Medicine and Health Sciences Commons^™

The Promising Use Of An Emergency Department Observation Unit To Manage Patients With Opioid Use Disorder, Thai Tran, Nicholas Imperato, Akiva Dym, Anthony Rosania, Lewis Nelson, Christine Ramdin, Cynthia Santos

Faculty, Staff and Student Publications

Introduction: The opioid epidemic continues to grow, placing a significant strain on Emergency Departments (EDs), resulting in patients presenting daily with opioid-related concerns including intoxication, withdrawal, infections, injury, and death. Consequently, in recent years many EDs, including our own, have utilized Emergency Department Observation Units (EDOU) to not only manage withdrawal and overdose, but also initiate long-term treatment. This study aims to evaluate the outcomes of patients with opioid use disorder (OUD) who were managed in our EDOU.

Methods: This was a retrospective study of patients placed in an EDOU who had the primary diagnosis of OUD in a single …

Is There An Association Between Inflammatory Biomarkers And Organ Space Surgical Site Infection After Emergency Laparotomy In Massively Transfused Trauma Patients?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Chelsea J Guy-Frank, James M Klugh, Xu Zhang, Erin E Fox, Charles E Wade, Kimberly A Mankiewicz, Lillian S Kao

Faculty, Staff and Student Publications

Background: The relationship between inflammatory biomarkers (IB) and organ space surgical site infections (OS-SSIs) after emergency laparotomy (EL) is poorly understood.

Methods: Retrospective, single-center analysis of patients in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who underwent EL and survived 48 h after admission was performed. IB levels of IL-6, IL-8, G-CSF, MCP-1, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio were analyzed. IB and OS-SSIs association was evaluated using the Wilcoxon rank sum test.

Results: Of 74 eligible patients, 80 % were male, 69 % sustained blunt trauma, the injury severity score was 31 (24-41), …

Encoding 3d Information In 2d Feature Maps For Brain Ct-Angiography, Uma M Lal-Trehan Estrada, Sunil Sheth, Arnau Oliver, Xavier Lladó, Luca Giancardo

Faculty, Staff and Student Publications

We propose learnable 3D pooling (L3P), a CNN module designed to compress 3D information into 2D feature maps using anisotropic convolutions and unidirectional max pooling. Specifically, we used L3P followed by a 2D network to generate predictions from 3D brain CT-Angiography (CTA) in the context of large vessel occlusion (LVO). To further demonstrate its versatility, we extended its application to 3D brain MRI analysis for brain age prediction. First, we designed an experiment to classify the LVO-affected hemisphere (left or right), projecting the input CTA into the sagittal plane, which allowed to assess the ability of L3P to encode the …

Stress, Employment Changes, And Psychological Distress Among Caregivers Of Patients With Head And Neck Cancer, Lama Abdurrahman, Vlad C Sandulache, Cielito Reyes-Gibby, Erich M Sturgis, Pavan Jhaveri, Hoda Badr

Faculty, Staff and Students Publications

Importance: Patients undergoing external beam radiation therapy (EBRT) for head and neck cancer (HNC) often experience adverse effects that require substantial caregiving. The burdens of caregiving can impact caregiver employment and mental health over time, yet this topic remains underexplored.

Objective: To examine the associations between caregiving for patients with HNC who undergo EBRT and caregiver stress, employment status, and psychological distress.

Design, setting, and participants: This was a secondary analysis of data from a longitudinal survey study that surveyed caregivers at baseline (ie, at initiation of EBRT) and at 4-month and 12-month follow-ups. The study was conducted at 2 …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Kyle B Spier, Natalie A West, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

Baseline Characteristics Of The Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer): Successful Enrollment Of A Diverse Clinical Trial Cohort At Risk For Cognitive Decline, Rachel A Whitmer, Laura D Baker, Maria C Carrillo, Heather M Snyder, Maryjo L Cleveland, Darren R Gitelman, Miia Kivipelto, Xiaoyan I Leng, Laura Lovato, Kathryn V Papp, Valory N Pavlik, Stephen P Salloway, Christy C Tangney, Sarah Tomaszewski Farias, Jeff D Williamson, Sharon Wilmoth, Nancy Woolard, Melissa Yu, Mark Andrew Espeland, U.S. Pointer Study Group

Faculty, Staff and Students Publications

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2-year randomized controlled trial of two lifestyle interventions in 2111 older adults at increased risk for cognitive decline.

Methods: Sociodemographic and clinical characteristics and rates of ancillary study participation were described with means and frequencies.

Results: U.S. POINTER successfully enrolled a cohort, ages 60-79 years, which was ethno-racially inclusive (>30% individuals from groups often under-represented in clinical trials with cognitive outcomes) and 18% residing in neighborhoods with moderate or high levels of socioeconomic deprivation. Enrollees were cognitively intact but at increased …

Comparing The Performance Of 3 Sarcopenia Definitions For Predicting Adverse Events Prior To Liver Transplant, Heidi E Johnston, Hannah L Mayr, Melita Andelkovic, Tahnie G Takefala, Yanyan Chen, Aaron P Thrift, Graeme A Macdonald, Ingrid J Hickman

Faculty, Staff and Students Publications

Background: Sarcopenia is a syndrome of severe muscle wasting, associated with adverse outcomes related to liver transplantation (LT). There are several approaches used to identify sarcopenia. We aimed to investigate the prevalence of sarcopenia using 3 different criteria and determine how these performed in relation to clinical outcomes.

Methods: The cohort study included 237 adults with cirrhosis referred for LT. Sarcopenia was identified using (1) CT-defined; and the (2) original and (3) updated European Working Group on Sarcopenia in Older People criteria (EWGSOP1 and 2). Logistic regression was used to estimate OR and 95% CI for the relationships between sarcopenia …

Clinical Manifestations, Disease Penetrance, And Treatment In Individuals With Socs1 Insufficiency: A Registry-Based And Population-Based Study, Jerome Hadjadj, Anna Wolfers, Oleg Borisov, Derek Hazard, Ronan Leahy, Marie Jeanpierre, Alexandre Belot, Shahrzad Bakhtiar, Fabian Hauck, Pui Y Lee, Stefano Volpi, Serena Palmeri, Vincent Barlogis, Nathalie Aladjidi, Georg Ebetsberger-Dachs, Jerome Avouac, Fabienne Charbit-Henrion, Morgane Cheminant, Jean Donadieu, Sujal Ghosh, David P Hoytema Van Konijnenburg, Julia Körholz, Jacinta Bustamante, Jeremie Rosain, Lisa Forbes Satter, Ingrid Selmeryd, Georgios Sogkas, Benedicte Neven, Frederic Rieux-Laucat, Stephan Ehl

Faculty, Staff and Students Publications

Background: Suppressor of cytokine signalling 1 (SOCS1) insufficiency is an inborn error of immunity affecting the negative regulation of cytokine and growth factor signalling. We aimed to enhance the understanding of clinical manifestations, disease trajectories, disease penetrance, and the effect of Janus kinase (JAK) inhibition in individuals with SOCS1 insufficiency.

Methods: This study used data from two independent cohorts: the European Society for Immunodeficiencies (ESID) registry and the UK Biobank. Participants from the ESID registry were from nine European countries (Austria, Belgium, France, Germany, Ireland, Italy, Portugal, Sweden, and Ukraine), China, Taiwan, and the USA. Participants from the ESID registry …

Histologic- And Genomic-Directed Adjuvant Therapy For Ampullary Adenocarcinoma: A Hidden Genome-Derived Analysis, Brett L Ecker, Kenneth Seier, Ankur Choubey, Austin M Eckhoff, Gabriella N Tortorello, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Charles M Vollmer, Alice C Wei, Sabino Zani, Australian Pancreatic Genome Initiative, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Background: The benefit of adjuvant chemotherapy (AC) for ampullary adenocarcinoma is unclear. The Hidden Genome model classifies prognostic subtypes with greater accuracy than standard histologic classification (intestinal [INT] vs pancreatobiliary [PB]), but its predictive capacity to guide the use of AC remains unstudied.

Methods: We applied the Hidden Genome model to an international cohort of 183 patients with resected ampullary adenocarcinoma who underwent genomic sequencing. The model quantified the predicted cell of origin (colorectal vs pancreas/distal bile duct) in all specimens. Overall survival (OS) was compared using Kaplan-Meier estimates, stratified by AC use versus surgery alone (SA).

Results: Most patients …

Middle Meningeal Artery Embolization As A Perioperative Adjunct To Surgical Evacuation Of Nonacute Subdural Hematomas: An Multicenter Analysis Of Safety And Efficacy, Walid K Salah, Cordell Baker, Jonathan P Scoville, Joshua C Hunsaker, Christopher S Ogilvy, Justin M Moore, Howard A Riina, Elad I Levy, Alejandro M Spiotta, Brian T Jankowitz, C Michael Cawley, Alexander A Khalessi, Omar Tanweer, Ricardo Hanel, Bradley A Gross, Okkes Kuybu, Alex Nguyen Hoang, Ammad A Baig, Mir Hojjat Khorasanizadeh, Aldo A Mendez, Gustavo Cortez, Jason M Davies, Sandra Narayanan, Brian M Howard, Michael J Lang, Adnan H Siddiqui, Ajith Thomas, Peter Kan, Jan-Karl Burkhardt, Mohamed M Salem, Ramesh Grandhi

Faculty, Staff and Students Publications

Background

By 2030, nonacute subdural hematomas (NASHs) will likely be the most common cranial neurosurgery pathology. Treatment with surgical evacuation may be necessary, but the recurrence rate after surgery is as high as 30%. Minimally invasive middle meningeal artery embolization (MMAE) during the perioperative period has been posited as an adjunctive treatment to decrease the potential for recurrence after surgical evacuation. We evaluated the safety and efficacy of concurrent MMAE in a multi-institutional cohort.

Methods

Data from 145 patients (median age 73 years) with NASH who underwent surgical evacuation and MMAE in the perioperative period were retrospectively collected from 15 …

Impact Of Length Of Stay On Diagnostic Yield In The Epilepsy Monitoring Unit: A Multi-Center Retrospective 12-Year Veterans Health Administration Study, Maximillian S Feygin, Autumn Smith, Sruthi Gopinath Karicheri, Khadar Haroun, Omar Khan, Maria R Lopez, Stephan Eisenschenk, John Jones, Stephanie Reeder, Alan R Towne, Christopher Ransom, Karen Medin, James Chen, Tung Tran, Nina I Garga, Noemi Rincon-Flores, Marissa Kellogg, Steven Tobochnik, Zulfi Haneef

Faculty, Staff and Students Publications

Objective: Epilepsy Monitoring Units (EMUs) in Veterans Health Administration (VHA) Epilepsy Centers of Excellence (ECoE) are critical for the diagnosis and management of seizure disorders. Whether a shorter length of stay (LOS) in the EMU due to scheduling impacts diagnostic yield is unclear.

Methods: Data from 7074 EMU visits across 15 VHA EMUs (2012-2024) were analyzed. Based on usual admission schedules, EMUs were divided into "fixed" (typically Monday-Friday) or "flexible" subgroups. Diagnostic outcomes were classified as epileptic seizures (ES), psychogenic non-epileptic seizures (PNES), other non-epileptic events, and inconclusive. Diagnostic rates were compared between fixed and flexible sites using cumulative distribution …

Recreational Outdoor Injury And Mortality In Texas State Parks Between 2012 And 2021, Mohammad I Hirzallah, Ebubechi K Adindu, Julliet C Ogu, Tania Allison, May Kamleh

Faculty, Staff and Students Publications

Introduction

Methods

Age-Related Mesenchymal Stromal Cell Senescence Is Associated With Progression From Mgus To Multiple Myeloma, Natalya Plakhova, Sheila A Stewart, Et Al.

2020-Current year OA Pubs

The risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) increases with advancing age, suggesting that progression may be influenced by age-related changes within the bone marrow (BM) microenvironment. We hypothesise that senescent mesenchymal stromal cells (MSCs), which accumulate in the BM with age, may contribute to MGUS progression to MM. Here, we show that, like BM MSCs from aged non-cancer controls, BM MSCs from both MM and MGUS patients exhibit a senescent phenotype characterised by enlarged, flattened morphology, increased β-galactosidase activity and CDKN2A expression, and decreased proliferation rate compared with BM MSCs from healthy …

The Medial Antebrachial Cutaneous Nerve Is A Low-Morbidity Alternative To The Standard Sural Nerve Autograft, Stahs Pripotnev, Sai L Pinni, Suzanne Zhou, Gary Skolnick, Susan E Mackinnon

2020-Current year OA Pubs

BACKGROUND: Nerve interposition grafting is an important technique in nerve reconstructive surgery that is used when a primary repair is not feasible without significant tension. This study sought to evaluate the long-term morbidity of the medial antebrachial cutaneous (MABC) nerve as an alternative donor nerve in comparison with sural nerve harvest.

METHODS: A single surgeon and institution retrospective chart review was performed to identify all patients who underwent nerve autografting using the sural and MABC as donor nerves between January 1, 2000 and December 31, 2019. Surveys assessed overall patient satisfaction with surgery, as well as donor and recipient site …

Compression Of The Ulnar Nerve By The Arcade Of Struthers: Look And You Shall Find, Shady Elmaraghi, Ruby Taylor, Isaac Tung, Megan M Patterson, Susan E Mackinnon

2020-Current year OA Pubs

BACKGROUND: The arcade of Struthers was first proposed by Kane et al in 1973. Clinical investigations of this structure have been limited to small case series, focusing on the arcade as an isolated cause of compressive ulnar neuropathy. The purpose of our study was to investigate the incidence of this structure in patients undergoing ulnar nerve transposition.

METHODS: A retrospective chart review of prospectively maintained data in a single surgeon's practice was performed. Records of patients undergoing surgery for compressive ulnar neuropathy at the cubital tunnel were evaluated for documentation of a compressive arcade of Struthers. In addition, a scoping …

Cardiovascular And Renal Treatment In Heart Failure Patients With Hyperkalemia Or High Risk Of Hyperkalemia: Rationale And Design Of The Care-Hk In Hf Registry, Stephen J Greene, Michael Böhm, Biykem Bozkurt, Javed Butler, John G F Cleland, Andrew J S Coats, Nihar R Desai, Diederick E Grobbee, Ellie Kelepouris, Fausto Pinto, Giuseppe Rosano, Isabelle Morin, Peter Szecsödy, Solenn Fabien, Sandra Waechter, Maria G Crespo-Leiro, Martin Hülsmann, Tibor Kempf, Otmar Pfister, Anne-Catherine Pouleur, Andrew J Sauer, Manish Saxena, Martin Schulz, Maurizio Volterrani, Stefan D Anker, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Background: Despite guideline recommendations, many patients with heart failure (HF) do not receive target dosages of renin-angiotensin-aldosterone system inhibitors (RAASis) in clinical practice due, in part, to concerns about hyperkalemia (HK).

Methods and results: This noninterventional, multinational, multicenter registry (NCT04864795; 111 sites in Europe and the USA) enrolled 2558 eligible adults with chronic HF (mostly with reduced ejection fraction [HFrEF]). Eligibility criteria included use of angiotensin-converting-enzyme inhibitor/angiotensin-II receptor blocker/angiotensin-receptor-neprilysin inhibitor, being a candidate for or treatment with a mineralocorticoid receptor antagonist, and increased risk of HK (eg, current serum potassium > 5.0 mmol/L), history of HK in the previous …

Worldwide Prevalence Of Chagas Cardiomyopathy-An Analysis From The Global Burden Of Disease Dataset, Abdul Mannan Khan Minhas, Rachel Marcus, Salim S Virani, Michael D Shapiro, Robert J Mentz, Luis E Echeverria, Jonathan T Arcobello, Dmitry Abramov

Faculty, Staff and Students Publications

Purpose: The worldwide prevalence of Chagas Cardiomyopathy (CCM) as well as the trends in the prevalence of CCM over time have not been well characterized.

Methods: An analysis of the Global Burden of Disease (GBD) data from 1990 to 2019 was conducted to assess the burden of CCM. This study focused on determining the prevalence of CCM, along with its age-standardized prevalence rate (ASR) per 1,00,000 people, considering various patient demographics and geographical regions as defined in the GBD. Additionally, the study examined the temporal trends over this 30-year period by calculating the estimated annual percentage change (EAPC) in CCM …

Eye Catching, Alec B Rezigh, Anand D Jagannath, Austin C Rezigh, Ann Marie Kumfer, Stephanie V Sherman

Faculty, Staff and Students Publications

A 55 year-old man with type 2 diabetes mellitus presented to the emergency department with subacute nausea, vomiting, and abdominal pain. He was found to have epididymitis and hyperglycemia that improved with antibiotics and supportive care. However, he was also discovered to have significant acute kidney injury and chronic, relapsing-remitting bouts of eye pain and redness, confirmed to be uveitis on ophthalmologic evaluation. Despite completing an appropriate course of antibiotics, his pyuria and kidney injury persisted. An extensive infectious, autoimmune, and malignancy work-up was negative. As such, renal biopsy was pursued and revealed findings consistent with tubulointerstitial nephritis. With a …

Protein Biomarkers Of Interstitial Lung Abnormalities In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

Results: Of 237 relatives from …

Utility Of Revised Risk Analysis Index As A Predictor Of Mortality And Morbidity In Orthopaedic Trauma., Chirag Soni, Victor Koltenyuk, Nithin Gupta, Haad A Arif, Aruni Areti, Taylor Manes, Luke A Lopas, Jan P Szatkowski, Christian A Bowers, Benjamin C Taylor, Jack W Weick

Trauma and Acute Care Articles

OBJECTIVES: The aim of this study was to determine the applicability of the Revised Risk Analysis Index (RAI-Rev) in orthopaedic trauma and compare the predictive discrimination for the RAI-Rev and the 5-Item Modified Frailty Index (mFI-5) for 30-day postoperative outcomes.

DESIGN: This is a retrospective cohort study.

SETTING: The American College of Surgeons National Surgical Quality Improvement database was used.

PATIENT SELECTION: All patients aged 18 or older who underwent surgical treatment for forearm, humerus, pelvis, acetabulum, femur, tibia, and hindfoot fractures from 2015 to 2020 were included.

OUTCOME: 30-day postoperative mortality, major complications, and wound complications consisting of surgical …

Joint Analysis Of The Npod-Virus Group Data: The Association Of Enterovirus With Type 1 Diabetes Is Supported By Multiple Markers Of Infection In Pancreas Tissue, Sarah J Richardson, Teresa Rodriguez-Calvo, Jutta E Laiho, John S Kaddis, Julius O Nyalwidhe, Irina Kusmartseva, Sofia Morfopoulou, Joseph F Petrosino, Vincent Plagnol, Kathrin Maedler, Margaret A Morris, Jerry L Nadler, Mark A Atkinson, Matthias Von Herrath, Richard E Lloyd, Heikki Hyoty, Noel G Morgan, Alberto Pugliese, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from organ donors with type 1 diabetes (with broad age and disease duration) and donors with disease-associated autoantibodies (AAbs), the latter representing preclinical disease. Two accompanying manuscripts from the nPOD-Virus Group report primary data from a coordinated analysis of multiple enterovirus indices. We aimed to comprehensively assess the association of multiple enterovirus markers with type 1 diabetes.

Methods: The nPOD-Virus …

Polyclonal Plasma Cell (Polypc) Signature As A Key Indicator For Predicting The Progression Of Mgus To Multiple Myeloma, Fumou Sun, Yan Cheng, Catherine Ma, Hongwei Xu, Clyde Bailey, David Mery, Timothy Cody Ashby, Daisy Alapat, Yong Li, Ken H Young, Samer Al Hadidi, Sharmilan Thanendrarajan, Carolina Schinke, Maurizio Zangari, Frits Van Rhee, Guido Tricot, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Students Publications

Background

Multiple myeloma (MM) is virtually always preceded by monoclonal gammopathy of undetermined significance (MGUS). Elevated serum markers are used to classify MGUS patients into clinical risk categories. Previous research has indicated that the absence of a normal plasma cell signature in MGUS is linked to early progression.

Objective

To confirm that the presence of a “polyclonal plasma cell (PolyPC) signature” serves as a robust negative predictor of MGUS progression.

Methods

374 MGUS patients were enrolled, including 334 patients with stable disease and 40 patients who progressed to MM within 10 years. An oligonucleotide microarray analysis was performed on mRNA …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Hiroko Yano, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

METHODS: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

RESULTS: NF2 loss-of-function (LOF) …

Phase 2 Open-Label Study Of Sacituzumab Govitecan As Second-Line Therapy In Patients With Extensive-Stage Sclc: Results From Tropics-03, Afshin Dowlati, Anne C Chiang, Andrés Cervantes, Sunil Babu, Erika Hamilton, Shu Fen Wong, Andrea Tazbirkova, Ivana Gabriela Sullivan, Cédric Van Marcke, Antoine Italiano, Jilpa Patel, Sabeen Mekan, Tia Wu, Saiama N Waqar

2020-Current year OA Pubs

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of …

Clinical Trial Readiness In Limb Girdle Muscular Dystrophy R1 (Lgmdr1): A Grasp Consortium Study, Stephanie M Hunn, Amanda Clause, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Identifying functional measures that are both valid and reliable in the limb girdle muscular dystrophy (LGMD) population is critical for quantifying the level of functional impairment related to disease progression in order to establish clinical trial readiness in the context of anticipated therapeutic trials.

METHODS: Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 subjects with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each subject completed a battery of clinical outcome assessments (COA), including the North Star Assessment for Limb Girdle-Type Dystrophies (NSAD), 10-m walk/run, and Performance of the …

Claustrum Volume Is Reduced In Multiple Sclerosis And Predicts Disability, Nicole Shelley, Bradley Judge, Dmitriy A Yablonskiy, Robert T Naismith, Matthew R Brier, Anne H Cross

2020-Current year OA Pubs

OBJECTIVE: The claustrum is a small, thin structure of predominantly gray matter with broad connectivity and enigmatic function. Little is known regarding the impact of claustrum pathology in multiple sclerosis (MS).

METHODS: This study assessed whether claustrum volume was reduced in MS and whether reductions were associated with specific disability domains. We compared the impact of claustrum volume reductions on neurological disability versus the well-studied thalamus. Data from the 15,793 participants in the MS PATHS study were used for primary analyses. A second cohort of 71 people with MS and healthy controls from our center was used for validation.

RESULTS: …

Burst Steroid Therapy And Quality Of Life In Patients With Acute Heart Failure: Insights From The Cortahf Trial, Matteo Pagnesi, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Patients hospitalized with acute heart failure (AHF) treated with a 7 day prednisone course in the CORTAHF pilot trial had a greater improvement in health-related quality of life (QoL) at Day 7 in both the overall population and in patients with baseline interleukin 6 > 13 pg/mL. This post-hoc analysis examines the specific QoL domains and the relationship between clinical signs of congestion and QoL.

METHODS: In the CORTAHF pilot trial, patients with AHF and high-sensitivity C-reactive protein (hsCRP) > 20 mg/L were randomized 1:1 to once-daily oral 40 mg prednisone for 7 days plus usual care or usual care alone. …

Large-Scale Network Analysis Of The Cerebrospinal Fluid Proteome Identifies Molecular Signatures Of Frontotemporal Lobar Degeneration, Rowan Saloner, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. Here we leveraged aptamer-based proteomics (>4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations (C9orf72, GRN and MAPT) compared with 39 non-carrier controls. Network analysis identified 31 protein co-expression modules. Proteomic signatures of genetic FTLD clinical severity included increased abundance of RNA splicing (particularly in C9orf72 and GRN) and extracellular matrix (particularly in MAPT) modules, as well as decreased abundance of synaptic/neuronal and autophagy modules. The generalizability of genetic FTLD proteomic …

Plasma Mtbr-Tau243 Biomarker Identifies Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Rama K Koppisetti, Nicolas R Barthélemy, Yingxin He, Chihiro Sato, Brian A Gordon, Hong Jiang, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer's disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma …

Colorectal Cancer And The Risk Of Mortality Among Individuals With Suicidal Ideation, Srikanta Banerjee, Jagdish Khubchandani, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Suicide is a major public health problem that has grown at alarming rates in the last two decades. Colorectal cancer (CRC) is one of the most common causes of cancer deaths in the United States in both males and females. However, the influence of suicidal ideation (SI) on the association between CRC and risk of mortality has not been well examined.

METHODS: For this study, the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of United States adults aged 20 years or older, was utilized. CRC survivorship was determined from self-reported data on CRC, and mortality …