Hawai‘i Chapter Scientific Meeting 2017

February 25, 2017

Pomaika‘i Ballrooms at Dole Cannery Honolulu, HI

Hot Topics This live activity has been designated for 5 CME credits.

1 Learning Objectives At the conclusion of this activity, the participant will be able to: • Improve clinical internal medicine practice by incorporating major developments in physician wellness. • Describe elements and limits of knowledge of marijuana pharmacology. • Discuss physician-assisted suicide in modern political and regulatory climates. • List characteristics and complications of Zika virus infection for adults and infants.

CME Accreditation The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The American College of Physicians designates this live activity for a maximum of 5 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Resident/Fellows' and Medical Students’ Activities Clinical vignettes, posters, and research papers prepared by Resident/Fellow Members and Medical Students will be presented at the meeting. Winners will receive a cash prize and be eligible for entrance into the national competition held during Internal Medicine 2018.

Pathways to Fellowship Attendance at chapter meetings can help all ACP members meet the qualifications for advancement to Fellowship. It is especially important for those applying under the pathway that calls for five years of activity as a member.

Governor Mary Ann Antonelli, MD, FACP Phone: (808)433-0645 E-mail: mantonel@hawaii.edu

Program Committee

Chair: Lisa Camara, MD, FACP Committee: Mary Ann Antonelli, MD, FACP S. Kalani Brady, MD, MPH, MACP Kent DeZee, MD, FACP Alvin Furuike, MD, FACP Jone Geimer-Flanders, DO, FACP Donald Helman, MD, FACP Lori Karan, MD, FACP Kuo-Chiang Lian, MD, FACP Glenn Rediger, MD, FACP Elizabeth Tam, MD, FACP 2 Faculty Robert Centor, MD, MACP, Past-Chair ACP Board of Regents, Regional Dean, UAB, Huntsville Regional Medical Campus, Professor, Department of Medicine, UAB, Huntsville, AL

David John, MD, Associate Clinical Professor of Medicine, University of Hawaii, John A. Burns School of Medicine, Honolulu

Chad Kawakami, PharmD, Assistant Professor of Pharmacy Practice, Department of Veteran’s Affairs Pacific Islands Health Care System, Honolulu

Marian Melish, MD, Professor of Pediatrics, University of Hawai‘i, John A Burns School of Medicine, Honolulu

Craig Nakatsuka, MD, FACP, Kaiser Permanente, Honolulu

Between scientific sessions, please visit the College table where you can find information on new ACP programs, and many other products. There’s always something new at the College table. Stop by and see for yourself.

3 Program Schedule

Saturday, February 25, 2017 7:30 AM Check-In/Poster Judging

7:55 AM Governor’s Welcome Dr. Mary Ann Antonelli, MD, FACP

8:00 AM Podium Presentation (2) Moderator: Dr. Kent DeZee, MD, FACP

Wanted And Unwanted Care: The Double Edged Sword Of Partial Do-Not-Resuscitate Orders Dr. Nobuiro Ariyoshi, MD

The Incidence Of Immune-Related Adverse Events In Cancer Treatment: A Meta-Analysis Dr. Takeo Fujii, MD

8:30 AM Session #1–Update on Zika Virus Dr. Marian Melish, MD

9:30 AM Break/Poster Judging

10:00 AM Session #2–Physician Assisted Suicide Dr. Craig Nakatsuka, MD, FACP

11:00 AM Podium Presentation (2) Moderator: Dr. Kuo-Chiang Lian, MD, FACP

Predictors For Antimicrobial De-Escalation Among Hospitalized Patients With Culture-Positive Pneumonia Dr. Zao Zhang, MD

Evaluating The Effect Of A Wellness Curriculum On Overall Resident Well-Being And Burnout Dr. Nishal Brahmbhatt, MD

11:30 AM Dr. Irwin J. Schatz, MD, MACP Lectureship: Learning to think like a Clinician 2017 Meeting/Lunch/Posters Dr. Robert Centor, MD, MACP

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1:00 PM Podium Presentation (2) Moderator: Dr. Linda Anegawa, MD, FACP

Late-Life Handgrip Strength Predicts Incident Stroke: The Kuakini Honolulu Heart Program Dr. Eleanor R. Hastings, MD

Low Ankle-Brachial Index And Risk Of Cognitive Decline In Elderly Japanese-American Men: The Kuakini Honolulu-Asia Aging Study Dr. James Templeman, MD

1:30 PM Session #3– Medical Marijuana : Clearing the Smoke Dr. Chad Kawakami, PharmD

2:30 PM Break/Last Poster Judging

3:00 PM Podium Presentation (2) Moderator: Dr. Jone Flanders DO, FACP

Augmented Reality Presentation Of Anatomical Variations: Example With Aberrant Right Subclavian Arteries Trudy Hong

Oral And Intratympanic Steroid Therapy For Idiopathic Sudden Sensorineural Hearing Loss Julia Zhang

3:30 PM Session #4–Physician Well-Being Dr. David John, MD

4:30 Doctor’s Dilemma/ Pupus

Exhibits are open for the entire day.

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JEFFREY L. BERENBERG, MD, MACP : ACP Hawai‘i’s Newest Master

Jeffrey L. Berenberg, MD, MACP is a native of Massachusetts but has called Hawaii home since 1983. Jeff attended Boston University School of Medicine after graduating Cum Laude from Harvard College. He completed Internal Medicine internship and residency training at Peter Bent Brigham Hospital in Boston and was a Clinical Fellow in Medicine at Harvard University in 1970. Afterward, he completed fellowship training in Hematology & Oncology at Walter Reed Army Medical Center. Colonel Berenberg was then assigned to Tripler Army Medical Center where he served as Chief of Hematology & Oncology from 1983-2010. After retiring from the Army, Dr. Berenberg has continued as a full-time physician while pursuing his clinical and academic endeavors. He is widely recognized by both peers and patients for his evidence-based and compassionate care.

Dr. Berenberg remains one of Hawaii’s most distinguished scholar-clinicians. He joined the faculty of the John A. Burns School of Medicine in 1988 where currently holds the rank of Clinical Professor and serves as the Chief, Division of Medical Oncology. Dr. Berenberg also holds academic positions with the Uniformed Services University of the Health Sciences as well as the University of Hawaii Cancer Center. Jeff is a member of the key clinical faculty of Tripler’s Internal Medicine residency program and regularly hosts visiting students & residents from Hawaii and the mainland. He has mentored trainees on innumerable presentations at Hawaii ACP meetings and elsewhere. Jeff is kindly regarded as one of the best teachers in the Department of Medicine.

Dr. Berenberg is the Principal Investigator for the Hawaii Minority Based Community Clinical Oncology Program and has been an investigator on multiple Southwest Oncology Group and other national trials. He is a member of the National Adjuvant Project for Breast and Bowel Cancers. Jeff takes an active role locally and nationally with the American Cancer Society and he sits on the Governor’s Blue Ribbon Panel on Cancer Care. Colonel Berenberg is the recipient of many military awards, including the Legion of Merit Award and was selected to the Order of Military Medical Merit. Since publishing his first paper in 1972, Dr. Berenberg has gone on to author over 50 peer-reviewed publications.

Dr. Berenberg is uniquely deserving of selection for Mastership in the American College of Physicians. Jeff is the doctor’s doctor. He has devoted himself to a life of service to his patients and his colleagues. He promotes excellence in Internal Medicine in Hawaii. And, even after 49 years of practice, Dr. Berenberg continues to be a role model for the next generation. Mastership in the ACP is a capstone -- recognizing his decades of service and advocacy to the College and to his patients.

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PODIUM PRESENTATIONS

9 Podium 8:00AM

WANTED AND UNWANTED CARE: THE DOUBLE EDGED SWORD OF PARTIAL DO-NOT- RESUSCITATE ORDERS

Nobuiro Ariyoshi, MD1, Masayuki Nogi, MD1, Damon Sakai, MD1, Eiji Hiraoka, MD, PhD2, Daniel Fischberg, MD, PhD1,3,4

1 Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 2 Department of Internal Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Chiba, Japan 3Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 4 Pain & Palliative Care Department, The Queen’s Medical Center, Honolulu, HI

BACKGROUND: The interpretation of do-not-resuscitate (DNR) orders may vary in non-arrest situations. In order to reduce ambiguity, many hospitals allow patients to elect a partial DNR code status. The aim of this study was to investigate the effect of partial DNR orders on hospitalists, internal medical residents, and medical students’ willingness to perform cardiopulmonary resuscitation (CPR) and non-CPR related procedures.

METHODS: Scenario-based questionnaire surveys were administered between October 2015 and March 2016 to hospitalists at a tertiary-care academic medical center, and internal medicine residents and medical students at a single medical school. A partial DNR order was identified as a DNR with Adult Emergency Protocols (AEP) order. Each survey presented three patient scenarios followed by ten interventions: case 1 with advanced multiple myeloma and dementia that had a DNR order with AEP; case 2 with advanced breast cancer that had a DNR order without AEP (full DNR); and case 3 with advanced AIDS-related illness that had a DNR order with AEP. We categorized the following groups: pre-clerkship students as group 1; clerkship students as group 2; residents as group 3; and hospitalists as group 4.

RESULTS: Responses from 275 of 366 eligible subjects were collected from 134 pre-clerkship students (49%), 85 clerkship students (31%), 34 residents (12%), and 22 hospitalists (8%). Among the respondents, 46.5% (n=128) were men and 5.5% (n=15) were international medical graduates. Compared to the case with a full DNR order, the presence of a DNR with AEP order was positively associated with subjects’ willingness to provide AEP procedures in all groups (p < 0.001) and CPR in groups 1 to 3 (p < 0.05). The number of training or practice years was positively associated with a decision not to perform CPR in all cases as follows: case 1 (p < .001); case 2 (p < .05); and case 3 (p < .001).

CONCLUSIONS: A partial DNR order made our respondents more willing to provide adult emergency protocols but also more likely to initiate resuscitation. These findings suggest an ongoing need to develop and validate better means of incorporating patients’ medically achievable goals of care into orders that more faithfully guide care for both pre-arrest and arrest situations.

10 Podium 8:15AM

THE INCIDENCE OF IMMUNE-RELATED ADVERSE EVENTS IN CANCER TREATMENT: A META-ANALYSIS

Takeo Fujii, MD, MPH, Associate, Keisuke Miyamoto, MD, Janina Sy, MD, Reid Ikeda, MD, FACP, FCCP, Dennis T. Bolger, Jr. MD, MPH, FACP, University of Hawaii John A. Burns School of Medicine, Honolulu, HI.

BACKGROUND: There has been rapid development of immunotherapies in cancer treatment lately. Among several types of immunotherapies, one type called “immune checkpoint inhibitors” is especially showing promise. Some immune checkpoint inhibitors are approved by the FDA and are currently used as standard of care. Immune checkpoint inhibitors have unique adverse events called immune-related adverse events (irAEs), such as colitis, hypophysitis, and hypothyroidism, which conventional systemic cancer drugs rarely cause. Given the recent rise of immune checkpoint inhibitors, internists will certainly see more patients being treated with these types of drugs, and so understanding the frequency of irAEs in the clinic would be important. However, the overall incidence of irAEs in patients treated with immune checkpoint inhibitors is still unknown. To answer our clinical question, we performed a meta-analysis to estimate the risk of irAEs by immune checkpoint inhibitors in cancer treatment. To the best of our knowledge, this is the first meta-analysis to investigate the risk of irAEs by immune checkpoint inhibitors.

METHODS: We searched PubMed, Embace, and Cochrane Library databases for articles published before July 2016 and selected articles by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We included randomized controlled trials of cancer treatments that compared non-immunotherapy (control arm) and immune checkpoint inhibitors (trial arm) of one of the following: ipilimumab, nivolumab, pembrolizumab, tremelimumab, and pidilizumab. Trials comparing more than two different immune checkpoint inhibitors in one arm were excluded. Two authors (TF and KM) independently performed a comprehensive literature search and review. Any disagreements were resolved by discussion with another author (JS). For irAEs, we included hyperthyroidism, hypothyroidism, pneumonitis, hypophysitis and/or hypopituitarism, adrenal insufficiency, and colitis in the analysis. The primary outcome was the incidence of irAEs. We used random-effects models to estimate odds ratios of each treatment. I2 statistics were used to test the heterogeneity among the included studies. Potential publication bias was evaluated using funnel plots.

RESULTS: We identified 10 clinical trials with a total of 5,800 patients. The trial arm resulted in a significantly higher incidence of irAEs than did the control arm, odds ratio 14.5 (95% CI: 8.9-23.5). I2 was 25.9%, suggesting low heterogeneity among included trials. Funnel plot analysis did not show significant publication bias.

CONCLUSION: General internists should be cognizant of irAEs when caring for their cancer patients who are treated with immunotherapies.

11 Podium 11:00AM

PREDICTORS FOR ANTIMICROBIAL DE-ESCALATION AMONG HOSPITALIZED PATIENTS WITH CULTURE-POSITIVE PNEUMONIA

Zao Zhang, MD1; Nobuhiro Ariyoshi, MD1; Lorrance Majewski, DO1; Heath Chung, MD1; Jonathan Dworkin, MD1; Gehan Devendra, MD1,2

1 Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI 2 Pulmonary and Critical Care, The Queen’s Medical Center, Honolulu, HI

INTRODUCTION: De-escalation optimizes antimicrobial use by minimizing antibiotic resistance and decreasing health care cost. Despite positive culture results, not all patients are applied with this strategy. In general, factors associated with de-escalation and its clinical impact have not been widely studied.

METHODS: We conducted a retrospective observational study of hospitalized adult patients with culture-positive pneumonia at a tertiary academic medical center between January 2013 and December 2014. Among patients alive and hospitalized beyond 72 hours, factors associated with de-escalation and secondary outcomes including in-hospital mortality, hospital-free days, intensive care unit (ICU)-free days, and ventilator-free days were analyzed.

RESULTS: We reviewed 2487 patients’ medical records, and 289 patients (11.6%) met the predetermined criteria including hospitalized beyond 72 hours and have positive culture results. The most frequently seen organisms were Haemophilus influenzae (N=46, 15.9%), Pseudomonas aeruginosa (N=44, 15.2%), and Streptococcus pneumoniae (n=41, 14.2%). Antimicrobial de- escalation was performed in 171 patients (59.2%). In a multiple logistic regression analysis, de- escalation was independently associated with higher Sequential Organ Failure Assessment (SOFA) score (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.03 to 1.22, P<0.05), health care-associated pneumonia (HCAP) (OR, 4.10; 95% CI, 2.26 to 7.73, P<0.001), comorbidities of neoplastic disease (OR, 5.22; 95% CI, 2.28 to 13.25, P<0.001), and assignment to medical resident team (OR, 2.13; 95% CI, 1.23 to 3.73, P<0.05). No significant association was appreciated between de-escalation and in-hospital mortality (OR, 1.35; 95% CI, 0.6 2 to 3.13, P=0.465), hospital-free days (coefficient, –6.49; 95% CI, –13.35 to 0.38, P=0.06), ICU-free days (coefficient, –1.27; 95% CI, –3.33 to 0.79, P=0.23), and ventilator-free days (coefficient, –2.07; 95% CI, –4.27 to 0.13, P=0.07).

CONCLUSIONS: Among hospitalized patients with pneumonia in both ICU and non-ICU settings, antimicrobial de-escalation occurs more often in comparatively severe and complicated patients. De-escalation had no significant impact on in-hospital mortality and morbidity.

12 Podium 11:15AM

EVALUATING THE EFFECT OF A WELLNESS CURRICULUM ON OVERALL RESIDENT WELL-BEING AND BURNOUT.

Nishal Brahmbhatt MD, Nani Morgan MD, Michael Tom MD, Kamal Masaki MD, Reid Ikeda MD FACP FCCP. Departments of Medicine and Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu Hawaii.

INTRODUCTION: Physician burnout is a long-term stress reaction characterized by depersonalization, including cynical or negative attitudes towards patients, emotional exhaustion, a feeling of decreased personal achievement, and a lack of empathy for patients. Medical residents have been identified as a particularly vulnerable population, with estimated burnout rates as high as 75% among those in Internal Medicine training programs.

METHODS: We developed a wellness curriculum with the following aims: 1) educating residents about wellness and how to achieve it, 2) providing experiences targeted at self-reflection, stress- relief, relaxation, and teambuilding, and 3) enhancing appreciation for diversity. The curriculum consists of a 10-session monthly series built into the existing dedicated didactic schedule. Each session features a cultural spotlight in which residents are asked to share something from their culture (e.g. language, food, traditions, etc.) as well as an experiential learning activity (e.g. Yoga, mindfulness-meditation, reflective drawing, etc.). Outcome measures include a self-report survey on the wellness curriculum, and the Maslach Burnout Inventory (MBI), measured at baseline and quarterly thereafter.

RESULTS: The chief wellness series questionnaire was completed by 35 participants, 60% being male, and 51% being interns (PGY1). Most respondents agreed that the chief wellness curriculum contributed to their overall well-being, provided opportunities for stress relief, relaxation, team-building and enhanced appreciation for cultural diversity. The four most valuable sessions were noted to be Yoga (32.1%), Time capsule (25%), Hula (21.4%) and Art/Medicine (17.9%). When asked about interests in future activity topics, 57.1% expressed interest in fitness, 37.1% Arts, 37.1% Cultural competency, 34% emotional health and 31% team- building. Burnout levels were measured twice, in July and November 2016. Using t-tests, burnout scores were significantly higher in November compared to July (total score 14.2 vs. 10.1, p=0.03). Similarly, depersonalization scores on the MBI were significantly higher in November compared to July (total score 13.6 vs. 10.0, p=0.05). Similarly, senior resid ents (PGY2 or 3) had significantly higher scores than interns (PGY1) on burnout (14.9 vs. 9.5, p=0.003) and depersonalization (14.4 vs. 9.3, p=0.005).

CONCLUSION: The resident wellness curriculum was well received and rated highly. Levels of burnout noted within the Internal Medicine program were consistent with national levels of burnout. There is a trend towards an increased level of burnout during the winter months, which is traditionally the mid-point in the training cycle. More data are needed to study the full impact of the wellness curriculum on resident burnout.

13 Podium 1:00PM

LATE-LIFE HANDGRIP STRENGTH PREDICTS INCIDENT STROKE: THE KUAKINI HONOLULU HEART PROGRAM

Eleanor R. Hastings, MD 1; Randi Chen, MS 2; G. Webster Ross, MD 1,3; Robert Abbott, PhD 1,4; Helen Petrovitch, MD 1,3; Aida Wen, MD 1; Cody Takenaka, MD 1; Bruce Tamura, MD 1; Kamal Masaki, MD 1,2.

1 The John A. Hartford Foundation Center of Excellence in Geriatrics, Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; 2 Kuakini Medical Center, Honolulu, Hawaii; 3 Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii; 4 Shiga University, Shiga, Japan.

BACKGROUND: Handgrip strength has been associated with mortality and general disability in a variety of settings. There are few studies on the predictive value of handgrip strength on coronary heart disease and stroke, and none in Japanese populations. We studied whether late- life handgrip strength was a predictor of incident stroke in an elderly Japanese-American male cohort.

METHODS: The Kuakini Honolulu Heart Program is a longitudinal cohort study of cardiovascular diseases in Japanese-American men that began in 1965. At exam 4 (1991-1993), 3,741 men ages 71-93 years participated. Handgrip strength was measured using a handheld dynamometer. After excluding those with prevalent stroke at baseline, 3,522 men were prospectively followed for incident stroke for 8 years, through December 1999. Stroke was classified as all strokes (ALL- CVA), thromboembolic stroke (TE-CVA), and hemorrhagic stroke (HEM-CVA) using a comprehensive surveillance system. Subjects were divided into quartiles of handgrip strength for analysis (strongest, intermediate-strong, intermediate-weak, and weakest).

RESULTS: Age-adjusted rates of incident ALL-CVA were significantly associated with handgrip quartiles; results were 8.8, 9.1, 14.3 and 15.0 per 1,000 person years follow-up, in the strongest to weakest quartiles respectively, p=0.0003. Relative risks for incident stroke were calculated by quartiles of handgrip strength using Cox regression, with strongest as the reference group. After full adjustment for age, BMI, physical activity index, pack-years smoking, hypertension, diabetes, total and HDL cholesterol, and alcohol intake, we found an increased risk for ALL-CVA among those in the weakest group (RR=1.99, 95%CI=1.30-3.07, p=0.002) and in the intermediate-weak group (RR=1.71, 95%CI=1.14-2.56, p=0.009), p for trend <0.001. Similar results were seen for incident TE-CVA, while results for incident HEM-CVA were inconsistent.

CONCLUSIONS: Among older Japanese-American men in Hawaii, weak handgrip strength was an independent predictor of incident overall stroke and thromboembolic stroke over 8 years of follow-up. This simple, inexpensive test may have useful implications for risk stratification and prevention of stroke.

Funding Sources: Kuakini Medical Center, The John A. Hartford Foundation, National Institute on Aging (NIA), National Heart, Lung and Blood Institute (NHLBI), Veterans Affairs Pacific Islands Health Care System (VA), and Hawaii Community Foundation.

14 Podium 1:15PM

LOW ANKLE-BRACHIAL INDEX AND RISK OF COGNITIVE DECLINE IN ELDERLY JAPANESE- AMERICAN MEN: THE KUAKINI HONOLULU-ASIA AGING STUDY

James Templeman, MD 1; Randi Chen, MS 2; Robert Abbott, PhD 1; G. Webster Ross, MD 1,3; Helen Petrovitch, MD 1,3; Lenore Launer, PhD 4; Michiko Inaba, MD, PhD 1; Lauren Okamoto, MD 1; Matthew Uechi, MD 1; Kamal Masaki, MD 1,2.

1 The John A. Hartford Foundation Center of Excellence in Geriatrics, Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; 2 Kuakini Medical Center, Honolulu, Hawaii; 3 Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii; 4 National Institute on Aging, Bethesda, Maryland.

BACKGROUND: Measurement of the Ankle-Brachial Index (ABI, ratio of ankle to arm blood pressure) is an easy, noninvasive test used mainly in peripheral arterial disease. A low ABI (<0.9) is a marker of generalized atherosclerosis and predicts cardiovascular diseases, mortality, and even vascular dementia. We studied the association of low ABI and cognitive decline in older men.

METHODS: The Honolulu Heart Program (HHP) is a prospective cohort study of Japanese- American men since 1965. The Honolulu-Asia Aging Study began with HHP exam 4 (1991-93) in 3,734 men ages 71-93 years. Low ABI was defined as a ratio <0.9. Baseline global cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI), with a score range of 0-100. Follow-up CASI scores were available from exams 3, 6 and 8 years later. Cognitive decline was defined as a drop in CASI score of >= 1 SD of change (>=10 points at 3 years, and >= 14 points at 6 and 8 years).

RESULTS: Cognitive decline was significantly more common in those with low vs. normal ABI (29.2% vs. 18.5%, p<0.0001; 28.1% vs. 19.9%, p=0.01; 32.2% vs. 22.9%, p=0.02) at 3, 6 and 8 years respectively. Using logistic regression, the odds of 3-year cognitive decline were significantly increased with low ABI (OR=1.81, 95% CI=1.38-2.38, p<0.0001). After adjusting for age, education, apolipoprotein E4 allele, prevalent stroke, baseline CASI, time of follow-up and cardiovascular risk factors, this relationship remained significant (OR=1.46, 95% CI=1.06-2.01, p=0.02). The relationship between low ABI and 6-year and 8-year cognitive decline did not remain significant after adjustment for covariates. The association between low ABI and 3-year cognitive decline remained significant in a subgroup multivariate analysis excluding those with prevalent dementia or cognitive impairment at baseline (OR=1.55, 95% CI=1.10-2.20, p=0.01).

CONCLUSIONS: Low ABI was significantly associated with short-term cognitive decline, but not over a longer period. This cheap, easily available test may be useful in clinical practice as part of a complete patient assessment.

Funding Sources: Kuakini Medical Center, John A. Hartford Foundation, NIA, NHLBI, Veterans Affairs Pacific Islands Health Care System (VA), and Hawaii Community Foundation.

15 Podium 3:00PM

AUGMENTED REALITY PRESENTATION OF ANATOMICAL VARIATIONS: EXAMPLE WITH ABERRANT RIGHT SUBCLAVIAN ARTERIES

Trudy Hong, BA, Jesse Thompson, BA, Beth K. Lozanoff, BS, Steven Labrash, CFSP, Takashi Matsui, MD, PhD, Scott Lozanoff, PhD John A. Burns School of Medicine, Honolulu, Hawaii

INTRODUCTION: Recognition of anatomical variations is critical for proper diagnosis and management. Although the literature provides detailed descriptions and images, structures and mechanisms are still often difficult to conceptualize. Augmented reality (AR) is a novel visualization tool that could enable effective understanding of variations. Here we use AR to present aberrant right subclavian arteries (ARSA), and assess its usefulness within the context of anatomy education within the medical school curriculum.

METHODS: Two ARSA’s were identified during routine dissections and quantitative characterization was performed. A plastinated heart was created and subjected to photogrammetry. Utilizing quantitative features of dissected specimens, ARSA was modeled and viewed within 3D space. An animation of its embryological mechanism was also created. The goal of this study was to assess the usefulness of this animation and AR for learning ARSA. First year medical students (N=61) participated in the online activity (including pre- and post-tests) utilizing text, images and a 3D SketchFab (www.sketchfab.com) model to learn ARSA, and either text or narrated animation for its embryological mechanism. Students then completed a quiz and perception survey based on traditional resources alone or after visualization of the ARSA hologram as well. Comparisons were analyzed using paired sample t-tests with p <.05 as the level of statistical significance.

RESULTS: Groups performed similarly on the typical structures quiz (79.8% and 77.8%) and ARSA pre-test (48.6% and 44.2%). Post-test scores improved overall, and although the group with animation scored better, difference was not statistically significant (82.4%, compared to 75.0% (text), (NS). Students found the SketchFab model to be helpful for learning ARSA, rating it as 4.4/5 (1: Not helpful; 5: Very helpful). For the embryological mechanism, 89% found the narrated animation more helpful than text. Regarding AR, both groups scored similarly, 71.6% (no AR) and 82.0% (with AR) (NS). Students viewed AR favorably, rating its helpfulness as 4.02/5 and ranked resources for learning ARSA from most to least helpful as follows (most common): 1) AR tool, 2) QuickTime, 3) SketchFab model, 4) Text.

CONCLUSION: Augmented reality, alongside traditional resources, is promising as a tool that could facilitate better understanding and retention of anatomical variations. In the classroom, AR could also be used for teaching complex anatomy concepts, and in clinical practice, for patient education and procedural planning. Work is currently being directed at developing models from actual medical scans for AR viewing and at developing tools to further assess usefulness of AR.

16 Podium 3:15PM

ORAL AND INTRATYMPANIC STEROID THERAPY FOR IDIOPATHIC SUDDEN SENSORINEURAL HEARING LOSS

Julia Zhang, Jared Hara, Anna Flaherty, MD, Marcia Leung, Lawrence Burgess, MD and Wayne Barber, MD John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI

Sudden sensorineural hearing loss (SSNHL) is considered an otologic emergency with rapid hearing loss developing within 72 hours; immediate recognition and treatment are critical. It most commonly affects patients 65 years and older and etiology is idiopathic in 71% of cases. In clinical practice, oral steroid therapy is often the mainstay of therapy, and intratympanic (IT) steroids are being increasingly used as either salvage therapy, combined therapy with oral steroids, or even initial therapy. A better understanding of clinical outcomes would allow determination of how best to incorporate IT therapy in the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL).

We conducted a retrospective review of patients treated for SSNHL in a private practice setting from January 1, 2011- April 12, 2015 with the following exclusion criteria: lack of pre- and post- treatment audios, treatment initiated >90 days after onset, and an identified cause of hearing loss. Fifty-three ISSNHL patients were analyzed in the following subgroups: oral steroids (n=8), combination oral+IT (n=39), and IT (n=6).

The pure tone average (PTA) changes for all treatment groups improved by 8.0+19.5dB (p=0.004); for thirty-one patients treated <2 weeks after onset, PTA improved by 13.8+16.6 dB (p<0.001). A multivariate analysis was conducted to investigate the association between PTA changes for all treatment groups adjusted for age, gender, time to treatment, and vertigo. Earlier time to treatment and older age were statistically correlated towards improved outcomes. As time to treatment increased by each day, change in PTA decreased by 0.324 [95% CI (0.12, 0.52), p=0.002]. As age increased by each year, change in PTA increased by 0.802 [95% CI (0.36, 1.24), p<0.001]. For the oral+IT group alone, PTA changes for concurrent oral+IT (n=20, 7.10dB) and delayed/salvage oral+IT (n=19, 5.43dB) were not statistically different (p=0.79); earlier time to treatment (p=0.001) and older age (p=0.006) remained statistically correlated towards improved outcomes.

The results suggest that outcomes can be improved with early identification of ISSNHL and oral steroid therapy by primary care providers. The poorer prognosis for younger patients suggests a need for more aggressive or adjunctive therapies for this sub-group.

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PODIUM PRESENTATIONS

19 Poster #1

CLINICAL PREDICTION RULE FOR DRUG-RESISTANT ORGANISMS IN HOSPITALIZED PATIENTS WITH PNEUMONIA

Nobuhiro Ariyoshi, MD1, Dr. Ivy Melgarejo, MD1, Gehan Devendra, MD1,2

1Department of Internal Medicine, John A. Burns School of Medicine University of Hawaii at Manoa, Honolulu, HI, USA 2Department of Pulmonary & Critical Care Medicine, The Queen’s Medical Center, Honolulu, HI, USA

BACKGROUND: No single clinical prediction rule has yet demonstrated sufficient accuracy for the presence of drug-resistant organisms (DROs).

METHODS: We conducted a retrospective study at a tertiary academic medical center from January 2013 to December 2014 to determine factors associated with the presence of DROs and create a clinical prediction rule for DROs in hospitalized patients with culture-positive pneumonia.

RESULTS: In total, 311 hospitalized patients were analyzed and DROs were isolated in 32.8%. The mean age was 66.72 ± 16.61 years, and 59.2% were men. In multivariate analyses, 4 independent predictive factors were associated with DROs: structural lung disease (OR, 3.41; 95% CI, 1.86-6.43; p < 0.001); non-ambulatory status (OR, 6.11; 95% CI, 3.00-12.85; p < 0.001); history of DROs (OR, 5.06; 95% CI, 2.63-9.93; p < 0.001); and immunosuppression (OR, 12.07; 95% CI, 5.71-26.80; p < 0.001). Based on this result, we created a clinical prediction rule named LARI score (structural Lung disease, non-Ambulatory status, history of drug-Resistant organisms, and Immunosuppression). We assigned points as follows: 1 point for structural lung disease; 2 points for non-ambulatory status and a history of DROs; and 4 points for immunosuppression, resulting in a maximum of 9 possible points. LARI score showed better discriminating power, as measured by an area under the receiver-operating characteristic of 0.83, compared with other clinical prediction rules including the criteria for healthcare-associated pneumonia.

CONCLUSIONS: The new clinical prediction rule; LARI score had good accuracy for the presence of DROs and could prevent unnecessary use of broad-spectrum antibiotic therapy.

20 Poster #2

INVESTIGATING CAUSES OF SERIOUS ADVERSE EVENTS IN PATIENTS WITH DEMENTIA IN THE MIND AT HOME STUDIES

Lindsey Carvalho, MS21, Deirdre Johnston, MD2, Betty Black, PhD2, Melissa Reuland, MS 2, Constantine G. Lykesos, MD2, Quincy M. Samus, PhD2 1 John A Burn School of Medicine, Honolulu, Hawaii 2 Johns Hopkins University, Baltimore, Maryland

BACKGROUND: In the US, total health care costs of Alzheimer’s Disease and Related Dementia (ADRD) exceed other major chronic conditions. In the context of two ongoing studies of the Maximizing Independence at Home (MIND at Home) to improve outcomes and lower care costs, this cross-sectional report aims to (1) describe the rates of serious adverse events and disenrollment events among the current study participants, and (2) describe the most common causes of these events to identify and address potentially modifiable causes.

METHODS: MIND at Home comprises an interdisciplinary community-based approach to dementia care to enable patients to live at home, improve quality of life, and reduce costs of hospital care. We analyzed a total of 456 ADRD community-residing study participants from 03/01/15-06/30/16. Serious adverse events (SAE) were defined as a hospitalization, long-term care placement, inpatient hospice care, and/or death. Disenrollment included reaching a study endpoint (i.e. death, permanent long-term care placement, moving out of area). SAE reports were collected by staff from family caregivers and included date and cause of the event. SAEs were then sorted into the following categories: falls, problem behavior, cardiovascular, respiratory, UTI/dehydration, functional decline, pain, caregiver decision, and other.

RESULTS: Of the sample,11% (n=42), had a disenrollment event and 19% (n=88) had > 1 SAE over an average 8-month follow-up period. Permanent long term care placement was the most common disenrollment event (43%), followed by death (24%). Of the total of 136 SAEs, 67% were hospitalizations, with other common reported causes being falls (22%), cardiovascular events (15.4%), UTI/Dehydration (13%), and behavior problems (11%). Long-term care facility placement comprised 13% of all SAEs, and the most common reasons for placement was caregiver decision (44.4%) and behavioral problems (22%).

CONCLUSIONS: In order to maximize life quality, clinical outcomes and reduce health care costs in the context of ADRD, reducing the risk of preventable hospitalizations and long term care placements should be a priority. In this study, reported chief causes of hospitalizations, including falls, UTI/dehydration, and problem behaviors, are potentially modifiable and should be primary targets for preventative intervention efforts.

21 Poster #3

CALCIPHYLAXIS IN END STAGE RENAL DISEASE

Mark Chinen MDR, Brian Lee MD, Kaiser Permanente Hawaii

OBJECTIVE: Calciphylaxis or calcific uremic arteriolopathy (CUA) is a disease of vascular calcification and small vessel thrombosis leading to skin ulceration and tissue necrosis. Though still considered rare, incidence has been increasing since 2007 and studies have shown prevalence of up to 4% in HD patients. High mortality rates are a result of infections due to impaired wound healing, increasing likelihood of death 2.5-3 fold in dialysis patients. Proposed risk factors include: ESRD, warfarin usage, female gender, obesity, autoimmune conditions, nutritional vitamin D use, and DM. Optimal treatment is unknown. We performed this study to evaluate baseline characteristics of ESRD patients in Hawai’i who develop calciphylaxis, as well as potential risk factors for development of calciphylaxis.

METHODS: We searched the KP Hawaii Clarity database for calciphylaxis dx or use of the term “calciphylaxis” in inpatient/outpatient progress notes and biopsies from January 2004 to January 2016. We reviewed the search results manually to determine true cases that were either biopsy- confirmed or thought to be CUA with clinical certainty. ESRD patients with CUA were matched by age, sex, and duration of dialysis in a 1:4 ratio to ESRD patients without CUA. Variables we measured included warfarin usage over 30 days, dialysis modality, ESRD etiology, STS usage, BMI, and 1 year mortality rates. Conditional logistic regression was used to analyze cases vs. controls using R, version 3.2.3.

RESULTS: The average age of ESRD patients who develop calciphylaxis at time of diagnosis is 54.6 years (st dev +/- 13.6) with females making up 52% of patients. The median number of days between RRT initiation and calciphylaxis development was 1003 days (interquartile range 314 – 1866 days). 35% of patients were on peritoneal dialysis and 65% were on HD. 52% of patients were on warfarin, with a median duration of 851 days (interquartile range 287-1476 days). In analysis, we found that CUA was a significant RF for death in ESRD (OR 4.97; 95% CI 1.34 to 18.4). Significant risk factors associated with calciphylaxis in ESRD included DM (OR 0.29; 95% CI 0.09 to 0.94), warfarin usage over 30 days (OR 18.52; 95% CI 4.99 to 68.72), and PD modality (OR 6.43; 95% CI 1.73 to 23.87).

CONCLUSION: Calciphylaxis is a significant risk factor for mortality in ESRD. Warfarin and peritoneal dialysis are strong risk factors for development of calciphylaxis in ESRD patients. Interestingly, we found DM is a negative risk factor for developing calciphylaxis in ESRD. Optimal treatment regarding calciphylaxis in ESRD is still being defined. We found trends toward increased survival in patients who stopped warfarin and in those who were treated with sodium thiosulfate, though these results were not statistically significant.

22 Poster #4

WHEN LUNG CANCER ISN’T; A NOVEL APPLICATION OF NEXT GENERATION SEQUENCING

Daniel Desmond, MD, John Ellis, MD, Jordanna Hostler, MD (FACP), Tamie Kerns, DO (FACP), Tripler Army Medical Center, Honolulu, Hawaii.

Introduction: A core tenant of oncology is that tumor histology determines therapy. In the setting of an occult primary this approach is limited and infrequently results in successful treatment. Immunohistochemical staining (IHC) and molecular diagnostics have shown explosive progress in recent years, making it possible to determine distinct tumor histologies and gene expression. Striking as the technology is, there remains a paucity of data linking advanced diagnostics to improved outcomes. We present a case of suspected lung cancer whose novel molecular gene expression was used to direct therapy, resulting in a near complete response to treatment.

Case: Our patient is a 68 year old female, former smoker without significant past medical history who arrived to our institution with a productive cough and dyspnea. She was noted to have a right middle lobe mass with associated effusion which was sampled, revealing adenocarcinoma. A PET/CT demonstrated avidity in the right middle lobe, in the mediastinal lymph nodes, and diffuse, scattered disease in the axial skeleton, suggestive of a lung primary. Further tissue was obtained with pleuroscopy and IHC analysis revealed cells that were TTF-1 negative, mammaglobulin positive, and GATA 3 positive, consistent with a breast primary. The cancer cells were negative for estrogen, progesterone, and HER2 by IHC. Interestingly, the patient had a normal screening mammogram three months prior to diagnosis. Further diagnostic testing via tumor genome sequencing was pursued to guide therapeutic interventions. Tumor genome sequencing was positive for TP53 mutation and an ERBB2 exon 20 mutation; also known as HER2. The patient was started on nab-paclitaxel as well as trastuzumab, a monoclonal antibody that blocks the HER2/neu receptor. After three months of therapy a PET/CT-revealed a dramatic response to treatment with near resolution of the right middle lobe mass and marked decrease in the size of the pleural effusion.

Discussion: This case demonstrates a clear disconnect between the tumor’s driver gene expression and the phenotypic expression of HER2 by IHC. IHC has been the gold standard method for evaluating expression of HER2 on breast cancer cells. The use of tumor genome sequencing in this case presented an opportunity for directed personalized cancer treatment with a far less toxic therapy. In the era of genome focused, individualized cancer care, these exciting new diagnostic modalities stand to become the new mainstay of oncology.

23 Poster #5

THE EFFECTS OF INTRACELLULAR CALCIUM LEVEL ON THE PROPAGATION OF CELL-TO-CELL CARDIOMYOCYTE DEATH IN AN IN VITRO MODEL

Jayden Galamgam, BS, Yuichi Baba, MD, Dustyn Uchiyama, BS, and Takashi Matsui, MD, PhD Department of Anatomy, Biochemistry and Physiology John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI

Patients who suffer from acute myocardial infarction (MI) have a better prognosis due to many improvements in reperfusion therapy, including coronary stents. However, we cannot control reperfusion injury as seen with the increased prevalence of ischemia-reperfusion (I/R) injury. We previously reported that in a mouse model of I/R injury caused by short ligation of the left anterior descending artery, fibrotic scarring extends specifically from the infarction region and continues along myofibers in the midcardium. At the previous meeting, we reported that cardiomyocyte (CM) cell death extends along routes of “cell-to-cell” via gap junctions in our new in vitro model of CM cell death induced by a cylindrical acidic gel. Previous studies suggest that increasing intracellular calcium closes and uncouples gap junctions, whereas decreasing intracellular calcium opens gap junctions. However, an appropriate in vitro model to examine the role of the gap junctions on “cell-to-cell propagation of CM cell death has not been developed yet.

To define the role of the intracellular calcium level on gap junctions in the “cell-to-cell” propagation of CM cell death, we examined the effect of a selective calcium chelator, EGTA, in the new model of CM cell death induced by a cylindrical acidic gel. We cultured H9c2 cells, originally derived from embryonic rat ventricles, in a 60-mm dish. Once the cells reached approximately 90% confluency they were exposed to a modified growth media containing either 1 mM, 2mM, or 5 mM EGTA. A cylindrical gel (pH = 6.4) was then placed in the center of the dish to induce local CM cell death via acidosis and hypoxia, where are observed in I/R injury in vivo. Five hours after placing the cylinder gel, necrotic cell death was evaluated using Evans Blue (EB) dye. In multiple trials (> 4 times), we observed “cell-to-cell” death shown by a blue line extended from the dead cells under the gel to the peripheral cells in both control and treated dishes. Intriguingly, treatment with EGT A increased linear CM cell death extension in a dose-dependent manner.

These findings suggest that a decrease in intracellular calcium level exaggerated the extension of “cell-to-cell” CM death in part by a change in gap junction gate control. A better understanding of this unique “cell-to-cell” propagation of CM cell death will lead to better treatment and prevention of I/R injury following an acute MI.

24 Poster #6

RECURRENT HEMATURIA: AN INTERESTING PRESENTATION OF DISSEMINATED TUBERCULOSIS WITH GENITOURINARY AND MUSCULOSKELETAL INVOLVEMENT

Lauren J. Hu, MD, Jaclyn E. Kagihara, MD, Thomas Aldan, MD, Dennis T. Bolger Jr., MD, MPH University of Hawaii Internal Medicine Program

INTRODUCTION: Extra-pulmonary mycobacterium tuberculosis (Mtb) has significant morbidity and mortality when left untreated. New guidelines for extra-pulmonary Mtb infection indicate that diagnostic nucleic acid amplification testing (NAAT) should be performed on specimens gathered from extra-pulmonary sites. Furthermore, positive NAAT testing can now be utilized as evidence of extra-pulmonary Mtb infection. We present a case of extra-pulmonary Mtb infection initially diagnosed using the mycobacterium tuberculosis/resistance to rifampin (MTB/RIF) assay on urine and synovial fluid specimens.

CASE REPORT: A 61 year old Filipino man with history of gross hematuria, hypertension, right knee tibial insufficiency fracture secondary to gout, end-stage-renal-disease on hemodialysis, diabetes mellitus type II, penile ulcers, cytomegalovirus gastritis, and recent hospitalizations for sepsis secondary to urinary tract infection and recurrent gross hematuria due to unknown etiology presented with recurrent hematuria. Previous urologic work up included cystoscopy with clot removal, right ureteral stent placement and bladder fulguration. Patient was also noted to have a 3-month history of recurrent fevers. On admission, physical examination was notable for multiple flat, linear penile ulcers on the glans of the penis with light yellow ulcer base without exudate or discharge. During the course of his hospitalization, the patient continued to have fevers that were previously thought to be due to gout. Re-evaluation of his fevers led to a CT chest that showed innumerable bilateral pul monary nodules (3-4 millimeters in size) consistent with miliary tuberculosis (TB). Eventually, he was found to have Mtb in his urine on MTB/RIF assay and later knee synovial fluid was positive on MTB/RIF assay. Eventual work up grew Mtb on acid-fast bacilli (AFB) sputum culture and right knee aspirate. Additional testing for TB meningitis, bacteremia and endocarditis were negative. The patient was started on RIPE therapy and his recurrent fevers resolved. Prior to discharge, patient was found to have a low CD4 count despite negative human-immunodeficiency virus (HIV) testing, which was suggestive of idiopathic CD4 lymphocytopenia. His penile ulcers were repeatedly negative for AFB, herpes simplex virus, and cytomegalovirus.

DISCUSSION: This case illustrates an interesting presentation of disseminated tuberculosis that was diagnosed through NAAT of non-pulmonary specimens. This patient was found to be MTB/RIF assay positive in specimens from his urine as well as his right knee joint. Current committee guidelines consider a positive NAAT adequate to confirm extra-pulmonary Mtb. This case demonstrated that NAAT is a key adjunct to AFB cultures in the diagnosis of extra- pulmonary Mtb, even though current guidelines recognize there are no FDA-approved NAATs for use with extra-pulmonary specimens.

25 Poster #7

POLYMORPHIC VENTRICULAR TACHYCARDIA AFTER "DUSTING"

Kinsley A. Hubel MB BCh BAO (ACP Associate), Phillip B. Hitchcock, MD (ACP Associate), Gregory M. Sprowl, MD (ACP Associate), Jesse R. Sherratt, DO, Jessica Bunin, MD (FACP) Department of Medicine, Tripler Army Medical Center, Hawaii.

INTRODUCTION: Volatile substance misuse (VSM) or “dusting” are broad terms that describes the inhalation of volatile substances in order to achieve an intoxicating effect. The leading cause of death among inhalant abusers is Sudden Sniffing Death Syndrome. It is likely caused by changes in myocardial electrical conduction and sensitivity to catecholamines that leads to cardiac arrhythmias. We report a case of a patient who suffered life threatening ventricular arrhythmias following prolonged VSM of 1,1-difluoroethane (DFE).

CASE PRESENTATION: A 20-year-old man was brought to the Emergency Department (ED) after having two syncopal events. He admitted to inhaling several cans of air dust cleaner daily over a period of months with a recent binge of at least five cans per day. In the ED, he was initially hemodynamically stable with only a mild tremor of his upper extremities. He had an episode of non-sustained polymorphic ventricular tachycardia (PMVT) in the ED prompting ICU admission. Upon arrival in the ICU he relapsed into pulseless PMVT. After initial resuscitation, telemetry demonstrated sinus tachycardia with a prolonged QTc interval and frequent episodes of unstable PMVT treated with recurrent defibrillation. A total of 63 defibrillations were required over 18 hours. He became hemodynamically stable after numerous rounds of resuscitation (ACLS). He received multiple doses of epinephrine, amiodarone, magnesium sulfate, and aggressive correction of acid-base & electrolyte disturbances. In collabor ation with Poison Control we initiated a lidocaine bolus followed by an infusion that stabilized his myocardium. A transthoracic echocardiogram (TTE) revealed global dysfunction with a left ventricular ejection fraction of 30%. He spent five days in the ICU and three weeks on the medicine ward with psychiatry consultation. One month after discharge, an outpatient TTE showed full recovery of cardiac function.

DISCUSSION: Lidocaine should be considered early in the management of “dusting” related arrhythmias. Inhalation of halogenated hydrocarbons, such as DFE, confers a significant risk for cardiotoxicity and Sudden Sniffing Death Syndrome. Prompt recognition of inhalant misuse, close monitoring for cardiac arrhythmias, and awareness of advanced treatment options are crucial aspects in the care of these patients. Our patient did not respond to standard resuscitative measures and required specialized therapies to include the class Ib antiarrhythmic, lidocaine. Lidocaine contributed to myocardial stabilization in this patient suffering from hydrocarbon cardiotoxicity and should be considered as a potential lifesaving intervention in this population.

26 Poster #8

AVAILABILITY, LOGISTICS, AND FEATURES OF PATIENT PORTAL SHARED ACCESS FUNCTIONALITY

V Kim1, JM Griffin2, RA Stametz3, S Mintz4, JL Wolff5 1University of Hawaii John A. Burns School of Medicine, Honolulu, HI, United States. 2 Mayo Clinic, Rochester, MN, United States. 3 Geisinger, Danville, PA, United States. 4 Family Caregiver Advocacy, Kensington, MD, United States. 5 Johns Hopkins University, Baltimore, MD, United States.

BACKGROUND: Patient portals offer patients electronic access to their health information and the ability to perform health management tasks. Some institutions allow patients to explicitly share access to their account with family or friend (“care partners”). Little is known about shared access availability, registration processes, and functionality.

METHODS: An environmental scan of 20 integrated or academic health systems’ availability and mode of shared access registration and functionality was completed between July 2016 and August 2016.

RESULTS: All 20 systems had patient portals, offering shared access for patients who are children (n=19), adolescents (n=14), or adults (n=18); 1 system limited access to adults with disabilities. No information about uptake of shared access was reported. Mode of registration for shared access was online (n=7), by mail/fax (n=8), or in-person (n=8). Of 18 systems with shared access for adult patients, 3 reported that they allow designation of multiple care partners, 2 allowed 1 care partner, and 13 had contradictory or ambiguous statements regarding numbers of care partners. Ability to designate access to different patient portal features varied: 16 systems offered only full-access and 1 system allowed patients to select from levels of access to care partners and included separation of care partner and patient messaging. Duration of shared access for adult patients varied from until terminated by patient with no pre- specified date (n=7), a patient pre-specified termination date (n=5) , required reauthorization every 2 years (n=2), or required reauthorization every 1o years (n=1). One system allowed adult patients to authorize 6, 12, 18, or 24 months of shared access to their patient portal account.

CONCLUSIONS: Our scan found that integrated health systems offer patients the ability to provide care partners electronic access to their patient portal accounts. Shared access registration processes and functionality vary widely: most systems only offer full access to the patient portal. Broader adoption and technical implementation of shared access will require greater attention to transparency regarding availability, documentation of capabilities, and ease of access and use.

Financial Disclosure: National Institute on Aging (NIA)

27 Poster #9

SLOW GAIT SPEED AS A PREDICTOR OF MORTALITY IN ELDERLY JAPANESE-AMERICAN MEN: THE KUAKINI HONOLULU HEART PROGRAM

Angel Kirkham, MD 1; Randi Chen, MS 2; Bradley Willcox, MD 1,2; Samina Ahsan, MD 1; Karen Lubimir, MD 1; Pia Lorenzo, MD 1; Kamal Masaki, MD 1,2. 1 The John A. Hartford Foundation Center of Excellence in Geriatrics, Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; 2 Kuakini Medical Center, Honolulu, Hawaii.

BACKGROUND: Previous studies have established that gait speed in older adults can be a useful prognostic indicator of mortality risk, over 3 to 15 years of follow-up. There have been no studies with longer follow-up, few studies in Asian populations, and none among Asian Americans, who have the greatest life expectancy of U.S. ethnic groups. We examined the association between gait speed and all-cause mortality in a cohort of older Japanese-American men for up to 25 years of follow-up.

METHODS: The Kuakini Honolulu Heart Program is a prospective population-based study of cardiovascular diseases in Japanese-American men that started in 1965. At exam 4 (1991-1993), 10-foot gait speed was measured in 3,606 men ages 71-93 years. Subjects were divided into tertiles of gait speed for analysis, and mean gait speed was 2.9, 4.0 and 6.9 seconds in the fastest, intermediate and slowest groups, respectively. All-cause mortality data through December 2015 were analyzed as the primary outcome.

RESULTS: Age-adjusted mortality rates per 1,000 person years follow-up showed a significant increase by gait speed groups, from 85.0 in the fastest, to 91.9 in the intermediate, to 118.6 in the slowest gait speed group, p<0.0001. Cox regression found an increased relative risk of mortality in the intermediate group (RR=1.28, 95% CI=1.19-1.39, p<0.001) and the slowest group (RR=2.11, 95% CI=1.94-2.30, p<0.001), using the fastest group as reference, p for trend <0.001. This association remained significant after adjusting for age, BMI, hypertension, diabetes, physical activity index, pack-years smoking, total and HDL-cholesterol, and alcohol intake; intermediate group (RR=1.12, 95% CI=1.03-1.22, p=0.008) and slowest group (RR=1.48, 95% CI=1.34-1.63, p<0.001), p for trend <0.001. A subgroup analysis excluding subjects with prevalent stroke, dementia or Parkinson’s disease at baseline yielded similar results.

CONCLUSIONS: In older Japanese-American men, gait speed was an independent predictor of all-cause mortality over a long follow-up period. Timed walk is a simple test that captures global functioning and frailty, and can be done in a variety of clinical settings. It can be a useful tool to help with prognostication and decision-making in terms of life expectancy in older adults.

Funding Sources: Kuakini Medical Center, The John A. Hartford Foundation, National Institute on Aging, National Heart, Lung and Blood Institute, Veterans Affairs Pacific Islands Health Care System, and Hawaii Community Foundation.

28 Poster #10

HMG-CoA REDUCTASE AUTOIMMUNE NECROTIZING MYOPATHY: A RARE SIDE EFFECT TO A COMMONLY PRESCRIBED MEDICATION

Todd Devere, MD; Tina Kuribayashi, DO Kaiser Permanente Hawaii Internal Medicine Residency Program & Department of Neurology

BACKGROUND: HMG-CoA Reductase Inhibitors represent a subset of lipid lowering medications that are beneficial in the treatment of dyslipidemias and in primary and secondary prevention of cardiovascular events. Statins are one of the most highly prescribed classes of medications. Muscle-related complaints reportedly occur in 10 to 25% of statin users, the majority of whom experience resolution of these complaints after cessation of the drug. We report a series of patients in Kaiser Permanente Hawaii with a rare statin-induced autoimmune necrotizing myopathy in which stopping the drug did not improve their symptoms, and immunosuppression therapy was needed.

METHODS: We reviewed the records of patients who presented with proximal muscle weakness and elevated serum Creatine Kinase (CK) levels and subsequently referred to the Department of Neurology for evaluation. Work-up included, electromyography, muscle biopsy and HMG-CoA Reductase antibody testing. The patients had EMG findings, positive HMG-CoA Reductase antibody titers, and muscle biopsy results that were characteristic of earlier published reports of a rare autoimmune myopathy associated with statin use. The incidence of this condition in our program was compared to national estimates, and an extensive review of the patient medical records was undertaken to compare demographics, clinical presentation, co-morbidities, medication use, and response to treatment.

RESULTS: Our series comprised of 9 patients, 5 women and 4 men, with an average age of 66.8 years. 8 of 9 patient’s ethnicities were Asian/Pacific Islander, with 1 being Caucasian. 7 of 9 patients had prior statin exposure with a mean time of first exposure to any statin before clinical presentation of myopathy of 7.1 years. All 7 were on a moderate to high intensity statin prior to symptom onset. 6 of 7 statin-exposed patients have diabetes mellitus. The average peak CK level was 15,736. All 9 patients had positive levels of HMG-CoA Reductase antibody. 8 of 9 underwent EMG, and the findings for all 8 were an “irritable myopathy.” 8 of 9 underwent muscle biopsy, and 7 (the statin exposed patients) showed a characteristic non-inflammatory necrotizing myopathy. 8 of 9 patients were treated with steroids and additional immunosuppressive medications which achieved an improvement in symptom complaints as well as reduction in CK.

CONCLUSION: Statin-associated necrotizing autoimmune myopathy associated with HMG CoA reductase antibodies is a rare complication of statin therapy. It should be considered in a patient with persistent proximal muscle weakness and elevated CK that does not improve when the drug is discontinued and require long-term immunosuppressive therapy. We report an incidence of 5/100,000 stain users compared to 2-3/100,000 in published reports.

29 Poster #11

MORTALITY PREDICTORS OF ENDOVASCULAR VS. OPEN REPAIR OF ABDOMINAL AORTIC ANEURYSM IN THE ELDERLY

Rachel Lee1, Satinderjit Locham2, MD, Mahmoud Malas2, MD; 1University of Hawaii School of Medicine; 2Johns Hopkins University School of Medicine, Surgery, Baltimore, MD, USA

BACKGROUND: Prior RCTs have reported better perioperative outcomes following endovascular aneurysm repair (EVAR) as compared to open aneurysm repair (OAR). EVAR-1 and DREAM trials reported significantly higher mortality for OAR as compared to EVAR. However, most of these studies excluded the elderly. Objective of the study is to provide recent real world outcomes using NSQIP, exclusively looking at mortality predictors in a large elderly cohort. Methods: Using the NSQIP vascular database (2010-2014), we identified all patients over 70 years of age who underwent OAR and EVAR for non-ruptured AAA. Explanatory analyses using Pearson’s Chi-square and Student’s t-tests were performed. Univariate and multivariable logistic regression analyses were implemented and adjusted for patient demographics and characteristics.

RESULTS: 5,332 non-ruptured AAA repairs were performed [OAR: 809 (15%) vs. EVAR: 4,523 (85%)]. Majority were male (77%) and Caucasian (81%) with a mean age of 78 ± 6 years. Diabetes mellitus and obesity were more prevalent in the EVAR group (15% vs. 12%, p=0.01) and (30% vs. 25%, p=0.002) respectively, whereas history of COPD (22% vs. 19%, p=0.02) and smoking status (35% vs 23%, p<0.0001) were more likely to be seen in patients undergoing OAR. On average, the operative time in minutes (250 vs. 151) and mean length of stay in days (11 vs. 3) was also longer for patients undergoing OAR versus EVAR (p<0.001). Mortality was higher following OAR versus EVAR (8% vs 3%, p<0.001). Compared to EVAR, OAR was associated with higher rates of cardiac (7% vs. 2%), renal (7% vs. 1%), pulmonary (20% vs. 3%) and any wound complications (4% vs. 2%) (all p<0.05). After adjusting for patients’ characteristics and comorbidities, OAR was associated with 3 times higher mortality than EVAR [O R(95%CI): 3.04(2.01-4.57), p<0.001]. Predictors of mortality in our elderly cohort were age, female gender, smoking status, functional dependency, history of COPD, steroid use, bleeding disorders, progressive renal failure, transfusion, aneurysm diameter and Type IV TAAA.

CONCLUSIONS: Endovascular approach was associated with significant reduction in the risk of postoperative cardiac, pulmonary, and renal complications in the elderly. Open repair was associated with a 3-fold increase in mortality compared to EVAR and should be avoided in the elderly.

30 Poster #12

FOCAL FIBROSIS IN THE SEPTUM IN HUMAN HEARTS WITH CARDIAC HYPERTROPHY

William Lee, BA, Yuichi Baba, MD, Briana K. Shimada, BA, Jason K. Higa, PhD, Ari AuWinitzky, MSc, Scott Lozanoff, PhD, and Takashi Matsui, MD, PhD Department of Anatomy, Biochemistry, and Physiology John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI

Ventricular tachycardia (VT), which frequently occurs in patients with cardiac hypertrophy, is a major risk factor for sudden death. Sustained monomorphic VT is commonly a result of reentry, which is generated in a region of fibrotic scarring in the myocardium. Studies using late gadolinium-enhanced MRI, which indicates regions of myocardial fibrosis, demonstrated focal positive regions in the anterior and posterior septal walls. At the previous meeting, we reported a similar pattern of focal fibrosis in in vivo mouse models of cardiac hypertrophy induced by pressure overload. However, focal fibrosis in the septal wall is not characterized well in the human heart. To determine the relationship between focal fibrosis in the septum and the level of hypertrophy in human hearts, we assessed focal fibrotic changes in human cadaveric hearts by histopathological assays.

We examined a total of 7 hearts from cadavers (Average age 81 +/- 10, Male 1, Female 6). All individuals had no clinical history of ischemic heart diseases. Tissue samples were obtained from the septal and lateral free wall regions of seven cadaveric hearts. Prior to tissue sampling, each heart was weighed to differentiate the hearts into two groups (“Non-hypertrophy”, <350g; “Hypertrophy”, >350g). No difference in body mass indices (BMI) between the two groups was observed. Each tissue sample was sectioned into 5-micrometer sections for Masson’s trichrome staining (MTS). For each tissue sample, images were taken at random from both the lateral free wall and septal wall regions. The extent of fibrosis (% fibrosis) was assessed by image analysis using ImageJ software.

Consistent with our previous study, microscopic examination of MTS sections indicated the presence of fibrotic scarring in the anterior and/or posterior septal wall regions. Percent fibrosis in the septal wall region was significantly higher in the “Hypertrophy” group than “Non- Hypertrophy” group (40.3±2.3 vs. 28.1±6.0 %, p<0.05; n=3 and 4), suggesting a stronger positive correlation between the size of the heart, but independent of BMI. Comparison of heart weight and percent fibrosis between the septal and lateral free wall regions showed a stronger positive linear relationship in the septal wall region (r2=0.63), relative to the lateral free wall region (r2=0.03).

This study demonstrates an increased sensitivity of the septal wall regions to fibrotic change in cardiac hypertrophy. Determining mechanisms underlying hypertrophy-induced focal fibrosis in the septal wall may provide a novel approach for preventing a lethal ventricular arrhythmia in cardiac hypertrophy.

31 Poster #13

METRONIDAZOLE CAUSING PROFOUND DRUG-INDUCED IMMUNE THROMBOCYTOPENIA

Jeffrey Lew MD ACP Associate, Jeffrey Berenberg MD, MACP Hematology Oncology Service, Tripler Army Medical Center, HI

INTRODUCTION: Drug-Induced Immune Thrombocytopenia (DITP) is mediated by drug dependent platelet antibodies (DDabs). A lengthy and continuously growing list of drugs cause DITP. A diagnosis of DITP is best established by case report data with specific criteria, serum samples with positive drug dependent platelet-reactive antibodies, and from review of the Food and Drug Administration’s Adverse Event Reporting System (AERS) database. Metronidazole has not been reported in a case report and tested concurrently using serum analysis. We present the unique case of metronidazole-associated DITP proven by detection of DDabs in the patient’s serum.

CASE PRESENTATION: A 68 year-old caucasian man was hospitalized for a temporal lobe abscess and was treated with vancomycin, metronidazole and cefepime. After 5 days of antibiotics the patient underwent a mastoidectomy as well as biopsy and drainage of the abscess. After 12 days of antibiotic therapy the patient’s platelet count began to decrease; dropping precipitously from 250 x10^9/L to 140 x10^9/L on day 13 and to 17 x10^9/L on day 14 of antibiotics. The patient’s MPV was normal. The patient was asymptomatic without evidence of bleeding. Repeat platelet count utilizing a citrated tube showed platelet count of 7 x10^9/L. Fibrin degradation products, fibrin D-dimer, fibrinogen, PT, PTT, INR were within normal limits. Peripheral blood smear showed paucity of platelets and no schistocytes. The HIT panel testing for anti-heparin PF4 antibodies was negative. As DITP was suspected the patient’s antibiotics were changed to daptomycin and moxifloxacin. Over the next 4 days the pla telets rose to above 150 x10^9/L. The patient’s serum was sent to the Blood Center of Wisconsin for flow cytometry which detected drug dependent platelet antibodies strongly positive to metronidazole.

DISCUSSION: Metronidazole is a commonly used antibiotic and previous literature had not clearly shown a causal relationship between the drug and thrombocytopenia. The causality of between drugs and DITP can be firmly established with the use of systematic methods: published clinical case reports, drug-dependent antibody testing, and reports of adverse effects from the AERS database. In our case metronidazole showed a relationship with thrombocytopenia; it was administered before thrombocytopenia occurred and recovery was complete and sustained after cessation of the drug. The contribution of metronidazole in our case is further supported with strongly positive drug dependent antibody testing by flow cytometry. In the future metronidazole should be added to the large list of drugs causing thrombocytopenia so that providers will be aware of this effect.

32 Poster #14

MALIGNANCY MASQUERADING AS HENOCH SCHONLEIN PURPURA WITH ASCITES.

Dayna Lucuab-Fegurgur, MD, UHIMRP and LTC Jefferson R. Roberts, MD, TAMC

Henoch-Schonlein Purpura (HSP) is considered a predominantly pediatric disease that typically manifests in individuals under age 20, and is the most common form of systemic vasculitis in children. Recent reports have revealed increasing numbers of adult-onset HSP associated with malignancy. This is the case of a patient presenting in a rural setting with acute dyspnea, ascites, and palpable purpura, found to have biopsy proven HSP and malignancy of unknown primary with peritoneal carcinomatosis.

The patient is a 66 year old. female with a history of diabetes who initially presented to a rural pacific island hospital with a chief complaint of altered mental status and dyspnea, admitted for hypoglycemia and pneumonia. Her hospitalization included acute onset ascites and worsening hypoxia and dyspnea despite broad-spectrum antibiotics, with a subsequent diagnosis of subsegmental pulmonary embolism. A 4-slice CT scan of the abdomen did not reveal any abnormalities so she was transferred to a larger facility on a neighboring island for specialty consultation. During this admission she developed palpable purpura and petechiae to the abdomen and lower extremities. Her laboratory studies were notable for acute kidney injury, lactic acidosis, leukocytosis, and an albumin gradient of 1.1 with no evidence of infection on ascitic fluid analysis.

Due to rural limitations she was medevaced to a tertiary facility for further management. Rheumatologic work-up was negative with the exception of an elevated ESR and urinalysis showed dysmorphic RBCs with proteinuria. A skin biopsy revealed leukocytoclastic vasculitis with IgA deposition by immunofluorescence consistent with a diagnosis of HSP. Abdominal MRI was remarkable for subtle biliary abnormalities and omental caking. She was later found to have an elevated CEA and CA 19-9. Her course was complicated by intermittent upper and lower GI bleeding. EGD and colonoscopy were negative for malignancy or compromised mucosa. Omental biopsy results and cytology of subsequent peritoneal fluid samples were consistent with malignant adenocarcinoma. Given the severity of her diagnosis, the patient decided to transition to hospice and return to her native island.

This patient’s intriguing presentation of HSP associated with malignancy demonstrates that recognizing HSP in the adult population is critical. It also highlights the importance of considering secondary causes when presented with an immune complex-mediated small vessel vasculitis. The incidence of vasculitis and malignancy is as high as 5%, and HSP in particular is more commonly associated with solid tumor malignancies. Approximately 50 case reports of HSP associated with solid-malignancy were discussed in a 2012 review by Podjasek et.al. Moreover, the ABIM certification exam now includes questions regarding adult-onset HSP, likely due to the rising number of cases similar to the one presented here.

33 Poster #15

THE COST-BENEFIT BALANCE OF STATINS IN HAWAI’I: A MOVING TARGET

Corey J. Lum, D.O.1, Kazuma Nakagawa, M.D.2, Ralph V. Shohet, M.D.1, Todd B. Seto, M.D., M.P.H1 and Debra A. Taira, Sc.D.3

1Division of Cardiology, Department of Medicine, University of Hawai’i John A. Burns School of Medicine, Honolulu, HI; 2Department of Neurology, University of Hawai’i John A. Burns School of Medicine, Honolulu, HI; 3University of Hawai’i The Daniel K. Inouye College of Pharmacy, Hilo, HI

BACKGROUND: Statins are lipid-lowering medications used for primary and secondary prevention of atherosclerotic disease and represent a substantial portion of drug costs in the United States. A better understanding of prescribing patterns and drug costs should lead to more rational utilization and help constrain health care expenditures in the United States.

METHODS: The 2013 Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File for the state of Hawai’i was analyzed. The number of prescriptions for statins, total annual cost, and daily cost were calculated by prescriber specialty and drug. Potential savings from substituting the highest-cost statin with lower-cost statins were calculated.

RESULTS: Over 421,000 prescriptions for statins were provided to Medicare Part D beneficiaries in Hawai’i in 2013, which cost $17.6M. The three most commonly prescribed statins were simvastatin (33.4%), atorvastatin (33.4%) and lovastatin (13.9%). Although rosuvastatin comprised 5.4% of the total statin prescriptions, it represented 30.1% of the total cost of statins due to a higher daily cost ($5.53/day) compared to simvastatin ($0.25/day) and atorvastatin ($1.10/day). Cardiologists and general practitioners prescribed the highest percentage of rosuvastatin (8% each). Hypothetical substitution of rosuvastatin would have resulted in substantial annual cost savings (Simvastatin would have saved $1.3M for 25% substitution and $5.1M for 100% substitution, while atorvastatin would have saved $1.1M for 25% substitution and $4.3M for 100% substitution).

CONCLUSIONS: Among Medicare Part D beneficiaries in Hawai’i, prescribing variation for statins between specialties were observed. Substitution of higher-cost with lower-cost statins may lead to substantial cost savings.

34 Poster #16

SEVERE RHABDOMYOLYSIS FROM RED YEAST RICE

Ivy R. Melgarejo, MD1, Therese F. Posas-Mendoza, MD1, Michael Vaughn F. Mendoza, MD1, Ma Clarisse Santos, MD2 1University of Hawaii, Internal Medicine Residency Program, 2Department of Nephrology, Kuakini Medical Center

Red yeast rice (RYR) is a Chinese dietary supplement known to have similar properties to statin by inhibiting HMG CoA reductase. It contains monacolin, a chemical homologue of lovastatin. Although several studies have proven its efficacy as a lipid lowering agent, it still carries the risk of myopathy and liver dysfunction. There were several case reports of myopathy caused by RYR, however none has been reported to cause acute kidney injury requiring renal replacement therapy. We hereby present a case of a 73 year old Chinese female with a history of coronary artery disease, hypertension, and dyslipidemia who developed severe non-traumatic rhabdomyolysis and acute kidney injury requiring renal replacement therapy from intake of red yeast rice. She presented with a one-week history of myalgia and jaundice. She had been prescribed with simvastatin 80 mg daily but reported to have been taking it inconsistently and was taking red yeast rice instead. Initial work up revealed a creatine k inase (CK) level of 15,500 U/L, serum creatinine of 1.9 mg/dL, GFR of 28 ml/min//1.73 m2 and a total bilirubin of 15.8 mg/dL. Liver function showed a hepatocellular pattern of injury, with negative viral hepatitis and autoimmune panels. Her renal function continued to decline, and CK levels peaked at more than 120,000 U/L despite aggressive volume resuscitation. A nephrology consult was then obtained and the patient was subsequently started on renal replacement therapy.

A recent review about RYR reported muscle symptoms between 0-23.8%, without reports of rhabdomyolysis. The only reported case of rhabdomyolysis from RYR occurred in a renal transplant patient. In our patient, with discontinuation of red yeast rice and statin, aggressive hydration and renal replacement therapy, there was eventual resolution of renal injury. In this case, there is a high temporal association of rhabdomyolysis with RYR, given the timing of intake and the onset of muscle, kidney and liver dysfunction. This case highlights that rhabdomyolysis leading to severe acute kidney injury can be a complication of red yeast rice. Patients should be cautioned on this potential side effect of this dietary supplement.

35 Poster #17

CLINICAL DECEPTION: ATYPICAL POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES) IN SLE

Michael Vaughn F. Mendoza, MD1, Therese F. Posas-Mendoza, MD1, Ivy R. Melgerajo, MD1, Emilio Ganitano, MD2, Alberto S. Santos-Ocampo, MD3 1University of Hawaii, Internal Medicine Residency Program, 2Department of Critical Care Medicine, Straub Medical Center, 3Department of Rheumatology, Straub Medical Center

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is an autoimmune disease that can present as cerebritis with new onset seizures, mental status changes, and strokes. Posterior reversible encephalopathy (PRES) can present very similarly. We discuss the case of a 22 year old Korean female with SLE who was admitted with acute renal failure, thrombocytopenia, hypertensive emergency, seizures, visual impairment, and MRI findings consistent with both lupus cerebritis and PRES.

CASE REPORT: A 22-year-old Korean female with known SLE and past history of mesenteric vasculitis presented with new onset seizures and renal insufficiency. Outpatient regimen was hydroxychloroquine and low dose prednisone. Labs showed anemia, thrombocytopenia, ANA of 1:2560, anti-dsDNA of 1:1280, positive SSA, SSB, histone antibodies, C3 and C4 hypocomplementemia, elevated creatinine, and nephrotic range proteinuria. Initial brain MRI revealed abnormal T2 hyperintense signals bilaterally in the frontal, parietal and occipital lobes consistent with lupus cerebritis. She received pulsed steroids, hemodialysis, and plasma exchange for lupus cerebritis, nephritis, and thrombotic thrombocytopenia. Despite these measures, she developed cortical blindness, recurrent seizures and altered mentation several days later. CSF was negative for protein and infections. Brain MRI revealed non-obstructive hydrocephalus and new edema in both cerebellar hemispheres with infarcts and extensive mass effect more consi stent with PRES rather than lupus cerebritis. She was treated with ventriculostomy, aggressive blood pressure control, mycophenolate, pulsed steroids, and IV cyclophosphamide. Her neurologic status improved and repeat imaging revealed improvement in cerebral edema.

DISCUSSION: PRES is a disorder of cerebral autoregulation and endothelial dysfunction that typically presents with seizures, altered mental status, visual impairment and MRI findings of bilateral asymmetrical cerebral edema in the parietotemporo-occipital regions. It is associated with severe hypertension, renal dysfunction, autoimmune disorders (i.e. SLE), and immunosuppressive therapy. Our patient had a severe lupus flare with initial MRI findings of lupus cerebritis, confounded by development of PRES as her hypertension and renal failure worsened. This case was unusual because it presented with cerebellar edema. In a 2008 meta- analysis, 17 of the reported 170 PRES cases had preexisting SLE. Only 11.8% of the 17 presented with cerebellar edema.

Distinguishing PRES from lupus cerebritis becomes critical because management is entirely different. The mainstay of PRES treatment is aggressive blood pressure control, while lupus cerebritis requires intensification of immunosuppressive therapy. It is important to recognize both disorders as one can mimic the other, as seen in this severely ill patient. Delays in diagnosis and management can affect clinical outcomes.

36 Poster #18

T CELL PROLYMPHOCYTIC LEUKEMIA MASQUERADING AS GRANULOMATOUS INTERSTITIAL NEPHRITIS

Daniel Thomas Miles1, MD (ACP Associate), Jorge Martinez1,2, MD (FACP Member), Tamie Kerns1,3, DO (FACP Member), Jeff Berenberg1,3, MD (MACP Member) 1Department of Medicine, 2Nephrology Service, 3Hematology-Oncology Service, Tripler Army Medical Center, Hawaii

INTRODUCTION: Granulomatous interstitial nephritis (GIN) is an uncommon cause of acute renal failure representing 0.5-0.9% of all renal biopsies. Possible etiologies of GIN include: medications, sarcoidosis, infections, and uncommonly B-cell Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia. We describe an atypical presentation of GIN secondary to T-cell Prolymphocytic leukemia (T-PLL), a very rare neoplasm.

CASE PRESENTATION: A 60-year-old Asian female with Type II Diabetes Mellitus, primary biliary cirrhosis, and recurrent urinary tract infections on recurrent antibiotics, presented with fatigue, blurry vision, and an elevated creatinine at 2 mg/dL (baseline 0.8mg/dL) rising to a maximum of 6 mg/dL over the course of 2 months.

Physical examination revealed bilateral periorbital edema and injected conjunctiva. Additional studies were significant for BUN 66 mg/dl, microalbumin/creatinine of 33 mg/g and bilateral renal enlargement on ultrasound. A renal biopsy demonstrated acute interstitial nephritis without interstitial fibrosis, with an area of focal granulomatous inflammation, suggestive of GIN. The biopsy also disclosed an atypical lymphoid infiltrate of T-cells positive for cell differentiation (CD) markers 3, 5, 4, 8, 7, and 2. Patient began to improve on a steroid trial, but did not tolerate this treatment due to uncontrollable blood sugars requiring hospitalization. Initiation of mycophenylate resulted in a partial response with a decrease in creatinine to 4.0 mg/dL. Three months after the initial documentation of renal function deterioration the patient developed persistent lymphocytosis leading to a peak absolute lymphocyte count of 20,000/L. T-cell gene rearrangement testing revealed a ga mma/beta rearrangement and flow cytometry confirmed T-PLL with CD markers 52 and 4/8 positivity. Bone marrow showed extensive involvement of the marrow with medium sized lymphocytes. Re-evaluation of the renal biopsy confirmed infiltration of the kidneys with medium sized, CD 52 positive lymphocytes.Following 16 weeks of alemtuzumab, the bone marrow and peripheral blood cleared of T-PLL; however, the creatinine remained elevated at ~4mg/dL.

DISCUSSION: The pathologic appearance of both the direct lymphoid infiltration and granulomatous inflammation are characteristic of GIN. PLL therapy led to clearance of the bone marrow and peripheral blood without any resolution of renal failure; this is more characteristic of GIN than lymphomatous infiltration causing the renal insufficiency in our patient. While, B- cell CLL/SLL has infrequently been described as etiology of GIN; our case of GIN was caused by T- PLL and uncommon leukemia variant.

37 Poster #19

THE ROLE OF mTOR ON CARDIOMYOCYTE CONTRACTION AND CALCIUM HANDLING

Kiyonari Noguchi, BA, Briana Shimada, BA, Takashi Matsui, MD, PhD Department of Anatomy, Biochemistry, and Physiology Center for Cardiovascular Research John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI

The mechanistic target of rapamycin (mTOR) signaling pathway is a central regulator of cellular metabolism, growth, and survival, and its deregulation is associated with many pathological conditions, including diabetes and cancer. mTOR, a serine/threonine protein kinase that is localized to the mitochondria and cytosol in the heart, forms two structurally and functionally distinct complexes called TOR complex 1 (mTORC1) and TOR complex 2 (mTORC2). Previously we reported that overexpression of cardiac mTOR protects the heart against ischemia- reperfusion injuries for both in vivo and ex vivo models. However, the role of cardiac mTOR in cardiomyocyte (CM) function is not characterized well.

We hypothesized that cardiac mTOR plays a crucial role in CM contraction. Intracellular calcium handling is a key regulatory system on excitation-contraction (EC) coupling in CMs. To define the role of mTOR in cardiac EC coupling, we assessed CM contraction and intracellular calcium handling in CMs from cardiac-specific mTOR-knockout (mTOR-KO). CMs were isolated from either mTOR-KO mice or littermate control wild-type (WT) mice, and the sarcomere length contraction and intracellular calcium handling were measured by IonOptix system. CMs were isolated from mTOR-KO mice or WT using Langendorff preparation with calcium-free buffers containing collagenases and proteases to degrade the extracellular matrix around the CMs. The CMs were loaded with calcium using a series of calcium-containing buffers of increasing concentrations (0.06 mM, 0.24 mM, 0.6 mM, and 1.2 mM). To detect calcium transients, fura- 2AM, a calcium-sensitive dye, was added to the buffer that contains CMs. CMs were then pa ced at 2.0 Hz. mTOR-KO CMs showed shorter contractions and lower calcium transient ratios than controls. The CM peak shortening, measured as % cell length, for the control (n=12) and mTOR- KO (n=8) were found to be 4.60±0.37 % and 2.06±0.20 %, respectively (p<0.0001). The calcium transient ratio for the control and mTOR-KO were found to be 41.28±3.72 and 27.95±5.11, respectively (p<0.05). This reinforces the previously reported cardioprotective effects of mTOR, and we can infer that mTOR is necessary for normal cell contraction and calcium handling.

The study demonstrated that cardiac mTOR is necessary to preserve EC coupling with normal calcium handling in CMs. Understanding the role of cardiac mTOR on CM function further will provide potential therapeutic strategies for patients with heart failure.

38 Poster #20

RHEUMATOID ARTHRITIS AND CARDIAC COMPRESSION BY A LARGE FIBROTIC INTRAPERICARDIAL MASS: A CASE REPORT

Therese Posas-Mendoza, MD1, Kazue Okajima, MD2, Diane Tran, MD3, Robert Hong, MD3 1University of Hawaii, Internal Medicine Residency, 2University of Hawaii, Cardiology Fellowship, 3Department of Cardiology, Queens Medical Center

Rheumatoid arthritis is a chronic inflammatory disease that affects the synovial membrane, but may have extraarticular manifestations. The most common cardiac manifestations include pericarditis, pericardial effusions, myocardial disease, coronary vasculitis, diastolic dysfunction, and valvular lesions. We present the case of a 58 year female with rheumatoid arthritis who was found to have a fibrotic pericardial mass.

CASE REPORT: The patient is a 58 year old female with a past medical history significant for hypertension and rheumatoid arthritis on hydroxychloroquine, prednisone, golimumab and leflunomide. She initially presented with exertional dyspnea and lower extremity edema, and was found to have an ectopic atrial tachycardia. A transthoracic echocardiogram was obtained and it revealed a 2.5cm circumferential pericardial effusion with right ventricular diastolic collapse and a possible mass compressing the right ventricle. The patient underwent pericardiocentesis with removal of 320cc hemorrhagic fluid. Analysis of the fluid did not reveal evidence of malignancy or infection. Repeat TTE documented resolution of the effusion, but findings were consistent with a constrictive process and thickened pericardium. A cardiac MRI was done revealing a 3.5cm uniformly enhanced soft tissue mass within the pericardial sac overlying and compressing the right ventricle. The patient underwent open sternotomy with remov al of the pericardial mass. Pathologic evaluation revealed a 7.2x6x1cm mass with acellular fibrinous debris with cholesterol clefts but no evidence of malignancy. The pericardium appeared fibrotic with evidence of chronic inflammation.

DISCUSSION: In a 2013 meta-analysis done on cardiac abnormalities in rheumatoid arthritis patients, none were found to have a fibrotic pericardial mass. Our patient was found to have a fibrotic pericardial mass with evidence of chronic inflammation. She was taking leflunomide and golimumab. Interestingly, both leflunomide and TNF-α inhibitors (eg golimumab) have been associated with pulmonary lung nodule formation/fibrosis. Leflunomide is a known cause of nodulosis, and often presents with pulmonary and subcutaneous nodules. TNF-α inhibitors, on the other hand, have both profibrotic and antifibrotic effects. In vivo studies have produced contradictory data, showing both induction and reduction of fibroproliferative lesions (mostly in pulmonary fibrosis). Placebo controlled trials are needed to elucidate the effects of TNF-α inhibitors on fibrosis. To our knowledge, there have been no reported cases of pericardial nodules associated with leflunomide and TNF-α inhibitors. This case may suppor t the theory that both drugs have profibrotic effects. While this remains conjectural, the awareness of an association between rheumatoid arthritis, leflunomide, TNF-α inhibitors, and the development of an intrapericardial fibrotic mass should be increased.

39 Poster #21

ANTI-NMDA RECEPTOR ENCEPHALITIS PRESENTING AS AN ACUTE PSYCHIATRIC EPISODE

Resham Ramkissoon, MS41; , Kuo-Chiang. Lian, MD2. 1John A. Burns School of Medicine. 2The Queen’s Medical Center.

BACKGROUND: Anti-NMDA receptor encephalitis is a severe form of autoimmune encephalitis that commonly affects young women and is a known paraneoplastic syndrome of ovarian teratomas [1-3]. The clinical course starts with a non-specific, flu-like prodrome followed by prominent psychiatric symptoms including psychosis, agitation and confusion [4, 5]. The initial psychiatric symptomatology is so common that patients are often initially admitted to psychiatric wards. As the disease progresses, patients begin to develop seizures, movement abnormalities, autonomic instability and require ICU-level care [6]. If untreated, or misdiagnosed, this condition can be fatal or result in severe, long-term disability.

AIMS: Describe the initial psychiatric symptoms of anti-NMDA receptor encephalitis.

METHODS: Case report and literature review.

RESULTS: A 22-year old female presented with a headache for 5 days and AMS for 1 day. She previously presented to another medical center with similar symptoms but the definite diagnosis was not revealed. She did not respond to questions, spoke incoherently, and had right-sided weakness. A urine toxin screen was negative for any substances. Her CSF showed a lymphocytic pleocytosis, but a head CT and MRI (without contrast) showed no acute intracranial abnormality. A BIOFIRE assay was performed and was negative for any bacteria, viruses or fungi. A PET/CT scan showed asymmetric brain metabolism consistent with diffuse encephalopathy. A paraneoplastic or autoimmune etiology was suspected and the patient was started on a 5 day regimen solumedrol and IVIG, however her neurological status did not improve after completing the regimen. A workup for ovarian teratomas (including TVUS with doppler, pelvic CT/MRI, CA- 125) returned unremarkable. She was started on plasmapheresis and her neurologic al exam began to improve slightly. An anti-NMDA receptor antibody assay returned positive and weekly rituximab was added to her regimen, which resulted in a marked improvement in her neurological status. The patient continued to improve and was discharged to a regional hospital in stable condition on tube feeds and seizure prophylaxis.

CONCLUSION: This case report highlights the importance of considering anti-NMDA receptor encephalitis when acute psychiatric symptoms are accompanied by extrapyramidal symptoms, autonomic dysfunction and neurological decompensation. This consideration is especially important for psychiatrists, as most patients are initially evaluated by psychiatry before neurology or hospitalist teams become involved in the patient’s care. About 4% of NMDA- receptor encephalitis patients present with isolated psychiatric episodes, without any neurologic involvement [7]. More research and dissemination of knowledge are required to improve clinicians' ability to make the diagnosis of anti-NMDA receptor encephalitis, as well as exclude high utility diseases based on clinical and radiological evidence.

40 Poster #22

A RARE PARANEOPLASTIC SYNDROME: SECONDARY MEMBRANOUS GLOMERULONEPHROPATHY ASSOCIATED WITH LOW GRADE FOLLICULAR LYMPHOMA

Maria Rodionova, D.O., Jorge Martinez Osorio, M.D., Mark Carmichael, M.D. Tripler Army Medical Center, Honolulu, Hawaii

INTRODUCTION: The association between glomerulopathy and solid tumors in the setting of a paraneoplastic syndrome is well described. However, the relationship between glomerulopathy and non-solid malignancies is rare and less well understood. We describe a case of a membranous glomerulonephritis (GN) secondary to a lymphoma-induced paraneoplastic syndrome. Our case illustrated how recognizing this link impacted our choice of therapy and resulted in a favorable outcome.

CASE DESCRIPTION: A 68 yo male patient with diabetic nephropathy, chronic kidney disease (CKD) 3 with preadmission creatinine 1.9, indolent lymphoma (Follicular, Stage 1A), one year after radiation and chemo-immunotherapy (bendamustine, rituximab) was clinically in remission with minimal residual lymphoma on imaging. He presented with an oliguric acute kidney injury (AKI), serum creatinine of 4.27, nephrotic syndrome, massive proteinuria of 17 gm and severe anasarca. No preceding nephrotoxin exposures or hypotensive episodes were evident. No hydronephrosis, renal artery stenosis or evidence of a paraproteinemia was found. Viral hepatitis and HIV studies were negative, and urine microscopy consistently showed hyaline casts without RBC or WBC sedimentation. Renal biopsy revealed Stage 1 Membranous GN. PLA2R glomerular deposits and circulating PLA2R autoantibiodies were not detected. These findings were inconsistent with a primary idiopathic membranous GN. Secondary etiologies of a mem branous GN, such as infection, autoimmune disease and nephrotoxin exposure were not identified.

Initial therapy with high-dose steroids was chosen, but yielded a poor response. We then elected to target lymphoma with a combination of rituximab and steroids, and improvement in GFR, proteinuria and creatinine was immediate and progressive. AKI and anasarca resolved. Steroids were tapered, and after completing a month-long induction course, patient was continued on maintenance-dose rituximab. Two months following the initiation of therapy, patient remained in clinical remission, with creatinine at baseline of 1.6 and markedly improved proteinuria of 0.4 gm on spot analysis.

DISCUSSION: This case highlights the possibility of a non-solid malignancy inducing a paraneoplastic syndrome. The absence of PLA2R glomerular deposits and circulating autoantibodies, and the patient’s failure to respond to steroids, argued against a primary membranous GN. We then concluded that the most plausible etiology among secondary GN causes was a lymphoma-induced paraneoplastic syndrome. When lymphoma was targeted with therapy, patient showed an excellent clinical response. The absence of a worsening lymphoma burden on imaging did not deter us from initiating treatment, as paraneoplastic syndromes often appear disproportionately to malignant activity. Recognizing this rare phenomenon impacted our selection of the most appropriate therapy. Better understanding and recognition of this association will contribute to an improved standard of care.

41 Poster #23

CASE REPORT OF RECURRENT CHEST PAIN IN A PATIENT WITH A CONGENITALLY ABSENT PERICARDIUM

Tomoki Sempokuya, M.D., Corey J. Lum, D.O., Mahdi Veillet-Chowdhury, M.D., Kahealani Rivera, M.D. Division of Cardiology, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI

BACKGROUND: A congenitally-absent pericardium is a rare disorder often found incidentally in asymptomatic patients. However, symptoms may manifest as positional or pleuritic chest pain, dyspnea on exertion, or palpitations. Patients may often be mistakenly diagnosed with other cardiac conditions such as ischemic heart disease, aortic dissection, pulmonary embolism, or acute pericarditis.

CASE DESCRIPTION: We describe a 24-year old female with a history of Swyer-James-MacLeod syndrome, which is characterized by obliteration of the small airways secondary to bronchiolitis and a severe emphysematous appearance, who presented with acute onset of pleuritic chest pain and was diagnosed with acute pericarditis. 12-lead electrocardiogram (ECG) showed classic diffuse ST elevations. Symptoms resolved rapidly with ibuprofen and colchicine oral therapy but recurred when therapy was discontinued following a 3 month course. Workup, including labs, transthoracic echocardiography and cardiac magnetic resonance imaging (cMRI), was initially unrevealing. The transthoracic echocardiogram showed normal left ventricular function with mild right ventricular dilatation. Review of raw chest x-ray images revealed a “Snoopy Sign”, which is pathognomonic for a congenitally-absent pericardium, and was not reported on the original study. A “Snoopy Sign” is characterized by a lucent area between the base o f the heart and the left hemidiaphragm, loss of the right heart border, a prominent pulmonary artery, and a flattened and elongated left ventricular contour. The diagnosis of an absent pericardium was suggested upon re-review of the echocardiogram and cardiac MRI and confirmed by cardiac CT. The patient was subsequently and successfully treated with a prolonged tapering course of oral anti-inflammatory therapy. In retrospect, her previous diagnosis of Swyer-James-MacLeod syndrome was incorrect and was actually due to leftward displacement of the heart.

DISCUSSION: Since it is a rare disease, there are no standardized treatments, but surgical reconstruction might be beneficial for controlling severe symptoms in select patients. In our case, the use of oral anti-inflammatory medications successfully reduced symptoms, and may potentially be an alternative therapy prior to consideration of surgical reconstruction. Conclusion: A congenitally-absent pericardium is a rare disorder, often undetected, and mistaken for other diseases. There are characteristic findings on chest X-ray such as a “Snoopy Sign”, which can be missed or misdiagnosed due to its rarity. Our goal of this report is to educate health care providers about this rare disorder.

42 Poster #24

WHERE ARE THE WORMS?: WHEN PERIPHERAL EOSINOPHILIA DOESN’T MEAN HELMINTH

Alexandra Stewart, DO (ACP Associate), Kinsley A Hubel (ACP Associate), Mark Carmichael, MD, Mazer Ally, MD (FACP) Department of Medicine, Tripler Army Medical Center, Hawaii

INTRODUCTION: Hypereosinophilic Syndrome (HES), a rare group of blood disorders, can be rapidly fatal. It is characterized by peripheral eosinophilia affecting multiple organ systems. HES most commonly involves the lung, skin, heart and nervous system. We present a case that manifested with diarrhea due to pancolitis associated with extensive multi-system thrombi.

CASE PRESENTATION: A 53 year old male with remote history of a hemicolectomy and chronic alcoholism presented with worsening abdominal pain, diarrhea and bright red blood per rectum. His abdominal was diffusely tender and distended on exam. His labs were significant for leukocytosis (WBC count of 30x103/mm3), peripheral eosinophilia (10%), anemia (acute drop in hemoglobin from 10 to 8 g/dl) and thrombocytopenia (95x103/mcL). Colonoscopy demonstrated pancolitis with multiple large ulcers. Pathology showed marked transmural eosinophilic inflammation with eosinophilic cryptitis. He was treated for a presumed bacterial gastroenteritis and helminthic infection given the peripheral eosinophilia. However, despite dual anti-helminthic agents his condition deteriorated, with development of multiple venous thromboses in the right lower extremity. An IVC filter was placed due to his thrombocytopenia. Stool testing including culture, ova and parasite, clostridium difficile, Ascaris antibody and Strongyloides antibody was negative. He had dramatic improvement (>80% decrease) in his peripheral eosinophilia after receiving high dose methylprednisolone. After initial improvement his abdominal pain returned and a CT revealed multi-venous, multi-system thrombotic occlusions. An evaluation for heparin induced thrombocytopenia and disseminated intravascular coagulation was negative. A bone marrow biopsy was negative for malignancy with normal cytogenetics. FIP1L1/PDGFR, BCR/ABL, JAK2, KIT, B and T cell clones were all negative. He was discharged on apixaban and a prednisone taper to 30mg daily. Repeat colonoscopy five months later was significantly improved, with one small ulcer visualized and without evidence of eosinophilic infiltration.

DISCUSSION: HES with predominantly gastrointestinal involvement has been rarely reported in the literature. Our case demonstrates the confounding features that may contribute to delay of diagnosis. This patient presented with pancolitis and marked thrombocytopenia rapidly responsive to high dose corticosteroids. Typically HES is associated with development of cardiomyopathy, thromboembolic disease, neuropathy, skin lesions and sometimes hepatosplenomegaly. However, it is rarely seen with gastrointestinal involvement, especially the development of pancolitis with diffuse eosinophilic invasion through the mucosa and into the submucosal layers.

43 Poster #25

SERTRALINE USE IN AN IMMUNOCOMPETENT PATIENT WITH CRYPTOCOCCUS GATTII PULMONARY INFECTION

Eric Szu, MD, Paula Morzenti, BA, Tomas Ferguson, MD, FACP, Maryann Ally, MD, FACP Department of Medicine, Tripler Army Medical Center, Honolulu, Hawaii

Cryptococcus gattii is an endemic fungus manifesting most often as life-threatening meningoencephalitis or pulmonary disease. Treatment has been extrapolated from management of immunocompromised patients with other systemic mycoses. Sertraline is a selective serotonin reuptake inhibitor used commonly as an antidepressant, but new studies have demonstrated powerful antifungal properties when used in adjunct with traditional Cryptococcal medications. We present an immunocompetent patient with disseminated Cryptococcus gattii treated with sertraline, liposomal amphotericin B, and flucytosine.

A 67 year old American Samoan male presented with intermittent, painless, gross hematuria for five years. His medical history includes chronic non-cirrhotic Hepatitis C, type 2 diabetes mellitus, hypothyroidism, and a 10-pack year smoking history. He lives in central California and American Samoa with his wife and previously worked on an oil refinery. Physical exam was unremarkable and his prostate was normal on palpation. Complete blood count, immunoglobulins, electrolytes, and liver function tests were normal. CT intravenous pyelogram (CT IVP) showed anterior wall thickening concerning for malignancy and an incidental right lower lobe nodule. He complained of intermittent cough without other constitutional symptoms. Because of the CT IVP findings, a pre-operative chest CT was ordered and demonstrated a superior right lower lobe segmental consolidation with internal cavitation, multiple small pulmonary nodules, the largest measuring 1.2 cm, and bibasilar bronchiectasis. Sputum cultu re grew Cryptococcus gattii. Serum cryptococcal antigen titers were greater than 1:512. CSF cryptococcal antigen was negative and brain MRI demonstrated no meningeal enhancement. HIV antibody and tuberculin skin tests were negative. He completed four weeks of flucytosine 100mg/kg PO daily, three weeks of progressively increased IV liposomal amphotericin B from 3mg/kg/hr to 5mg/kg/hr, and two weeks of oral sertraline 100mg daily. Sertraline use was abbreviated due to acute interstitial nephritis and acute kidney injury, possibly due to drug toxicity. Due to disabling fatigue, his liposomal amphotericin B dose was decreased to 3mg/kg/day for three weeks. Prior to discharge, a chest radiograph demonstrated resolution of a left lower nodule and stable right lower lung airspace disease. He was discharged on Fluconazole 200mg PO daily for twelve months and scheduled to follow up in clinic.

Sertraline’s antifungal efficacy was first documented in women with complete resolution of recurrent vulvovaginal candidiasis while being treated for premenstrual dysmorphic disorder with sertraline. Studies have demonstrated powerful synergistic antifungal activity in previously resistant Cryptococcal serotypes, especially given sertraline’s excellent penetration of the blood brain barrier leading to higher concentrations in the CSF and brain. With pending follow-up, we expect to see a faster recovery with sertraline due to his immunocompetence.

44 Poster #26

OUTCOMES OF STEREOTACTIC BODY RADIATION THERAPY FOR PRIMARY HEPATOCELLULAR CARCINOMA

Jamie S.K. Takayesu BS1, Jeffrey Burkeen MD2, Daniel Simpson MD2, Jona Hattangadi-Gluth MD2 1John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 2Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California

BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer- related deaths worldwide. Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for unresectable HCC, but there are limited data for patients with poor liver function (Child-Pugh (CP) B or C). This study aimed to report a single institution experience of SBRT in treating primary hepatocellular carcinoma, including CP A, B and C.

METHODS: This retrospective cohort of 18 patients was treated with SBRT for primary non- resectable HCC. Patients were followed at 1-week, 1-month, 3-months and 6-months after treatment. Toxicity grading was based on the worst toxicity experienced using the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Tumor progression was determined according to mRECIST criteria. Overall survival (OS) was determined by Kaplan-Meier survival analysis.

RESULTS: Median follow-up time was 6 months (range 0-36 months). Median tumor size was 3.3 cm (range 1.7-14.0 cm) and median SBRT dose was 41 Gy (range 25-60 Gy). Patients were CP A (39%), B (28%) or C (33%). Tumor progression at 6 months was categorized as stable disease (28%), partial response (17%), or complete response (28%). Five patients (28%) were either lost to follow-up, or died before follow-up imaging could be obtained. OS 1-year was 64% and OS 2- years was 38%. 17% of patients experienced an adverse event grade ≥3, and all cases were due to new-onset or severely increased ascites.

CONCLUSIONS: Overall survival in this single institution cohort was comparable to other studies where patients had primarily CP A or B, suggesting that SBRT may be an effective treatment modality for those with more advanced cirrhosis. Toxicity of ascites may have been a result of natural disease progression.

45 Poster #27

PHARMACOLOGICAL TRIGGERS FOR STUDYING CELL-TO-CELL DEATH IN CARDIOMYOCYTES

Jonathan Woo, BS, Yuichi Baba, MD, Takashi Matsui, MD, PhD Department of Anatomy, Biochemistry, and Physiology, Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii

Advances in treatment of myocardial infarction (MI), including coronary stents and bypass grafts, have decreased mortality. However, heart failure (HF) following MI remains a major contributor to morbidity and mortality in the US. The risk of future HF is directly correlated to the magnitude of cardiomyocyte (CM) cell death caused by acute MI. We previously reported CM injury extends along myofibers in ischemia-reperfusion (I/R) injury using 3-dimensional images rendered from multiple tissue sections. Previous reports using isolated CMs and histological assays showed cell-to-cell death propagation as a key pathophysiological feature in hypoxic contracture observed in I/R injury. However, mechanisms underlying myocardial scarring along myofibers following I/R injury still remain undefined.

Although many pharmacological triggers such as the endogenous reactive oxygen species (ROS) hydrogen peroxide (H2O2) have been used in in vitro models for studying CM cell death, no specific inducers of cell-to-cell death propagation have been identified. At the previous meeting, we reported a positive correlation between iron deposition and fibrotic scar size in mouse I/R models. Recently, a new form of regulated cell death mediated by iron, aptly named ferroptosis, has been recognized. Thus, we hypothesized that ferroptosis would be the primary mechanism of the observed cell-to-cell damage propagation seen in CMs. To determine the role of iron- mediated cell death in CMs, we assessed the pattern of cell death caused by the ferroptosis inducer erastin and compared that with the pattern seen in oxidative damage induced by H2O2.

We cultured H9c2 cells, originally derived from embryonic rat ventricles, in 12-well plates containing DMEM with 10% FBS. Cells were cultured to about 90% confluency and treated with 2-4 micromol/L erastin or DMSO alone (control) for 24 hours in the erastin model, and 100-200 micromol/L H2O2 or control for 4 hours in the H2O2 model. Cell death was analyzed with Live/Dead Cell Viability Assay (Roche) and randomized images were taken under fluorescent microscopy. Multiple experiments (>3 independent experiments) showed a clear difference in the pattern of cell death between erastin and H2O2 models. The former demonstrated “clusters” of death consistent with the cell-to-cell death hypothesis; the latter showed a diffuse pattern of cell death.

This study suggests erastin is an effective inducer of in vitro cell-to-cell death, which is likely mediated through ferroptosis. Further investigation using this model may elucidate a therapeutic target aimed at stopping damage from extending past the initial area of infarction during an MI. Minimizing this area of injury will reduce morbidity and mortality from subsequent HF.

46 Poster #28

OPPORTUNISTIC SCREENING FOR OSTEOPOROSIS IN OLDER WOMEN WITH TRAUMATIC INJURY: A MISSED OPPORTUNITY

Elisabeth S. Young1,2, Joel A. Gross, MD2, Tam N. Pham, MD2, Lisa A. Taitsman, MD2, Saman Arbabi, MD, MPH2, May J. Reed, MD2, Stephen J. Kaplan, MD, MPH2,3 1University of Hawaii, Honolulu, HI, 2University of Washington, Seattle, WA, 3Virginia Mason Medical Center, Seattle, WA

BACKGROUND: Older adults admitted for traumatic injury provide an opportunity to screen for chronic disease. Opportunistic analysis of bone density via computed tomography (CT) is a method to identify chronic bone loss. The purpose of this study was to assess the prevalence of osteoporosis in older adult women with traumatic injury and measure recognition of this chronic disease by acute care providers.

METHODS: In this retrospective cohort study, we analyzed lumbar vertebral body density at the L1 level in women age ≥65 who sustained traumatic injury, had CT imaging of L1, and were admitted to the ICU at a single level 1 trauma center during a 3-year period. Women with head injury severity scores ≥3, death within 24 hours, out-of-state addresses, or inadequate L1 imaging were excluded. Osteoporosis was defined as average L1 Hounsfield units <110 (90% specificity, Pickhardt et al. 2013). Patient, injury, and clinical details were queried through the state trauma registry. Diagnosis and treatment of osteoporosis were abstracted from discharge data. Analysis was conducted comparing women with osteoporosis to those without.

RESULTS: Of the 296 women meeting inclusion criteria, 81 were excluded. The remaining 215 comprised the study cohort; 101 (47%) were retrospectively diagnosed with osteoporosis by CT scan. Women with osteoporosis were older (82 [IQR 74-87] vs. 77 [71-83], p<0.001) and more likely to sustain a ground-level fall (41 [41%] vs. 29 [25%], RR 1.5 [95%CI 1.1-2.4], p=0.018). There were no differences between groups in injury severity, hospital length of stay, or discharge disposition. However, only 55 (59%) of the 94 patients with osteoporosis who survived to discharge had a listed osteoporosis diagnosis and/or corresponding evaluation/treatment plan.

CONCLUSIONS: Nearly half of older women admitted with traumatic injuries had underlying osteoporosis. However, 41% of those women did not have documentation conveying this finding. Inpatient admission for traumatic injury is an opportunity to screen older women for osteoporosis, to initiate appropriate intervention if indicated, and to plan follow up. Multidisciplinary acute care teams should consider screening patients, especially those of advanced age or presenting with ground-level falls.

47 Poster #29

MEASLES WITH ATYPICAL PRESENTATION IN A VACCINATED WOMAN

Zao Zhang, MD1; Melissa Viray, MD2; Erlaine Bello, MD 1,3 1 University of Hawaii Internal Medicine Residency Program, Honolulu, HI 2 Disease Outbreak Control Division, Hawaii Department of Health 3 Department of Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI

INTRODUCTION: The United States declared the elimination of measles in 2000. However, sporadic cases still occur throughout the country and warrant attention for outbreak prevention.

CASE PRESENTATION: A healthy 54-year-old Asian woman presented with 7 days of fever, non- productive cough and rhinorrhea. Three days after her initial flu-like symptoms, she was given oseltamivir empirically before an influenza test returned negative. Subsequently, she noticed a non-pruritic rash spreading downward from her face and neck. She denied recent travel or sick contact. She reported completing usual childhood vaccines. Vital signs showed temperature 39 ℃, BP 119/63 mm Hg, pulse 119/minute and respirations 17/min. Physical examination revealed conjunctival injection, facial edema, mild occipital lymphadenopathy and bilateral expiratory rhonchi. A blanching, confluent erythematous maculopapular rash were noted at face, neck and trunk. Initial labs showed reactive lymphocytosis, elevated transaminases and a positive measles-specific IgG antibody. Chest radiograph was negative for pneumonia. She remained in airborne isolation after hospitalized for sepsis. The measles-specific IgM antibody subs equently returned positive. The nasopharyngeal swab obtained for influenza testing also returned positive for measles RNA by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). She was confirmed to have measles.

DISCUSSION: The explanation for measles infection in this person with a history of vaccination remains unclear. The patient presented with flu-like syndrome with late-onset exanthem, respiratory symptoms, and elevated transaminases. This atypical presentation is more often seen in measles-immunized persons. There was no history of travelling to measles-endemic region, and no measles cases were reported in Hawaii before the incubation period, therefore the source of disease transmission is unclear. High suspicion of measles in persons with fever and typical rash is important for early diagnosis. Maintaining appropriate isolation based on typical clinical features pending definitive IgM serology prevents potential nosocomial transmission of measles.

48 Poster #30

MEMBRANOUS NEPHROPATHY ASSOCIATED WITH DUODENAL SCHWANNOMA

Zao Zhang, MD1; Rick Hayashi, MD2; Helmut Rennke, MD3 1 University of Hawaii Internal Medicine Residency Program, Honolulu, HI 2 Department of Nephrology, Spark M. Matsunaga VA Medical Center, Honolulu, HI 3 Department of Pathology, Brigham and Women’s Hospital, Boston, MA

INTRODUCTION: Membranous nephropathy (MN) is one of the most common causes of nephrotic disease. Up to 20% cases are secondary to other underlying conditions.

CASE PRESENTATION: A 69-year-old man was evaluated for recurrent proteinuria. He was diagnosed with nephrotic syndrome at age 56. He underwent a homeopathic remedy with resolution of symptoms and negative proteinuria at follow-up visits. However, pedal edema and proteinuria recurred 5 months before this presentation. He denied rashes, joint pain or analgesic use. Labs revealed albumin 2.2 mg/dl, BUN 21 mg/dl, creatinine 1.0 mg/dl and LDL 230 mg/dl. The 24-hour urine protein excretion was 3.5 g. Clinically he was diagnosed nephrotic syndrome. Work-ups were negative for viral hepatitis, HIV, lupus and paraprotein. A computed tomography (CT)-guided renal biopsy was consistent with MN and negative stain for phospholipase A2 receptor (PLA2R), which favored a diagnosis of secondary MN. Incidentally, a 7.6 cm duodenal wall mass was detected and removed surgically. He was confirmed to have duodenal schwannoma. Following the tumor resection, the proteinuria resolved gradually. No immunosuppressant including glu cocorticoid was used.

DISCUSSION: PLA2R, a specific podocyte autoantigen responsible for development of MN is positive in 75% of primary MN. A negative test usually suggests a secondary MN. In our case, the incidental finding of duodenal schwannoma was the only condition that could account for the MN, assuming this was a secondary form. Schwannoma, a rare form of neurofibroma, was described in one previous report connecting MN with spinal schwannoma. Although the direct causal relation between neoplasm and MN is controversial, recent reports support that the risk of malignancy among patients with MN is up to 12 times higher than that in the general population. Cancer screening remains essential after a diagnosis of secondary MN, if no other causes are found.

49 INDEX Fischberg, 10 Kirkham, 28 Flaherty, 17 Kuribayashi, 29 Abbott, 14, 15 Flanders, 2 Ahsan, 28 Fujii, 4, 11 Aldan, 25 Furuike, 2 Labrash, 16 Ally, 43, 44 Lee, 22, 31 Anegawa, 5 Lee, 30 Antonelli, 2, 4 Galamgam, 24 Leung, 17 Arbabi, 47 Ganitano, 36 Lew, 32 Ariyoshi, 4, 10, 12, 20 Griffin, 27 Lian, 2, 4, 40 AuWinitzky, 31 Gross, 47 Locham, 30 Lorenzo, 28 Lozanoff, 16, 31 Baba, 24, 31, 46 Hara, 17 Lubimir, 28 Barber, 17 Hastings, 5, 14 Lucuab-Fegurgur, 33 Bello, 48 Hattangadi-Gluth, 45 Lum, 34, 42 Berenberg, 7, 8, 32, 37 Hayashi, 49 Lykesos, 21 Black, 21 Helman, 2 Bolger, 11, 25 Higa, 31 Brady, 2 Hiraoka, 10 Majewski, 12 Brahmbhatt, 4, 13 Hitchcock, 26 Malas, 30 Bunin, 26 Hong, 5, 16, 39 Martinez, 37 Burgess, 17 Hostler, 23 Masaki, 13, 14, 15, 28 Burkeen, 45 Hu, 25 Matsui, 16, 24, 31, 38, Hubel, 26, 43 46 Melgarejo, 20, 35, 36 Camara, 2 Melish, 3, 4 Carmichael, 41, 43 Ikeda, 11, 13 Mendoza, 35, 36 Carvalho, 21 Miles, 37 Centor, 3, 4 Mintz, 27 Miyamoto, 11 Chen, 14, 15, 28 John, 3 Morgan, 13 Chinen, 22 Johnston, 21 Chung, 12 Morzenti, 44

Kagihara, 25 Nakagawa, 34 Desmond, 23 Kaplan, 45, 47 Nakatsuka, 3, 4 Devendra, 12, 20 Karan, 2 Nogi, 10 Devere, 29 Kawakami, 3, 5 Noguchi, 38 DeZee, 2, 4 Kerns, 23 Dworkin, 12 Kerns, 37 Kim, 27 Ferguson, 44 Okajima, 39

50 Osorio, 41 Sempokuya, 42 Seto, 34 Uchiyama, 24 Sherratt, 26 Petrovitch, 14, 15 Shimada, 31, 38 Shohet, 34 Posas-Mendoza, 35, 36, Vaughn, 35, 36 39 Simpson, 45 Sprowl, 26 Veillet-Chowdhury, 42 Stametz, 27 Viray, 48 Stewart, 43 Ramkissoon, 40 Sy, 11 Rediger, 2 Szu, 44 Wen, 14 Reed, 8, 47 Willcox, 28 Rennke, 49 Wolff, 27 Reuland, 21 Woo, 46 Rivera, 42 Taira, 34 Taitsman, 47 Roberts, 33 Rodionova, 41 Takayesu, 45 Ross, 14, 15 Takenaka, 14 Young, 47 Tam, 2, 47 Tamura, 14 Templeman, 5, 15 Sakai, 10 Zhang, J, 5 Thompson, 16 Samus, 21 Zhang, Z, 4, 12, 17, 48, Tom, 13 Santos, 35, 36 49 Tran, 39 Santos-Ocampo, 36 Schatz, 4

51