Medicine and Health Sciences Commons^™

The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer …

Utility Of Blood Cellular Indices In The Risk Stratification Of Patients Presenting With Acute Pulmonary Embolism., Brett Slajus, Yevgeniy Brailovsky, Iman Darwish, Jawed Fareed, Amir Darki

Division of Cardiology Faculty Papers

Pulmonary embolism (PE) clinical manifestations vary widely, and that scope is not fully captured by current all-cause mortality risk models. PE is associated with inflammatory, coagulation, and hemostatic imbalances so blood cellular indices may be prognostically useful. Complete blood count (CBC) data may improve current risk models like the simplified pulmonary embolism severity index (sPESI) for all-cause mortality, offering greater accuracy and analytic ability. Acute PE patients (n = 228) with confirmatory diagnostic imaging were followed for all-cause mortality. Blood cellular indices were assessed for association to all-cause mortality and were supplemented into sPESI using multivariate logistic regression. Multiple blood …

A Systematic Review Of Health State Utility Values In The Plastic Surgery Literature, Adrienne Christopher, Martin P Morris, Viren Patel, Kevin Klifto, John P Fischer

Department of Surgery Faculty Papers

Cost-utility analyses assess health gains acquired by interventions by incorporating weighted health state utility values (HSUVs). HSUVs are important in plastic and reconstructive surgery (PRS) because they include qualitative metrics when comparing operative techniques or interventions. We systematically reviewed the literature to identify the extent and quality of existing original utilities research within PRS.

Methods: A systematic review of articles with original PRS utility data was conducted in accordance with the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines. Subspecialty, survey sample size, and respondent characteristics were extracted. For each HSUV, the utility measure [direct (standard gamble, time …

Igg4-Mediated Neurologic Autoimmunities: Understanding The Pathogenicity Of Igg4, Ineffectiveness Of Ivig, And Long-Lasting Benefits Of Anti-B Cell Therapies, Marinos Dalakas

Department of Neurology Faculty Papers

Background and objectives: Describe the unique functions of immunoglobulin G4 (IgG4) in IgG4-neurologic disorders (IgG4-ND) and explain why, in contrast to their IgG1-counterparts, they respond poorly to intravenous immune globulin (IVIg) but effectively to anti-B cell therapies.

Methods: The IgG4 structure and isotype switch, B cells and plasmablasts relevant to IgG4 production, and IgG4-induced disruption of the targeted antigens are reviewed and compared with IgG1-mediated autoimmune ND, where IVIg inhibits IgG1-triggered inflammatory effects.

Results: The main IgG4-ND include muscle-specific kinase myasthenia; nodal/paranodal chronic inflammatory demyelinating polyradiculoneuropathy with antibodies to neurofascin-155, contactin-1/caspr-1, or pan-neurofascins; antileucine-rich, glioma-inactivated-1 and contactin-associated protein-like 2 associated-limbic …

Multi-Institutional Study Validates Safety Of Intraoperative Cesium-131 Brachytherapy For Treatment Of Recurrent Head And Neck Cancer, Adam J. Luginbuhl, Alyssa Calder, David Kutler, Chad Zender, Trisha Wise-Draper, Jena Patel, Michael Cheng, Vidhya Karivedu, Tingting Zhan, Bhupesh Parashar, Shuchi Gulati, Min Yao, Pierre Lavertu, Vinita Takiar, Alice Tang, Jennifer Johnson, William M. Keane, Joseph Curry, David Cognetti, Voichita Bar-Ad

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Introduction: Surgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection.

Methods and materials: Findings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts-surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)-were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated.

Results: Forty-nine patients were enrolled in …

A Spatial Model Of Hepatic Calcium Signaling And Glucose Metabolism Under Autonomic Control Reveals Functional Consequences Of Varying Liver Innervation Patterns Across Species, Aalap Verma, Alexandra Manchel, Rahul Narayanan, Jan B. Hoek, Babatunde A Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rapid breakdown of hepatic glycogen stores into glucose plays an important role during intense physical exercise to maintain systemic euglycemia. Hepatic glycogenolysis is governed by several different liver-intrinsic and systemic factors such as hepatic zonation, circulating catecholamines, hepatocellular calcium signaling, hepatic neuroanatomy, and the central nervous system (CNS). Of the factors regulating hepatic glycogenolysis, the extent of lobular innervation varies significantly between humans and rodents. While rodents display very few autonomic nerve terminals in the liver, nearly every hepatic layer in the human liver receives neural input. In the present study, we developed a multi-scale, multi-organ model of hepatic metabolism …

Spinal Anesthesia Or General Anesthesia For Hip Surgery In Older Adults, Mark D. Neuman, Rui Feng, Jeffrey L. Carson, Lakisha J. Gaskins, Derek Dillane, Daniel I. Sessler, Frederick Sieber, Jay Magaziner, Edward R. Marcantonio, Samir Mehta, Diane Menio, Sabry Ayad, Trevor Stone, Steven Papp, Eric S. Schwenk, Nabil Elkassabany, Mitchell Marshall, J. Douglas Jaffe, Charles Luke, Balram Sharma, Syed Azim, Robert A. Hymes, Ki-Jinn Chin, Richard Sheppard, Barry Perlman, Joshua Sappenfield, Ellen Hauck, Mark A. Hoeft, Mark Giska, Yatish Ranganath, Tiffany Tedore, Stephen Choi, Jinlei Li, M. Kwesi Kwofie, Antoun Nader, Robert D. Sanders, Brian F. S. Allen, Kamen Vlassakov, Stephen Kates, Lee A. Fleisher, James Dattilo, Ann Tierney, Alisa J. Stephens-Shields, Susan S. Ellenberg

Department of Anesthesiology Faculty Papers

Background: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied.

Methods: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 …

Spect Functional Neuroimaging Distinguishes Adult Attention Deficit Hyperactivity Disorder From Healthy Controls In Big Data Imaging Cohorts, Daniel G Amen, Theodore A Henderson, Andrew Newberg

Marcus Institute of Integrative Health Faculty Papers

Background: The diagnosis of attention deficit hyperactivity disorder (ADHD) relies on history and observation, as no reliable biomarkers have been identified. In this study, we compared a large single diagnosis group of patients with ADHD (combined, inattentive, and hyperactive) to healthy controls using brain perfusion single-photon emission computed tomography (SPECT) imaging to determine specific brain regions which could serve as potential biomarkers to reliably distinguish ADHD. Methods: In a retrospective analysis, subjects (n = 1,135) were obtained from a large multisite psychiatric database, where resting state (baseline) and on-task SPECT scans were obtained. Only baseline scans were analyzed in …

Promoter Considerations In The Design Of Lentiviral Vectors For Use In Treating Lysosomal Storage Diseases, Estera Rintz, Takashi Higuchi, Hiroshi Kobayashi, Deni S Galileo, Grzegorz Wegrzyn, Shunji Tomatsu

Department of Pediatrics Faculty Papers

More than 50 lysosomal storage diseases (LSDs) are associated with lysosomal dysfunctions with the frequency of 1:5,000 live births. As a result of missing enzyme activity, the lysosome dysfunction accumulates undegraded or partially degraded molecules, affecting the entire body. Most of them are life-threatening diseases where patients could die within the first or second decade of life. Approximately 20 LSDs have the approved treatments, which do not provide the cure for the disorder. Therefore, the delivery of missing genes through gene therapy is a promising approach for LSDs. Over the years, ex vivo lentiviral-mediated gene therapy for LSDs has been …

Is Living In A Region With High Groundwater Arsenic Contamination Associated With Adverse Reproductive Health Outcomes? An Analysis Using Nationally Representative Data From India, Jessie Pinchoff, Brent Monseur, Sapna Desai, Katelyn Koons, Ruben Alvero, Michelle J Hindin

Department of Medicine Faculty Papers

Background: Exposure to groundwater arsenic via drinking water is common in certain geographies, such as parts of India, and causes a range of negative health effects, potentially including adverse reproductive health outcomes.

Methods: We conducted an ecological analysis of self-reported rates of stillbirth, recurrent pregnancy loss, and infertility in relation to groundwater arsenic levels in India. We used a gridded, modeled dataset of the probability of groundwater arsenic exceeding 10 μg/L (World Health Organization drinking water limit) to calculate mean probabilities at the district level (n = 599 districts). A spatial integration approach was used to merge these estimates with …

Efficacy And Safety Of Fremanezumab In Clinical Trial Participants Aged ≥60 Years With Episodic Or Chronic Migraine: Pooled Results From 3 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies, Stephanie J. Nahas, Steffen Naegel, Joshua M Cohen, Xiaoping Ning, Lindsay Janka, Verena Ramirez Campos, Lynda J Krasenbaum, Dagny Holle-Lee, David Kudrow, Christian Lampl

Department of Neurology Faculty Papers

Background: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM).

Methods: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and …

Return-To-Play Rates And Clinical Outcomes Of Baseball Players After Concomitant Ulnar Collateral Ligament Reconstruction And Selective Ulnar Nerve Transposition., Somnath Rao, Taylor D'Amore, Donald P. Willier, Richard J. Gawel, Robert A Jack, Steven B. Cohen, Michael G. Ciccotti

Rothman Institute Faculty Papers

Background: Injury to the ulnar collateral ligament (UCL) leading to medial elbow instability and possible ulnar neuritis is common in overhead-throwing athletes. Treatment may require UCL reconstruction (UCLR) and concomitant ulnar nerve transposition (UNT) for those with preoperative ulnar neuritis.

Purpose: To evaluate the return-to-play (RTP) rates, clinical outcomes, and rates of persistent ulnar neuritis after concomitant UCLR and UNT in a cohort of baseball players with confirmed preoperative ulnar neuritis.

Study Design: Case series; Level of evidence, 4.

Methods: Eligible patients were those who underwent concomitant UCLR and UNT at a single institution between January 2008 and June 2018 …

Fever In A Returning Traveler: A Case And Literature Review Of Melioidosis, Akanksha Arya, Hamadullah Shaikh, Devin Weber, Matthew Pettengill, Sean Moss

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Burkholderia pseudomallei is an aerobic, motile, non-spore-forming gram-negative bacillus found in tropical endemic environments that causes the disease melioidosis. Melioidosis displays a diversity of clinical presentations ranging from septic shock to chronic latent infection, often with characteristic abscesses in multiple organs. Melioidosis is an opportunistic infection, with risk factors, including diabetes, alcohol use, chronic lung disease, and chronic renal disease, and these risk factors increase the severity of disease (Wiersinga et al., 2006) [1]. In this case report, we illustrate a case of a 32 year old man with several risk factors and recent travel to an endemic region presenting …

Attitudes Toward Osteopathic Medicine Scale: Development And Psychometrics, Mohammadreza Hojat Professor, Jennifer Desantis, Robert A Cain, Mark R Speicher, Lynn Bragan, Leonard H Calabrese

Department of Medicine Faculty Papers

Objective: To develop a valid and reliable instrument for measuring attitudes toward osteopathic medicine.

Methods: Participants included 5,669 first-year students from 33 U.S. colleges of osteopathic medicine, who completed an online survey at the beginning of the 2019-2020 academic year. Using data from the nationwide Project in Osteopathic Medical Education and Empathy, we developed a 13-item instrument: Attitudes Toward Osteopathic Medicine Scale (ATOMS) and demonstrated the validity and reliability of its scores. The social desirability response bias was controlled in statistical analyses.

Results: The corrected item-total score correlations were all positive and statistically significant, and the effect sizes of item …

Metabolic Adaptation To The Chronic Loss Of Ca 2+ Signaling Induced By Ko Of Ip 3 Receptors Or The Mitochondrial Ca 2+ Uniporter, Michael P. Young, Zachary T Schug, David M. Booth, David I Yule, Katsuhiko Mikoshiba, György Hajnóczky, Suresh K Joseph

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic …

Depression In Black Men: Disparities In Diagnosis And Treatment, Amy Nwaobasi, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Objectives

• Review epidemiology
• Review risk factors and protective factors that are associated with depression in black men
• Understand causes of disparities in diagnosis
• Understand barriers to treatments
• Explore ways physicians can address these disparities

Native Valve Endocarditis Complicated By Abscess Formation Caused By Rothia Mucilaginosa, S Haddad, Y Saade, B Ramlawi, B Kreidieh, B Gilbert, S Rao

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Rothia mucilaginosa is increasingly recognized as an emerging pathogen associated with endocarditis. It has mostly been reported a causative agent for prosthetic valve endocarditis. The previously reported cases of native valve endocarditis caused by this organism only required medical treatment with no surgical intervention. We report a case of R. mucilaginosa native valve endocarditis complicated by abscess formation requiring surgical intervention and review the literature of native valve endocarditis caused by this organism.

Tera-Seq: True End-To-End Sequencing Of Native Rna Molecules For Transcriptome Characterization, Fadia Ibrahim, Jan Oppelt, Manolis Maragkakis, Zissimos Mourelatos

Department of Biochemistry and Molecular Biology Faculty Papers

Direct sequencing of single, native RNA molecules through nanopores has a strong potential to transform research in all aspects of RNA biology and clinical diagnostics. The existing platform from Oxford Nanopore Technologies is unable to sequence the very 5′ ends of RNAs and is limited to polyadenylated molecules. Here, we develop True End-to-end RNA Sequencing (TERA-Seq), a platform that addresses these limitations, permitting more thorough transcriptome characterization. TERA-Seq describes both poly-and non-polyadenylated RNA molecules and accurately identifies their native 5′ and 3′ ends by ligating uniquely designed adapters that are sequenced along with the transcript. We find that capped, full-length …

A Quasi-Experimental Study Of Medicaid Expansion And Urban Mortality In The American Northeast., Cyrus Ayubcha, Pedram Pouladvand, Soussan Ayubcha

Marcus Institute of Integrative Health Faculty Papers

Objectives: To investigate the association of state-level Medicaid expansion and non-elderly mortality rates from 1999 to 2018 in Northeastern urban settings.

Methods: This quasi-experimental study utilized a synthetic control method to assess the association of Medicaid expansion on non-elderly urban mortality rates [1999-2018]. Counties encompassing the largest cities in the Northeastern Megalopolis (Washington D.C., Baltimore, Philadelphia, New York City, and Boston) were selected as treatment units (n = 5 cities, 3,543,302 individuals in 2018). Cities in states without Medicaid expansion were utilized as control units (n = 17 cities, 12,713,768 individuals in 2018).

Results: Across all cities, there …

Prognostic Values Of G-Protein Mutations In Metastatic Uveal Melanoma, Mizue Terai, Ayako Shimada, I Chervoneva, Liam Hulse, Meggie Danielson, Jeff Swensen, Marlana Orloff, Philip B Wedegaertner, Jeffrey L Benovic, A E Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (GNAQ) and G protein subunit alpha 11 (GNA11). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). GNA11 (41/87) and GNAQ (39/87) mutations were most predominantly seen in MUM. Most GNA11 mutations were Q209L (36/41), whereas GNAQ mutations comprised Q209L (14/39) and …

Expression And Purification Of Phage T7 Ejection Proteins For Cryo-Em Analysis, Nicholas A. Swanson, Ravi K Lokareddy, Fenglin Li, Chun-Feng Hou, Mikhail Pavlenok, Michael Niederweis, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Bacteriophages of the Podoviridae family densely package their genomes into precursor capsids alongside internal virion proteins called ejection proteins. In phage T7 these proteins (gp14, gp15, and gp16) are ejected into the host envelope forming a DNA-ejectosome for genome delivery. Here, we describe the purification and characterization of recombinant gp14, gp15, and gp16. This protocol was used for high-resolution cryo-EM structure analysis of the T7 periplasmic tunnel and can be adapted to study ejection proteins from other phages. For complete details on the use and execution of this protocol, please refer to Swanson et al.

16th Annual Pancreatic Cancer And Related Diseases Patient Symposium, Charles Yeo, Md, Facs, Adam C. Mueller, Md, Phd, Harish Lavu, Md, Facs, Theresa Yeo, Phd, Aochp, Acnp-Bc, Faanp, Avinoam Nevler, Md, Daniel Lin, Md, Msc, Wilbur Bowne, Md, Ira Sharp, Md

Pancreatic Cancer & Related Diseases Symposium

On November 13, 2021, Charles J. Yeo, MD, FACS, and the multidisciplinary team of clinicians and scientists hosted the 16th Annual Pancreatic Cancer & Related Diseases Symposium.

The video of the event is available here: vimeo.com/646517712/36786afe68.

View our Pancreatic Cancer Program 2021 Update to learn more about Dr. Yeo and the team’s great work!

PROGRAM

Welcome and Program Overview
Charles J. Yeo, MD, FACS
Samuel D. Gross Professor and Chair of Surgery

Advances in FT in Treating Pancreatic Cancer
Adam Mueller, MD, PhD
Instructor, Radiation Oncology

KRAS Mutation Allele Frequency Impacts Prognosis in Pancreatic Ductal Adenocarcinoma Using Next-Generation Sequencing …

A Strategy To Detect Emerging Non-Delta Sars-Cov-2 Variants With A Monoclonal Antibody Specific For The N501 Spike Residue, Rama Devudu Puligedda, Fetweh H Al-Saleem, Christoph Wirblich, Chandana Devi Kattala, Marko Jović, Laura Geiszler, Himani Devabhaktuni, Giora Z Feuerstein, Matthias J. Schnell, Markus Sack, Lawrence L Livornese, Scott K Dessain

Department of Microbiology and Immunology Faculty Papers

Efforts to control SARS-CoV-2 have been challenged by the emergence of variant strains that have important implications for clinical and epidemiological decision making. Four variants of concern (VOCs) have been designated by the Centers for Disease Control and Prevention (CDC), namely, B.1.617.2 (delta), B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), although the last three have been downgraded to variants being monitored (VBMs). VOCs and VBMs have shown increased transmissibility and/or disease severity, resistance to convalescent SARS-CoV-2 immunity and antibody therapeutics, and the potential to evade diagnostic detection. Methods are needed for point-of-care (POC) testing to rapidly identify these variants, protect …

Ifit3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) Modulates Stat1 Expression In Small Extracellular Vesicles., Nicole M Naranjo, Israa Salem, Maisha A Harris, Lucia R Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

We have previously shown that the αvβ6 integrin plays a key role in promoting prostate cancer (PrCa) and it can be transferred to recipient cells via small extracellular vesicles (sEVs). Furthermore, we have reported in a proteomic analysis that αvβ6 integrin down-regulation increases the expression of IFIT3 (interferon induced protein with tetratricopeptide repeats 3) in PrCa cells and their derived sEVs. IFIT3 is a protein well known for being an antiviral effector, but recently its role in cancer has also been elucidated. To study the relationship between IFIT3 and STAT1 (signal transducer and activator of transcription 1), an upstream regulator …

Alterations In Functional Connectivity Measured By Functional Magnetic Resonance Imaging And The Relationship With Heart Rate Variability In Subjects After Performing Orgasmic Meditation: An Exploratory Study, Andrew B. Newberg, Nancy Wintering, Chloe Hriso, Faezeh Vedaei, Marie Stoner, Reneita Ross

Department of Radiology Faculty Papers

Background: We measured changes in resting brain functional connectivity, with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), associated with a creative meditation practice that is augmented by clitoral stimulation and is designed to not only achieve a spiritual experience but to help individuals manage their most intimate personal relationships. Briefly, the meditative state is attained by both the male and female participants while the male stimulates the woman's clitoris. The goal of this practice, called orgasmic meditation (OM), according to the practitioners is not sexual, but to use the focus on clitoral stimulation to facilitate a meditative …

The Fate Of Periprosthetic Joint Infection Following Megaprosthesis Reconstruction, Kamolsak Sukhonthamarn, Timothy L Tan, John Strony, Scot A. Brown, David Nazarian, Javad Parvizi

Rothman Institute Faculty Papers

Background: A megaprosthesis may be used for reconstruction in patients with massive bone loss or a periprosthetic fracture. Periprosthetic joint infection (PJI) may occur after a megaprosthesis reconstruction and may pose a major challenge. The outcomes of managing PJI in patients with a megaprosthesis is relatively unclear. The aim of this study was to investigate the clinical course and outcomes of PJI in patients with a megaprosthesis in place.

Methods: From a total of 219 patients who underwent megaprosthesis replacement for non-oncologic conditions, 38 (17.4%) developed subsequent PJI. A retrospective review of the medical record was performed to ascertain the …

Surgical Treatment Of Femoroacetabular Impingement: Minimum 10-Year Outcome And Risk Factors For Failure, Hamed Vahedi, Steven Yacovelli, Claudio Diaz, Javad Parvizi

Rothman Institute Faculty Papers

Background: Femoroacetabular impingement (FAI) is a well-known cause of hip pain and dysfunction in young adults. Surgical treatment has been widely popularized during the past decade. However, most reported results have been limited to short-term and intermediate-term follow-up. The long-term success rate and risk factors for failure are largely unknown. This study aimed to report the long-term (minimum, 10 years) clinical outcomes of surgical treatment of FAI and to describe the clinical and radiographic parameters associated with the failure of treatment involving femoroacetabular osteoplasty (FAO) and labral repair.

Methods: Using our prospective hip preservation database, 164 patients (178 hips) who …

Thrombotic Microangiopathy, An Unusual Form Of Monoclonal Gammopathy Of Renal Significance: Report Of 3 Cases And Literature Review., Edward J. Filippone, Eric D. Newman, Li Li, Rakesh Gulati, John L. Farber

Department of Medicine Faculty Papers

Monoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS. Such cases may lack systemic features of TMA, such as a microangiopathic hemolytic anemia, and the disease may be kidney limited. There is no direct deposition of the paraprotein in the kidney, and the presumed mechanism is disordered …

Postoperative Outcomes In Oesophagectomy With Trainee Involvement., Oesophago-Gastric Anastomosis Study Group (Ogaa) On Behalf Of The West Midlands Research Collaborative

Department of Surgery Faculty Papers

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting.

METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed …

Inability To Switch From Arid1a-Baf To Arid1b-Baf Impairs Exit From Pluripotency And Commitment Towards Neural Crest Formation In Arid1b-Related Neurodevelopmental Disorders, Luca Pagliaroli, Patrizia Porazzi, Alyxandra T Curtis, Chiara Scopa, Harald M M Mikkers, Christian Freund, Lucia Daxinger, Sandra Deliard, Sarah A Welsh, Sarah Offley, Connor A Ott, Bruno Calabretta, Samantha A Brugmann, Gijs W E Santen, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Subunit switches in the BAF chromatin remodeler are essential during development. ARID1B and its paralog ARID1A encode for mutually exclusive BAF subunits. De novo ARID1B haploinsufficient mutations cause neurodevelopmental disorders, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we leveraged ARID1B+/- Coffin-Siris patient-derived iPSCs and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF). ARID1B-BAF regulates exit from pluripotency and lineage commitment by attenuating thousands of enhancers and genes of …