Medical Specialties Commons^™

Update On Mri In Evaluation And Treatment Of Endometrial Cancer, Ekta Maheshwari, Stephanie Nougaret, Erica B Stein, Gaiane M Rauch, Ken-Pin Hwang, R Jason Stafford, Ann H Klopp, Pamela T Soliman, Katherine E Maturen, Andrea G Rockall, Susanna I Lee, Elizabeth A Sadowski, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, …

Landmark Mediation Survival Analysis Using Longitudinal Surrogate, Jie Zhou, Xun Jiang, H Amy Xia, Brian P Hobbs, Peng Wei

Faculty, Staff and Student Publications

Clinical cancer trials are designed to collect radiographic measurements of each patient's baseline and residual tumor burden at regular intervals over the course of study. For solid tumors, the extent of reduction in tumor size following treatment is used as a measure of a drug's antitumor activity. Statistical estimation of treatment efficacy routinely reduce the longitudinal assessment of tumor burden to a binary outcome describing the presence versus absence of an objective tumor response as defined by RECIST criteria. The objective response rate (ORR) is the predominate method for evaluating an experimental therapy in a single-arm trial. Additionally, ORR is …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Comparison Of Psma-Based 18f-Dcfpyl Pet/Ct And Pelvic Multiparametric Mri For Lesion Detection In The Pelvis In Patients With Prostate Cancer, Trinh T Nguyen, Priya R Bhosale, Guofan Xu, Tinsu Pan, Peng Wei, Yang Lu

Faculty, Staff and Student Publications

Purpose: To directly compare the performance of pelvic mpMRI versus recently approved and increasingly used PSMA-based 18F-DCFPyL PET/CT in intermediate-high risk and biochemical recurrent prostate cancer patient cohort while exploring their potential differing applications in specific clinical scenarios.

Methods: A retrospective analysis was performed on patients who had 18F-DCFPyL PET/CT and pelvic mpMRI done from September 2021 to January 2022 at a single institution. The inclusion criteria were paired exams within a 3-month interval. Exclusion criteria were intervening treatment between exams, a change in PSA by more than 50% and absolute difference more than 1 ng/mL, or concurrent history of …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson, Ambro Van Hoof

Faculty, Staff and Student Publications

The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Growth In Achondroplasia Including Stature, Weight, Weight-For-Height And Head Circumference From Clarity: Achondroplasia Natural History Study-A Multi-Center Retrospective Cohort Study Of Achondroplasia In The Us, Julie E Hoover-Fong, Kerry J Schulze, Adekemi Y Alade, Michael B Bober, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria E Serna, Cory Smid, Chengxin Liu, John Mcgready

Faculty, Staff and Student Publications

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments …

Phase 3 Safety And Efficacy Of Azd1222 (Chadox1 Ncov-19) Covid-19 Vaccine, Ann R Falsey, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene Mcevoy, Edwin Dejesus, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele, Susan Buchbinder, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Martha C Nason, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS: …

Intra-Tumoral Nerve-Tracing In A Novel Syngeneic Model Of High-Grade Serous Ovarian Carcinoma, Jeffrey L Barr, Allison Kruse, Anthony C Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J Vermeer, Caitlin S Williamson, Daniel W Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A Mitchell, Anna Budina, Dalia K Omran, Lauren E Schwartz, Ronny Drapkin, Paola D Vermeer

Faculty, Staff and Student Publications

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. …

Radioembolization With Chemotherapy For Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase Iii Trial, Mary F Mulcahy, Armeen Mahvash, Marc Pracht, Amir H Montazeri, Steve Bandula, Robert C G Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S Johnson, Constantinos T Sofocleous, Siddharth A Padia, Robert J Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem

Faculty, Staff and Student Publications

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).

METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and

RESULTS: Four hundred twenty-eight patients from …

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Development And Testing Of The Stakeholder Quality Improvement Perspectives Survey (Squips), Eric Fris, Emily Sedlock, Jason Etchegaray, Madelene J Ottosen, Ronald Pucio, Tejal Mistry, Tamara Saunders, Andrada Tomoaia-Cotisel, Eric J Thomas

Faculty, Staff and Student Publications

BACKGROUND: To create a theory-informed survey that quality improvement (QI) teams can use to understand stakeholder perceptions of an intervention.

METHOD: We created the survey then performed a cross-sectional survey of QI stakeholders of three QI projects. The projects sought to: (1) reduce unplanned extubations in a neonatal intensive care unit; (2) maintain normothermia during colorectal surgery and (3) reduce specimen processing errors for ambulatory gastroenterology procedures. We report frequencies of responses to survey items, results of exploratory factor analysis, and how QI team leaders used the results.

RESULTS: Overall we received surveys from 319 out of 386 eligible stakeholders …

Temperature Changes During Implant Osteotomy Preparations In Human Cadaver Tibiae Comparing Mis® Straight Drills With Densah® Burs, Andrew C Griggs, Crystal M Fausett, Richard J Simonson, Kimberly N Williams, Tiffany M Bisbey, Elizabeth H Lazzara, Joseph R Keebler, Deborah Diazgranados, Vimal K Mishra, Eric J Thomas, Eduardo Salas

Faculty, Staff and Student Publications

INTRODUCTION: Telerounding is slated to become an important avenue for future healthcare practice. As utilization of telerounding is increasing, a review of the literature is necessary to distill themes and identify critical considerations for the implementation of telerounding. We provide evidence of the utility of telerounding and considerations to support its implementation in future healthcare practice based on a scoping review.

METHOD: We collected articles from nine scientific databases from the earliest dated available articles to August 2020. We identified whether each article centered on telerounding policies, regulations, or practice. We also organized information from each article and sorted themes …

Central Line Associated Bloodstream Infection Caused By Kodamaea Ohmeri In A Young Child, Amier Haidar, Farhana Khaja, Brian Simms, Amr Issam Elgehiny, Tracy Omoegbele, Nikita Khetan

Faculty, Staff and Student Publications

INTRODUCTION:

CASE REPORT: The patient is a 5-year-old male with a history of short gut syndrome, and total parenteral nutrition (TPN) dependence who presented to the emergency room with a two-day history of productive-cough, rhinorrhea, and fever. Antibiotic therapy was initiated with cefepime and vancomycin for suspected CLABSI. However, within the first twenty-four hours of his admission, his initial blood culture from his central venous catheter became positive for yeast so fluconazole was added due to suspicion of candidemia. During his admission, his initial central line and peripheral blood culture were later speciated as

CONCLUSIONS: This case report further acknowledges …

Dietary Supplementation Of Bacillus-Based Probiotics On The Growth Performance, Gut Morphology, Intestinal Microbiota And Immune Response In Low Biosecurity Broiler Chickens, Mohammad Arif, Md Akteruzzaman, Tuhin-Al-Ferdous, Sk Shaheenur Islam, Bidhan Chandra Das, Mahbubul Pratik Siddique, S M Lutful Kabir

Faculty, Staff and Student Publications

A feeding trial was conducted to evaluate the effects of Bacillus-based probiotics on growth performance, intestinal histo-morphology, gut microbial population and immune response in broilers. A total of 2000 Hubbard Classic day-old chicks were randomly enrolled in four experimental groups and 4 replicates of 500 birds in each group, and reared for 35 days under a low- level of biosecurity measures. The trial groups were assigned treatment-1 (T1): basal diet(control), treatment-2 (T2): basal diet plus Bacillus licheniformis (DSM17236), treatment-3 (T3): basal diet plus Bacillus subtilis (PB6), and treatment-4 (T4) basal diet plus 4% Flavomycin. All four groups were fed …

Tavr In Older Adults: Moving Toward A Comprehensive Geriatric Assessment And Away From Chronological Age: Jacc Family Series, Joy M Schmitz, Scott D Lane, Michael F Weaver, Ponnada A Narayana, Khader M Hasan, Delisa D Russell, Robert Suchting, Charles E Green

Faculty, Staff and Student Publications

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This …

Modeling Recurrence In Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow, Kyle Kimura, Liping Du, Lynn D Berry, Li-Ching Huang, Sheau-Chiann Chen, David O Francis, Alexander Gelbard

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

METHODS: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS

RESULTS: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year, prospective study comparing surgical treatment efficacy and 385 had appropriate PEF …

Limitations Of Available Blood Products For Massive Transfusion During Mass Casualty Events At Us Level 1 Trauma Centers, James Williams, Michael Gustafson, Yu Bai, Samuel Prater, Charles E Wade, Oscar D Guillamondegui, Mansoor Khan, Megan Brenner, Paula Ferrada, Derek Roberts, Tal Horer, David Kauvar, Andrew Kirkpatrick, Carlos Ordonez, Bruno Perreira, Artai Priouzram, Juan Duchesne, Bryan A Cotton

Faculty, Staff and Student Publications

INTRODUCTION: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospital's supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs.

METHODS: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete …

Defining The Epidemiology Of Safety Risks In Neonatal Intensive Care Unit Patients Requiring Surgery, Daniel J France, Jason Slagle, Emma Schremp, Sarah Moroz, L Dupree Hatch, Peter Grubb, Timothy J Vogus, Matthew S Shotwell, Amanda Lorinc, Christoph U Lehmann, Jamie Robinson, Marlee Crankshaw, Maria Sullivan, Timothy A Newman, Tamara Wallace, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

OBJECTIVE: The aim of the study was to determine the incidence, type, severity, preventability, and contributing factors of nonroutine events (NREs)-events perceived by care providers or skilled observers as a deviations from optimal care based on the clinical situation-in the perioperative (i.e., preoperative, operative, and postoperative) care of surgical neonates in the neonatal intensive care unit and operating room.

METHODS: A prospective observational study of noncardiac surgical neonates, who received preoperative and postoperative neonatal intensive care unit care, was conducted at an urban academic children's hospital between November 1, 2016, and March 31, 2018. One hundred twenty-nine surgical cases in …

Profile Of Autism Spectrum Disorder In Tuberous Sclerosis Complex: Results From A Longitudinal, Prospective, Multisite Study, Jamie K Capal, Marian E Williams, Deborah A Pearson, Robin Kissinger, Paul S Horn, Donna Murray, Kristn Currans, Bridget Kent, Martina Bebin, Hope Northrup, Joyce Y Wu, Mustafa Sahin, Darcy A Krueger, Tacern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is highly associated with autism spectrum disorder (ASD). Objectives of the study were to characterize autistic features in young children with TSC.

METHODS: Participants included 138 children followed from ages 3 to 36 months with TSC from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study aimed at understanding the underlying mechanisms of ASD in TSC. Developmental and autism-specific assessments were administered, and a clinical diagnosis of ASD was determined for all participants at 36 months. Further analyses were performed on 117 participants with valid autism assessments based …

Patient-Derived Ipscs Link Elevated Mitochondrial Respiratory Complex I Function To Osteosarcoma In Rothmund-Thomson Syndrome, Brittany E Jewell, An Xu, Dandan Zhu, Mo-Fan Huang, Linchao Lu, Mo Liu, Erica L Underwood, Jun Hyoung Park, Huihui Fan, Julian A Gingold, Ruoji Zhou, Jian Tu, Zijun Huo, Ying Liu, Weidong Jin, Yi-Hung Chen, Yitian Xu, Shu-Hsia Chen, Nino Rainusso, Nathaniel K Berg, Danielle A Bazer, Christopher Vellano, Philip Jones, Holger K Eltzschig, Zhongming Zhao, Benny Abraham Kaipparettu, Ruiying Zhao, Lisa L Wang, Dung-Fang Lee

Faculty, Staff and Student Publications

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays …

Pre-Exposure Prophylaxis With Various Doses Of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure To Covid-19: A Randomized Controlled Trial, Fibhaa Syed, Muhammad Hassan, Mohammad Ali Arif, Sadia Batool, Rauf Niazi, Ume E Laila, Sadia Ashraf, Junaid Arshad

Faculty, Staff and Student Publications

Objective This trial aimed to evaluate the safety and efficacy of pre-exposure prophylaxis (PrEP) with various hydroxychloroquine (HCQ) doses against a placebo among healthcare personnel (HCP) with high-risk exposure to coronavirus disease 2019 (COVID 19). Methods A phase II, randomized, placebo-controlled trial was conducted including 200 subjects with no active or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (antibody testing and reverse transcription-polymerase chain reaction (RT-PCR) were taken at the time of enrollment). Subjects of experimental groups one to three received HCQ in various doses and the control group received a placebo. The study outcomes in terms of …

Mission-Based Filters In The Electronic Residency Application Service: Saving Time And Promoting Diversity, Jennifer L Swails, Sasha Adams, Mark Hormann, Emma Omoruyi, Omowunmi Aibana

Faculty, Staff and Student Publications

BACKGROUND: Holistic review promotes diversity, but widespread implementation remains limited.

OBJECTIVE: We aimed to develop a practical approach to incorporate holistic review principles in screening applicants in the Electronic Residency Application Service (ERAS) and to assess the impact on diversity.

METHODS: Three residency programs (internal medicine [IM], pediatrics, and surgery) at McGovern Medical School developed filters to identify applicants with experiences/attributes aligned with the institutional mission. These filters were retroactively applied to each program's 2019-2020 applicant pool using built-in ERAS capabilities to group applicants by user-defined features. We compared the demographics of applicants reviewed during the cycle with those identified …

Resistin Levels Decrease As Insulin Resistance Increases In A Mexican-American Cohort, Absalon D Gutierrez, Carlos A Flores, Sapna Naik, Minjae Lee, Parisa Asgarisabet, Masha Resman, Miryoung Lee, Joseph B Mccormick, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

AIMS: Links between resistin, insulin resistance (IR), and resistin-stimulated cytokine signaling remain unknown in Mexican-Americans. A Mexican-American cohort was examined to determine (1) relationships between circulating resistin and IR, (2) resistin's associations with cytokines and demographic and anthropometric variables, and (3) similar measurements with other adipokines.

METHODS: For cross sectional analyses, 953 adults (367 males and 586 females) in the Cameron County Hispanic Cohort (CCHC) were stratified into three groups: normal glucose tolerance, prediabetes, and diabetes mellitus. Differences in resistin and other adipokine levels were examined using linear regression via unadjusted model (Model 1), model adjusted for cytokines (Model 2), …