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The Bulletin: Sidney Kimmel Medical College At Thomas Jefferson University, Volume 67, Issue 3, Fall 2018

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

This issue includes:

• Explaining Uncertainty
• A Series of Fortunate Events
• 2018 Alumni Weekend
• The Dean's Column
• Findings
• The Jefferson Legacy
• Time Capsule
• On Campus
• Jefferson Researcher Explores Cell Death Controls and Effects
• New Alumni Association President
• Class Notes
• In Memoriam
• By the Numbers

Severe Lumbar Disability Is Associated With Decreased Psoas Cross-Sectional Area In Degenerative Spondylolisthesis, Scott C. Wagner, Arjun S. Sebastian, James C. Mckenzie, Joseph S. Butler, Ian D. Kaye, Patrick B. Morrissey, Alexander R. Vaccaro, Christopher K. Kepler

Rothman Institute Papers

Study Design: Retrospective cohort. Objectives: Alterations in lumbar paraspinal muscle cross-sectional area (CSA) may correlate with lumbar pathology. The purpose of this study was to compare paraspinal CSA in patients with degenerative spondylolisthesis and severe lumbar disability to those with mild or moderate lumbar disability, as determined by the Oswestry Disability Index (ODI). Methods: We retrospectively reviewed the medical records of 101 patients undergoing lumbar fusion for degenerative spondylolisthesis. Patients were divided into ODI score ≤40 (mild/moderate disability, MMD) and ODI score >40 (severe disability, SD) groups. The total CSA of the psoas and paraspinal muscles were measured on preoperative …

Designing The Ideal Perioperative Pain Management Plan Starts With Multimodal Analgesia., Eric S. Schwenk, Edward R. Mariano

Department of Anesthesiology Faculty Papers

Multimodal analgesia is defined as the use of more than one pharmacological class of analgesic medication targeting different receptors along the pain pathway with the goal of improving analgesia while reducing individual class-related side effects. Evidence today supports the routine use of multimodal analgesia in the perioperative period to eliminate the over-reliance on opioids for pain control and to reduce opioid-related adverse events. A multimodal analgesic protocol should be surgery-specific, functioning more like a checklist than a recipe, with options to tailor to the individual patient. Elements of this protocol may include opioids, non-opioid systemic analgesics like acetaminophen, non-steroidal anti-inflammatory …

Strategic Leadership Perspective, Larry Hirschhorn, Phd, John Ervin, Paula Smith-Benson, Pamela Tull

School of Continuing and Professional Studies Student Papers

The project purpose was to identify the program constraints through cause and effect linkages, determine whether the root causes identified had program benefits and identify the driving causes of undesirable effects through Method of Synchronization:

1. Articulation
2. Interdependency
3. Process
4. Flow of Information
5. Sense of Urgency/Prioritization

Furthermore, we wanted to enlarge our perspective from a process mindset to a whole systems perspective looking at the systems that comprise JCIPE and how the systems are interconnected and interdependent and affect the purpose of the organization. Our overview led us to analyze possible physical, policy or cultural constraints that impose upon the JCIPEs success …

Three Years Of Growth Hormone Therapy In Children Born Small For Gestational Age: Results From The Answer Program, Robert Rapaport, Peter Lee, Judith L. Ross, Paul Saenger, Vlady Ostrow, Giuseppe Piccoli

Department of Pediatrics Faculty Papers

Growth hormone (GH) is used to treat short stature and growth failure associated with growth disorders. Birth size and GH status variably modulate response to GH therapy. The aim of this study was to determine the effect of birth size on response to GH therapy, and to determine the impact of GH status in patients born small for gestational age (SGA) on response to GH therapy. Data from the prospective, non-interventional American Norditropin® Studies: Web-Enabled Research (ANSWER) Program were analyzed for several growth outcomes in response to GH therapy over 3 years. GH-naïve children from the ANSWER Program were included …

Complications Associated With Volar Locking Plate Fixation Of Distal Radial Fractures., Todd H. Alter, Asif M. Ilyas

Rothman Institute Papers

• Volar locked plating is the most frequently utilized method for internal fixation of distal radial fractures.
• The overall complication rate for volar plating of distal radial fractures appears to be relatively low compared with other operative fixation methods.
• Carpal tunnel syndrome is the most commonly reported complication.
• However, this may occur after a distal radial fracture regardless of treatment method, with reported rates ranging from 0% to 20% with conservative management and 0% to 14% with volar plating.
• Extensor tendon rupture has been reported at rates of 0% to 4% and is the most frequent complication requiring plate removal.
• Variable-angle …

Stress Fractures Of The Elbow In The Throwing Athlete: A Systematic Review., Shelby R. Smith, Nirav K. Patel, Alex E. White, Christopher J Hadley, Christopher C. Dodson

Rothman Institute Papers

Background: Stress fractures of the elbow are rare in throwing athletes and present a challenge from both a management and rehabilitation perspective. Although the incidence of stress fractures of the elbow is increasing, there is a lack of data in the literature focused on throwers.

Purpose: To evaluate studies regarding the management and outcomes of stress fractures of the elbow in throwing athletes.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review was conducted by searching the Scopus, PubMed, and Cochrane Library electronic databases to identify studies reporting on the management and outcomes of stress fractures in …

Bath-Related Headache, Aliza Kumpinsky, Stephanie J. Nahas

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to summarize the most up-to-date literature on bath-related headache, a rare disorder.

RECENT FINDINGS: Initially described in middle-aged Asian women, it is now reported in a wider demographic. More information is available about the pathophysiology of bath-related headache, including its classification as a subtype of reversible cerebral vasoconstriction syndrome (RCVS). Nimodipine can be effective in patients both with and without vasospasm. Bath-related headache is a rare form of thunderclap headache. Although its mechanism is still unclear, it is associated with vasospasm and RCVS. Controlled trials investigating the use of nimodipine and …

Era Of Direct Acting Anti-Viral Agents For The Treatment Of Hepatitis C., Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents (DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.

Polymicrobial Sepsis Influences Nk-Cell-Mediated Immunity By Diminishing Nk-Cell-Intrinsic Receptor-Mediated Effector Responses To Viral Ligands Or Infections., Isaac J. Jensen, Christina S. Winborn, Micaela G. Fosdick, Peng Shao, Mikaela M. Tremblay, Qiang Shan, Sandeep Kumar Tripathy, Christopher M. Snyder, Hai-Hui Xue, Thomas S. Griffith, Jon C. Houtman, Vladimir P. Badovinac

Department of Microbiology and Immunology Faculty Papers

The sepsis-induced cytokine storm leads to severe lymphopenia and reduced effector capacity of remaining/surviving cells. This results in a prolonged state of immunoparalysis, that contributes to enhanced morbidity/mortality of sepsis survivors upon secondary infection. The impact of sepsis on several lymphoid subsets has been characterized, yet its impact on NK-cells remains underappreciated-despite their critical role in controlling infection(s). Here, we observed numerical loss of NK-cells in multiple tissues after cecal-ligation-and-puncture (CLP)-induced sepsis. To elucidate the sepsis-induced lesions in surviving NK-cells, transcriptional profiles were evaluated and indicated changes consistent with impaired effector functionality. A corresponding deficit in NK-cell capacity to produce …

Clinical Framework For Quality Improvement Of Cancer Cachexia., Clara Granda-Cameron, Mary Pat Lynch

College of Nursing Faculty Papers & Presentations

The objective of this article is to introduce the Clinical Framework for Quality Improvement of Cancer Cachexia (Cachexia Care Framework) as a tool to demonstrate the relevance of integrating the clinical components of cancer cachexia and the organizational strategies of a cancer institution on the quality of patient care and delivery of services throughout the cancer cachexia continuum. The data sources included peer-reviewed literature relevant to cancer cachexia and quality cancer care, and the authors' expertise. The Cachexia Care Framework results from a combination of the international consensus definition of cancer cachexia, the Institute of Medicine report Ensuring Quality Cancer …

Treatment-Related Decisional Conflict, Quality Of Life, And Comorbidity In Older Adults With Cancer., Jeannette M. Kates

College of Nursing Faculty Papers & Presentations

Objective: The present study aims to examine the relationships between and among cancer treatment-related decisional conflict, quality of life, and comorbidity in older adults with cancer.

Methods: A convenience sample of 200 older adults was recruited from outpatient medical oncology and radiation oncology practices in the northeastern United States. A cross-sectional, descriptive, correlational study design was used employing a survey method. Survey instruments included the Decisional Conflict scale (DCS) (with five subscales, including informed, values clarity, support, uncertainty, and effective decision); Self-administered comorbidity questionnaire (SCQ); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (including five function …

A Word From The Writing Team (October 2018), Jennifer Wilson, Ms, Els, Pam Walter, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• Writing Lessons from Ted-Ed
• WHYY's Maiken Scott on Communicating Science
• Paywall: The Business of Scholarship

Epidemiology Of Moderate Alcohol Consumption And Breast Cancer: Association Or Causation?, Samir Zakhari, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate …

A Systematic Review Of Treating Recurrent Head And Neck Cancer: A Reintroduction Of Brachytherapy With Or Without Surgery., Julianna Rodin, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer Johnson, Chad Zender, Laura Doyle, David Kutler, Benjamin E. Leiby, William M. Keane, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates.

Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting.

Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, …

Nci-Match Arms N & P: Phase Ii Study Of Pi3k Beta Inhibitor Gsk2636771 In Patients (Pts) With Cancers (Ca) With Pten Mutation/Deletion (Mut/Del) Or Pten Protein Loss, F. Janku, O. Jegede, S. L. Puhalla, P. Konstantinopoulos, F. Meric-Bernstam, E. P. Mitchell, J. A. Zwiebel, L. M. Mcshane, S. Li, L. V. Rubinstein, L. A. Doyle, D. Patton, B. A. Conley, P. J. O'Dwyer, L. N. Harris, C. Arteaga, P. M. Williams, S. R. Hamilton, A. P. Chen, K. T. Flaherty

Department of Medical Oncology Faculty Papers

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.

Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete …

Synthetic Dna Immunotherapy In Biochemically Relapsed Prostate Cancer, N. Shore, E. I. Heath, L. T. Nordquist, H. Cheng, K. Bhatt, M. Morrow, T. Mcmullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, S. T. Tagawa, L. J. Appleman, R. Tutrone, J. Garcia, Y. Whang, W. Kelly, I. Csiki, M. L. Bagarazzi

Department of Medical Oncology Faculty Papers

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).

Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) >3 months (mos), testosterone >150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM …

Larotrectinib Efficacy And Safety In Trk Fusion Cancer: An Expanded Clinical Dataset Showing Consistency In An Age And Tumor Agnostic Approach, U. N. Lassen, C. M. Albert, S. Kummar, C. M. Van Tilburg, S. G. Dubois, B. Geoerger, L. Mascarenhas, N. Federman, R. J. Schilder, F. Doz, J. D. Berlin, D. Y. Oh, S. S. Bielack, R. Mcdermott, D. S. Tan, S. Cruickshank, N. C. Ku, M. C. Cox, A. Drilon, D. S. Hong

Department of Medical Oncology Faculty Papers

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19^thFeb 2018.

Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials …

Pan-Squamous Genomic Profiling Stratified By Anatomic Tumor Site And Viral Association, M. Montesion, C. H. Chung, E. S. Sokol, S. A. Khan, H. Kang, L. A. Albacker, J. M. Johnson, G. M. Frampton, V. A. Miller, J. S. Ross, S. M. Ali

Department of Medical Oncology Faculty Papers

Background: Squamous cell carcinomas (SCC) have diverse anatomic etiologies but may share common genomic biomarkers. We profiled 7,871 unique SCCs across nine anatomic sites to investigate commonality in genomic alterations (GA), tumor mutational burden (TMB), human papillomavirus (HPV) association, and mutational signatures.

Methods: Tissue from over 8,100 unique SCC samples originating from nine anatomic sites (anogenital (anus, cervix, penis, vagina, vulva), esophagus, head and neck, lung, and skin) were sequenced by hybrid capture-based comprehensive genomic profiling to evaluate GA and TMB. About 3% of non-cutaneous SCC samples had UV signatures, indicative of potential primary site misdiagnoses, and were filtered from …

Androgen Decline And Outcome In Castration Resistant Prostate Cancer(Mcrpc) Patients Treated With Docetaxel (Doc), Prednisone1/-Bevacizumab (B), C. J. Ryan, S. Dutta, W. Kelly, M. J. Morris, M-E. Taplin, S. Halabi

Department of Medical Oncology Faculty Papers

No abstract provided.

Intestinal Barrier Tightening By A Cell-Penetrating Antibody To Bin1, A Candidate Target For Immunotherapy Of Ulcerative Colitis., Sunil Thomas, Kevther Hoxha, Walker Alexander, John Gilligan, Rima Dilbarova, Kelly Whittaker, Andrew Kossenkov, George C. Prendergast, James M. Mullin

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) …

Neuroprotective Role Of Phytochemicals., Bharath Kumar Velmurugan, Baskaran Rathinasamy, Bharathi Priya Lohanathan, Varadharajan Thiyagarajan, Ching-Feng Weng

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer's disease (AD) and Parkinson's disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more …

Pediatric Obesity: Influence On Drug Dosing And Therapeutics, Barbara Ameer Pharmd, Mba, Bcps, Fcp, Michael Weintraub Md

Department of Medicine Faculty Papers

Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of US children and adolescents. Severe obesity (³120% of the 95^th percentile of BMI-for-age, or a BMI of ³35 kg/m²) is the fastest growing subgroup and now approaches 6% of all US youth. Health consequences (e.g., type 2 diabetes, coronary heart disease) are related in a dose-dependent manner to severity of obesity. Since therapeutic interventions are less effective in severe obesity, prevention is a high priority.

Treatment plans involving combinations of …

Clinical Perspective On Passive Audio Vocal Measurement In The Evaluation Of Selective Mutism., Helen Y Xu, Jacob Stroud, Renee K. Jozanovic, Jon Clucas, Jake Jungwoo Son, Bonhwang Koo, Juliet Schwarz, Arno Klein, Rachel Busman, Michael P. Milham

Student Papers, Posters & Projects

Selective Mutism (SM) is an anxiety disorder often diagnosed in early childhood and characterized by persistent failure to speak in certain social situations but not others. Diagnosing SM and monitoring treatment response can be quite complex, due in part to changing definitions of and scarcity of research about the disorder. Subjective self-reports and parent/teacher interviews can complicate SM diagnosis and therapy, given that similar speech problems of etiologically heterogeneous origin can be attributed to SM. The present perspective discusses the potential for passive audio capture to help overcome psychiatry's current lack of objective and quantifiable assessments in the context of …

Formulation, Characterization And Evaluation Of Morusin Loaded Niosomes For Potentiation Of Anticancer Therapy, Srishti Agarwal, M. Sheikh Mohamed, Sreejith Raveendran, Ankit K. Rochani, Toru Maekawa, D. Sakthi Kumar

College of Pharmacy Faculty Papers

Morusin, a water-insoluble prenylated flavonoid is known for its numerous medicinal properties. It manifests its anticancer potential by suppression of genes involved in tumor progression. However, poor solubility of the drug results in low bioavailability and rapid degradation thus hindering its clinical utilization. In order to overcome this, we have synthesized a niosome system composed of non-ionic surfactant span 60 and cholesterol using a thin-layer evaporation technique to improve the aqueous-phase solubility of the drug. Highly cytocompatible niosomes of 479 nm average size with smooth and uniform spherical morphology were synthesized in a facile manner. Unlike free morusin, nanomorusin was …

A Word From The Writing Team (September 2018), Jennifer Wilson, Ms, Els, Pam Walter, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• Boost Your Communication Skills with Nature
• Win a Prize for Writing About Health Care

Extracellular Interactions Between Fibulins And Transforming Growth Factor (Tgf)-Β In Physiological And Pathological Conditions., Takeshi Tsuda

Department of Pediatrics Faculty Papers

Transforming growth factor (TGF)-β is a multifunctional peptide growth factor that has a vital role in the regulation of cell growth, differentiation, inflammation, and repair in a variety of tissues, and its dysregulation mediates a number of pathological conditions including fibrotic disorders, chronic inflammation, cardiovascular diseases, and cancer progression. Regulation of TGF-β signaling is multifold, but one critical site of regulation is via interaction with certain extracellular matrix (ECM) microenvironments, as TGF-β is primarily secreted as a biologically inactive form sequestrated into ECM. Several ECM proteins are known to modulate TGF-β signaling via cell⁻matrix interactions, including thrombospondins, SPARC (Secreted Protein …

Strategic Leadership Newsletter: Volume 4, Number 3, Larry Starr, Phd

Leadership Doctorates Newsletter (Formerly Strategic Leadership Newsletter)

Jefferson Strategic Leadership Newsletter reports information relevant to the Jefferson (Philadelphia University + Thomas Jefferson University) Doctor of Management Program in Strategic Leadership (DSL) and its community including personal and professional events and accomplishments, new practices, research, opportunities, and suggestions.

Neurological Complications Of Immune Checkpoint Inhibitors: What Happens When You 'Take The Brakes Off' The Immune System., Marinos Dalakas

Department of Neurology Faculty Papers

Patients with advanced malignancies treated with immune checkpoint inhibitors are at increased risk for developing immune-related neurological complications. It is a phenomenon of immunological twist when immunotherapy against co-stimulatory molecules activates previously normal T cells to kill tumor cells but, in so doing, the T cells become unrestrained, triggering other autoimmune diseases for which conventional immunotherapy is needed. The most common autoimmune neurological diseases, usually occurring within 2-12 weeks after immune checkpoint inhibitor initiation, include: inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis. The neurological events …

Pepducin-Mediated Cardioprotection Via Β-Arrestin-Biased Β2-Adrenergic Receptor-Specific Signaling, Laurel A. Grisanti, Toby P. Thomas, Rhonda L. Carter, Claudio De Lucia, Erhe Gao, Walter J. Koch, Jeffrey L. Benovic, Douglas G. Tilley

Department of Biochemistry and Molecular Biology Faculty Papers

Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. β-arrestin (βarr)-biased β-adrenergic receptor (βAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte death at the time of reperfusion to better preserve function. However, a lack of efficacious βarr-biased orthosteric small molecules has prevented investigation into whether this pathway relays protection against ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a small lipidated peptide fragment designed from the first intracellular loop of β2AR, allosterically engaged pro-survival signaling cascades in a βarr-dependent manner in …