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Clonal Hematopoiesis Of Indeterminate Potential (Chip) And Incident Type 2 Diabetes Risk, Deirdre K Tobias, Alisa K Manning, Jennifer Wessel, Sridharan Raghavan, Kenneth E Westerman, Alexander G Bick, Daniel Dicorpo, Eric A Whitsel, Jason Collins, Adolfo Correa, L Adrienne Cupples, Josée Dupuis, Mark O Goodarzi, Xiuqing Guo, Barbara Howard, Leslie A Lange, Simin Liu, Laura M Raffield, Alex P Reiner, Stephen S Rich, Kent D Taylor, Lesley Tinker, James G Wilson, Peitao Wu, April P Carson, Ramachandran S Vasan, Myriam Fornage, Bruce M Psaty, Charles Kooperberg, Jerome I Rotter, James Meigs, Joann E Manson

Faculty, Staff and Student Publications

OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident type 2 diabetes (T2D) is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.

RESEARCH DESIGN AND METHODS: CHIP was derived from whole-genome sequencing of blood DNA in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) prospective cohorts. We performed analysis for 17,637 participants from six cohorts, without prior T2D, cardiovascular disease, …

Time To Endoscopy Or Colonoscopy Among Adults Younger Than 50 Years With Iron-Deficiency Anemia And/Or Hematochezia In The Vha, Joshua Demb, Lin Liu, Caitlin C Murphy, Chyke A Doubeni, Maria Elena Martinez, Samir Gupta

Faculty, Staff and Student Publications

IMPORTANCE: to date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized.

OBJECTIVE: to evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with …

Clinical Outcome And Therapeutic Impact On Neuroendocrine Neoplasms Of The Breast: A National Cancer Database Study, Libo Yang, Heather Lin, Yu Shen, Madhuchhanda Roy, Constance Albarracin, Qingqing Ding, Lei Huo, Hui Chen, Bing Wei, Hong Bu, Isabelle Bedrosian, Yun Wu

Faculty, Staff and Student Publications

Purpose: Neuroendocrine neoplasms (NENs) of the breast are rare and not well-studied. NEN are subcategorized as well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC). The objectives of the current study were to review the clinicopathologic features of NENs, therapeutic efficacy of current systemic therapy and clinical outcomes of NEN of the breast.

Methods: Between 2004 and 2015, 420 NET, 205 NEC, 146 Adenocarcinoma with NE differentiation (ACNED) and 1,479,520 of invasive carcinoma, not otherwise specified (IC-NOS) of the breast were identified in the National Caner Database. Overall survival was compared among groups using Kaplan-Meier method and Log-rank test. …

Remotely Delivered Cancer Genetic Testing In The Making Genetic Testing Accessible (Magenta) Trial: A Randomized Clinical Trial, Elizabeth M Swisher, Nadine Rayes, Deborah Bowen, Christine B Peterson, Barbara M Norquist, Tara Coffin, Kathleen Gavin, Deborah Polinsky, Jamie Crase, Jamie N Bakkum-Gamez, Stephanie V Blank, Mark F Munsell, Denise Nebgen, Gini F Fleming, Olufunmilayo I Olopade, Sherman Law, Alicia Zhou, Douglas A Levine, Alan D'Andrea, Karen H Lu

Faculty, Staff and Student Publications

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress.

Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing.

Design, setting, and participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US …

Next-Generation Chimeric Antigen Receptors For T- And Natural Killer-Cell Therapies Against Cancer, Ye Li, Katayoun Rezvani, Hind Rafei

Faculty, Staff and Student Publications

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, the broad application of this approach for myeloid malignancies and solid cancers has been limited by the paucity and heterogeneity of target antigen expression, and lack of bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead to unwanted on-target off-tumor toxicities that could undermine the desired antitumor effect. Recent advances in synthetic biology and genetic engineering have enabled reprogramming of immune effector cells to enhance their selectivity toward tumors, …

Stepwise Requirements For Polymerases Δ And Θ In Theta-Mediated End Joining, Susanna Stroik, Juan Carvajal-Garcia, Dipika Gupta, Alyssa Edwards, Adam Luthman, David W Wyatt, Rachel L Dannenberg, Wanjuan Feng, Thomas A Kunkel, Gaorav P Gupta, Mark Hedglin, Richard Wood, Sylvie Doublié, Eli Rothenberg, Dale A Ramsden

Faculty, Staff and Student Publications

Timely repair of chromosomal double-strand breaks is required for genome integrity and cellular viability. The polymerase theta-mediated end joining pathway has an important role in resolving these breaks and is essential in cancers defective in other DNA repair pathways, thus making it an emerging therapeutic target1 It requires annealing of 2-6 nucleotides of complementary sequence, microhomologies, that are adjacent to the broken ends, followed by initiation of end-bridging DNA synthesis by polymerase θ. However, the other pathway steps remain inadequately defined, and the enzymes required for them are unknown. Here we demonstrate requirements for exonucleolytic digestion of unpaired 3' tails …

Methods For Objective Assessment Of Skin Involvement In Systemic Sclerosis, Ruhani Desai, Harshdeep Chawla, Kirill Larin, Shervin Assassi

Faculty, Staff and Student Publications

Purpose of review: Skin fibrosis is the most prominent disease manifestation of systemic sclerosis (SSc). Although the treatment for other SSc manifestations has expanded over the years, there is limited progress in identifying effective treatment options for SSc skin involvement. This is in part due to limitations in the utilized outcome measures for assessment of skin fibrosis. This review focuses on different emerging assessment tools for SSc skin involvement and their potential use for clinical care and multicenter trials.

Recent findings: Durometer and other device-based methodologies requiring application of direct pressure to the affected skin have been studied in SSc. …

Plasma Biomarkers For Brain Injury In Extracorporeal Membrane Oxygenation, Shrey Kapoor, Anna Kolchinski, Aaron M Gusdon, Lavienraj Premraj, Sung-Min Cho

Faculty, Staff and Student Publications

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiorespiratory failure. Despite its benefits, ECMO carries a significant risk of neurological complications, including acute brain injury (ABI). Although standardized neuromonitoring and neurological care have been shown to improve early detection of ABI, the inability to perform neuroimaging in a timely manner is a major limitation in the accurate diagnosis of neurological complications. Therefore, blood-based biomarkers capable of detecting ongoing brain injury at the bedside are of great clinical significance. This review aims to provide a concise review of the current literature on plasma biomarkers for ABI in …

Hide Your Distance: Privacy Risks And Protection In Spatial Accessibility Analysis, Liyue Fan, Luca Bonomi

Faculty, Staff and Student Publications

Measuring spatial accessibility to healthcare resources and facilities has long been an important problem in public health. For example, during disease outbreaks, sharing spatial accessibility data such as individual travel distances to health facilities is vital to policy making and designing effective interventions. However, sharing these data may raise privacy concerns, as information about individual data contributors (e.g., health status and residential address) may be disclosed. In this work, we investigate those unintended information leakage in spatial accessibility analysis. Specifically, we are interested in understanding whether sharing data for spatial accessibility computations may disclose individual participation (i.e., membership inference) and …

Iron Overload Induces Cerebral Endothelial Senescence In Aged Mice And In Primary Culture In A Sex-Dependent Manner, Brian Noh, Maria Pilar Blasco-Conesa, Syed Mushfiqur Rahman, Sheelu Monga, Rodney Ritzel, Gary Guzman, Yun-Ju Lai, Bhanu Priya Ganesh, Akihiko Urayama, Louise D Mccullough, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived …

Editorial: Women Facing Crises, Margit Endler, Atziri Ramirez-Negrin, Timothy R B Johnson

Faculty, Staff and Student Publications

No abstract provided.

Distal Biceps Reconstruction: A Long-Term Follow-Up Of The Complications And Durability Of The Single-Incision Power Optimizing Cost-Effective (Spoc) Repair, Jefferson Li, Lucas M Seiler, Nathan A Hoekzema, Toby R Johnson, Julia Lee, Joanne L Ridenauer, Cary M Tanner

Faculty, Staff and Student Publications

Background: The Single-Incision Power Optimizing Cost-Effective Repair (SPOC) method reattaches the distal biceps tendon to its original posterior anatomic footprint and utilizes the anterior cortex of the supinated radius for fixation. The purpose of the study was to define the long-term complications and durability of the SPOC method.

Methods: Two hundred and eighteen patients underwent the SPOC repair of distal biceps ruptures from 2008 to 2020, with 185 having at least 1-year follow-up data. The average follow-up was 50.1 months. Information regarding smoking, body mass index, interval between injury and surgery, peripheral nerve injury, heterotopic ossification, vascular injury, re-rupture, chronic …

Clinical And Molecular Features Of Long-Term Response To Immune Checkpoint Inhibitors In Patients With Advanced Non-Small Cell Lung Cancer, Rohit Thummalapalli, Biagio Ricciuti, Chaitanya Bandlamudi, Daniel Muldoon, Hira Rizvi, Arielle Elkrief, Jia Luo, Joao V Alessi, Federica Pecci, Giuseppe Lamberti, Alessandro Di Federico, Lingzhi Hong, Jianjun Zhang, John V Heymach, Don L Gibbons, Andrew J Plodkowski, Vignesh Ravichandran, Mark T A Donoghue, Chad Vanderbilt, Marc Ladanyi, Charles M Rudin, Mark G Kris, Gregory J Riely, Jamie E Chaft, Matthew D Hellmann, Natalie I Vokes, Mark M Awad, Adam J Schoenfeld

Faculty, Staff and Student Publications

PURPOSE: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR).

EXPERIMENTAL DESIGN: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), next-generation sequencing (NGS), and whole-exome sequencing (WES) data were analyzed to identify characteristics enriched in patients achieving LTR compared with STR and non-LTR.

RESULTS: Among 3,118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival (OS) of 81% and 18% among LTR and STR patients, respectively. High TMB (≥50th percentile) enriched …

Assessing The Safety Of Deep Sedation In Outpatient Pediatric Oral Health Care, Henal Alpesh Gandhi, Greg Olson, Helen Lee, Kawtar Zouaidi, Alfa Yansane, Muhammad Walji, Elsbeth Kalenderian, Bunmi Tokede

Faculty, Staff and Student Publications

Background: Children are the patient subgroup with the lowest error tolerance regarding deep sedation (DS)-supported care. This study assessed the safety of DS-supported pediatric dental treatment carried out in an outpatient setting through retrospective review of patient charts.

Methods: An automated script was developed to identify charts of pediatric patients who underwent DS-supported dental procedures from 2017 through 2019 at a dental clinic. Charts were assessed for the presence of sedation-related adverse events (AEs). A panel of experts performed a second review and confirmed or refuted the designation of AE (by the first reviewer). AEs were classified with the Tracking …

Disparities In Screening Mammography Utilization Among Hispanic Women In Rural Texas From 2002 To 2018, Zhaoli Liu, Yong-Fang Kuo, Sharon H Giordano

Faculty, Staff and Student Publications

PURPOSE: To examine the trends of racial/ethnic and urban-rural disparities in screening mammography use with a focus on Hispanic women in rural Texas, as well as to further investigate barriers to mammography screening practices.

METHODS: A serial cross-sectional study was conducted on screening mammography including eligible female respondents (≥ 40 years) from the Texas Behavioral Risk Factor Surveillance System survey from 2002 to 2018.

FINDINGS: Weighted descriptive analyses showed persistent racial/ethnic and urban-rural disparities in mammography screening rates among eligible women (≥ 40 years) in Texas. Overall, the mammography screening rates for women in rural areas were significantly lower than …

Under Disguise: A Concealed Case Of Acute Hepatitis A Infection, Jordan C Malone, Ernesto Zamora, Joseph M Gosnell, Heather L Stevenson, Akshata Moghe

Faculty, Staff and Student Publications

Acute hepatitis A virus infection is routinely identified through a thorough patient history in conjunction with liver chemistries and viral serologies. The diagnosis has the potential to be delayed when the clinical picture is obscured with another, seemingly more urgent presenting pathology with overlapping features. Here, we describe the case of a young female who presented with acute calculous cholecystitis with concurrent acute hepatitis A virus infection.

Post-Zygotic Rescue Of Meiotic Errors Causes Brain Mosaicism And Focal Epilepsy, Katherine E Miller, Adithe C Rivaldi, Noriyuki Shinagawa, Sahib Sran, Jason B Navarro, Jesse J Westfall, Anthony R Miller, Ryan D Roberts, Yassmine Akkari, Rachel Supinger, Mark E Hester, Mohammad Marhabaie, Meethila Gade, Jinfeng Lu, Olga Rodziyevska, Meenakshi B Bhattacharjee, Gretchen K Von Allmen, Edward Yang, Hart G W Lidov, Chellamani Harini, Manish N Shah, Jeffrey Leonard, Jonathan Pindrik, Ammar Shaikhouni, James E Goldman, Christopher R Pierson, Diana L Thomas, Daniel R Boué, Adam P Ostendorf, Elaine R Mardis, Annapurna Poduri, Daniel C Koboldt, Erin L Heinzen, Tracy A Bedrosian

Faculty, Staff and Student Publications

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched …

Valosin-Containing Protein (Vcp/P97) Is Prognostically Unfavorable In Pediatric Aml, And Negatively Correlates With Unfolded Protein Response Proteins Ire1 And Grp78: A Report From The Children’S Oncology Group, Fieke W Hoff, Yihua Qiu, Brandon D Brown, Robert B Gerbing, Amanda R Leonti, Rhonda E Ries, Alan S Gamis, Richard Aplenc, Edward Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Gaye N Jenkins, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

Purpose: The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML).

Experimental design: Protein expression levels of valosin-containing protein (VCP), a chief element of ERAD, were measured in peripheral blood samples from in 483 pediatric AML patients using reverse phase protein array methodology. Patients participated in the Children's Oncology Group AAML1031 phase 3 clinical trial that randomized patients to standard chemotherapy (cytarabine …

Performance Of Ct-Based Deep Learning In Diagnostic Assessment Of Suspicious Lateral Lymph Nodes In Papillary Thyroid Cancer: A Prospective Diagnostic Study, Guibin Zheng, Haicheng Zhang, Fusheng Lin, Mark Zafereo, Neil Gross, Peng Sun, Yang Liu, Haiqing Sun, Guochang Wu, Shujian Wei, Jia Wu, Ning Mao, Guojun Li, Guoyang Wu, Haitao Zheng, Xicheng Song

Faculty, Staff and Student Publications

Background: Preoperative evaluation of the metastasis status of lateral lymph nodes (LNs) in papillary thyroid cancer is challenging. Strategies for using deep learning to diagnosis of lateral LN metastasis require additional development and testing. This study aimed to build a deep learning-based model to distinguish benign lateral LNs from metastatic lateral LNs in papillary thyroid cancer and test the model's diagnostic performance in a real-world clinical setting.

Methods: This was a prospective diagnostic study. An ensemble model integrating a three-dimensional residual network algorithm with clinical risk factors available before surgery was developed based on computed tomography images of lateral LNs …

Impact Of Rural Residence On The Presentation, Management And Survival Of Patients With Non-Metastatic Muscle-Invasive Bladder Carcinoma, Furkan Dursun, Ahmed Elshabrawy, Hanzhang Wang, Dharam Kaushik, Michael A Liss, Robert S Svatek, John L Gore, Ahmed M Mansour

Faculty, Staff and Student Publications

Purpose: To assess the impact of rural and remote residence on the receipt of guidelines-recommended treatment, quality of treatment and overall survival (OS) in patients with non-metastatic muscle-invasive bladder cancer (MIBC).

Materials and methods: Patients with MIBC were identified using National Cancer Database. Patients were classified into three residential areas. Logistic regression models were used to assess associations between geographic residence and receipt of radical cystectomy (RC) or chemoradiation therapy (CRT). Models were fitted to assess quality benchmarks of RC and CRT.

Results: We identified 71,395 patients. Of those 58,874 (82.5%) were living in Metro areas, 8,534 (11.9%) in urban-rural …

Phase Ii Study Of Cladribine, Idarubicin, And Ara-C (Clia) With Or Without Sorafenib As Initial Therapy For Patients With Acute Myeloid Leukemia, Tapan M Kadia, Farhad Ravandi, Matteo Molica, Alex Bataller, Gautam Borthakur, Naval Daver, Elias Jabbour, Courtney D Dinardo, Naveen Pemmaraju, Nitin Jain, Alessandra Ferrajoli, Musa Ylimaz, Prithviraj Bose, Rebecca Slack Tidwell, Kayleigh R Marx, Caitlin R Rausch, Rashmi Kanagal-Shamanna, Sa Wang, Rabiul Islam, Richard Champlin, Elizabeth Shpall, Marina Konopleva, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1-5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). …

Mitochondrial Health Index Correlates With Plasma Circulating Cell-Free Mitochondrial Dna In Bipolar Disorder, Rafaela C Cordeiro, Camila N C Lima, Gabriel R Fries, Giovana Zunta-Soares, Jair C Soares, João Quevedo, Giselli Scaini

Faculty, Staff and Student Publications

Although mitochondrial dysfunction is known to play an essential role in the pathophysiology of bipolar disorder (BD), there is a glaring gap in our understanding of how mitochondrial dysfunction can modulate clinical phenotypes. An emerging paradigm suggests mitochondria play an important non-energetic role in adaptation to stress, impacting cellular resilience and acting as a source of systemic allostatic load. Known as mitochondrial allostatic load, this (phenomenon) occurs when mitochondria are unable to recalibrate and maintain cell homeostasis. This study aimed to evaluate the composite mitochondrial health index (MHI) in BD subjects and non-psychiatry controls. We will also explore whether lower …

Long-Term Utilization And Benefit Of Luspatercept In Transfusion-Dependent, Erythropoiesis-Stimulating Agent-Refractory Or -Intolerant Patients With Lower-Risk Myelodysplastic Syndromes With Ring Sideroblasts, Uwe Platzbecker, Valeria Santini, Rami S Komrokji, Amer M Zeidan, Guillermo Garcia-Manero, Rena Buckstein, Dimana Miteva, Karen Keeperman, Natalia Holot, Jose Alberto Nadal, Yinzhi Lai, Sadanand Vodala, Barbara Rosettani, Ana Carolina Giuseppi, Aylin Yucel, Pierre Fenaux

Faculty, Staff and Student Publications

No abstract provided.

A Case Report Of Anesthesia-Induced Diffuse Alveolar Hemorrhage Presenting To The Emergency Department, Daniel Yiu, Christopher Stephens, Jacquelyn Mccullough, Lesley Osborn

Faculty, Staff and Student Publications

Introduction: The inhaled anesthetic sevoflurane is an uncommon etiology of diffuse alveolar hemorrhage (DAH). As DAH typically presents in the inpatient, postoperative setting, it has been infrequently reported in the anesthesiology literature and, to our knowledge, has not been reported in the emergency medicine literature to date.

Case report: We describe the presentation of a young, healthy male in respiratory distress to a busy urban emergency department (ED) after an outpatient surgical procedure. We highlight the etiology of post-anesthesia DAH and the acute management of this rare diagnosis in the ED.

Conclusion: With outpatient surgical centers becoming an increasingly popular …

Comparison Of Trends Of Inpatient Charges Among Primary And Revision Shoulder Arthroplasty Over A Decade: A Regional Database Study, Trevor Simcox, Aidan G Papalia, Brandon Passano, Utkarsh Anil, Charles Lin, William Mitchell, Joseph D Zuckerman, Mandeep S Virk

Faculty, Staff and Student Publications

Background: This study examined trends in inpatient charges for primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA), hemiarthroplasty (HA), and revision total shoulder arthroplasty (revTSA) over the past decade.

Methods: The New York Statewide Planning and Research Cooperative System was queried for patients undergoing primary aTSA, rTSA, HA, and revTSA from 2010 to 2020 using International Classification of Diseases procedure codes. The primary outcome measured was total charges per encounter. Secondary outcomes included accommodation and ancillary charges, charges covered by insurance, and facility volume. Ancillary charges were defined as fees for diagnostic and therapeutic services and …

Ramipril For The Treatment Of Covid-19: Ramic, A Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Daniel Q Huang, Veeral Ajmera, Christian Tomaszewski, Andrew Lafree, Ricki Bettencourt, Wesley K Thompson, Davey M Smith, Atul Malhotra, Ravindra L Mehta, Vaishal Tolia, Jeffrey Yin, Paul A Insel, Stone Leachman, Jinho Jung, Summer Collier, Lisa Richards, Kristin Woods, Maral Amangurbanova, Archana Bhatt, Xinlian Zhang, Oana M Penciu, Stuart Zarich, Tamrat Retta, Michelle S Harkins, J Pedro Teixeira, Brian Chinnock, Netanya S Utay, Jordan E Lake, Rohit Loomba

Faculty, Staff and Student Publications

Introduction: Retrospective studies report that angiotensin-converting enzyme inhibitors (ACEIs) may reduce the severity of COVID-19, but prospective data on de novo treatment with ACEIs are limited. The RAMIC trial was a randomized, multicenter, placebo-controlled, double-blind, allocation-concealed clinical trial to examine the efficacy of de novo ramipril versus placebo for the treatment of COVID-19.

Methods: Eligible participants were aged 18 years and older with a confirmed diagnosis of SARS-CoV-2 infection, recruited from urgent care clinics, emergency departments, and hospital inpatient wards at eight sites in the USA. Participants were randomly assigned to daily ramipril 2.5 mg or placebo orally in a …

Animal Models In Systemic Sclerosis: An Update, Xiongjie Bi, Tingting Mills, Minghua Wu

Faculty, Staff and Student Publications

Purpose of review: Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by early inflammation followed by excessive fibrosis in the skin and internal organs. Enhancing our comprehension of SSc pathogenesis is essential to develop effective therapeutic strategies. Animal models that mimic one or more aspects of SSc have been proven to be a valuable resource for investigating disease mechanisms. This review aims to provide an updated overview of the existing SSc animal models and the potentially relevant pathways to SSc pathogenesis.

Recent findings: This review focuses on the most recently generated and investigated animal models, which delve …

Optogenetic Stimulation Of Ca1 Pyramidal Neurons At Theta Enhances Recognition Memory In Brain Injured Animals, John I Broussard, John B Redell, Jing Zhao, Rebecca West, Ryota Homma, Pramod K Dash

Faculty, Staff and Student Publications

The hippocampus plays a prominent role in learning and memory formation. The functional integrity of this structure is often compromised after traumatic brain injury (TBI), resulting in lasting cognitive dysfunction. The activity of hippocampal neurons, particularly place cells, is coordinated by local theta oscillations. Previous studies aimed at examining hippocampal theta oscillations after experimental TBI have reported disparate findings. Using a diffuse brain injury model, the lateral fluid percussion injury (FPI; 2.0 atm), we report a significant reduction in hippocampal theta power that persists for at least three weeks after injury. We questioned whether the behavioral deficit associated with this …

Design And Development Of A Clot Burst Pressure Device To Investigate Resuscitation Strategies, Atharwa R Mankame, Jacob B Schriner, Max A Skibber, Mitchell J George, Jessica C Cardenas, Charles S Cox, Brijesh S Gill

Faculty, Staff and Student Publications

Introduction: A reduction in clot strength is a hallmark feature of trauma-induced coagulopathy. A better understanding of clot integrity can optimize resuscitation strategies. We designed a device to gauge clot strength by pressurizing fluids over a formed clot and measuring the pressure needed to dislodge the clot. We hypothesized that this device could distinguish between clots formed in hypocoagulable and hypercoagulable states by observing differences in the clot burst pressure.

Methods: Whole blood from healthy volunteers was collected into sodium citrate tubes and was treated with heparin or fibrinogen to generate clots in a hypocoagulable or hypercoagulable state, respectively. Small …

Elevated Blood Pressure Accelerates White Matter Brain Aging Among Late Middle-Aged Women: A Mendelian Randomization Study In The Uk Biobank, Li Feng, Zhenyao Ye, Chen Mo, Jingtao Wang, Song Liu, Si Gao, Hongjie Ke, Travis A Canida, Yezhi Pan, Marleen M J Van Greevenbroek, Alfons J H M Houben, Kai Wang, Kathryn S Hatch, Yizhou Ma, David K Y Lei, Chixiang Chen, Braxton D Mitchell, L Elliot Hong, Peter Kochunov, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear.

METHODS: In this study, we focused on N  = 228 473 individuals of European ancestry who had genotype data and clinical BP measurements available (103 929 men and 124 544 women, mean age = 56.49, including 16 901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity …