research is investigator-initiated Translational Oncology Research: Quest for Understanding & Exploration

Through her research program, medical director Judy Tjoe, MD, is dedicated to changing the face of breast cancer care and survivorship. Translational Oncology Research: TORQUE Quest for Understanding & Exploration (TORQUE) spans the spectrum from survivorship to clinical for longitudinal epidemiological and and lab-based research. Under the biomarker analyses. TORQUE umbrella, researchers study Based at Aurora Sinai Medical Center, the effects of exercise after cancer Dr. Tjoe collaborates internally with treatment through Team Phoenix. researchers in the Discovery Laboratory Employing a “bedside-to-bench” to study ways to trigger the patient’s approach, TORQUE scientists own immune system response to fight leverage patient data in the electronic cancer. Externally, she works with health record against tissue and biotechnology companies to better blood samples in the Biorepository understand how cancer develops, Brittany Last and Christian Donohoe, BSN, and Specimen Resource Center at discover biomarkers and develop new discuss a subject enrolled in multiple breast Aurora St. Luke’s Medical Center targeted drug therapies. cancer clinical trials.

Publications/presentations In 2015, Judy Tjoe, MD, shared her research findings through manuscript 2 and abstract publication in peer- reviewed journals. published manuscripts Notably, Dr. Tjoe et al. standardized best-practice care throughout Aurora Health Care by evaluating breast cancer diagnostic practices. 2 The evaluation led to collaboration published among surgeons and radiologists abstracts to make minimally invasive biopsy the diagnostic modality of choice systemwide. Her poster presentation on the study at the American College of Surgeons 2014 Clinical Congress was recognized as the Faculty Presentation of the Year by Aurora University of Wisconsin Medical Group. The findings were later published in the Journal of the American College of Surgeons and Dr. Tjoe was interviewed about the study for a MedicalResearch.com article.

Tom Smith and John Richards, TORQUE in the news PhD, analyze breast cancer cells using flow cytometry in the newly opened Discovery Laboratory. Flow TMJ 4: CBS 58: Kenosha cytometry is a core feature of the Ask the Expert: Team Phoenix News: new lab. What to do empowering women Cancer after a cancer who have survived survivors train diagnosis breast cancer for triathlon

Waukesha Freeman: FOX 6/FOX 11: Purple people leaders: “One small step at a time,” Cancer survivors Team Phoenix program that compete in triathlons to culminates in triathlon helping keep cancer at bay cancer patients heal

25 Aurora Research Institute | Annual Report 2015 Effects of exercise posttreatment: Team Phoenix survivorship program The Team how exercise affects heart function after Phoenix cardiotoxic breast cancer treatments as survivorship part of continuing efforts between TORQUE Team program helps ™ researchers and Marquette University. motivate breast PHOENIX Survivorship Rede ned Immunology and endocrinology researchers cancer survivors John Richards, PhD, and Hershel Raff, PhD, and improve together with collaborators at Marquette their quality of are investigating ways to improve quality life. Led by Judy Tjoe, MD, and cancer of life by reducing cancer-related fatigue in rehabilitation specialist Leslie Waltke, patients who have undergone treatment. DPT, patients train under medical guidance for a triathlon, learning best Studies conducted by TORQUE researchers practices for removing physical and are supported by generous donors. In 2015, psychological barriers for initiating and Team Phoenix received $25,000 from Vince maintaining a regular exercise routine Lombardi Cancer Foundation. after cancer treatment. Leslie Waltke, DPT, and Judy Tjoe, MD, Exercise physiologists and cardiologists lead the Team Phoenix breast cancer are working collaboratively to study survivorship program in which patients train under medical guidance for a triathlon. Patient spotlight Giving of yourself: Tissue donation advances research

Meaningful breast cancer research Quite the gem requires the focused energies of Ruby Stommel on A giving woman, Stommel hopes to invested patients, clinicians, scientists tissue donation: get back to her volunteerism, pushing and industry to create forward-moving wheelchairs at the local hospital and scientific momentum. “... if I could help playing games with residents at a nearby This collaborative atmosphere includes someone and save assisted living facility. TORQUE researchers and industry Her tissue is a valuable gift as it may partner Stemcentrx Inc. using residual them the grief that we contain hidden clues – genetic biomarkers tissue donated by patients to study went through? It was – that could lead researchers to predict the molecular makeup of tumor cells in which patients are susceptible to avatars, which improves understanding an easy decision.” progression from noninvasive to invasive about how cancer develops, allows disease. This knowledge may result in less discovery of genetic biomarkers and use of radiation, avoidance of potential spurs development of new targeted fellowship-trained breast oncology side effects and prevention of unnecessary drug therapies. surgeon Judy Tjoe, MD. surgery to remove one or both breasts. Breast cancer “There was so much information,” Without this knowledge, patients choose to survivor Ruby Stommel said. “Dr. Tjoe spent avoid the risk of recurrence. Stommel, 71, two hours with us. She went over of West Bend absolutely everything, even drawing “Choosing a bilateral mastectomy was willing diagrams.” ultimately was my decision,” Stommel said. to contribute “I didn’t want to take a chance of cancer her residual Stommel endured nine hours of coming back.” tissue after surgery for a bilateral mastectomy, TORQUE researchers continue to search approached four rounds of chemotherapy and for these biomarkers and develop genetic by certified reconstructive surgery. tests through additional partnerships clinical research “Throughout all of it, I tried to remain with Genentech Inc., Rock River Cancer coordinator focused and positive,” Stommel said. Research Foundation, Celcuity LLC and Brittany Last. “I couldn’t have done it without my others. “What good was it doing me?” husband of 52 years (Dick). He did Stommel asked. “And if I could help things for me. He was super.” someone and save them the grief Now Stommel is cancer-free. that we went through? It was an easy decision.” “I was told to go ahead and live my life,” she said. “It’s made me appreciate Ruby’s story what I have a little more and it’s made Diagnosed during a regular check- me thankful. I have six grandchildren I up, Stommel was put in touch with need to live for.” Early Phase Cancer Research Program

Led by medical research director Michael as a member of the ASCO Cancer 2009 2 Thompson, MD, PhD, the Early Phase Research Committee. He is also chair- 2010 1 Cancer Research Program is gaining 201 1 5 elect for the ASCO Community Research momentum at Aurora Health Care. 2012 2 Forum and chair-elect to the ASCO Cancer Education Committee as well as Ten early phase cancer clinical trials 2013 12 member of numerous other research and received initial Institutional Review Board 2014 8 educational activities at the national level. approval in 2015, a testament to the 2015 10 program’s mission to provide more early 0 2 4 6 8 10 12 (Phase I and II) therapeutic clinical trials Publications/presentations No. of early phase clinical trials offering the latest options for patients In 2015, Dr. Thompson shared his with cancer. research findings through manuscript Based on statistical power, Phase I trials A clinical trials advocate, Dr. Thompson publication in peer-reviewed journals evaluate safety and Phase II assess how was selected for the American Society and abstract presentation at national well investigational treatments work of Clinical Oncology (ASCO) Best and international meetings. before they can be tested against the Practices in Cancer Clinical Trials current standard of care (Phase III trials). Initiative. The process culminated with stakeholders collaborating on In the four years prior to Dr. Thompson best practices in clinical research, joining Aurora in 2013, two to three early 6 3 with the goal of promoting practical phase cancer clinical trials, on average, solutions to meeting existing regulatory published published received IRB approval a year. That and administrative requirements on manuscripts abstracts number increased to 12 in 2013, 8 in research. Dr. Thompson continues 2014 and 10 in 2015.

In the news Clinical trial spotlight

MDigitalLife press release: Genetic testing to guide chemotherapy Correcting and replacing new analysis of cancer-related tweets shows Testing the theory that therapy to genetically directed therapy will emergence of physician “superusers” designed for each individual’s tumor receive one of 12 different types will improve outcomes, Aurora Health of chemotherapy based on their Mayo Clinic News Network Care in 2015 joined a multicenter molecular biomarkers, indicators press release: Phase II clinical trial that uses genetic that may predict which treatment Leading experts prescribe how to testing to guide chemotherapy will best work against that particular make cancer drugs more affordable prescription in patients who did person’s tumor. not respond to treatment before M Magazine article: surgery and have residual breast cancer after surgery. New cancer centers provide lifesaving treatments Sponsored by Bryan Schneider, MD, of the Indiana University Melvin and Milwaukee Journal Bren Simon Cancer Center, the goal Sentinel article: of the trial is to compare two-year Overhyped stories on new cancer survival rates of subjects treated drugs do more harm than good with neoadjuvant chemotherapy with and without the information genetic Healthcare testing can provide (clinicaltrials.gov Professional Digital identifier: NCT02101385). Opinion Leaders blog: Researchers from about 25 study Digital Opinion Leaders have twice locations plan to enroll more than the reach online, shows ASCO study 130 subjects. Principal investigator Michael Thompson, MD, PhD, is leading Healthy Living article: the research at Aurora Health Care. Hashtags help organize online conversations about cancer Subjects with residual breast cancer care, research after surgery who are randomized

27 Aurora Research Institute | Annual Report 2015 Institute gives nearly $200,000 in start-up boosts for cancer-related research studies

Aurora Research Institute awarded $194,360 Pictured at left, through the Aurora Cancer Care Research James Weese, MD, vice president of Award to seven Aurora Health Care Aurora Cancer Care, investigators to conduct cancer-related receives a check for research. $2.2 million from Brent Morris on Funds for the program are available due to a behalf of the Vince Lombardi Cancer generous $1.2 million gift from Vince Lombardi Foundation. More Cancer Foundation. Read about how the gift than half the funds also is supporting the development of Aurora’s went to research. neuro-oncology research program on page 37.

2015 Aurora Cancer Care research award recipients Up to $25,000 each Study highlight

Sanjay Kansra, PhD* Reducing suffering for patients with advanced cancer Interrogating the primary and recurred lesions of breast atypia for With advanced cancer, open lines of different aspects of palliative care. concordance/discordance in their communication among caregivers, The purpose is to improve patients’ core cancer signaling networks the patient and family members can understanding of prognosis and ease difficult end-of-life discussions. treatment expectations and assess Kourosh Ravvaz, MD, PhD effectiveness of communication Hematologist oncologist Predicting clinical validity of bladder between the care team and family Cheruppolil Santhosh-Kumar, cancer nomograms and between the patient and MD, is assessing the impact of family. Richard Rovin, MD outpatient family conferences on Isolation and characterization of quality of life and satisfaction of The goals are to reduce suffering cancer stem cells from metastatic patients with advanced cancer for patients with advanced cancer brain tumors (read more on page 38) using $25,000 support from an and to offer a model for other Aurora Cancer Care Research institutions to follow in dealing with Cheruppolil Santhosh-Kumar, MD Award grant. such sensitive topics. Dr. Santhosh- Outpatient family conferences Kumar presented preliminary The Vince Lombardi Cancer Clinic in advanced cancer to improve findings at the American Society in Sheboygan is the pilot site for communication of Clinical Oncology 2015 Palliative the study. Attending the family Care in Oncology Symposium conferences are the oncologist, a Amin Kassam, MD in October. The abstract was nurse navigator, a social worker, Establishment of brain tumor stem published in the Journal of Clinical an occupational therapist, the cell bank (second-year continuation) Oncology. patient and loved ones. During the Santhi Konduri, PhD conferences, patients learn about Preclinical evaluation of disulfiram as combination therapy in breast cancer (second-year continuation) FAMILY

Preclinical evaluation of disulfiram as CONFERENCES combination therapy in pancreatic cancer (second-year continuation) Nurse Patient & Social Occupational Oncologist Navigator Loved Ones Worker Therapist Dhimant Patel, MD A Phase I/II study to determine the safety and efficacy of curcumin in patients with oral mucositis Improved Knowledge of secondary to chemotherapy and/or Palliative Care Aspects radiation (second-year continuation)  Radiation Oncology  Dietician  Interventional Radiology  Pharmacy * Due to staffing changes, this project is  Psychology  Pain Management temporarily on hold. Funding will be used  Chaplain  Integrative Medicine to resume the biomarker analysis in 2016.

aurora.org/research 28 Patient spotlight One and not quite done: Patient agrees to be followed for clinical trial

A new option for treating early stage “They said my eyes lit up right away,” breast cancer, available in Wisconsin “I thought ‘go Blashka said. “(IORT) was less invasive only at Aurora BayCare Medical Center, and you wouldn’t have to go back for provides select patients with one targeted for it.’ They might radiation.” dose of radiation during surgery rather find a cure for With IORT, radiation delivery time is than the traditional method of 33 doses about 20 to 35 minutes during surgery. over the course of more than six weeks. this someday and With the support of her husband, As part of a national clinical trial, William we might have Richard, three children, five grandchildren Owens, MD, is leading the research at and other family and friends, Blashka is Aurora BayCare to treat select patients helped.” cancer-free. with intraoperative radiation therapy (IORT) and then follow the patients Mary’s story “They were behind me 100 percent,” for complications and breast cancer Blashka said. “My husband was with me recurrence (TARGIT-US, clinicaltrials.gov After finding a lump, Blashka the entire time.” identifier: NCT01570998). underwent testing – mammography, ultrasound and, eventually, biopsy. Other than the expected recovery from Opting for the Her diagnosis was breast cancer. undergoing surgery, Blashka suffered new treatment, none of the side effects from traditional Mary Blashka, “Dr. Owens was excellent from radiation therapy to the breast, such as 67, of Manitowoc day one,” Blashka said. “He writes redness, discomfort and fatigue. agreed to enroll everything down for you and charts in the registry it out.” Trial details trial, which Because the cancer was diagnosed University of California-San Francisco is requires physical at an early stage and did not have sponsoring the trial with a goal to enroll examinations aggressive characteristics, she 755 subjects at about 25 sites in the at least every was eligible for IORT. Dr. Owens United States. Patients selected for six months for informed Blashka that she could have breast-conserving surgery who are three years and lumpectomy rather than mastectomy considered to have a low risk of recurrence yearly at four and to surgically treat her breast cancer, may be eligible. It is estimated that 25 five years post- but traditionally the lumpectomy would percent of new breast cancer patients treatment. then be followed by weeks of radiation. at Aurora BayCare will qualify. “I thought ‘go for it,’” said Blashka, who It was welcome news when she learned Sarah Peterson, RN, is serving as site underwent surgery in October 2015. that because of the clinical trial at coordinator for the clinical trial. “They might find a cure for this someday Aurora BayCare, she qualified to have and we might have helped.” the radiation performed as a single treatment during surgery. Blashka’s experience should not be used to predict outcomes of the clinical trial. Data collection continues.

Clinical trial for bladder cancer treatment tests chemotherapy prior to surgery

Patients with bladder cancer that is surgery (clinicaltrials.gov identifier: likely to recur and spread typically NCT02412670). Researchers are studying undergo surgery to remove the affected This National Cancer Institute Phase initiation of chemotherapy upper urinary tract. However, this II trial is sponsored by Eastern prior to surgery. surgery often affects kidney function, Cooperative Oncology Group (ECOG)- preventing patients from receiving American College of Radiology chemotherapy after surgery. be more effective in killing or stopping Imaging Network (ACRIN) Cancer the growth or division of tumor cells. Rubina Qamar, MD, is leading a clinical Research Group. Blood, urine and tumor specimen from trial at sites throughout Aurora Health Researchers are testing whether the about 60 patients to be enrolled will Care to test an investigational approach chemotherapy before surgery, when the be evaluated for potential markers of to aggressive urinary tract cancer kidneys are at peak performance, may chemotherapy response or resistance. of initiating chemotherapy prior to

29 Aurora Research Institute | Annual Report 2015 Results show combination therapy extends life in advanced prostate cancer; follow-up continues

Only a small percentage gov identifier: NCT00309985). (ACRIN) Cancer Research Group. of prostate cancers Rubina Qamar, MD, serves as principal Nationwide, sites enrolled 790 subjects spread, and for most investigator at Aurora Health Care. who will be followed for up to 10 years. patients with advanced Produced in the testicles and adrenal prostate cancer there glands, androgens can cause prostate is no cure. Current cancer cells to grow. The current An investigational treatments attempt standard of care is androgen ablation to slow its spread, combination therapy therapy, a minimally invasive procedure improving survival and that destroys abnormal cells. The quality of life. purpose of this Phase III clinical extended life Results from a clinical trial was to determine if adding the trial showed that an investigational chemotherapy drug docetaxel, which by more than combination therapy extended life works in a different way to stop the by more than a year for men with growth of cancer cells, is more effective a year metastatic prostate cancer. Published in in improving survival. for men with The New England Journal of Medicine This National Cancer Institute trial is in 2015, the results of the CHAARTED metastatic prostate sponsored by the Eastern Cooperative trial compared chemotherapy plus Oncology Group (ECOG)-American androgen ablation therapy to androgen cancer. College of Radiology Imaging Network ablation therapy alone (clinicaltrials. NCORP update Aurora NCORP on track to double enrollments

In the first year of its five-year grant, Aurora NCORP doubling enrollment from the year increased enrollments in National Cancer Institute-sponsored before the grant was available. clinical trials from 84 to 140. New membership to the Wake In August 2014, NCI designated Aurora Health Care as one of Forest, University of Rochester 34 institutions in the country an NCI Community Oncology Cancer Center and Alliance Research Program site. With the designation comes $3.9 for Clinical Trials in Oncology million over five years to bring NCI-sponsored clinical trials research bases played a key role directly to the community. in increasing patient enrollment.

Led by principal investigators Thomas Saphner, MD, and NCORP includes a range of Michael Thompson, MD, PhD, Aurora NCORP is on pace cancer prevention, screening, to reach 165 enrollments in year two of the grant, nearly control and treatment clinical trials. Currently, there are more than 50 NCI trials open to enrollment throughout Aurora.

An example of a cancer control study, which focuses on Aurora Health Care was the enhancing quality of life and cancer care, is URCC’s PSYCH (Evaluation of Psychoeducation for Cancer Patients Eligible for Clinical Trials, clinicaltrials.gov identifier: NCT02054715). top NCORP site Aurora researchers recruited subjects to determine how different educational interventions affect patient in the Midwest to credit clinical trial preparedness for clinical trial participation.

enrollments to research group NRG Aurora NCORP also features precision medicine, studies Oncology for 2014-2015. Aurora like the ALCHEMIST trials (clinicaltrials.gov identifiers: NCT02194738, NCT02193282, NCT02201992). Using NCORP ranked fourth nationwide a subject’s genetic information, researchers prescribe for enrollments among NCORP sites treatment targeted specifically to genetic abnormalities. Neha Glandt serves as the research program administrator affiliated with the group. in collaboration with oncology clinical trials manager Jan DeBartolo, MSN.

aurora.org/research 30 Wife’s legacy continues to live on as center’s focus transitions to cardio-oncology specialty

Karen Yontz Women’s Cardiac patients at greatest risk for developing Awareness Center, located inside Aurora cardiac toxicity so that their physicians St. Luke’s Medical Center, has offered can individually tailor drug dosing education about heart disease to women and cardiac monitoring when using for 20 years. Ken Yontz made the initial drugs with the potential to cause heart gift that helped start the center in 1996 disease. in honor of his late wife Karen. Going “This could change how cancer patients forward, its focus will shift to the rapidly are cared for in the future,” Dr. Weese evolving cardio-oncology specialty. said. “Especially women, as many of the “This new focus will really fit well into drugs being studied are often used to the cause of Karen’s death,” Ken said. treat breast cancer.” “She had Hodgkin’s in her 20s and had a Dr. Khandheria said some patients, significant amount of chemotherapy and depending on their risk, will require radiation. She died from a heart attack heart screenings before, during and at the age of 48. Her heart disease was after their cancer treatment to see what all related to her cancer treatment.” kind of effect chemotherapy is having That all too common result is precisely Artist rendering of Karen Yontz, who died on the heart. at age 48 of a heart attack related to cancer the kind of tragedy the cardio-oncology treatment she received in her 20s for Ken is excited about the impact the specialty was created to prevent. The Hodgkin’s lymphoma. program is going to have. new program, dubbed Karen Yontz Center for Cardio Oncology at Aurora “I’m just really encouraged,” Ken said. Health Care, will be one of the first of said cardiologist Bijoy Khandheria, MD. “The doctors who are involved are its kind to feature a unique collaboration “This will allow us to track any cardiac extremely impressive individuals and between cardiology and cancer service side effects resulting from the cancer they are very engaged. There’s a real lines, advancing an initiative that has treatment and modify treatment plans need for this.” gained traction over the past few years. as appropriate.” “Because of donors like Ken, we’re “We’re building a database that will James Weese, MD, vice president of going to advance the field and not just monitor patients who are treated with Aurora Cancer Care, said the center compete in it,” Dr. Weese said. “This is potentially cardiotoxic chemotherapy,” will use molecular studies to find those setting a new standard.” Studying Cardio-Oncology

Launching of Karen Yontz Center for Cardio Oncology at Aurora Health Care will advance Aurora-based research of new and better ways to diagnose and treat patients susceptible to the cardiotoxic effects of certain chemotherapy drugs. Existing research includes:

• In August 2015, Aurora authors • A meta-analysis led by • A special issue on Bijoy Khandheria, MD, Rubina senior research scientist cardio-oncology Qamar, MD, and Charles Scarlet Shi, PhD, reviewed published in summer Bomzer, MD, along with the incidence and risk 2014 has been JPCRR’s several Italian collaborators, factors of cardiotoxicity most popular issue published a manuscript on using the breast cancer to date. Guest edited the different imaging options chemotherapy drug by Drs. Bomzer and used in cardio-oncology in trastuzumab. The findings Khandheria, the Journal of Oncology. The paper were presented at Aurora issue includes the identified the conventional and Scientific Day 2015 and journal’s top four most newer modalities available for the abstract published downloaded articles detecting the earliest alterations in Journal of Patient- – all featuring Aurora of heart function, allowing Centered Research and authors – through the timely treatment management. Reviews. end of 2015. JPCRR Vol. 1, Issue 3: Focus on cardio-oncology

31 Aurora Research Institute | Annual Report 2015 Social Media Support Clinical Trials Department supports #CHUCKSTRONG

Championing cancer research, the Clinical Trials In honor of Indianapolis Colts coach Chuck Pagano, the Department in collaboration with the Vince campaign celebrates champions who exhibit strength, Lombardi Cancer Foundation participated in the perseverance and compassion, and promotes support of #CHUCKSTRONG social media campaign in May 2015. cancer research. Pagano is a cancer survivor.

Oncology volumes (new cases) – systemwide

Source: Cancer Registry 2013 2014 2015* 2013 2014 2015* Primary site of disease Primary site of disease Oral cavity 134 149 210 Female genital 451 528 563 Lip 4 4 2 Cervix uteri 46 55 67 Tongue 44 47 52 Corpus uteri 240 272 291 Oropharynx 9 7 40 Ovary 111 118 123 Hypopharynx 5 10 67 Vulva 39 61 62 Other 72 81 49 Other 15 22 20 Digestive system 1,074 1,036 1,061 Male genital 872 895 935 Esophagus 79 70 89 Prostate 838 851 874 Stomach 81 75 78 Testis 27 36 59 Colon 322 319 420 Other 7 8 2 Rectum 159 143 137 Urinary system 599 580 616 Anus/anal canal 21 27 27 Bladder 376 317 368 Liver 97 78 90 Kidney/renal 202 241 243 Pancreas 205 191 175 Other 21 22 14 Other 110 133 45 Brain & central nervous system 233 366 542 Respiratory system 883 914 931 Brain (benign) 144 280 378 Nasal/sinus 4 7 13 Brain (malignant) 74 73 124 Larynx 47 36 46 Other 15 13 40 Lung/bronchus 815 855 843 Endocrine 168 225 257 Other 17 16 29 Thyroid 130 153 161 Blood and bone marrow 546 497 541 Other 38 72 96 Bone 7 11 10 Lymphatic system 322 324 331 Connect/soft tissue 31 36 64 Unknown primary 68 80 92 Skin 383 393 465 Other/ill-defined 40 34 31 Breast 1,325 1,237 1,264 Total 7,136 7,305 7,913 *Estimated. Complete data not available at time of publication.

aurora.org/research 32 Oncology Research Committees

Cancer Leadership Council Research Committee Oncology Research Steering Committee Jan DeBartolo, MSN Sara Planton, BSN Jane Bubik, PharmD Manish Pant, MD Judy Tjoe, MD Carla Fuentes Rubina Qamar, MD Jan DeBartolo, MSN Dhimant Patel, MD Carol Tutino, BSN, MS Neha Glandt Richard Rovin, MD Elizabeth Dickson, MD Sara Planton, BSN Mark Waples, MD Randall Lambrecht, PhD Thompson Saphner, MD Carla Fuentes Rubina Qamar, MD (chair) Jim Weese, MD Gary Neitzel, MD Michael Thompson, MD, PhD (co-chair) Sebouh Gueyikian, MD Antony Ruggeri, MD Ellen Ziaja, MD Vani Nilakantan, PhD Judy Tjoe, MD Scott Kamelle, MD Thomas Saphner, MD Frank Zuehl, MD Dhimant Patel, MD (co-chair) James Weese, MD Jennifer Lester, PharmD Corey Shamah, MD Tom Zukowski, MD Michael Mullane, MD Michael Thompson, MD, PhD

Oncology publications 2015 Aurora-authored, peer-reviewed

Levine R, Link MP, Lippman SM, Lonial S, Lyman GH, Herrera AV, Hilgeman B, Buelow M, Lemke MA. Journal articles/Book chapters Markman M, Mendelsohn J, Meropol NJ, Messinger Mailed at-home FIT intervention to increase colorectal Bobustuc GC, Patel A, Thompson M, Srivenugopal Y, Mulvey TM, O’Brien S, Perez-Soler R, Pollock R, screenings at Sixteenth Street Community Health KS, Frick J, Weese J, Konduri SD. MGMT inhibition Prchal J, Press O, Radich J, Rai K, Rosenberg SA, Centers. J Patient Cent suppresses survivin expression in pancreatic cancer. Rowe JM, Rugo H, Runowicz CD, Sandmaier BM, Res Rev 2015;2:212. Pancreas 2015;44:626-35. Saven A, Schafer AI, Schiffer C, Sekeres MA, Silver RT, Siu LL, Steensma DP, Stewart FM, Stock W, Jawa ZA, Perez RM, Garlie L, Singh M, Qamar R, Fenske TS, Shah NM, Kim KM, Saha S, Zhang C, Stone R, Storb R, Strong LC, Tallman MS, Thompson Khandheria BK, Jahangir A, Shi Y. A meta-analysis of Baim AE, Farnen JP, Onitilo AA, Blank JH, Ahuja H, M, Ueno NT, Van Etten RA, Vose JM, Wiernik PH, incidence and risk factors of trastuzumab-induced Wassenaar T, Qamar R, Mansky P, Traynor AM, Mattison Winer EP, Younes A, Zelenetz AD, LeMaistre CA. In cardiotoxicity in breast cancer. J Patient Cent Res Rev RJ, Kahl BS. A phase 2 study of weekly temsirolimus support of a patient-driven initiative and petition 2015;2:207-8. and bortezomib for relapsed or refractory B-cell non- to lower the high price of cancer drugs. Mayo Clin Katz MS, Utengen A, Anderson PF, Thompson MA, Hodgkin lymphoma: A Wisconsin Oncology Network Proc 2015;90:996-1000. Fisch M, Johnston C, Attai DJ, Aase L, Miller RS, Lee study. Cancer 2015;121:3465-71. Thompson MA. Using social media to learn and T, Dizon DS. Disease-specific hashtags for online Katz MS, Utengen A, Anderson PF, Thompson MA, communicate: it is not about the tweet. Am Soc communication about cancer care. J Clin Oncol Attai DJ, Johnston C, Dizon DS. Disease-specific Clin Oncol Educ Book. 2015:206-11. (Meeting Abstracts) 2015;33(15_suppl):6520. hashtags for online communication about cancer care. Konduri S, Bangaru MLY, Do PT, Chen S, Woodliff JAMA Oncol 2016;2:392-4 [Epub 2015 Nov 5]. Thompson MA, Majhail NS, Wood WA, Perales MA, Chaboissier M. Social media and the practicing J, Kansra S. In vitro growth suppression of renal Konduri SD, Bangaru MLY, Do PT, Chen S, Woodliff hematologist: Twitter 101 for the busy healthcare carcinoma cells by curcumin. J Patient Cent Res Rev J, Kansra S. In vitro growth suppression of renal provider. Curr Hematol Malig Rep 2015;10:405-12. 2015;2:209. carcinoma cells by curcumin. J Patient Cent Res Perez RM, Rappelt M, Kossow K, Singh M. Incidence Rev 2015;2:156-64. Tjoe JA. Breast cancer screening: early detection is not enough. J Patient Cent Res Rev 2015;2:6-8. of breast, colorectal and lung cancers and mortality Lo J. The clinical breast examination: a useful among women within Midwestern states. J Patient screening tool? J Patient Cent Res Rev 2015;2:34-7. Tjoe JA, Greer DM, Ihde SE, Bares DA, Mikkelson Cent Res Rev 2015;2:214. WM, Weese JL. Improving quality metric adherence Mohindra P, Urban E, Pagan JD, Geye HM, Patel VB, to minimally invasive breast biopsy among Reid BB, Rodriguez KN, Thompson MA, Matthews Bayliss RA, Bender ET, Harari PM. Selective omission of surgeons within a multihospital health care GD. Cancer-specific Twitter conversations among level V nodal coverage for patients with oropharyngeal system. J Am Coll Surg 2015;221:758-66. physicians in 2014. J Clin Oncol (Meeting Abstracts) cancer: Clinical validation of intensity-modulated 2015;33(15_suppl):e17500. radiotherapy experience and dosimetric significance. Rosiak J, Seefeldt L, Tjoe J. Use of survivorship Head Neck 2016;38:499-505 [Epub 2015 Jun 16]. Abstracts care plans to improve cost effective care following Pemmaraju N, Gupta V, Mesa R, Thompson MA. adjuvant treatment for breast cancer. Oncol Nurs Arnold SM, Chansky K, Leggas M, Thompson Forum 2015;42:E192. Social media and myeloproliferative neoplasms M, Hamm J, Sanborn RE, Weiss GJ, Chatta K, (MPN) –– focus on Twitter and the development Baggstrom MQ. PhI study of carfilzomib (C) + Santhosh-Kumar CR, Gray D, Struve S, Huibregtse of a disease-specific community: #MPNSM. Curr irinotecan (I) in relapsed irinotecan sensitive solid C. Structured outpatient palliative care family Hematol Malig Rep 2015;10:413-20. tumors. J Thorac Oncol 2015;10:S625. conferences to enhance early integration of palliative Pizzino F, Vizzari G, Qamar R, Bomzer C, Carerj S, care in advanced cancer. J Clin Oncol (Meeting Bobustuc GC, Holmuhamedov A, Srivenugopal Abstracts) 2015;33(29S):#36. Zito C, Khandheria BK. Multimodality imaging in KS, Frick JC, Weese JL, Konduri SD. Disulfiram a cardiooncology. J Oncol 2015;2015:263950. dual MGMT and aldehyde dehydrogenase inhibitor Shamah CJ, Saphner TJ, Frick JC, Huibregtse C, Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain sensitizes pancreatic cancer to gemcitabine and Stiemke GS. Integration of a clinical pathways KS, Hayes DF, Geyer Jr CE, Dees EC, Perez EA, Olson abraxane. Cancer Res 2015;75:3493. software into an EHR in a large, multisite, hospital JA, Zujewski JA, Lively T, Badve SS, Saphner TJ, Wagner affiliated community oncology setting. J Clin Oncol Cabrera O, Cho C, Dalmar A, Mahdavi A. Role of (Meeting Abstracts) 2015;33(15_suppl):e17555. LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, surgical staging and adjuvant chemotherapy in Keane MM, Gomez Moreno HL, Reddy PS, Goggins the treatment of uterine carcinosarcoma. Gynecol Sparano JA, Zhao F, Martino S, Ligibel J, Saphner TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani Oncol 2015;137(S1):96-7. T, Wolff AC, Sledge GW Jr, Perez EA, Wood WC, VG, Atkins JN, Berenberg JL, Sledge GW. Prospective Davidson NE Ten year update of E1199: Phase III validation of a 21-gene expression assay in breast Das GM, Mukhopadhyay UK, Bansal S, study of doxorubicin-cyclophosphamide followed by cancer. N Engl J Med 2015;373:2005-14. Wickramasekera N, Medisetty R, Swetzig paclitaxel or docetaxel given every 3 weeks or weekly WM, Miller A, Wang J, Oturkar C, Mukhopadhyay in patients with axillary node-positive or high-risk Tefferi A, Kantarjian H, Rajkumar SV, Baker LH, Abkowitz A, Konduri S. p53 status as a determinant of JL, Adamson JW, Advani RH, Allison J, Antman KH, node-negative breast cancer. Cancer Res 2015;75(9 estrogen receptor beta function in breast cancer. Suppl):Abstract S3-03. Bast RC Jr, Bennett JM, Benz EJ Jr, Berliner N, Bertino Cancer Res 2015;75(15 Suppl):Abstract 3465. J, Bhatia R, Bhatia S, Bhojwani D, Blanke CD, Bloomfield Timler AM, Dennert K, Talatzko R 3rd, Halliday CD, Bosserman L, Broxmeyer HE, Byrd JC, Cabanillas F, Dennert K. Algorithm for administration of C, Padmanabhan A, Matthaeus W, Sanchez F, Canellos GP, Chabner BA, Chanan-Khan A, Cheson B, plerixafor pre-apheresis for adult autologous stem Taylor R, Garlie N. Optimizing PBSC collection for Clarkson B, Cohn SL, Colon-Otero G, Cortes J, Coutre cell transplantation. Biol Blood Marrow Transplant hematopoietic stem cell transplantation. Cytotherapy S, Cristofanilli M, Curran WJ Jr, Daley GQ, DeAngelo DJ, 2015;21:S132-3. 2015;17:S60. Deeg HJ, Einhorn LH, Erba HP, Esteva FJ, Estey E, Fidler IJ, Foran J, Forman S, Freireich E, Fuchs C, George JN, Godana S, Flejsierowicz M. Pancytopenia as initial Tjoe JA, Gascard P, Zhao J, Neitzel GF, Singh M, Last Gertz MA, Giralt S, Golomb H, Greenberg P, Gutterman presentation of hodgkin lymphoma: a case report. B, Marx J, Tlsty T, Kansra S. Does the expression of J, Handin RI, Hellman S, Hoff PM, Hoffman R, Hong WK, 2015 American College of Physicians Wisconsin Ki-67, p16 and COX-2 at initial diagnosis of breast Horowitz M, Hortobagyi GN, Hudis C, Issa JP, Johnson Chapter Annual Meeting (displayed posters). atypia or usual ductal hyperplasia predict a second BE, Kantoff PW, Kaushansky K, Khayat D, Khuri FR, Available at: https://www.acponline.org/system/ clinically significant event? J Patient Cent Res Rev Kipps TJ, Kripke M, Kyle RA, Larson RA, Lawrence TS, files/documents/about_acp/chapters/wi/15mtg/ 2015;2:215-6. godana.pdf.

33 Aurora Research Institute | Annual Report 2015 Amin Kassam, MD Vice President, Aurora Neurosciences

Establishing the Aurora Neuroscience Innovation Institute more than two years ago, Dr. Kassam leads a multidisciplinary team dedicated to cutting-edge research throughout Aurora Health Care. Neurosciences research

22 164 neurosciences clinical trials open to total neurosciences clinical trial accrual and follow-up as of Dec. 31, 2015 enrollments in 2015

Surgical Surgical (138) 84% Neuro-Oncology (6) 27% (7) 32%

Interventional Radiology (4) 18% Stroke (1) 5%

Stroke Neuro-Oncology Multiple (1) 1% Sclerosis (12) 7% (2) 9% Epilepsy Interventional (2) 9% Multiple Radiology Sclerosis (10) 6% (3) 2%

~$1.7 million in external grant funding awarded for investigator-initiated neurosciences research studies 6% of Aurora’s research is neurosciences-related 29% of Aurora’s neurosciences research is investigator-initiated Aurora Neuroscience Innovation Institute Setting the standard for innovation and patient-centered neurological care

Eighteen months after joining Aurora With more than $1.4 million in Health Care to lead the system’s equipment granted or donated neurosciences service line, neurosurgeon by a variety of medical device Amin Kassam, MD, realized his vision of a companies, the neuroanatomical state-of-the-art facility to treat and study laboratory is equipped with surgical complex brain procedures. stations and imaging tools that ANII replicate a neurosurgery suite to Opened in May 2015, his reality – enable mock surgical procedures on Aurora Neuroscience Innovation Institute cadaver specimens for training and Publications/presentations (ANII) – includes a multidisciplinary research purposes. clinic, education suite, neuroanatomical In 2015, the ANII team shared its laboratory and four neurosurgical New imaging technology allows research findings through manuscript operating suites featuring first-in-the- scientists to visualize intricate anatomy publication in peer-reviewed journals world technology (see story on page 36) in the brain that has never been seen and abstract presentation at national at Aurora St. Luke’s Medical Center. before and will lead to the discovery and international meetings. of safe approaches to access deep seated lesions in the brain without Sharing their expert knowledge through disrupting normal brain anatomy. textbook chapters, ANII team members literally wrote the book on endonasal After refining them in the endoscopic surgery of skull base tumors. neuroanatomical lab, Aurora researchers and clinicians will translate advanced neurosurgical techniques to the operating room, making procedures more accurate, less invasive and safer for patients. 20 3 published published Nina Garlie, PhD, leads tours of the Research associates Sarika Walia, neuroanatomical laboratory during the grand manuscripts abstracts opening of Aurora Neuroscience Innovation MD, and Srikant Chakravarthi, MD, Institute at Aurora St. Luke’s Medical Center. support activities in the lab.

Sarika Walia, MD, and Srikant Chakravarthi, MD, train on state-of-the-art neurosurgical equipment in the neuroanatomical laboratory.

35 Aurora Research Institute | Annual Report 2015 First in the world to use ANII robotic optical microscope in the news In a breakthrough with the potential to improve outcomes and reduce CBS 58: the risks of complex brain Understanding a brain aneurysm surgeries, the neurosurgical after the sudden loss of community team at Aurora St. Luke’s advocate Marc Marotta Medical Center on April 20, 2015, successfully completed a first-in-the-world procedure with newly Food and Drug The operation utilized the entire suite Administration-cleared of Synaptive Medical Neurosurgical technology for planning Solutions: BrightMatter™ Guide, and resection. Plan, Vision and Servo. This system is comprised of four technologies: advanced optical visualization with efficient light delivery to the surgical field, automated positioning of the optical system at the command of the Richard Rovin, MD, discusses brain aneurysms with CBS 58 newscasters following the death surgeon, visualization of interaction of community advocate Marc Marotta. of surgical tools with medical images and three-dimensional tractography planning. As a result, the procedure was successfully performed with FOX 6: Milwaukee neurosurgeon reaches out an awake anesthetic technique and to White House after POTUS calls on minimal risk to the patient’s brain VP Biden to cure cancer function. (see page 38)

Aurora Neuroscience Innovation Institute neuroradiologist Melanie Milwaukee Journal Sentinel: Fukui, MD, and neurosurgeons Amin NEWaukee’s ‘speaker crawl’ draws Neurosurgeon Richard Rovin, MD, consults Kassam, MD, and Richard Rovin, MD, hundreds to Milwaukee Public Museum with neuroradiologist Melanie Fukui, MD. With neurosurgeon Amin Kassam, MD, they worked together to plan and perform successfully completed a first-in-the-world the surgery. procedure. Milwaukee Journal Sentinel: Neurosurgeon Richard Rovin, MD, performs an awake craniotomy using Synaptive Medical Powerful imaging system — and patient’s Neurosurgical Solutions at Aurora St. Luke’s Medical Center. voice — help guide brain surgeon

Milwaukee Magazine: Brain gain: How a world-renowned neurosurgeon is making medical history in Milwaukee

BizTimes: Aurora performs world’s first neurosurgery using new technology (additional coverage)

BizTimes: Aurora Neuroscience Innovation Institute unveiled (additional coverage)

Fond du Lac Reporter: Cancer patient beating the odds

aurora.org/research 36 Researchers kick start neuro-oncology research program with funds from Vince Lombardi Cancer Foundation

With a generous $1 million grant from Vince Lombardi Cancer Foundation, vice president of Aurora Neurosciences Amin Kassam, MD, is leading the development of a neuro-oncology research program.

Stem cell bank Access to human brain tumor samples is essential for a successful neuro- oncology research program to thrive since the stem cells derived from the samples will be used to test new cancer therapies in the lab.

With an initial Aurora Cancer Care Research Award in 2014 and continued funding in 2015 totaling $50,000, Dr. Kassam established a brain tumor stem cell bank. The research award program is generously supported by Vince Lombardi Cancer Foundation.

Using residual tissue from surgeries to remove brain tumors, researchers are collecting samples to grow and store stem cells. The project was initiated in an existing laboratory in the Regenerative Medicine Center at Aurora St. Luke’s Medical Center. The proximity of the lab to the operating Animal models rooms was advantageous to facilitate Researchers effective communication between the After construction of Discovery study team, operating room staff and collected 76 samples Laboratory and the vivarium at pathology, and efficient transfer of the of a variety of brain Aurora Sinai Medical Center, the neuro-oncology researchers moved into tumor tissue from the operating room tumors. Using a novel to the lab. the state-of-the-art facility, setting up culture method, the shop and beginning the next phase of Coordination and streamlining of the the research – characterization of the process required the collaboration team had an above cells in animal models. of neurosciences research nurse average success rate Led by senior research scientist of 54%, with 68% Chang-Hyuk Kwon, PhD, and for brain and spine neurosurgeon Richard Rovin, MD, the goal of the laboratory research tumors. is to determine whether the cells are able to reinitiate tumor growth in mice, since this stem cell characteristic of self-renewal contributes to tumor coordinators, representatives of the recurrence in humans. Biorepository and Specimen Resource Center, researcher scientists and In 2016, researchers will use new technologists, and the surgeons. methods of magnetic resonance imaging, ramen spectroscopy and From 60 patients, researchers collected optical coherence tomography to 76 samples of a variety of brain tumors. identify differences between healthy The research team developed a novel and unhealthy tissue at molecular and method to culture the tumor stem cells structural levels. Research associate Deb Donohoe uses a with an above-average success rate microscope to analyze tumor stem cells in of 54%, with 68% for brain and spine MRI uses strong magnetic fields to the Discovery Laboratory on the Aurora Sinai tumors, or gliomas. Tissue collection Medical Center campus. create detailed images of tissues by is ongoing. detecting protons in water molecules.

37 Aurora Research Institute | Annual Report 2015 OCT is a “light” ultrasound that measures tissue topography and structure. RS uses light to measure tissue chemistry, akin to chemical fingerprinting.

Researchers are using these highly specialized imaging technologies before and after the tumor is removed from the patient, before the tumor stem cells are injected into mice and after the tumor has regrown in the mouse.

The next phase of the program is to test new therapeutics on the tumor stem cells and in tumor- bearing mice, using the imaging modalities to detect tumor shrinkage or elimination. One method Three weeks after injecting brain includes reengineering tumor stem cells into the brain of a brain tumor stem cells and mouse avatar, a large tumor formed. redeploying them using viral An infrastructure-building year, new staff joined Aurora Research Institute’s The arrow points to an area of dead neuro-oncology program: Chang-Hyuk Kwon, PhD, senior research cells caused by the tumor, which vectors, the most effective scientist; Denise Coley, research associate; Monica Cucciare, research were continuing to multiply. means of gene transfer. associate; and Amber LaCrosse, PhD, postdoctoral research fellow. Award highlight Neurosurgeon believes cancer cure is possible

“We, like you and President (Barack) and characterize cancer stem cells from Obama, believe we can cure cancer.” metastatic brain tumors. The research award program is generously supported Finding an efficient In an open letter, neurosurgeon by Vince Lombardi Cancer Foundation. way to grow stem cells Richard Rovin, MD, invited Vice President Joe Biden to check out the To study these cancer stem cells in the from brain tumors is clinical and basic science research lab, they need to be separated from the first step. being conducted at Aurora Health the rest of the cells in the tumor. There Care, particularly in Aurora Research are several different methods to do Institute’s new Discovery Laboratory. this, but none have been used to grow metastatic brain tumors by comparing cancer stem cells from metastatic brain the two different methods. Dr. Rovin, recipient of a $25,000 tumors. The purpose of this research Aurora Cancer Care Research Award, is to find a reliable and efficient way Five patients with breast or non-small is studying two methods to isolate of growing cancer stem cells from cell lung cancer who underwent brain surgery at Aurora St. Luke’s Medical Center have provided metastatic brain tumor tissue for the study. Enrollment continues with a goal of 25 subjects.

A collaborative effort, the Biorepository and Specimen Resource Center is assisting with collection and storing of the tissues.

Neurosurgeon This research is the first step toward Richard Rovin, the long-term goal of finding the MD, provides a tour of Discovery molecular and genetic changes Laboratory during that take place in the stem cells an interview on of metastatic brain tumors. This FOX 6 News. The reporter reached knowledge will help explain how and out to Dr. Rovin why tumors spread to the brain. It after he posted will also help researchers find ways to an open letter to Vice President prevent metastasis and to treat tumors Joe Biden. once metastasis has happened.

aurora.org/research 38 Making lemonade: Woman enrolls in trial to fight cancer

When faced with a lemon-sized went to the emergency department at tumor in the right side of her brain, Aurora Medical Center in Grafton with N H3C Heidi Zellmer of Cedarburg began a stroke-like symptoms. journey that would lead the wife and It wasn’t a stroke though. A CAT scan mother of three boys to enroll in a revealed the tumor. N clinical trial testing an investigational N H combination of chemotherapy for H glioblastoma multiforme, a fast- One-two punch growing brain cancer. After being transported via ambulance to Aurora St. Luke’s Medical Center, H2N O One fall day a few months before her Zellmer spent about a week in the 50th birthday, Zellmer completed a neurointensive care unit undergoing A depiction of how veliparib works in the fight five-mile hike along the bluffs tests before Amin Kassam, MD, against cancer. of Devil’s Lake in south central performed the awake craniotomy to Wisconsin. About a week later, she remove the tumor. George Bobustuc, MD, took over her cancer care that included six weeks of chemotherapy as a one-two punch, the chemotherapy Chemotherapy and radiation at Aurora Grafton. damages the cancer cell and the veliparib, a PARP inhibitor, prevents the damages the cancer Near the end of her treatment cycle, body from producing a protein that Dr. Bobustuc informed Zellmer cell and the veliparib would repair the cell, thereby making it about a clinical trial testing whether easier to kill. prevents the body temozolomide chemotherapy is from producing a more effective with veliparib at As part of the research protocol, improving overall survival in subjects subjects are randomized to receive the protein that would with a particular genetic indications chemotherapy and PARP inhibitor or repair the cell. (National Cancer Institute, clinicaltrials. the chemotherapy and placebo. Zellmer gov identifier: NCT02152982). Acting agreed to enroll in the trial, even though she couldn’t be sure she would receive the PARP inhibitor. John and Heidi Zellmer about six days after her brain surgery to remove a lemon-sized tumor at Aurora St. Luke’s Medical Center. “If it could extend my life, why not?” Zellmer said.

Surrounded by beauty The family’s vacation to Hawaii, originally planned for Christmas, transformed into Zellmer’s 50th birthday celebration in February. Though she didn’t want to feel ill from the therapy during the trip, she didn’t want it looming over her head either. She started the first round of the study treatment, an oral therapy, in Hawaii.

“It was still worth it,” Zellmer said. “Being in Hawaii, being outside surrounded by beauty, was very good for my well-being.”

Feeling ill the first two days, she checked in with research study coordinator Lynda Yanny, BSN, who told her how to “stay ahead” of the symptoms.

Support and care A spiritual person, Zellmer has relied on her Christian faith, positivity and extensive support system to carry her through. Not only has her immediate family – husband John and sons Zachary, 22, Benjamin, 10, and Aaron, 8 – stepped up, her mother and sister in Washington, her brother in Alaska as well as friends and neighbors – “people we didn’t even know” – have pitched in.

39 Aurora Research Institute | Annual Report 2015 Making lemonade: Woman enrolls in trial to fight cancer Clinical trial spotlight And she couldn’t say enough about her care team throughout Aurora Health Care. “I feel like I’m getting the best care I can Researchers track outcomes get,” she said. of new multiple sclerosis drug Looking forward Zellmer takes one day at a time. She’s Recurring attacks, or relapses, of neurological looking forward to seeing Zachary symptoms are common in multiple sclerosis. graduate college in Seattle this June. Study The drug dimethyl fumarate cuts down on the treatments wrap up then, though she will be number of relapses. followed for 10 years. James Napier, MD, is leading an observational “I think medicine has changed a lot,” Zellmer clinical trial at Aurora BayCare Medical Center said. “I’m thankful it is the decade we live to track serious adverse events that lead to the in now and hope there are more studies to discontinuation of dimethyl fumarate in patients cure this.” with relapsing multiple sclerosis (ESTEEM, Walking a mile a day, Zellmer hopes to hike clinicaltrials.gov identifier: NCT02047097). the bluffs of Devil’s Lake again this fall. She Sponsored by the goes for an MRI every eight weeks to see if The drug drug’s manufacturer the tumor has grown back. Her scan in March dimethyl Biogen Inc., the global was clear of tumors. study will follow about fumarate cuts 5,000 subjects for five years. Researchers Zellmer is participating in a trial being conducted by down on the will track different serious adverse events, Alliance for Clinical Trials in Oncology. Alliance is a including infections, hepatic events, member of the National Cancer Institute National Clinical number of Trials Network and serves as a research base for the NCI malignancies and renal events. Community Research Oncology Program. Aurora St. Luke’s relapses. Medical Center is member of the Alliance NCTN network. Jennifer Homa, MS, is serving as site coordinator. Zellmer’s experience should not be used to predict outcomes of the clinical trial. Data collection continues. Targeted Neuro Research Committees treatment Neurosciences Research Committee George Bobustuc, MD Deb Donohoe Chang-Hyuk Kwon, PhD Testing new precision Juanita Celix, MD Amin Kassam, MD (co-chair) Amber Lacrosse, PhD Srikant Chakravarthi, MD Melanie Fukui, MD Natalie Polinske, MS cancer therapies Denise Coley Nina Garlie, PhD Richard Rovin, MD (co-chair) Monica Cucciare Santhi Konduri, PhD Sarika Walia, MD Developing new strategies to treat the most frequent forms of brain cancer is the Clinical Innovation Committee driving force behind the research of senior research scientist Santhi Konduri, PhD, and Juanita Celix, MD Melanie Fukui, MD Sammy Khalili, MD Srikant Chakravarthi, MD Nina Garlie, PhD Nathaniel Kojis neuro-oncologist George Bobustuc, MD. Shannon Clark, MBA Jonathan Jennings, MD Richard Rovin, MD (co-chair) Patient-derived cancer cells are tested to Martin Corsten, MD Amin Kassam, MD (co-chair) Sarika Walia, MD identify different markers associated with glioblastoma multiforme and meningioma brain cancers. The long-term goal is to Neuroscience Clinical Trials Research Committee understand molecular changes that occur George Bobustuc, MD Carol Halliday, RN Carol Tutino, BSN, MS during tumor development and to use Srikant Chakravarthi, MD Tonya Hollrith, RTE (MR) Sarika Walia, MD these molecular markers as therapeutic Martin Corsten, MD Amin Kassam, MD (co-chair) Valerie Werner, BSN Gary Dennison, CIP Jennifer Mathieu Lynda Yanny, BSN targets, individualizing treatment to the Melanie Fukui, MD Richard Rovin, MD (co-chair) patient’s specific genetic make-up. Nina Garlie, PhD Lori Schwingshakl, RN The ultimate goal is to design a safe, effective system allowing for use of a combination of drugs and therapies unique to each patient.

aurora.org/research 40 Neurosciences volumes – systemwide

Source: Aurora Smart Chart and Medipac 2013 2014 2015 Cases* Epilepsy 3,239 3,210 4,317 Stroke 2,394 2,433 1,645 Ischemic 1,316 1,510 1,094 Transient ischemic attack 576 552 304 Hemorrhagic 502 371 247 Interventional radiology** 339 387 446

*For cancers of the brain and central nervous system, see table on page 32. **Number of patients

Neurosciences publications 2015 Aurora-authored, peer-reviewed

Kassam A, Labib MA, Prevedello DM, Carrau R. Mirza SK, Tragon TR, Fukui MB, Hartman MS, Journal articles/Book chapters In reply: an endoscopic roadmap of the internal Hartman AL. Microbiology for radiologists: Bockmühl U, Carrau RL, Otto BA, Prevedello DM, carotid artery. Neurosurgery 2015;77:E154-5. how to minimize infection transmission in Kassam AB. The sinonasal corridor. In: Draf W, the radiology department. Radiographics Lawrence JE, Bammert CE, Belton RJ Jr, Rovin Carrau RL, Bockmühl U, Kassam AB, Vajkoczy P 2015;35:1231-44. RA, Winn RJ. Targeting DNA repair mechanisms (eds). Endonasal Endoscopic Surgery of Skull Base to treat glioblastoma. In: Chen CC (ed). Advances Pinheiro-Neto CD, Kasemsiri P, Carrau RL, Tumors: An Interdisciplinary Approach. Stuttgart, in DNA Repair. Rijeka, Croatia: InTech, 2015. Prevedello DM, Kassam AB. Transpterygoid Germany: Thieme, 2015. approaches. In: Draf W, Carrau RL, Bockmühl Lawrence JE, Steele CJ, Rovin RA, Belton Corsten MJ, Hearn M, McDonald JT, Johnson- U, Kassam AB, Vajkoczy P (eds). Endonasal RJ Jr, Winn RJ. Dexamethasone alone and Obaseki S. Incidence of differentiated thyroid Endoscopic Surgery of Skull Base Tumors: An in combination with desipramine, phenytoin, cancer in Canada by city of residence. J Interdisciplinary Approach. Stuttgart, Germany: valproic acid or levetiracetam interferes with Otolaryngol Head Neck Surg 2015;44:36. Thieme, 2015. 5-ALA-mediated PpIX production and cellular Ditzel Filho LF, de Lara D, Prevedello DM, Solari retention in glioblastoma cells. J Neurooncol Prevedello DM, Ditzel Filho LF, Fernandez- D, Otto BA, Kassam AB, Carrau RL. Anatomy of 2016;127:15-21 [Epub 2015 Dec 7]. Miranda JC, Solari D, do Espírito Santo MP, Wehr anterior, central, and posterior skull base: vessels AM, Carrau RL, Kassam AB. Magnetic resonance Lee TJ, Haque F, Shu D, Yoo JY, Li H, Yokel RA, and nerves. In: Draf W, Carrau RL, Bockmühl imaging fluid-attenuated inversion recovery Horbinski C, Kim TH, Kim SH, Kwon CH, Nakano U, Kassam AB, Vajkoczy P (eds). Endonasal sequence signal reduction after endoscopic I, Kaur B, Guo P, Croce CM. RNA nanoparticle Endoscopic Surgery of Skull Base Tumors: An endonasal transcribiform total resection of as a vector for targeted siRNA delivery into Interdisciplinary Approach. Stuttgart, Germany: olfactory groove meningiomas. Surg Neurol Int glioblastoma mouse model. Oncotarget Thieme, 2015. 2015;6:158. 2015;6:14766-76. Draf W, Carrau RL, Bockmühl U, Kassam AB, Zeylikman Y, Shah V, Shah U, Mirsen TR, McLaughlin N, Carrau RL, Kassam AB, Prevedello Vajkoczy P (eds). Endonasal Endoscopic Surgery Campellone JV. False-positive serum botulism DM, Deinsberger W, Bockmühl U. Multidisciplinary of Skull Base Tumors: An Interdisciplinary bioassay in Miller-Fisher syndrome. J Clin endoscopic skull base centers: delivering Approach. Stuttgart, Germany: Thieme, 2015. Neuromuscul Dis 2015;17:27-9. integrated care. In: Draf W, Carrau RL, Bockmühl Iancu D, Lum C, Ahmed ME, Glikstein R, Dos U, Kassam AB, Vajkoczy P (eds). Endonasal Santos MP, Lesiuk H, Labib M, Kassam AB. Flow Endoscopic Surgery of Skull Base Tumors: An Abstracts diversion in the treatment of carotid injury and Interdisciplinary Approach. Stuttgart, Germany: carotid-cavernous fistula after transsphenoidal Thieme, 2015. Britz GW, Kassam A, Labib M, Young R, Zucker L, surgery. Interv Neuroradiol 2015;21:346-50. McLaughlin N, Prevedello DM, Fernandez-Miranda Maioriello A, Day JD, Gallia G, Kerr R. Minimally invasive subcortical parafascicular access Johnson-Obaseki SE, Labajian V, Corsten MJ, JC, Carrau RL, Kassam AB. 360° access to the skull base. In: Draf W, Carrau RL, Bockmühl for clot evacuation. A paradigm shift. Stroke McDonald JT. Incidence of cutaneous malignant 2015;46:AWMP120. melanoma by socioeconomic status in Canada: U, Kassam AB, Vajkoczy P (eds). Endonasal 1992-2006. J Otolaryngol Head Neck Surg Endoscopic Surgery of Skull Base Tumors: An Dagnew Y, Hamed R, Reid K. Is 20 years old too 2015;44:53. Interdisciplinary Approach. Stuttgart, Germany: young for a stroke? 2015 American College of Thieme, 2015. Physicians Wisconsin Chapter Annual Meeting Kassam AB, Labib MA, Bafaquh M, Ghinda D, (displayed posters). Available at: https://www. Mark J, Houlden D, Fukui MB, Nguyen T, Corsten McLaughlin N, Prevedello DM, Kelly DF, Carrau RL, Kassam AB. Expanded endoscopic endonasal acponline.org/system/files/documents/about_ M, Piron C, Rovin R. Part I: The challenge of acp/chapters/wi/15mtg/dagnew.pdf. functional preservation: an integrated systems approaches. In: Draf W, Carrau RL, Bockmühl approach using diffusion-weighted, image-guided, U, Kassam AB, Vajkoczy P (eds). Endonasal Gebremedhin T, Battiola R. Brain abscess: the exoscopic-assisted, transulcal radial corridors. Endoscopic Surgery of Skull Base Tumors: An great mimicker. 2015 American College of Innovative Neurosurgery 2015;3(1-2):5-23. Interdisciplinary Approach. Stuttgart, Germany: Physicians Wisconsin Chapter Annual Meeting Thieme, 2015. (displayed posters). Available at: https://www. Kassam AB, Labib MA, Bafaquh M, Ghinda D, McLaughlin N, Prevedello DM, Kelly D, Fernandez- acponline.org/system/files/documents/about_ Fukui MB, Nguyen T, Corsten M. Part II: An acp/chapters/wi/15mtg/gerbremedhin.pdf. evaluation of an integrated systems approach Miranda J, Carrau RL, Kassam AB. Tumor-specific using diffusion-weighted, image-guided, strategies: meningiomas. In: Draf W, Carrau exoscopic-assisted, transculcal radial corridors. RL, Bockmühl U, Kassam AB, Vajkoczy P (eds). Innovative Neurosurgery 2015;3(1-2)25-33. Endonasal Endoscopic Surgery of Skull Base Tumors: An Interdisciplinary Approach. Stuttgart, Germany: Thieme, 2015.

41 Aurora Research Institute | Annual Report 2015 Aurora Research Institute investigators engage in strategic research that includes:

• ORTHOPEDICS • GERIATRICS • WOMEN’S HEALTH • FAMILY PRACTICE • OBSTETRICS/GYNECOLOGY • POPULATION HEALTH

Additional strategic research

23 101 additional strategic research clinical trials open total additional strategic research to accrual and follow-up as of Dec. 31, 2015 clinical trial enrollments in 2015

Orthopedics Orthopedics (69) 68% Humanitarian (7) 30% Use Device/ Compassionate Use (8) 35%

Asthma Asthma (18) 18% (3) 13%

Women’s Health (1) 4% Humanitarian Emergency Use Device/ Pulmonology Medicine Compassionate Use (1) 1% Sleep (2) 9% (11) 11% Medicine Pulmonology Women’s Sleep (1) 4% (1) 4% Health Medicine (1) 1% (1) 1%

>$800,000 in external grant funding awarded for investigator-initiated additional strategic research studies 18% of Aurora’s research fits in the additional strategic research category 75% of Aurora’s additional strategic research is investigator-initiated Gender prediction: Is mother’s intuition more accurate than a coin flip?

There are numerous prediction tests to Obstetrics sonographer Michael McFadzen, determine a child’s gender before the BS, ARDMS, questioned whether maternal baby is born. Is the mother carrying intuition might be a more accurate low? Expect a boy. Fetal heart rate predictor. Based at Aurora Sheboygan more than 140 bpm? Expect a girl. A Clinic, McFadzen tested his hypothesis, Chinese model uses the month and presenting the preliminary findings at mother’s age at conception. Aurora Scientific Day.

The accuracy of these methods is All patients between 17 and 23 weeks dubious at best. pregnant were asked if they had an

intuition about the baby’s gender during their second trimester screening ultrasound. Patients with advance knowledge of fetal gender from imaging results were excluded from the study.

Ultrasound was used to confirm or debunk the mother’s intuition. Data collection wrapped up in 2015 and manuscript preparation is in progress.

David Dielentheis, MD, and Ronda Kasten contributed to the study.

Sonographer Michael McFadzen shares his findings on maternal intuition with attendees of the poster session at Aurora Scientific Day. McFadzen completed data collection in 2015 and hopes to publish his findings in 2016.

Study helps patients get treatment for bowel, bladder dysfunction, then measures quality-of-life improvements

Bowel and bladder dysfunction are a specialist. The difficult topics to discuss, even with questionnaire a health care provider. To avoid allows identification Bowel and the embarrassment, many people of patients who adjust their habits and lifestyles to may otherwise go bladder accommodate the management of untreated. symptoms. conditions Those who agree to A survey study measuring subject a consultation have • prolapse satisfaction is offering a discrete way the opportunity to for underserved people suffering with participate in a series • stress urinary these conditions to get the medical of surveys exploring incontinence care they need. quality-of-life improvements with • urgent urinary Patients arriving at an Aurora Family treatment over the incontinence Practice, Internal Medicine or Women’s course of a year. Health clinic will have an opportunity • fecal urgency to fill out a questionnaire on their Urogynecologist Alexis Chesrow, MD, • fecal incontinence bowel and bladder function and is leading the study at Aurora West indicate whether they are interested Allis Medical Center. Lori Bowhousen • constipation in setting up a consultation with is serving as site coordinator.

43 Aurora Research Institute | Annual Report 2015 Podiatrists study new approaches to foot surgeries

Recognized as Principal Investigators of the initial findings and inherent advantages, Year during the Aurora BayCare Medical the researchers recommend further study. Center Fall Research and Medical Education Led by Dr. Scharer, the researchers Reception for completing two innovative compared two surgical approaches for studies, BayCare Clinic podiatrists treating bunions. Chevron osteotomy is J. George DeVries, DPM, and Brandon the standard treatment, which corrects Scharer, DPM, presented their findings at the alignment of the bone. With the the 2016 American College of Foot and distal oblique approach, which has not Ankle Surgeons Conference. been applied to bunions, the surgeon Led by Dr. DeVries, the researchers studied approaches the surgery at an angle. Randall Lambrecht, PhD, J. George DeVries, outcomes of a grafting process that utilized DPM , and Dhimant Patel, MD. Both outcomes and patient satisfaction a manufactured bone morphogenetic between the two techniques were similar. protein rather than a bone fragment to fuse bones in the foot and ankle, a Taylor Romdenne coordinated the harvested from elsewhere in the body treatment to relieve pain. With promising studies.

Women’s Health volumes – systemwide

Source: AIM/Epic Hospital and Professional Billing Data 2013 2014 2015 2013 2014 2015 Breast Health Procedures Gynecology (Primary Procedures)

Mammography 158,709 154,771 157,283 Hospital procedures 6,227 6,149 6,236 Screening 131,683 128,289 126,882 Outpatient 5,082 5,561 5,629 Diagnostic 27,026 26,482 30,401 Inpatient 1,145 588 607 Digital (%) 96% 100% 100% Cancer (%) 8.2% 7.0% 7.6% Breast ultrasound 16,155 17,534 16,826 Hysterectomy 2,151 2,295 2,129 Core biopsy 3,180 3,456 3,373 Outpatient (%) 68.3% 77.4% 81.0% Ultrasound-guided 2,146 2,203 2,179 Laparoscopic (%) 55.2% 58.7% 59.1% Stereotactic 1,188 1,096 1,283 Laparoscopic assist (%) 10.9% 11.2% 10.3% MRI-guided 29 41 45 Robotic assist (%) 27.8% 25.5% 26.3% Breast MRI 1,372 1,419 1,269 Open (%) 15.5% 14.5% 16.1% Cancer (%) 11.7% 13.7% 10.9% Needle localization 391 412 451 Urogynecology Obstetrics/Newborn Urogynecology surgical procedures 1,563 1,697 1,732 Hospital deliveries 12,883 12,327 12,798 Prolapse 835 986 1,092 C-section (%) 26.2% 27.5% 27.4% Incontinence 692 669 607 Hospital newborns 13,246 12,754 13,221 Revision mesh 36 42 33 Hospital newborn NICU admissions 1,425 1,406 1,476 Level III unit 1,101 1,027 1,114 Level II unit 324 379 362 Average length of stay (days) 15.7 16.0 16.0 Average daily census 62.2 61.7 64.6 Orthopedic volumes – Maternal Fetal Medicine Ultrasounds 36,850 37,987 40,893 systemwide Office visits 3,003 3,305 3,524 Source: Aurora Smart Chart Fertility 2013 2014 2015*

IVF cycles 291 297 420 Admits/Visits Aurora West Alis 164 175 253 Hand/Wrist/Forearm 11,140 11,837 13,020 Aurora Green Bay 127 122 167 Knee 12,112 12,413 13,541 Gynecology (Primary Diagnostic) Visits Lower Leg/Foot/Ankle 19,983 20,789 24,503 Pelvis/Hip/Femur 8,364 9,022 10,883 Other disorders of female genital tract 107,981 111,818 112,693 Shoulder/Elbow/Upper Arm 15,487 16,833 20,304 Routine gynecologic exam 64,504 73,377 75,944 Spine/Back/Neck 57,109 61,837 68,413 Contraceptive management 45,972 47,351 47,826 Other 17,057 19,371 25,030 Benign gynecology 7,610 7,202 7,029 Totals 141,252 152,102 175,694 General fertility management 6,915 6,727 6,825 *2015 data annualized

aurora.org/research 44 Aurora UW Medical Group

The Aurora UW Medical Group Research Core is responsible for supporting, growing and coordinating research and scholarly activity manuscripts and among AUWMG faculty and Aurora Health Care residents, students >100 abstracts published and fellows. Dennis Baumgardner, MD, directs these activities.

Obstetrics/gynecology research

Led by Marie Forgie, DO, a randomized Studying whether tumor diameter is clinical trial comparing Foley catheter an important predictor in determining insertion techniques – stylette versus whether low-risk women can avoid no stylette – for the induction of labor surgery to remove their lymph nodes was selected as one of the Aurora after being diagnosed with endometrial Scientific Day Rieselbach distinguished cancer, the team led by Callie Cox Bauer, papers and won the Central Association DO (pictured at right), won the Dr. of Obstetrics and Gynecology 2015 George W. Morley Memorial Paper Award Community Hospital Award. at the Central Association of Obstetrics and Gynecology annual meeting. Published in early 2016 in the American Journal of Obstetrics and Gynecology, The study, later published in the Journal the manuscript concludes that the use of Gynecologic Oncology, found Geriatrics research of a stylette to guide catheter insertion that tumor diameter is an important does not improve speed of insertion, predictor for identifying whether the The U.S. Health Resources and reduce patient pain levels or decrease cancer has spread. Ultimately, use of Services Administration awarded failure of catheter placement when the study’s proposed risk model, which more than $396,000 over three compared to insertion without a stylette. incorporated tumor diameter and years to Aurora Senior Services for its Neither technique – stylette versus no myometrial invasion, may reduce the Geriatrics Scholars Program. Project stylette – was deemed superior. number of surgeries for lymph node director Michael Malone, MD, with removal in low-risk women. Jessica Kram, MPH, Danielle Greer, assistance from co-project director PhD, Kiley Vander Wyst, MPH, Nikki Danielle Greer, PhD, Jessica Kram, MPH, Aaron Malsch, MSN, will lead the Salvo, MD, and Danish Siddiqui, MD, and Scott Kamelle, MD, contributed to program, which will develop three contributed to the study and manuscript. the study and manuscript. teams to improve care and transitions for older adults.

Family medicine research The Sponsored Programs Office was instrumental in securing the grant. Winning the 2015 Aurora Quality Presenting at the Wisconsin Research Improvement Award and presenting and Education Network Convocation of findings at the Wisconsin Research and Practices, Fabiana Kotovicz, MD, and Ariba Khan, MD, was named to Education Network Convocation of medical resident Courtney Pokrzywa a research award for her project Practices, a team of Aurora UW Medical shared findings on the use of opioids presented at the 2015 Delirium Boot Group researchers assessed how well a for chronic pain management. Camp at Harvard Medical School/ unified workflow improved medication Beth Israel Deaconess Medical The findings fuel the fire of the reconciliation for Aurora St. Luke’s Center. The award was sponsored by controversy over this national epidemic. Family Practice patients. the Center of Excellence for Delirium Opioid prescription for chronic pain in Aging: Research, Training and The team found that implementation of management was inconsistent and did Educational Enhancement. a systematic workflow and education not adhere to recommended guidelines for the care team led to overall at the two clinics studied, though Dr. Khan will build on the studies she improvement in accuracy of electronic further research is required. led to develop an automated model health record medication reconciliation. using electronic health record data to To address the problem, Dr. Kotovicz This quality improvement project led identify delirium in hospitalized older and a team of researchers developed to identification of multiple barriers adults and older adults at risk for 30- an educational intervention to to accuracy, which could then be day hospital readmission and 30-day empower family medicine residents on addressed. mortality. She presented the studies safe opioid prescribing. The findings at the American Geriatrics Society Loras Even, DO, Jessica Konarske, DO, were presented at the Society of 2015 annual scientific meeting. Katherine Meyers, DO, Christopher Teachers of Family Medicine annual Maharaj Singh, PhD, Hina Singh, MD, Klink, PharmD, Jessica Kram, MPH, and spring conference in 2016. Ayesha Maria, Michelle Simpson, Dennis Baumgardner, MD, contributed Michael McNett, MD, Kayla Flores, MD, PhD, RN, Mary Hook, PhD, RN- to the study. Dr. Meyers won third place Stephanie McDearmon, MD, Brandon BC, Marsha Vollbrecht, RN, Aaron for her oral presentation at Aurora Phelps, DO, Brian Wallace, MD, Jessica Malsch, MSN, and Michael Malone, Scientific Day. Kram, MPH, and Dennis Baumgardner, MD, contributed to the studies. MD, contributed to the study.

45 Aurora Research Institute | Annual Report 2015 Aurora Scientific Day

Aurora Scientific Day, an annual conference In 2015, more than 150 people supported held in May, provides a forum for research research by attending the presentations – presentation by students, residents, fellows, 21 judged posters, 16 general and student teaching and research faculty, and other allied posters, 15 oral presentations and three health professional at Aurora Health Care. Rieselbach distinguished paper sessions.

Rieselbach Judged posters Oral presentations distinguished papers 1st place tie – Zuber S. Ali, MD 1st place – Dakisha N. Lewis, MD • Marie M. Forgie, DO – Androgen Deprivation Therapy for Model Assessment and A Randomized Control Trial Prostate Cancer Increases Systolic and Development of Risk Stratification of Foley Catheter Placement Diastolic Dysfunction of Surgical Site Infection Following Cesarean Delivery for a High-Risk, for Induction of Labor: 1st place tie – Ariba Khan, MD, MPH Urban Population Stylette Versus No Stylette Using an Automated Model to Identify • Mir za Nubair Ahmad, MD – Older Patients at Risk for 30-Day 2nd place – Callie Cox Bauer, DO Validation of a Diagnostic Hospital Readmission and 30-Day Operating Room First Start Algorithm for Cardiopulmonary Mortality Efficiency throughout a Large Urban Hospital System Exercise Testing: Usefulness 2nd place – Ayalew T. Muluneh, MD, MPH in Clinical Cardiology / Evaluating MACE Associated with 3rd place – Katherine Meyers, DO Rafath Ullah, MD – Operating Temporary Discontinuation of Assessing the Effectiveness Test Characteristics of Antiplatelets for Acute GI Bleeding of Implementation of Unified Respiratory Exchange in Patients with Coronary Stents Workflow in Improvement of Ratio as a Noninvasive Medication Reconciliation for 3rd place – Yang Shi, PhD Measure of Anaerobic Aurora St. Luke’s Family Medicine Echocardiographic Predictors of Threshold Residency Outpatients Admission among Patients with Heart • Zuber S. Ali, MD – Failure with Reduced Ejection Fraction Effects of Testosterone Supplement Therapy on Cardiovascular Outcomes in (Right) Nichole Nikolic and Men with Low Testosterone Mary Hook, PhD, RN-BC, at her poster on knowledge-based nursing at Aurora Scientific Day.

(Below) Randall Lambrecht, PhD, and biostatistician Maharaj Singh, PhD, listen as senior research scientist Ahmed Dalmar, MD, describes a study.

aurora.org/research 46 Center for Urban Population Health

Established in 2001, Center for Urban Population Health advances health services research, professional education and health promotion programming to improve the health of individuals and populations in urban communities. A collaboration of the University of Wisconsin-Milwaukee, University of Wisconsin School of Medicine and Public Health and Aurora Health Care, the center is an independent entity Extramural funding focused on identifying the determinants of sources in 2015 health and disease, designing and implementing preventive interventions that promote the health and well-being of populations, and measuring State their effectiveness. and local foundations 29% State and local 22 $1.4 contracts Federal grants and = 54% 17% contracts awarded million

Linking patients Increasing colorectal cancer screening to appropriate care Though 72 percent of Wisconsin adults were considered up Through the Milwaukee Health Care to date on their colorectal cancer screening in 2012, the rate Partnership’s Emergency Department was only 34 percent for federally qualified health centers and Care Coordination initiative, avoidable community clinics, which serve a high population of black, emergency department usage has Hispanic and Hmong adults living below the poverty line in the decreased with high-risk patients Milwaukee area. connected to primary care services. With funding from Centers for Disease Control and Prevention, Patients researchers are partnering with all Milwaukee federally qualified presenting health centers and Aurora’s Walkers Point Clinic to increase with one of colorectal cancer screening rates closer to the National five priority Colorectal Cancer Roundtable’s goal of 80 percent by 2018. conditions at any of the 10 participating Assessing the health of communities Milwaukee County hospital emergency departments are partnered with a social Findings from the Milwaukee Health important health indicators. With that worker, who schedules an appointment Care Partnership’s 2015 Community information, we can establish concrete for the patient with his or her new Health Needs Assessment of goals for health education, interventions medical home – a local community clinic. Milwaukee County revealed that access and investments.” to affordable health care services Center researchers are evaluating Each hospital and local health department continues to rank as a pressing need, appointment data to measure the in Milwaukee will select priorities and but chronic disease management and initiative’s success. develop individualized plans to improve prevention rose as a high priority. the health of the community it serves. “Aurora Family Service, in partnership Other top issues included violence, lack with Aurora Sinai Medical Center, Center researchers analyze key informant of access to oral health and behavioral launched an intensive case management interviews and focus group feedback, health care services, and difficulty in pilot program for patients identified as compile secondary data reports and navigating complex systems of care. high utilizers of emergency department create a summary of all the reports for services,” said Robert Marrs, MS, “This assessment builds on more than the assessment every three years. manager of Integrated Family Support a decade of community health survey Services, Aurora Health Care. “These are data that has been instrumental to patients with significant comorbidity hospitals and local health departments Access to affordable and 11-plus visits over a 12-month period. in the region,” said Mark Huber, Results of the initial pilot of 47 patients MS, senior vice president of social health care and chronic demonstrated a 57 percent decrease responsibility, Aurora Health Care, disease management in hospital charges and a 50 percent and the partnership’s assessment decrease in ED visits after six months committee chair. “The assessment data are high priorities. of enrollment.” helps us target health disparities and

47 Aurora Research Institute | Annual Report 2015 Nursing research 2015 EXTRAMURAL Study examines impact of bundled AWARD RECIPIENTS program for care of older adults John Brill, MD The Helen Daniels Bader Fund, a University of Wisconsin/State of Bader Philanthropy, is dedicated to Wisconsin supporting efforts that improve the $140,165 health of older adults. Aurora Lakeland rural training track HDBF awarded a $125,000 grant to Aurora Health Care. Principal Michelle Simpson, PhD, RN investigators Michelle Simpson, PhD, RN, and Michael Malone, MD, Bader Philanthropies Inc. will study ways to prevent delirium $125,000 and functional decline among older Prevention and early identification of adults receiving care in a rural setting. rural older adults’ clinical deterioration: The research project will implement develop an evidence-based hospital The bundled HELP at Home intervention the evidence-based Hospital readmission risk score for older adults Elder Life Program (HELP) at two receiving home care. Combining Michael Farrell, MD rural Aurora medical centers and HELP with the risk score model and Aurora UW Medical Group continue the program in the home continuing HELP in the home care care setting. HELP utilizes an setting, clinicians will intervene on $44,000 innovative model of care to maintain vulnerable older adults who are Rapid-throughout assessment and physical and cognitive functioning discharged to their home with the feedback of caregivers’ communication throughout hospitalization, assist bundled program. quality at the point of care with the transition from hospital Researchers will examine the impact to home and prevent unplanned of the bundled program in the two readmission for older adults. Michelle Simpson, PhD, RN rural hospitals and the corresponding Bader Philanthropies Inc. Using a previous grant from the home care market on clinical HDBF, Dr. Simpson led a study to outcomes and patient experience. $40,000 Improving home health care for the elderly: Predicting clinical deterioration among older adults with and without dementia in the home care setting Gastrointestinal focus The gastrointestinal department at supplement, analyzed data on the Jessica Chapin, PhD Aurora St. Luke’s Medical Center competency of advanced endoscopy American Academy of Clinical continues to conduct clinical research. trainees, establishing minimum training Neuropsychology Foundation time and procedure volume required $12,000 Under the mentorship of to successfully perform endoscopic gastroenterologist Nalini Guda, MD, Impact of neuropsychological retrograde cholangiopancreatography. the GI research team presented evaluations for dementia on health findings for multiple studies Sutyanisth Agrawal, MD, presented the care utilization and quality indicators: at the 2015 Digestive Diseases findings. Brian Rajca, MD, Julia Leo, a multicenter study Week, an international annual MD, Veena Kumaravel, MD, Jonathan conference organized by American Fahler, MD, and Hershel Raff, PhD, Ron Cisler, PhD Gastroenterology Association, contributed to the study. Center for Urban Population Health/ American Society of Gastrointestinal Dr. Kumaravel also analyzed data on Medical College of Wisconsin Endoscopy and Society for Surgery correlating abnormalities detected of Alimentary Tract. $1,000 on different imaging modalities to The Proficient Study, published endoscopy findings. The findings Understanding, developing and measuring outcomes that matter for in a Gastrointestinal Endoscopy will help identify patients needing healthy weight in African-American endoscopic follow-up for abnormal women imaging studies. The Proficient Study Mohamed Mahmoud, MD, Dominic established criteria for Klyve, PhD, and Lyndon Hernandez, minimum training time MD, contributed to the study, which and procedure volume. was published in the Gastrointestinal Endoscopy supplement.

aurora.org/research 48 U.S. News rankings Aurora St. Luke’s Medical Center among U.S. News best hospitals

Aurora St. Luke’s Medical Center Aurora St. Luke’s was the only program was recognized as a top hospital in in the state nationally ranked in Wisconsin by U.S. News & World Report cardiology and heart surgery. in its annual rankings. For 2015-16, Additionally, Aurora St. Luke’s was also Aurora St. Luke’s is ranked number deemed a “high performing” hospital one in the Milwaukee metro area and in the areas of cancer, gynecology, number two in the state. nephrology, neurology and neurosurgery, Ranked specialties: orthopedics, pulmonology and urology. • car diology and heart surgery U.S. News evaluated hospitals in 16 adult • diabetes and endocrinology specialties and ranked the top 50 in • gastroenterology and GI surgery most of the specialties. • geriatrics

Additional Strategic Research publications 2015 Aurora-authored, peer-reviewed

Bosco SMG, Bagagli E, Baumgardner DJ. DuCanto J. Supraglottic airways: their evolution as Journal articles/Book chapters Blastomicose. In: Megid J, Ribeiro MG, Paes tracheal tube introducers. Anesthesiology News Al-Haddad MA, Kowalski T, Siddiqui A, Mertz AC (eds). Doenças Infecciosas em Animais de 2015 Aug;39-48. HR, Mallat D, Haddad N, Malhotra N, Sadowski B, Produção e Companhia (Portuguese). [Veterinary DuCanto J, Lungwitz Y, Koch A, Kähler W, Gessell Lybik MJ, Patel SN, Okoh E, Rosenkranz L, Karasik Infectious Diseases of Companion and Production L, Simanonok J, Roewer N, Kranke P, Winkler BE. M, Golioto M, Linder J, Catalano MF. Integrated Animals]. Rio de Janeiro, Brazil: Editora Roca, 2016, Mechanical ventilation and resuscitation under molecular pathology accurately determines the pp. 861-8. water: exploring one of the last undiscovered malignant potential of pancreatic cysts. Endoscopy Bowman E, Macias J, Akbar S, Soryal S, Hung W. environments--a pilot study. Resuscitation 2015;47(2):136-42. The Acute Care for Elders consult program. In 2015;93:40-5. Anderson MA, Akshintala V, Albers KM, Amann ST, Malone ML, Capezuti E, Palmer RM, eds. Geriatrics Ellinas H, Denson K, Simpson D. Low-cost Belfer I, Brand R, Chari S, Cote G, Davis BM, Frulloni Models of Care: Bringing ‘Best Practice’ to an Aging simulation: how-to guide. J Grad Med Educ L, Gelrud A, Guda N, Humar A, Liddle RA, Slivka A, America. New York, NY: Springer International 2015;7:257-8. Gupta RS, Szigethy E, Talluri J, Wassef W, Wilcox Publishing, 2015, pp. 39-49. CM, Windsor J, Yadav D, Whitcomb DC. Mechanism, Bub L, Boltz M, Malsch A, Fletcher K. The NICHE Endres L, DeFranco E, Conyac T, Adams M, Zhou assessment and management of pain in chronic program to prepare the workforce to address the Y, Magner K, O’Rourke L, Bernhard KA, Siddiqui pancreatitis: recommendations of a multidisciplinary needs of older patients. In: Malone ML, Capezuti E, D, McCormick A, Abramowicz J, Merkel R, Jawish study group. Pancreatology 2016;16:83-94 [Epub Palmer RM (eds). Geriatrics Models of Care: Bringing R, Habli M, Floman A, Magann EF, Chauhan SP; 2015 Nov 11]. ‘Best Practice’ to an Aging America. New York, NY: CAOG FAR Research Network. Association of fetal abdominal-head circumference size difference Attam R, Arain MA, Bloechl SJ, Trikudanathan Springer International Publishing, 2015, pp. 57-70. with shoulder dystocia: a multicenter study. AJP G, Munigala S, Bakman Y, Singh M, Wallace T, Burns J, Mullen TA. The role of traditional Chinese Rep 2015;5:e099-104. Henderson JB, Catalano MF, Guda NM. “Wet suction medicine in the management of chronic pain: a technique (WEST)”: A novel way to enhance biopsychosocial approach. J Patient Cent Res Rev Fink JT, Havens KK, Schumacher JA, Walker the quality of EUS-FNA aspirate. Results of a 2015;2:192-6. RE, Morris GL III, Nelson DA, Singh M, Cisler RA. prospective, single-blind, randomized, controlled Impact of the Heart WATCH program on patients trial using a 22-gauge needle for EUS-FNA of Butler DJ, Wolkenstein AS, Ruiz-Novero R, Wallace at risk of developing metabolic syndrome, solid lesions. Gastrointest Endosc 2015;81:1401-7. BK. See one, be one, teach one: faculty use of their prediabetes or cardiovascular disease. J Patient personal health narratives in teaching. Fam Med Cent Res Rev 2015;2:56-63. Bajwa TA Jr, Khan A, Jabeen S, Malone ML. Primary 2015;47:699-705. hyperparathyroidism in an older woman with Fink JT, Smith DR, Singh M, Ihrke DM, Cisler multiple comorbidities: a case study. J Am Geriatr Churchill RS. Stemless shoulder arthroplasty: RA. Obese employee participation patterns Soc 2015;63:413-4. current status. J Shoulder Elbow Surg in a wellness program. Popul Health Manag 2014;23:1409-14. 2016;19:132-5 [Epub 2015 Jun 18]. Basraon JS, Simpson D, Gupta A. Use of social media to promote continuous learning: a phased Churchill RS, Spencer EE Jr, Fehringer EV. Flood KL, Booth K, Pierluissi E, Danto-Norton ES, strategy for graduate medical education fellowship Quantification of B2 glenoid morphology in total Kresevic DM, Plamer RM. Acute care for elders. implementation. J Patient Cent Res Rev 2015;2:69-72. shoulder arthroplasty. J Shoulder Elbow Surg In: Malone ML, Capezuti E, Palmer RM (eds). 2015;24:1212-7. Geriatrics Models of Care: Bringing ‘Best Practice’ Baumgardner DJ. Clinical guidelines: where to an Aging America. New York, NY: Springer environment meets medicine. J Patient Cent Res Colman M, Pond J, Bachus K, Lawrence BD, Spiker International Publishing, 2015, pp. 3-23. Rev 2015;2:5. WR, Brodke DS. Fenestrated screws augmented with PMMA increase the pull-out strength of sacral Forgie MM, Greer DM, Kram JJ, Bernhard KA, Baumgardner DJ. Developmental problems in children. pedicle screws. J Spinal Disord Tech 2014 Dec 2 Salvo NP, Siddiqui DS. Foley catheter placement In: Paulman PM, Paulman AA, Jarzynka KJ, Falk NP [Epub ahead of print]. for induction of labor with or without stylette: a (eds). Taylor’s Manual of Family Medicine, 4th Edition. randomized clinical trial. Am J Obstet Gynecol Philadelphia, PA: Wolters Kluwer, 2015, pp. 116-22. Dewey CM, Turner TL, Perkowski L, Bailey J, 2016;214:397.e1-10 [Epub 2015 Dec 24]. Gruppen LD, Riddle J, Singhal G, Mullan P, Baumgardner DJ. One final goodbye. J Patient Poznanski A, Pillow T, Robins LS, Rougas SC, Horn Fuller BM, Mohr NM, Skrupky L, Fowler S, Cent Res Rev 2015;2:49-50. L, Ghulyan MV, Simpson D; 2012 National DMEFP Kollef MH, Carpenter CR. The use of inhaled Baumgardner DJ, Bernhard KA, Egan G. Pulmonary Conference Team. Twelve tips for developing, prostaglandins in patients with ARDS: a blastomycosis in Vilas County, Wisconsin: weather, implementing, and sustaining medical education systematic review and meta-analysis. Chest exposures and symptoms. J Patient Cent Res Rev fellowship programs: building on new trends and 2015;147:1510-22. 2015;2:25-33. solid foundations. Med Teach 2016;38:141-9 [Epub 2015 Sep 23].

49 Aurora Research Institute | Annual Report 2015 Gerald JK, Gerald LB, Vasquez MM, Morgan WJ, Kim SJ, Lee JH, Han B, Lam J, Bukowy E, Rao A, Nadim MK, Durand F, Kellum JA, Levitsky J, O’Leary Boehmer SJ, Lemanske RF Jr, Mauger DT, Strunk Vulcano J, Andreeva A, Bertelson H, Shin HP, Yoo JG, Karvellas CJ, Bajaj JS, Davenport A, Jalan R, RC, Szefler SJ, Zeiger RS, Bacharier LB, Bade JW. Effects of hospital-based physical therapy on Angeli P, Caldwell SH, Fernández J, Francoz C, E, Covar RA, Guilbert TW, Heidarian-Raissy H, hospital discharge outcomes among hospitalized Garcia-Tsao G, Ginès P, Ison MG, Kramer DJ, Mehta RL, Kelly HW, Malka-Rais J, Sorkness CA, Taussig LM, older adults with community-acquired pneumonia Moreau R, Mulligan D, Olson JC, Pomfret EA, Senzolo Chinchilli VM, Martinez FD. Markers of differential and declining physical function. Aging Dis M, Steadman RH, Subramanian RM, Vincent JL, Genyk response to inhaled corticosteroid treatment 2015;6:174-9. YS. Management of the critically ill patients with among children with mild persistent asthma. cirrhosis: a multidisciplinary perspective. J Hepatol J Allergy Clin Immunol Pract 2015;3:540-6.e3. Kim SJ, Park EC, Kim TH, Yoo JW, Lee SG. Mortality, 2016;64:717-35 [Epub 2015 Oct 28]. length of stay, and inpatient charges for heart failure Gehrand AL, Kaldunski ML, Bruder ED, Jia S, patients at public versus private hospitals in South O’Brien A, Weaver C, Settergren TT, Hook ML, Hessner MJ, Raff H. Intermittent neonatal hypoxia Korea. Yonsei Med J 2015;56:853-61. Ivory CH. EHR documentation: the hype and the elicits the upregulation of inflammatory-related hope for improving nursing satisfaction and quality genes in adult male rats through long-lasting Knox KE. Should primary care physicians address outcomes. Nurs Adm Q 2015;39:333-9. programming effects. Physiol Rep 2015;3:e12646. sleep to improve weight loss in obese patients? A Clin-IQ. J Patient Cent Res Rev 2015;2:197-201. Patterson RP, Roedl SJ, Farrell MH. Internet Guda NM, Freeman ML. Overview of ERCP searching after parents receive abnormal newborn complications: prevention and management. In: Lee Kram JJ, Borlaug G, Safdar N, Sethi A. Development screening results. J Commun Healthc 2015;8:303-15. LS (ed). ERCP and EUS. A Case-Based Approach. and distribution of educational materials for New York, NY: Springer-Verlag, 2015, pp. 37-56. carbapenem-resistant enterobacteriaceae among acute Petrik ML, Gutierrez PM, Berlin JS, Saunders SM. and long-term care facilities. WMJ 2015;114:48-51. Barriers and facilitators of suicide risk assessment Haas J, Leo J, Vakil N. Glucagon is a safe and in emergency departments: a qualitative study inexpensive initial strategy in esophageal food Kumar S. Cholangioscopy-directed endoscopic of provider perspectives. Gen Hosp Psychiatry bolus impaction. Dig Dis Sci 2016;61:841-5 [Epub intervention for post-liver transplantation 2015;37:581-6. 2015 Oct 24]. anastomotic biliary stricture. Gastrointest Endosc 2015;81:1014-5. Ping Tsao CI, Simpson D, Treat R. Medical student Haas JM, Singh M, Vakil N. Mortality and communication skills and specialty choice. Acad complications following surgery for diverticulitis: Kumar S. Cholestatic liver injury secondary to Psychiatry 2015;39:275-9. systematic review and meta-analysis. United artemisinin. Hepatology 2015;62:973-4. Polly DW, Cher DJ, Wine KD, Whang PG, Frank European Gastroenterol J 2016;61:841-5 [Epub 2015 Kumar S. Colonic Dieulafoy’s lesion. Gastrointest Nov 13]. CJ, Harvey CF, Lockstadt H, Glaser JA, Limoni RP, Endosc 2015;81:761. Sembrano JN; INSITE Study Group. Randomized Harris MR, Langford LH, Miller H, Hook M, Dykes Kumar S. Hepatology: Complete regression of controlled trial of minimally invasive sacroiliac PC, Matney SA. Harmonizing and extending locally advanced hepatocellular carcinoma following joint fusion using triangular titanium implants standards from a domain-specific and bottom-up Sorafenib monotherapy. J Gastroenterol Hepatol vs nonsurgical management for sacroiliac joint approach: an example from development through 2015;30:438. dysfunction: 12-month outcomes. Neurosurgery use in clinical applications. J Am Med Inform Assoc 2015;77:674-90; discussion 690-1. 2015;22:545-52. Kumar S. Hepatology: De novo primary sclerosing cholangitis post liver transplantation. Rao A, Khan A, Singh K, Anderson DL, Malone ML. Ho JC, Stitzlein RN, Green CJ, Stoner T, Froimson J Gastroenterol Hepatol 2015;30:1114. Neurosyphilis: an uncommon cause of dementia. MI. Return to sports activity following UKA and TKA. J Am Geriatr Soc 2015;63:1710-2. J Knee Surg 2016;29:254-95 [Epub 2015 Jul 10]. Kumar S. Oral contraceptive-induced hepatic sinusoidal dilatation. Dig Liver Dis 2015;47:e10. Reynolds KH. Small intestinal bacterial overgrowth: Hocker JD, Khan A, Singh M, Hook ML, Simpson a case-based review. J Patient Cent Res Rev M, Malsch A, Vollbrecht M, Malone ML. Can the Kuziemsky C, Adams MB, Kaplan B, Ravvaz K, 2015;2:165-73. electronic health record identify vulnerable older Koppel R. What medical informaticians do with adults in need of a palliative care assessment in the and think about an international medical informatics Schaefer C, Mann R, Masters ET, Cappelleri JC, Daniel hospital setting? J Am Geriatr Soc 2015;63:1479-81. listserv: member survey preliminary findings. Stud SR, Zlateva G, McElroy HJ, Chandran AB, Adams EH, Health Technol Inform 2015;216:1124. Assaf AR, McNett M, Mease P, Silverman S, Staud R. Holt A. Mindfulness-based stress reduction and The comparative burden of chronic widespread pain transcendental meditation: current state of Larkin BG, Zimmanck RJ. Interpreting arterial and fibromyalgia in the United States. Pain Pract research. J Patient Cent Res Rev 2015;2:64-8. blood gases successfully. AORN J 2015;102:343-54; 2015 May 16 [Epub ahead of print]. quiz 355-7. Hung WW, Macias Tejada JA, Soryal S, Akbar ST, Simpson D, Gusic ME, Anderson MB. How teaching Bowman EH. The Acute Care for Elders consult Leonhardt KK, Keuler M, Safdar N, Hunter P. Ebola expertise and scholarship can be developed, program. In: Malone ML, Capezuti E, Palmer RM preparedness planning and collaboration by recognized and rewarded. In: Abdulrahman KAB, (eds). Geriatrics Models of Care: Bringing ‘Best two health systems in Wisconsin, September to Mennin S, Harden R, Kennedy C (eds). Routledge Practice’ to an Aging America. New York, NY: December 2014. Disaster Med Public Health Prep International Handbook of Medical Education. Springer, 2015, pp. 39-49. 2015 Sep 15:1-7 [Epub ahead of print]. London, England: Routledge-Taylor and Francis, 2016, pp. 318-29 [eBook published July 22, 2015]. Jain R. Utility of saxagliptin in the treatment of Lewis J. Guest editorial: A care perspective: type 2 diabetes: review of efficacy and safety. palliative care. J Vasc Nurs 2015;33:2-3. Simpson D, Mahboob H, Battiola RJ, Brill JR. Case Adv Ther 2015;32:1065-84. study 23.1: Dr. Lasz Lo – clinician teacher (teaching L’Hommedieu T, DeCoske M, El Lababidi R, Ladell N. activity category). In: Abdulrahman KAB, Mennin S, Jambunathan J, Chappy S, Siebers JJ, Deda A. Utilizing pharmacy students in transitions-of-care Harden R, Kennedy C (eds). Routledge International Patient-centered care for chronic pain in the services. Am J Health Syst Pharm 2015;72:1266-8. Handbook of Medical Education. London, England: emergency department: a qualitative study. Int Routledge-Taylor and Francis, 2016, pp. 321-2. Emerg Nurs 2016;24:22-7 [Epub 2015 Jun 4]. Magnan EM, Palta M, Mahoney JE, Pandhi N, Bolt [eBook published July 22, 2015]. DM, Fink J, Greenlee RT, Smith MA. The relationship Kalil AC, Syed A, Rupp ME, Chambers H, Vargas of individual comorbid chronic conditions to Simpson D, Sullivan GM. Knowledge translation for L, Maskin A, Miles CD, Langnas A, Florescu DF. Is diabetes care quality. BMJ Open Diabetes Res education journals in the digital age. J Grad Med bacteremic sepsis associated with higher mortality Care 2015;3:e000080. Educ 2015;7:315-7. in transplant recipients than in nontransplant patients? A matched case-control propensity- Malone ML, Capezuti E, Palmer RM (eds). Geriatrics Skrupky LP, Drewry AM, Wessman B, Field RR, adjusted study. Clin Infect Dis 2015;60:216-22. Models of Care: Bringing ‘Best Practice’ to an Aging Fagley RE, Varghese L, Lieu A, Olatunde J, Micek America. New York, NY: Springer International ST, Kollef MH, Boyle WA. Clinical effectiveness of Kalra AS, Walker AJ, Benson ME, Soni A, Guda Publishing, 2015. a sedation protocol minimizing benzodiazepine NM, Misha M, Gopal DV. Comparison of capsule infusions and favoring early dexmedetomidine: a endoscopy findings to subsequent double May T. On the justifiability of ACMG before-after study. Crit Care 2015;19:136. balloon enteroscopy: a dual center experience. recommendations for reporting of incidental Diagn Ther Endosc 2015;2015:438757. findings in clinical exome and genome sequencing. Steiner ME, Ness PM, Assmann SF, Triulzi DJ, J Law Med Ethics 2015;43:134-42. Sloan SR, Delaney M, Granger S, Bennett-Guerrero Khan A, Simpson M, Singh M, Hook M, Geng Y, E, Blajchman MA, Scavo V, Carson JL, Levy JH, Malone ML. Innovative approach to measure delirium Melin AA, Schmid KK, Lynch TG, Pipinos II, Kappes Whitman G, D’Andrea P, Pulkrabek S, Ortel TL, in hospitalized older adults using the electronic S, Longo GM, Gupta PK, Johanning JM. Preoperative Bornikova L, Raife T, Puca KE, Kaufman RM, Nuttall health record. J Am Geriatr Soc 2015;63:593-4. frailty Risk Analysis Index to stratify patients GA, Young PP, Youssef S, Engelman R, Greilich undergoing carotid endarterectomy. PE, Miles R, Josephson CD, Bracey A, Cooke R, Khan A, Singh M, Saeed S, Siddiqui A, Aziz Z, J Vasc Surg 2015;61:683-9. Malone ML. A survey of concerns in end-of-life McCullough J, Hunsaker R, Uhl L, McFarland JG, care: perspective from Pakistan. J Am Geriatr Mohorek A. My time with E. J Patient Cent Res Park Y, Cushing MM, Klodell CT, Karanam R, Roberts Soc 2015;63:1955-7. Rev 2015;2:73-4. PR, Dyke C, Hod EA, Stowell CP. Effects of red-cell storage duration on patients undergoing cardiac Kim M, Juern AM, Paley S, Chiu YE. Vaccine- Mullen TA. Integrative medicine: in with the new. surgery. N Engl J Med 2015;372:1419-29. associated herpes zoster. J Pediatr 2015;167:494. J Patient Cent Res Rev 2015;2:153-5. Tillett J. Medication use during pregnancy and lactation: the new FDA drug labeling. J Perinat Neonatal Nurs 2015;29:97-9.

aurora.org/research 50 Tye S, Van Voorhees E, Hu C, Lineberry T. Cox Bauer C, Bernhard KA, Greer DM, Kamelle S. Kram JJF, Baumgardner DJ, Bernhard KA, Lemke Preclinical perspectives on posttraumatic stress Operating room first start efficiency throughout a MA. Geographic distribution of infant death disorder criteria in DSM-5. Harv Rev Psychiatry large urban hospital system. J Patient Cent Res Rev during birth hospitalization and maternal Group B 2015;23:51-8. 2015;2:202-3. streptococcus colonization: eastern Wisconsin. J Patient Cent Res Rev 2015;2:205-6. Vakil N. Rationale for a Helicobacter pylori test Cox-Bauer CM, Bernhard KA, Greer DM, Merrill DC. and treatment strategy in gastroesophageal reflux Maternal and neonatal outcomes in obese women Kumaravel V, Mahmoud M, Klyve D, Hernandez LV, disease. Gastroenterol Clin North Am 2015;44:661-6. who lose weight during pregnancy. Obstet Gynecol Guda NM. A prospective study on endoscopy for 2015;125:9S. luminal abnormalities on imaging and its impact Vakil N. Salivary pepsin to diagnose GORD? Gut on clinical management. Gastrointest Endosc 2015;64:361-2. Dalmar A, Singh M, Roloff SK, Chua TY. Fair weight 2015;81:AB237-8. loss after gastric rebanding for slippage. J Patient Vollbrecht M, Malsch A, Hook ML, Simpson MR, Cent Res Rev 2015;2:214-5. Lawrence C, Nieto J, Parsons WG, Roy A, Guda Khan A, Malone ML. Acute Care for Elders (ACE) NM, Steinberg SE, Hasan MK, Bucobo JC, tracker and “e-geriatrician” telemedicine program. Denson K, Simpson D, Malone M, Wessel B, Rehm Nagula S, Sherman SM, Buscaglia J. Evolution® In: Malone ML, Capezuti E, Palmer RM (eds). J; GET Collaborative. Acting locally to impact Biliary Stent System-Uncovered: a prospective, Geriatrics Models of Care: Bringing ‘Best Practice’ geriatric education globally. J Am Geriatr Soc multicenter study of deployment in malignant to an Aging America. New York, NY: Springer 2015;63:S50. strictures of the biliary tree. Gastrointest Endosc International Publishing, 2015, pp. 51-6. Denson K, Simpson D, Padua K, Currey A; GET 2015;81:AB347. Wannemuehler TJ, Elghouche AN, Kokoska MS, Collaborative. Quick quizzes: Geriatrics right in Lewis DN, Salvo NP, Bernhard KA, Greer DM. Deig CR, Matt BH. Impact of Lean on surgical your hand & at the point of care. J Am Geriatr Model assessment and development of risk instrument reduction: less is more. Laryngoscope Soc 2015;63:S49-50. stratification of surgical site infection following 2015;125:2810-5. Fok C, Kim Y, Case J, Haq C. Evaluating the efficacy Cesarean delivery for a high-risk, urban Whang P, Cher D, Polly D, Frank C, Lockstadt H, of Fondy Food Center’s farmer’s market. 2015 North population. J Patient Cent Res Rev 2015;2:202. Glaser J, Limoni R, Sembrano J. Sacroiliac joint American Primary Care Research Group Annual Mamman S, Weissert J, Pandey BK, Siegler K, fusion using triangular titanium implants vs. Meeting (online educational session SRF70). [Epub Hernandez LV, Ananthakrishnan AN, Guda NM, non-surgical management: six-month outcomes 2015 Oct 27.] Available at: http://www.napcrg.org/ Tonellato P. Longitudinal demographic trends from a prospective randomized controlled trial. Conferences/2015AnnualMeetingArchives/SearchEd of nationwide gastrointestinal-related Int J Spine Surg 2015;9:6. ucationalSessions?m=6&s=15884. emergency department visits. Gastrointest Woda A, Belknap RA, Haglund K, Sebern M, Garcia RM, Ward J, Salazar J, Jimenez H, Saavedra- Endosc 2015;81:AB238. Lawrence A. Factors influencing self-care Retzlaff M, Perez Valdez P, Buelow M. Helping Meyers K, Konarske J, Kram JJF, Baumgardner DJ. behaviors of African Americans with heart failure: Hands: an HIV peer mentoring program at Assessing the effectiveness of implementation of a photovoice project. Heart Lung 2015;44:33-8. Sixteenth Street Community Health Centers. 2015 unified workflow in improvement of medication North American Primary Care Research Group reconciliation for Aurora St. Luke’s family medicine Wu RR, Myers RA, McCarty CA, Dimmock D, Farrell Annual Meeting (online educational session P178). M, Cross D, Chinevere TD, Ginsburg GS, Orlando residency outpatients. J Patient Cent Res Rev [Epub 2015 Oct 25.] Available at: http://www. 2015;2:203. LA; Family Health History Network. Protocol for napcrg.org/Conferences/2015AnnualMeetingArchiv the “Implementation, adoption, and utility of family es/SearchEducationalSessions?m=6&s=15965. McFadzen MP, Dielentheis DP, Kasten R. Maternal history in diverse care settings” study. Implement intuition of fetal gender. J Patient Cent Res Rev Sci 2015;10:163. Hartlaub J, Muzi MA, Cairo MJ, Brill JR, Weese J, 2015;2:212. Rivera K, Hafemann S, Rohrer AM, Schumacher J, Yoo JW, Jabeen S, Bajwa T Jr, Kim SJ, Leander Vandenhouten TL. PRACTC: Practice Readiness Muralidharan M, Getzin A, Knox KE, Bobot BL, D, Hasan L, Punke J, Soryal S, Khan A. Hospital Academic Clinical Training Collaborative –– gap Forgie MM, Salvo NP, Simpson D. Triple aim readmission of skilled nursing facility residents: a analysis to advance clinical training for nurse for clinical teachers (TACT): faculty physician systematic review. Res Gerontol Nurs 2015;8:148-56. practitioner students. J Patient Cent Res Rev perceptions on their ability to balance clinical 2015;2:211. quality, trainee learning, and teaching efficiency. J Patient Cent Res Rev 2015;2:209-10. Abstracts Irani MS, Ernster L, Karafin M. Red cell exchange to mitigate a delayed hemolytic transfusion Ohly S, Rosenthal EL, Hargrove L, Smith S, Perez Agrawal ST, Rajca B, Leo J, Kumaravel V, Fahler reaction in a patient transfused with incompatible V. Capacity building for community health workers J, Raff H, Guda NM. Progression of fellow’s red blood cells. J Clin Apheresis 2015;30(2):93-4. integrating apprenticeships to get to the top of competence in ERCP training: the Proficient the mountain. American Public Health Association Study. Gastrointest Endosc 2015;81:AB164-5. Khan A, Hook ML, Singh M, Vollbrecht M, Malsch (online program #333866). [Epub 2015 Nov A, Malone ML. Using an automated model to 2]. Available at: https://apha.confex.com/ Aldag E, Farrell S, Pedersen R, Sahajpal A, identify older patients at risk for 30-day hospital apha/143am/webprogram/Paper333866.html. Clendenon J, Gunabushanam V, Kramer D. readmission and 30-day mortality. J Patient Cent Evaluation of the effects of N-acetylcysteine Res Rev 2015;2:203-4. Patel K, Battiola R, Jella A. Systemic lupus treatment in adult liver transplant recipients. erythmatosis (SLE) presenting as thrombotic Am J Transplant 2015;15(suppl 3). Available at: Khan A, Hook M, Singh M, Vollbrect M, Malsch A, thrombocytopenic purpura (TTP). 2015 American http://www.atcmeetingabstracts.com/abstract/ Malone M. Using an automated model to identify College of Physicians Wisconsin Chapter Annual evaluation-of-the-effects-of-n-acetylcysteine- patients at risk for 30-day hospital readmissions Meeting (displayed posters). Available at: https:// treatment-in-adult-liver-transplant-recipients/. and 30-day mortality. J Am Geriatr Soc www.acponline.org/system/files/documents/ 2015;63:S125. about_acp/chapters/wi/15mtg/patel.pdf. Basraon JS, Simpson D, Gupta A. Use of social media to promote continuous learning: a phased Khan A, Maria A, Hocker J, Singh M, Simpson M. Punke J, Khan A, Malone ML. Delirium recognition strategy for graduate medical education fellowship Prognostic indices for hospitalized older adults: in hospitalized older patients: a quality implementation. 2015 Association of Program a meta-analysis and systematic review. J Patient improvement project. J Patient Cent Res Directors in Internal Medicine Spring Meeting Cent Res Rev. 2015;2:206-7. Rev 2015;2:208. (programmatic innovation poster abstract #51). [Epub Khan A, Maria A, Hocker J, Singh M, Simpson 2015 Apr 29] Available at: www.im.org/d/do/5837. Punke J, Khan A, Malone ML. Delirium M, Akbar S, Yoo J, Nazir A, Kim S, Malone M. recognition in hospitalized older patients: a Batajoo R, Waldo M, Moses T, Buelow M. SEEDS: Prognostic indices for hospitalized older adults: quality improvement project. J Am Geriatr Soc Self-Esteem, Empowerment & Empathy, Discovery a meta-analysis and systematic review. J Am 2015;63:S194. of Self: a mental health treatment program. 2015 Geriatr Soc 2015;63:S64. North American Primary Care Research Group Spahr N, Enrique F. Group well child visits: Khan A, Singh M, Singh H, Maria A, Simpson M. implementation and evaluation. 2015 North Annual Meeting (online educational session SRF50). An automated model using electronic health [Epub 2015 Oct 27.] Available at: http://www.napcrg. American Primary Care Research Group Annual record data to identify delirium among Meeting (online educational session SRF72). org/Conferences/2015AnnualMeetingArchives/Sear hospitalized older adults: a pilot project. chEducationalSessions?m=6&s=15858. [Epub 2015 Oct 27.] Available at: http://www. J Patient Cent Res Rev 2015;2:206. napcrg.org/Conferences/2015AnnualMeetingArchi Baumgardner DJ. β-thujaplicin: a soil antifungal. Khan A, Singh M, Singh H, Maria A, Simpson M, ves/SearchEducationalSessions?m=6&s=15851. J Patient Cent Res Rev 2015;2:211-2. Malone M, Hook M. An automated model using Sullivan Vedder L, Simpson D, Bidwell JL, Brill JR, Brill JR, Ames D, Groth CB, Yu H. Chronic illness electronic health record data to identify delirium Frederick T. Aligning asthma education across management in teams of urban multidisciplinary in hospitalized older adults: a pilot project. J Am the continuum of physician education: impact scholars (CIMTUMS) –– part II. J Patient Cent Res Geriatr Soc 2015;63:S126. on clinical metrics. J Patient Cent Res Rev Rev 2015;2:207. Kram J, Baumgardner D, Bernhard K, Lemke M. 2015;2:213-4. Chua T, Dalmar A, Singh M, Roloff S. Fair weight Geographic distribution of infant death during Veeramachaneni J, Khan A, Malone ML, Singh loss after gastric rebanding for slippage. Surg birth hospitalization and maternal Group B K. Role of novel anticoagulants in a frail elderly Obes Rel Dis 2015;11:S80-1. streptococcus colonization: eastern Wisconsin. patient with multiple medical co-morbidity: a case 2015 North American Primary Care Research Group study. J Am Geriatr Soc 2015;63:S166. Cichon CY, Kram JJF, Mullen TA, Voelkers P, Annual Meeting (online educational session OB36). Magliocco KJ, Bernhard KA, Baumgardner DJ. [Epub 2015 Oct 27.] Available at: http://www. Vulcano JT. Reducing readmission rates in acute Disease-management in family medicine clinics napcrg.org/Conferences/2015AnnualMeetingArchiv pancreatitis through patient education and risk through the addition of a health coach: a pilot es/SearchEducationalSessions?m=6&s=15430. assessment. J Patient Cent Res Rev 2015;2:210. study. J Patient Cent Res Rev 2015;2:212-3.

51 Aurora Research Institute | Annual Report 2015 A $19.6 million operation in 2015, Aurora Research Institute supports more than 500 clinical trial, laboratory-based and investigator-initiated research studies throughout Aurora Health Care. Employing about 170 caregivers, the institute is focused on translating new discoveries to improve choices and outcomes that change not only the lives of individuals, but transform the health of populations. Randall Lambrecht, PhD, serves as president of the institute. About Aurora Research Institute 296 208 clinical trials open to accrual and open IIR studies as follow-up as of Dec. 31, 2015 of Dec. 31, 2015**

Cardiovascular (79) 27% Cardiovascular (95) 46%

Oncology Other* (34) 16% (23) 8% Oncology (172) 58%

Other (70) 34% Neurosciences (9) 4% Neurosciences (22) 7%

*includes orthopedics, asthma, emergency medicine, ** Source: Aurora Health Care pulmonology, sleep medicine, women’s health and Institutional Review Board humanitarian use device/compassionate use clinical trials

$19.6 million expenditures in 2015

Institutional Investment ($7,549,483) Industry 39% Contracts ($4,651,376) 24%

Other Foundation 18% Extramural Support Grants and ($1,423,509) Awards 7% ($2,361,089) 12% Research Business Services highlights

Led by: Kurt Waldhuetter, MS

Research Analytics Led by: Andy Marek 36 Research Analytics requests in 2015 (>3 days effort) • Continued to provide the highest-quality data possible in support of research data requests while initiating population health and clinical decision-support pilots.

• In addition to multiple carry-over projects, initiated 36 new data request projects and completed many, including a customized Other (14) 39% de-identified data extract of more than 250,000 patients and Cardiovascular 135,000,000 total records to support the development of an (14) 39% advanced pharmacogenomics decision-support model.

• Received Institutional Review Board approval for and built a customized geocoding resource that will allow researchers to link Women’s Oncology 2 (5%) geospatial characteristics to electronic health record data in a fully Health (5) 14% Neurosciences de-identified and compliant way. 1 (3%)

Research Business Operations Completed contracts in 2015 Led by: Katie Richter • Continued to achieve new levels of service commitment in support of all research contracting for clinical trials, 40 Confidentiality 38 disclosure agreements grants, materials, data and other academic service and completed 35 support agreements. Clinical trial contract 30 29 agreements completed • Progressed toward the use of common grant and Grant and other contract agreement templates containing standardized 25 24 contracts completed language in collaboration with legal counsel. 20 20 20 • Debuted multiple new tools to increase efficiency, 15 13 compliance and cost-coverage, including a contract 11 negotiation tracker, nine new standard operating 10 8 8 procedures and a robust fee schedule. 5 4 2 2 2 • Implemented significant improvements to electronic 00 0 Cardiovascular Oncology Neurosciences Women’s Other health record research billing functionality and the Health successful resolution of multiple billing issues identified during an in-depth process mapping effort.

Research Innovation Led by: Don Conrad New intellectual property disclosures and new • A dvanced two early-stage innovations to the entrepreneurial projects engaged in 2015 6 prototyping and patenting stage of development by 6 transitioning a physician-originated innovation from New intellectual small evaluation to systemwide adoption and through 5 property disclosures collaboration on APN Health LLC’s Navik 3D cardiac New entrepreneurial 4 projects mapping system. 3 3 • Defined processes and created willingness to support 3 2 2 2 more caregiver-initiated innovations. 2 1 • Spearheaded additional support for commercially 1 structured innovations, providing due diligence and 0 0 market research that led to about $2.35 million in Cardiovascular Oncology Neurosciences Other early-stage financing.

53 Aurora Research Institute | Annual Report 2015 Sponsored Programs Clinical Trials highlights Office highlights Led by: Sara Planton, BSN Managed by: Jan DeBartolo, MSN, Annette Paul, MAT, Led by: Vani Nilakantan, PhD Wendy Schmidt, RN, and Carol Tutino, BSN, MS

• Tracked awards totaling about $3.3 million, including $1 million • Enrolled more than 1,200 subjects in nearly 300 clinical from the Vince Lombardi Cancer Foundation to develop a trials available in the oncology, cardiovascular and neuro-oncology research program and more than $435,000 neurosciences services lines and additional strategic from National Institutes of Health, via Vanderbilt University, to areas of Aurora Health Care. personalize drug prescriptions with genetic testing. • Boos ted Commission on Cancer accreditations to • Administered four intramural award programs (Aurora Cancer gold status with two research-related commendations Care Research Award, Cardiac Research Award, Sullivan Cardiac for achieving a rate of greater than 8% in clinical trial Research Award for Residents and Fellows and Cardiovascular accruals and the public reporting of outcomes, in part, Surgery Research Award), awarding nearly $700,000. through Aurora Health Care’s medical journal, Journal • De veloped learning opportunities to simplify the grant of Patient-Centered Research and Reviews. application process, including both a hands-on workshop and • Strengthened relationships with research and industry online self-paced course to create a new National Institutes of sponsors, yielding $4.7 million in revenue, to offer new Health biosketch and SciENcv. A second workshop provided options for patients. tips on a winning and stress-free grant proposal and another online course provided step-by-step instructions for using • Enhanc ed caregiver skills in coordination and EndNote to create citations and bibliographies. regulation of clinical trials through training and educational opportunities. • Streamlined operations with development of systemwide policies and procedures on grant management.

Extramural grants awarded: Clinical trial revenues: $3.3 million in 2015 $4.7 million in 2015

Neurosciences Nonprofit ($98,513) ($1,495,414) Cardiovascular 2% 45% Industry ($707,211) ($3,382,132) Other** 21% 73% ($522,066) 11%

Oncology Federal ($648,665) ($951,485) 14% 29% State ($140,165) 4%

Intramural grants awarded: Clinical trial enrollments: $692,599 in 2015 1,202 in 2015

Cardiovascular ($489,239) 72% Cardiovascular Oncology Oncology Surgery Research ($194,360) 28% (348) Awards 29% ($318,287) 46% Neurosciences Aurora Cancer (164) 14% Care Research Awards* Cardiovascular Other** ($194,360) (589) Cardiac (101) 8% 28% 49% Research Sullivan Cardiac Awards Research Award for ($120,000) Residents and Fellows 17% ($59,952) 9%

* Supported by an extramural grant provided by Vince Lombardi **Includes orthopedics, asthma, emergency medicine, Cancer Foundation pulmonology, sleep medicine, women’s health and humanitarian use device/compassionate use clinical trials

aurora.org/research 54 Translational Research highlights

Led by: Nina Garlie, PhD, and Vani Nilakantan, PhD Managed by: David Krum, MS, and Bob Stoltz, MBA, MT

• With a more than $5 million capital • Continued to grow a multidisciplinary investment, constructed a unique core team of research scientists and environment, Discovery Laboratory, biostatisticians to engage in and for researchers to work from the facilitate more than 200 laboratory molecular to cellular levels to gain a and investigator-initiated research better understanding of genes and studies throughout Aurora Health proteins and how they react to new Care’s cardiovascular, oncology and existing therapies. and neurosciences service lines and additional strategic areas. • Expanded the animal research and care program with construction of • Es tablished or developed specialty a vivarium to provide avatars for centers and programs within the oncology research. service lines and strategic areas. Research associate Geoffrey Riddell conducts an – Aurora UW Medical Group experiment in Discovery Laboratory on the Aurora Research Core Sinai Medical Center campus. – Biorepository and Specimen Resource Center – Cardio-Oncology Research Program – Center for Urban Population Health • Supported laboratory research beyond – Early Phase Cancer Research Program programmatic areas. – Neuro-Oncology Research Program – Endocrine Research Laboratory – Neurosciences Research Program – Immunotherapy Research Laboratory – Precision Medicine Research Program – Neuroanatomical Laboratory – Regenerative Medicine Center • S trengthened internal relationships to – Sheikh Khalifa bin Hamad Al Thani ensure quality and compliant research Center for Integrative Research on that protected subjects and animals. Cardiovascular Aging (CIRCA) – Translational Oncology Research: • Offered informational presentations Quest for Understanding and on myriad topics by both internal and Exploration (TORQUE) external experts.

Nina Garlie, PhD, and Bob Stoltz, MBA, Senior research scientist Michael MT, lead Discovery Laboratory tours. Michalkiewicz, PhD, studies severe blood transfusion reactions.

Research associate Kate Dennert studies cells in Discovery Laboratory.

Randall Lambrecht, PhD, Arshad Jahangir, MD, and Vani Nilakantan, PhD.

55 Aurora Research Institute | Annual Report 2015 Biorepository and Specimen Resource Center Powered by ORBIT (Open-Access Robotic Biorepository and Informatics Technology)

Through its partnership with ACL research associate and research Laboratories, the BSRC accepts thousands of coordinator. Research Analytics, discarded samples on a daily basis. Hundreds led by Andy Marek, supports the of specimens have been used for studies data collection for the BSRC. conducted by Aurora Health Care researchers, and, using iSpecimen technology, thousands more have been shared with investigators More than 145,000 patients consented throughout the country. Biospecimen Utilization for their leftover biospecimens to be used for research purposes through the The BSRC also coordinates the targeted Committee Biorepository and Specimen Resource collection of tissues for specific research Diane Austin Center (BSRC). purposes. Examples include tumors from Compliance Officer Research, the breast (see story on page 26) and brain Aurora Health Care Since its inception eight years ago, the (see story on page 39). BSRC has amassed an inventory of more Julie Basquin, MS than 70,000 whole blood, plasma and Led by Natalie Polinske, MS, the BSRC Senior Research Business Analyst, serum samples for future research studies. team consists of a research lab assistant, Aurora Health Care Amy Bovi, MA Policy and Ethics Officer, Research lab assistant Kujana Clayton removes samples from a cryogenic freezer in the Aurora Health Care Biorepository and Specimen Resource Center, which is equipped with cutting-edge technology. Rachel Delaney, JD Corporate Counsel Research, Aurora Health Care

Rich Merkel Executive Director, STEM Forward

Gary Neitzel, MD Medical Director, ACL Laboratories

Vani Nilakantan, PhD Director, Investigator-Initiated Research Department and Sponsored Programs Office, Aurora Research Institute

Sara Planton, BSN Director, Clinical Trials Department, Aurora Research Institute

Natalie Polinske, MS Manager, Biorepository and Specimen Resource Center, Aurora Research Institute (COMMITTEE CHAIR) 2015 highlights • Distributed more than 700 biospecimens • Established Biospecimen Utilization through more than 20 biospecimen requests Committee to address all key perspectives (legal, compliance, ethics, • W ith help from the Sponsored Programs etc.) involved in the use of biospecimens Office, won a $50,000 competitive grant from Conversant Bio to enhance BSRC • Implemented a systemwide policy that operations and financial stability provides guidelines for the transfer and utilization of biospecimens • F eatured in biorepository media coverage (BizTimes.com, HealthITAnalytics.com, • Received Research Team Award at American Association for Clinical Chemistry’s Sixth annual Greater Milwaukee Clinical Clinical Laboratory News, wire services) Research Recognition Event Interdepartmental collaborations

To achieve the highest level of professional and ethical standards in research, the dedication of a diverse network of caregivers from departments throughout Aurora Health Care is required.

Among others, institute caregivers collaborated with the following Aurora departments over the past year:

• Research Subject • Servic e line leadership • Revenue Cycle • ACL Laboratories Protection Program/ and support • IT • Aurora Pharmacy institutional review boards • Hospital and clinic • Health Informatics • Aurora Ventures • Research Compliance caregivers • Medical Group • Enterprise Business Group • Aurora Health Care • L egal Operations • Human Resources Foundation • Financ e • Oper ations Improvement • Supply Chain • Service market leadership • A ccounting • Oper ations Project and support • Billing Management

Collaboration among caregivers from these departments improves the efficiency, transparency and safety of the research conducted at Aurora. Together, these teams have invested – and will continue to invest – countless hours to allow for greater involvement by Aurora in groundbreaking research.

Senior research nurse coordinator Elise Damico, BSN, obtains an investigational Council for Quality Assurance drug prescription from pharmacist Jennifer Lester, RPh, for a research subject participating in a cardiovascular clinical trial. and Improvement in Research

Charged with overseeing Aurora Research Institute’s Quality Management Plan, the Council for Quality Assurance and Improvement in Research ensures high-quality compliant research is conducted by Aurora researchers.

Chaired by Nina Garlie, PhD, the council includes a broad representation of the institute as well as members from the Research Subject Protection Program and Research Compliance.

The council is responsible for developing a strategic annual quality monitoring plan, assessing key performance indicators and making recommendations to improve the quality of research. Melanie Guenther, senior research quality specialist, administers the quality assurance activities and reports findings to the council on a monthly basis.

In 2015, quality monitoring activities included: • full protocol reviews of high-risk studies. • focus audits directed at specific aspects of research. • self-as sessments and external monitoring.

The purpose of routine monitoring is to provide objective feedback to investigators and study team members regarding study conduct in accordance with the protocol, federal regulations, good clinical practices and policies/procedures. The data derived from these monitoring activities provides insight into study management to help identify education needs, recognize best practices and track and trend performance over time.

57 Aurora Research Institute | Annual Report 2015 Working together

Research Subject Protection Program/ Institutional Review Boards

Led by Michelle Maternowski, Aurora’s Research Subject Protection Program is charged with the oversight of human and animal subject research conducted at Aurora. RSPP Responsibilities include management of Aurora’s institutional review boards. The RSPP and IRBs: IRB • R eview and approve research proposals according to the ethical principles and Steve Francaviglia, MBA, RN, Rhonda Plotkin, and guidelines of the Belmont Report, the Linda Francaviglia, RN. applicable sections of the Code of Federal Regulations and the International Conference of Harmonisation Good Clinical Practice guidelines.

• Safeguard the rights, welfare and dignity of the human and animal subjects who participate in the research process.

• Promote the highest ethical standards for conducting research.

• Pr ovide a strong foundation of knowledge and cooperative education to facilitate the conduct of biomedical and behavioral research.

David Krum, MS, Kurt Waldhuetter, MS, Margo Winter, Dara Winter and Michelle Schuerman.

Vinay Thohan, MD, Wendy Schmidt, RN, Mia Stone, MS, BSN, and Vani Nilakantan, PhD.

Acknowledgments For research to be meaningful and impactful, the commitment of many bright and talented researchers, physicians and caregivers along with the hope and generosity of friends and donors are required.

It also requires the commitment of Aurora Health Care, the Aurora Research Institute Board of Directors and leadership at sites Thank throughout the system, which provides the administrative fortitude and support that allows innovative research to be conducted. you! Randall Lambrecht, PhD, and Marie Golanowski, RN. But most importantly, discoveries can only be translated into patient care with the courage and involvement of patients and their families.

aurora.org/research 58 Purpose, Vision, Values

Purpose We help people live well through innovative research.

Vision Offer more treatment choices and improve patient outcomes through research and innovation

Values • Every patient and community deserves the best care. • Resources should be managed responsibly. • A healthy workplace is built through accountability, teamwork and respect.

960 N. 12th Street Suite 4120 Milwaukee, WI 53233 T 414-219-4763 F 414-219-5381

aurora.org/research