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The Medicine Forum: Volume 23

The Medicine Forum

The Journal of Thomas Jefferson University Hospital - Department of Internal Medicine, Volume 23, 2021-2022

TABLE OF CONTENTS

Case Reports

• Cardiology
• Gastroenterology and Hepatology
• Hematology and Oncology
• Pulmonary Medicine

Resident Reflection

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis And Therapeutic Strategies, Binsah S George, Binoy Yohannan, Anneliese Gonzalez, Adan Rios

Faculty, Staff and Student Publications

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. …

Immunotherapy For Type 1 Diabetes Mellitus By Adjuvant-Free Schistosoma Japonicum-Egg Tip-Loaded Asymmetric Microneedle Patch (Stamp), Haoming Huang, Dian Hu, Zhuo Chen, Jiarong Xu, Rengui Xu, Yusheng Gong, Zhengming Fang, Ting Wang, Wei Chen

Faculty, Staff and Student Publications

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy …

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …

Understanding Diagnostic Pathways In Systemic Sclerosis And Systemic Sclerosis-Associated Interstitial Lung Disease: A Retrospective Cohort Study, Shervin Assassi, Nan Shao, Ziwei Yin, Elizabeth R Volkmann, Donald F Zoz, Thomas B Leonard

Faculty, Staff and Student Publications

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is usually detected in a patient known to have SSc but may be diagnosed prior to SSc. We probed an insurance database to investigate documentation of ILD prior to SSc. Using Optum's Clinformatics® Data Mart Database, we identified patients with an SSc index date between January 1, 2010, and September 30, 2015, based on International Classification of Diseases (ICD)-9-Clinical Modification (CM) codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥3 years of continuous enrollment prior to SSc index date (ICD-9-CM cohort). We identified an ICD-10-CM cohort comprising patients …

Effect Of Wearing Masks In The Hospital On Patient-Provider Interaction: “They (Providers) Need To Stay Safe For Their Family And Keep Us Safe.”, Jana L. Wardian, Mikayla Peralta, Chad Vokoun, Sarah E. Richards

Patient Experience Journal

Since March 2020 when the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic was widespread in the U.S., masks became a primary form of protection for healthcare workers when caring for patients. While wearing masks was not a new phenomenon in the health field, there is little known on how the use of them affects the patient-provider relationship. This study explored the experience of wearing masks on the patient-provider relationship in the hospital. This qualitative study involved interviews with both providers and patients at an academic hospital in the Midwest. At the time of this study, in July 2021, hospital …

Adenosine Metabolized From Extracellular Atp Promotes Type 2 Immunity Through Triggering A2bar Signaling In Intestinal Epithelial Cells, Darine W El-Naccache, Fei Chen, Mark J Palma, Alexander Lemenze, Matthew A Fischer, Wenhui Wu, Pankaj K Mishra, Holger K Eltzschig, Simon C Robson, Francesco Di Virgilio, George S Yap, Karen L Edelblum, György Haskó, William C Gause

Faculty, Staff and Student Publications

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after …

Adenosine Metabolized From Extracellular Atp Promotes Type 2 Immunity Through Triggering A2bar Signaling In Intestinal Epithelial Cells, Darine W El-Naccache, Fei Chen, Mark J Palma, Alexander Lemenze, Matthew A Fischer, Wenhui Wu, Pankaj K Mishra, Holger K Eltzschig, Simon C Robson, Francesco Di Virgilio, George S Yap, Karen L Edelblum, György Haskó, William C Gause

Faculty, Staff and Student Publications

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A

Sclerosing Mesenteritis: A Rare Cause Of Abdominal Pain, Said Sharawi, Vincent A. Graffeo, Lynne J. Goebel

Internal Medicine

Sclerosing mesenteritis (SM) is a rare inflammatory fibrotic disease of the small intestine mesenteric fat often discovered incidentally on a CT scan. Clinical manifestations depend on the mass effect on the viscera and vessels. The most common symptoms are abdominal pain, bloating, and nausea. SM occurs predominantly in Caucasian men, during the fifth to seventh decades of life. We present a 69-year-old woman with SM whose symptoms were thought to be from irritable bowel syndrome. A 69-year-old female with a history of fibromyalgia presented with recurrent bouts of abdominal pain across her mid-abdomen lasting 30 minutes to an hour associated …

Structural Plasticity Can Produce Metaplasticity, Wenli Zhao, Shuo Han, Na Qiu, Wenbo Feng, Mengjie Lu, Wenru Zhang, Mu Wang, Qingtong Zhou, Shutian Chen, Wei Xu, Juan Du, Xiaojing Chu, Cuiying Yi, Antao Dai, Liaoyuan Hu, Michelle Y Shen, Yaping Sun, Qing Zhang, Yingli Ma, Wenge Zhong, Dehua Yang, Ming-Wei Wang, Beili Wu, Qiang Zhao

Faculty, Staff and Student Publications

Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of Gi1-bound SSTR2 in the presence of the …

Statins: Masked Anti-Epileptic Warriors, Govinda Khatri, Priya Kotak, Ayush Kumar, Mohammad Mehedi Hasan

Medical College Documents

No abstract provided.

Early Colonoscopy In Hospitalized Patients With Acute Lower Gastrointestinal Bleeding: A Nationwide Analysis., Kuldeepsinh P Atodaria, Samyak Dhruv, Joseph M Bruno, Brisha Bhikadiya, Shravya R Ginnaram, Shreeja Shah

Internal Medicine Resident Research

Background: Performing colonoscopy within 24 h of presentation to the hospital is the accepted standard of care for patients with an acute lower gastrointestinal bleed (LGIB). Previous studies have failed to demonstrate the benefit of early colonoscopy (EC) on mortality. In this study, we wanted to see if there was a change in inpatient deaths (primary outcome), length of stay (LOS), and hospitalization charges (TOTCHG) (secondary outcomes) with EC compared to previous studies.

Methods: Adults diagnosed with LGIB were identified using the International Classification of Disease 10th Revision codes from the National Inpatient Sample database for 2016 to 2019. EC …

Unusual Presentation Of Multisystemic Inflammatory Syndrome, Farah Ebrahim, George Moturi, Newnex Mongare, Reena Shah

Internal Medicine, East Africa

COVID-19 pneumonia in children presents with very mild symptoms through an entity of multisystem inflammatory syndrome and can result in a life-threatening hyperinflammatory condition, with involvement of at least four organ systems and a marked inflammatory state. We present an 18-year-old high school student who presented with a sore throat, macular rash, abdominal pain, diarrhea, fevers, and joint pains. He presented with acute kidney injury and confusion with multiple tests and was eventually diagnosed with multisystem inflammatory syndrome in children (MIS-C).

The Burden And Characteristics Of Hiv-Infected Covid-19 Patients At A Tertiary Care Hospital In Sub-Saharan Africa—A Retrospective Cohort Study, Alok Iyer, Jasmit Shah, Reena Shah

Internal Medicine, East Africa

Background: After the first case of COVID-19 caused by the novel SARS-CoV-2 virus was discovered in Wuhan, China, in December 2019, the disease spread viciously throughout the world. Little is known about the impact of HIV infection on the clinical outcomes of patients co-infected with SARS-CoV-2. Studying the characteristics and outcomes of COVID-19 among HIV-positive patients is key to characterising the risk of morbidity and mortality of HIV-positive patients from COVID-19.

Methods: In this retrospective cohort study, we included patients admitted to Aga Khan University Hospital, Nairobi, with laboratory-confirmed COVID-19 infection and who had consented to HIV screening. We compared …

Association Of Changes In Antithrombin Activity Over Time With Responsiveness To Enoxaparin Prophylaxis And Risk Of Trauma-Related Venous Thromboembolism, Laura E Vincent, Michael M Talanker, Dakota D Butler, Xu Zhang, Jeanette M Podbielski, Yao-Wei W Wang, Amber Chen-Goodspeed, Selina L Hernandez Gonzalez, Erin E Fox, Bryan A Cotton, Charles E Wade, Jessica C Cardenas

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity < 80%).

Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis.

Design, setting, and participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January …

Influenza-Induced Thrombotic Microangiopathy In A Patient With Cancer On Proteasome Inhibitor: A Diagnostic Dilemma, Christopher D Hamad, Zachary C Hoelscher, Amanda Tchakarov, Jaya Kala

Faculty, Staff and Student Publications

Thrombotic microangiopathy (TMA) in a cancer patient is a common complication of either cancer itself or anticancer therapy. Incidence of TMA from anticancer therapy was found to be > 15%, since the introduction of anti-angiogenic drugs like anti-vascular endothelial growth factor agents. It is, however, important to not ignore other causes of TMA such as bacteria, viruses, antiplatelet drugs, hereditary complement mutations, and autoimmune disorders. We present such a diagnostic dilemma in our patient who was admitted with influenza and was found to have TMA on renal biopsy, while on proteasome inhibitor (PI) therapy. With this case, we would like to …

Rationale And Design Of Savi-Aos: A Physiologic Study Of Patients With Symptomatic Moderate Aortic Valve Stenosis And Preserved Left Ventricular Ejection Fraction, Rob Eerdekens, Pim Tonino, Jo Zelis, Rik Adrichem, Jung-Min Ahn, Jesse Demandt, Ashkan Eftekhari, Mohamed El Farissi, Phillip Freeman, Abdul Rahman Ihdayhid, Nikolaos Kakouros, Dae-Hee Kim, Seung-Ah Lee, Nicolas M Van Mieghem, Waqas Qureshi, Nils P Johnson

Faculty, Staff and Student Publications

Background: Moderate aortic valve stenosis occurs twice as often as severe aortic stenosis (AS) and carries a similarly poor prognosis. Current European and American guidelines offer limited insight into moderate AS (MAS) patients with unexplained symptoms. Measuring valve physiology at rest while most patients experience symptoms during exertion might represent a conceptual limitation in the current grading of AS severity. The stress aortic valve index (SAVI) may delineate hemodynamically significant AS among patients with MAS.

Objectives: To investigate the diagnostic value of SAVI in symptomatic MAS patients with normal left ventricular ejection fraction (LVEF ≥ 50%): aortic valve area (AVA) …

Placental Pathology In Spontaneous And Iatrogenic Preterm Birth: Different Entities With Unique Pathologic Features, Lucy T Brink, Drucilla J Roberts, Colleen A Wright, Daan G Nel, Pawel T Schubert, Theonia K Boyd, David R Hall, Hein Odendaal

Faculty, Staff and Student Publications

INTRODUCTION: Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The aim of this study was to investigate these relationships.

METHODS: Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13.

RESULTS: In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Hepatic Recruitment Of Eosinophils And Their Protective Function During Acute Liver Injury, Long Xu, Yang Yang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Zhaoli Sun, Kyle L Poulsen, David R Hall, J Steve Bynon, Bin Gao, William M Lee, Jody Rule, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.

METHODS: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33

RESULTS: Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver …