From the Editors

We are excited to present you with the 16th annual edition of The Medicine Forum. This work is a culmination of months of effort on the part of medical students, residents, fellows and faculty to share clinical pearls from the last year of their experiences. Amongst the greatest strengths of medical professionals and patients alike is the ability to tell stories. Stories, and how they are told form the basis of medical care. The way in which a particular patient\u27s story unfolds has a lasting impact on physicians, trainees, other medical staff, and perhaps most importantly, on future patients. Stories of patient cases formed the earliest beginnings of evidence-based medicine. There is a Babylonian tablet dating earlier than 6000 B.C.E. which describes a case of dropsy , for the instruction of patients of this condition.1 Stories told amongst practitioners of medicine date back to the first published medical journal, the Acta Medicorum Berolinensium, from Berlin in 1722.

Grand Rounds Panel Discussion: Blood Thinners Peri-Operatively: What to do?

PANELISTS Mathew DeCaro, MD: Associate Professor of Cardiology, Director of the Coronary Cardiac Unit, Cardiology fellowship program director John Doherty, MD: Professor of Cardiology Gregary Markefka, MD: Associate Professor of Cardiology, Associate Director of the Coronary Cardiac Unit, Cardiology fellowship assistant program director Geno Merli, MD: Professor of Vascular Medicine, Co-director of Jefferson Vascular Center Srikanth Nagalla, MD, MS: Associate Professor of Medicine, Director, Clinical Hematology Eric Schwenk, MD: Assistant Professor of Anesthesiology, Director of orthopedic anesthesia Barry Ziring, MD: Clinical Associate Professor of Internal Medicine / Primary Care, Director of the division of Internal Medicin

From the Editors

Dear Students, Residents, Faculty, and Friends of the Forum, We are excited to present you with the 17th annual edition of The Medicine Forum. This work reflects the talent, passion, creativity, and scientific inquisitiveness of Jefferson medical students, residents, fellows and faculty. It also celebrates the diverse patients who serve as the centerpiece for each story. Unique to this issue is the initiation of Grand Rounds Discussions focusing on controversial medical topics with inputs from an array of experts. This year we discussed perioperative management of anticoagulation and antiplatelet agents, and we had exciting viewpoints from experienced cardiologists, a hematologist, a vascular medicine specialist, a primary care internal medicine physician, and an anesthesiologist who is specialized in regional anesthesia. They opened our eyes to the art of practicing medicine and how to interpret guidelines and consensus statements within the context of our patients. As Dr. William Osler eloquently expressed “medicine is a science of uncertainty and an art of probability.” We are excited to bring similar stimulating discussions to the Forum in the coming years

Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma

Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of complement-activating monoclonal antibodies. We conducted a phase I study (clinicaltrials.gov NCT00492167) to determine the safety of the combination of yeast-derived beta glucan (BG) and anti-GD2 murine monoclonal antibody 3F8 in patients with relapsed or refractory high-risk neuroblastoma. Patients received intravenous 3F8 (fixed dose of 10 mg/m2/day × 10 days) and oral BG (dose-escalated from 10–200 mg/kg/day × 17 days in cohorts of 3–6 patients each). Forty-four patients completed 141 cycles. One patient developed DLT: transient self-limiting hepatic transaminase elevation 5 days after starting BG (120 mg/kg/day). Overall, 1, 3, 12 and 24 evaluable patients had complete response, partial response, stable and progressive disease, respectively, at the end of treatment. Positive human anti-mouse antibody response and dectin-1 rs3901533 polymorphism were associated with better overall survival. BG dose level and serum BG levels did not correlate with response. Progression-free and overall survival at 2 years were 28% and 61%, respectively. BG lacked major toxicity. Treatment with 3F8 plus BG was associated with anti-neuroblastoma responses in patients with resistant disease. Although the maximal tolerated dose for yeast BG was not reached, considering the large volume of oral BG, we recommended 40 mg/kg/day as the phase II dose

A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission

We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011–Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient’s pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36–68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%), ≥4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2–39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability