Medical Specialties Commons^™

Case Report: Tocilizumab For The Treatment Of Sars-Cov-2 Infection In A Patient With Aplastic Anemia, Gina Keiffer, Zach French, Lindsay Wilde, Joanne Filicko-O'Hara, Usama Gergis, Adam Binder

Department of Medicine Faculty Papers

While cytokine storm develops in a minority of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, novel treatment approaches are desperately needed for those in whom it does. Tocilizumab, an interleukin-6 receptor antibody, has been utilized for the treatment of cytokine storm in a number of severe inflammatory conditions, including in patients with severe coronavirus disease 2019 (COVID-19). Here, we present the first published case utilizing this therapy in a patient with underlying immunodeficiency. Our patient with aplastic anemia developed cytokine storm due to COVID-19 manifested by fever, severe hypoxia, pulmonary infiltrates, and elevated inflammatory markers. Following treatment …

Which Sample Type Is Better For Xpert Mtb/Rif To Diagnose Adult And Pediatric Pulmonary Tuberculosis?, Mengyuan Lyu, Jian Zhou, Yuhui Cheng, Weelic Chong, Kang Wu, Teng Fang, Tianbo Fu, Binwu Ying

Department of Medicine Faculty Papers

OBJECTIVE: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample.

METHODS: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed.

RESULTS: A total of 50 articles were included. The respective sensitivity and specificity were 87% …

Anticoagulation And Bleeding Risk In Patients With Covid-19, Nancy Musoke, Kevin Bryan Lo, Jeri Albano, Eric Peterson, Ruchika Bhargav, Fahad Gul, Robert Dejoy, Grace Salacup, Jerald Pelayo, Padmavathi Tipparaju, Zurab Azmaiparashvili, Gabriel Patarroyo-Aponte, Janani Rangaswami

Department of Medicine Faculty Papers

BACKGROUND: There is no current standardized approach to anticoagulation in patients with Coronavirus Disease 2019 (COVID-19) while potential bleeding risks remain. Our study characterizes the patterns of anticoagulation use in COVID-19 patients and the risk of related bleeding.

METHODS: This is a single center retrospective analysis of 355 adult patients with confirmed diagnosis of COVID-19 from March 1 to May 31, 2020. Chi-square was used to analyze the relationship between degree of anticoagulant dose and bleeding events by site. Multivariable logistic regression was used to look at factors associated with inpatient death.

RESULTS: 61% of patients were being treated with …

Efficacy And Safety Of Bempedoic Acid For Prevention Of Cardiovascular Events And Diabetes: A Systematic Review And Meta-Analysis., Xing Wang, Yu Zhang, Huiwen Tan, Peng Wang, Xi Zha, Weelic Chong, Liangxue Zhou, Fang Fang

Department of Medicine Faculty Papers

BACKGROUND: Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes.

METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular …

The Roles Of Grks In Hemostasis And Thrombosis, Xi Chen, Xuefei Zhao, Matthew Cooper, Peisong Ma

Department of Medicine Faculty Papers

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, …

Fruit And Vegetable Consumption Is Associated With Lower Prevalence Of Asymptomatic Diverticulosis: A Cross-Sectional Colonoscopy-Based Study., Benjamin Maxner, Jessica Mcgoldrick, Danielle Bellavance, Po-Hong Liu, Ramnik J Xavier, Joseph C Yarze, Rocco Ricciardi, Kyle Staller, Daniel C Chung, Hamed Khalili

Department of Medicine Faculty Papers

BACKGROUND: Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis.

METHODS: Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios …

A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey

Department of Medicine Faculty Papers

PURPOSE: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease.

METHODS: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as …

The Rice Pentatricopeptide Repeat Protein Ppr756 Is Involved In Pollen Development By Affecting Multiple Rna Editing In Mitochondria., Qiannan Zhang, Yanghong Xu, Jishuai Huang, Kai Zhang, Haijun Xiao, Xiaojian Qin, Linlin Zhu, Yingguo Zhu, Jun Hu

Department of Medicine Faculty Papers

In land plants, the pentatricopeptide repeat (PPR) proteins form a large family involved in post-transcriptional processing of RNA in mitochondria and chloroplasts, which is critical for plant development and evolutionary adaption. Although studies showed a number of PPR proteins generally influence the editing of organellar genes, few of them were characterized in detail in rice. Here, we report a PLS-E subclass PPR protein in rice, PPR756, loss of function of which led to the abolishment of RNA editing events among three mitochondrial genes including

Dosing Common Medications In Hospitalized Pediatric Patients With Obesity: A Review, Barbara Ameer, Michael Weintraub

Department of Medicine Faculty Papers

Medication management in children and adolescents with obesity is challenging since both developmental and pathophysiologic changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics, and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 U.S. medical centers. A PubMed search revealed 33 studies providing pharmacokinetic and/or effectiveness data for 23% (16/70) of medications, 44% of which have just one study and can be considered exploratory. This …

Linkage Between Poverty And Smoking In Philadelphia And Its Impact On Future Directions For Tobacco Control In The City., Christine S. Shusted, Gregory C. Kane

Department of Medicine Faculty Papers

Poverty is linked to negative health consequences and harmful health behaviors such as smoking. Despite this established correlation, few comparative studies have investigated the relationship between local poverty rates and smoking in urban settings through a Social Ecological Model framework. The authors sought to examine the linkage between local poverty rates in Philadelphia, Pennsylvania and adult smoking rates by scrutinizing existing patterns and potential mediating factors via publicly accessible data in established planning districts. The authors determined several individual, interpersonal, organizational, community, and environmental factors, varying across these districts, that impact smoking in Philadelphia. Poverty rates influence the resources, demographic …

Endovascular Management And The Risk Of Late Failure In The Treatment Of Ureteroarterial Fistulas, George Titomihelakis, Anthony Feghali, Tuong Nguyen, Dawn Salvatore, Paul Dimuzio, Babak Abai

Department of Medicine Faculty Papers

Ureteroarterial fistula (UAF) is a rare and life-threatening source of hematuria. A high index of suspicion is warranted for early diagnosis and timely intervention. Because of high perioperative risk and comorbidities in UAF patients, the endovascular approach has become preferred for repair. Infection can complicate this mode of therapy, and treatment with antibiotics is important. Herein we present five cases of secondary UAFs treated with stent graft alone or stent graft and embolization.

Irisin Functions To Inhibit Malignant Growth Of Human Pancreatic Cancer Cells Via Downregulation Of The Pi3k/Akt Signaling Pathway., Deguo Zhang, Ping Zhang, Luan Li, Nan Tang, Fei Huang, Xianguo Kong, Xueying Tan, Guangjun Shi

Department of Medicine Faculty Papers

Introduction: Irisin is a newly identified cytokine that has gained increasing attention because of its potential therapeutic applications in metabolic diseases and human cancers. Recently, accumulating evidence indicates that irisin plays an important role in the development and metastasis of various tumors. The aim of this study was to evaluate the effects and underlying mechanisms of irisin on malignant growth of pancreatic cancer cells.

Materials and methods: The anti-proliferative effect of irisin was examined using the CCK-8 assay. Irisin-induced apoptosis was determined by the annexin V-FITC/PI staining assay. The effects of irisin on cell migration and invasion were assessed using …

Effects Of The 2017 Clinical Practice Guidelines On Hypertension In Children And Adolescents: A Commentary, Bonita Falkner

Department of Medicine Faculty Papers

No abstract provided.

Functionalization Of Cd36 Cardiovascular Disease And Expression Associated Variants By Interdisciplinary High Throughput Analysis., Namrata Madan, Andrew R. Ghazi, Xianguo Kong, Edward S. Chen, Chad A. Shaw, Leonard C. Edelstein

Department of Medicine Faculty Papers

CD36 is a platelet membrane glycoprotein whose engagement with oxidized low-density lipoprotein (oxLDL) results in platelet activation. The CD36 gene has been associated with platelet count, platelet volume, as well as lipid levels and CVD risk by genome-wide association studies. Platelet CD36 expression levels have been shown to be associated with both the platelet oxLDL response and an elevated risk of thrombo-embolism. Several genomic variants have been identified as associated with platelet CD36 levels, however none have been conclusively demonstrated to be causative. We screened 81 expression quantitative trait loci (eQTL) single nucleotide polymorphisms (SNPs) associated with platelet CD36 expression …

Symmetrical Peripheral Gangrene Associated With Low Output Cardiac Failure., Sijan Basnet, Priya Rajagopalan, Rashmi Dhital, Ataul Qureshi

Department of Medicine Faculty Papers

Symmetrical peripheral gangrene (SPG) is a rare entity characterized by ischemic changes of the distal extremities with maintained vascular integrity. We present the case of a 64-year-old man with bilateral necrotic toes and deranged liver function tests. This was thought to be related to severely depressed ejection fraction from non-ischemic etiology, presumably chronic alcohol ingestion. We hope that awareness of SPG and association with a low output state will aid in early detection and prevention.

Horizontal Rna Transfer Goes Deep: Platelet Consumption And Microrna Utilization By Vascular Smooth Muscle Cells., Lawrence E. Goldfinger, Leonard C. Edelstein

Department of Medicine Faculty Papers

No abstract provided.

Gpvi Inhibitor As Antitumor Gateway Drug., Lawrence E. Goldfinger

Department of Medicine Faculty Papers

In this issue ofBlood, Volz et al establish a potential antitumor strategy byexploiting the selective requirement for platelets to maintain vascular in-tegrity within the tumor microenvironment.1Their work demonstrates, forthefirst time, that functional inhibition of platelet-specific surface receptorglycoprotein (GP) VI, using F(ab9)2fragments to avoid platelet clearance,increases intratumoral hemorrhage and concomitant tumor cell apoptosis, aswell as enhanced accumulation of chemotherapeutic drugs. These effectswork additively to inhibit tumor growth, achieving results similar to thoseachieved by platelet depletion.

Maternal And Gestational Influences On Childhood Blood Pressure., Bonita Falkner

Department of Medicine Faculty Papers

Exposures that contribute to a sub-optimal intrauterine environment can have an effect on the developing fetus. Impaired fetal growth that results in low birth weight is an established risk factor for cardio-metabolic disorders later in life. Recent epidemiologic and prospective cohort studies that include the maternal and gestational period have identified maternal and gestational conditions that confer increased risk for subsequent cardio-metabolic disorders in the absence of low birth weight. Maternal pre-conception health status, including chronic obesity and type 2 diabetes, increase risk for childhood obesity and obesity-related higher blood pressure (BP) in child offspring. Maternal gestational exposures, including gestational …

Comparative Analysis Of Us Real-World Dosing Patterns And Direct Infusion-Related Costs For Matched Cohorts Of Rheumatoid Arthritis Patients Treated With Infliximab Or Intravenous Golimumab., Lorie A. Ellis, Elisabetta Malangone-Monaco, Helen Varker, Diana Stetsovsky, Maureen Kubacki, Raphael J. Dehoratius, Shelly Kafka

Department of Medicine Faculty Papers

Purpose: The objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective.

Methods: Adult RA patients with a new episode of GLM-IV or IFX treatment between January 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index …

Acute Exacerbations Of Progressive-Fibrosing Interstitial Lung Diseases., Martin Kolb, Benjamin Bondue, Alberto Pesci, Yasunari Miyazaki, Jin Woo Song, Nitin Y. Bhatt, John T. Huggins, Justin M. Oldham, Maria L. Padilla, Jesse Roman, Md, Shane Shapera

Department of Medicine Faculty Papers

Acute exacerbation of interstitial lung disease (ILD) is associated with a poor prognosis and high mortality. Numerous studies have documented acute exacerbation in idiopathic pulmonary fibrosis (IPF), but less is known about these events in other ILDs that may present a progressive-fibrosing phenotype. We propose defining acute exacerbation as an acute, clinically significant respiratory deterioration, typically less than 1 month in duration, together with computerised tomography imaging showing new bilateral glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILDs. Drawing on observations in IPF, it is suspected that epithelial injury or proliferation and autoimmunity are risk …

Rheumatoid Meningitis Sine Arthritis., Cathy Lee-Ching, Lawrence C. Kenyon, Matthew Berk, Chantel Park

Department of Medicine Faculty Papers

Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even …

Etiology And Surgical Management Of Cervical Spinal Epidural Abscess (Sea):: A Systematic Review., Justin Iorio, Yusef Mosley, Md, Srinivas Prasad, Joshua Pelta-Heller, Jack Jallo, Soroush Shahrokh, James Harrop

Department of Medicine Faculty Papers

Study Design: Systematic analysis and review.

Objective: Evaluation of the presentation, etiology, management strategies (including both surgical and nonsurgical options), and neurological functional outcomes in patients with cervical spinal epidural abscess (SEA).

Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were used to create a framework based on which articles pertaining to cervical SEA were chosen for review following a search of the Ovid and PubMed databases using the search terms "epidural abscess" and "cervical." Included studies needed to have at least 4 patients aged 18 years or older, and to have been published within the …

Presentation And Outcomes After Medical And Surgical Treatment Versus Medical Treatment Alone Of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review And Meta-Analysis., Davis G Taylor, Avery L Buchholz, Durga R Sure, Thomas J Buell, James H Nguyen, Ching-Jen Chen, Joshua M Diamond, Perry A Washburn, James Harrop, Christopher I Shaffrey, Justin S Smith

Department of Medicine Faculty Papers

Study Design: Systematic literature review.

Objectives: The aims of this study were to (1) describe the clinical features, disabilities, and incidence of neurologic deficits of pyogenic spondylodiscitis prior to treatment and (2) compare the functional outcomes between patients who underwent medical treatment alone or in combination with surgery for pyogenic spondylodiscitis.

Methods: A systematic literature review was performed using PubMed according to PRISMA guidelines. No year restriction was put in place. Statistical analysis of pooled data, when documented in the original report (ie, number of patients with desired variable and number of patients evaluated), was conducted to determine the most …

The Impact Of Depression On Patient Outcomes In Hip Arthroscopic Surgery., Robroy L. Martin, John J. Christoforetti, Ryan Mcgovern, Benjamin R. Kivlan, Andrew B. Wolff, Shane J. Nho, John P. Salvo, Thomas J. Ellis, Geoff Van Thiel, Dean Matsuda, Dominic S. Carreira

Department of Medicine Faculty Papers

Background: Mental health impairments have been shown to negatively affect preoperative self-reported function in patients with various musculoskeletal disorders, including those with femoroacetabular impingement.

Hypothesis: Those with symptoms of depression will have lower self-reported function, more pain, and less satisfaction on initial assessment and at 2-year follow-up than those without symptoms of depression.

Study Design: Cohort study; Level of evidence, 3.

Methods: Patients who were enrolled in a multicenter hip arthroscopic surgery registry and had 2-year outcome data available were included in the study. Patients completed the 12-item International Hip Outcome Tool (iHOT-12), visual analog scale (VAS) for pain, and …

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 …

Pth1r-Casr Cross Talk: New Treatment Options For Breast Cancer Osteolytic Bone Metastases., Yanmei Yang, Bin Wang

Department of Medicine Faculty Papers

Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth. Both the type 1 PTH receptor (PTH1R) and extracellular calcium-sensing receptor (CaSR) …

Coronary Slow-Flow Phenomenon As An Underrecognized And Treatable Source Of Chest Pain: Case Series And Literature Review., Chikezie Alvarez, Henry Siu, Md

Department of Medicine Faculty Papers

Background. Coronary slow-flow phenomenon (CSFP) is characterized by delayed distal vessel opacification of contrast, in the absence of significant epicardial coronary stenosis. CSFP has been reported as a cause of chest pain and abnormal noninvasive ischemic tests and is often underrecognized. Material and Methods. Charts and angiographic records from our institution were reviewed to identify 15 consecutive patients who were diagnosed with CSFP from January 2016 to January 2017. Results. Of the 15 patients (4 females and 11 males) studied, the mean age was 59.1 years (range = 45-86 years); all had left ventricular ejection fraction >45% …

The Childhood Role In Development Of Primary Hypertension., Bonita Falkner

Department of Medicine Faculty Papers

Primary hypertension is not just an adult disorder. Current US population data on children and adolescents demonstrate a prevalence of elevated blood pressure (BP) and hypertension combined of over 10%. Recent reports from prospective cohort studies describe an association of high BP in childhood with hypertension in young adulthood. Excess adiposity is strongly associated with higher BP in childhood and increases risk for hypertension in adulthood. In addition to overweight/obesity, other exposures that raise the risk for high BP include low birthweight, dietary sodium, and stress. Using intermediate markers of cardiovascular injury, studies on hypertensive children report findings of cardiac …

Synchronous Gastric And Duodenal Metastases From Head And Neck Squamous Cell Carcinoma: A Unique Presentation Of Upper Gastrointestinal Bleeding., Nicholas P. Tarangelo, Charles Andrew Kistler, Zachary Daitch, Wei Jiang, Daniel M. Quirk

Department of Medicine Faculty Papers

Metastatic disease to the stomach or duodenum is an infrequent diagnosis, and head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report the case of a 65-year-old man with human immunodeficiency virus infection and previously diagnosed HNSCC who presented with melena. The patient had a percutaneous endoscopic gastrostomy tube placed 3 months prior to his presentation. Laboratory testing was significant for normocytic anemia and a digital rectal examination was positive for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach as well as …

Dealing With Deans And Academic Medical Center Leadership: Advice From Leaders., Fred Sanfilippo, Deborah Powell, Robert Folberg, Mark Tykocinski

Department of Medicine Faculty Papers

The 2017 Association of Pathology Chairs Annual Meeting included a session for department chairs and other department leaders on "how to deal with deans and academic medical center leadership." The session was focused on discussing ways to foster positive relationships with university, medical school, and health system leaders, and productively address issues and opportunities with them. Presentations and a panel discussion were provided by 4 former pathology chairs who subsequently have served as medical deans and in other leadership positions including university provost, medical center CEO, and health system board chair. There was a strong consensus among the participants on …