Medicine and Health Sciences Commons^™

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

Factors Associated With Perceived Medication Safety During Transitions Of Care In Patients With Cancer: A Secondary Data Analysis Of A Cross-Sectional Survey, Youmin Cho, Misun Hwang, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: This study aimed to investigate perceived medication safety in patients with cancer during transitions of care and identify factors associated with their safety perceptions.

Methods: A secondary data analysis was performed on a cross-sectional survey data of from patients with four types of cancer (i.e., colorectal, lung, prostate, and breast). Perceived medication safety was measured by the sum score of four survey items that assessed patients' feelings about medication safety during transitions of care. Potential associated factors included sociodemographic and clinical factors (i.e., cancer types, taking oral anticancer agents), self-rated health, perceived safety in communicating with clinicians, beliefs about …

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Alterations In Gut Microbiome Composition And Increased Inflammatory Markers In Post-Covid-19 Individuals, Tatiana Barichello, Bruno Kluwe-Schiavon, Laura A Borba, Lucas C Pedro, Flávia S Niero, Laísa N Dos Santos, Letícia M Leonardo, Zuleide M Ignácio, Rodrigo Morales, Luciane B Ceretta, Gislaine Z Reus

Faculty, Staff and Student Publications

Dysfunctions in the immune system and alterations in the microbiome composition following SARS-CoV-2 infection contribute to persistent neurological issues observed in long COVID-19 survivors. We hypothesize that alterations in the gut microbiome composition and peripheral inflammatory profile following COVID-19 may play pivotal roles in behavior changes among individuals experiencing long-term illness. This cross-sectional study included a sample of post-COVID-19 and non-COVID-19 subjects. We assessed the presence of psychiatric conditions utilizing standardized diagnostic criteria, Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression (HAM-D), Biological Rhythms in Neuropsychiatry Assessment Interview (BRIAN), and Functional Assessment Short Test (FAST). Plasma samples …

Exploring Potential Ethnic Bias Among Mmpi-3 Scales In Assessing Personality Psychopathology, Nicole Shumaker, Tessa Long, Andy Torres, Alfonso Mercado, Ryan J Marek, Jaime L Anderson

Faculty, Staff and Student Publications

This study examined statistical bias in the measurement of personality psychopathology in the Latinx population using the Minnesota Multiphasic Personality Inventory-3 (MMPI-3). Data were extracted from two studies that yielded a composite data set of 103 White individuals and 250 Latinx individuals. All participants were administered the MMPI-2-Restructured Form-Extended Battery (MMPI-2-RF-EX) or MMPI-3 and the Personality Inventory for the DSM-5 Short Form (PID-5-SF). First, we conducted correlation analyses between theoretically overlapping scales of the PID-5-SF and the MMPI-3 among White and Latinx individuals. The majority of theoretically associated scales were found to be at least moderately associated in the …

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

Novel Treatment-Specific Causal Biomarkers For Colorectal Cancer By Omics Integration, Akram Yazdani, Azam Yazdani, Raul Mendez-Giraldez, Gianluigi Pillonetto, Esmat Samiei, Reza Hadi, Heinz-Josef Lenz, Alan P Venook, Ahmad Samiei, Andrew B Nixon, Joseph A Lucci, Scott Kopetz, Monica M Bertagnolli, Federico Innocenti

Faculty, Staff and Student Publications

While monoclonal antibody-based targeted therapies have substantially improved progression-free survival in cancer patients, the variability in individual responses poses a significant challenge in patient care. Therefore, identifying cancer subtypes and their associated biomarkers is required for assigning effective treatment. In this study, we integrated genotype and pre-treatment tissue RNA-seq data and identified biomarkers causally associated with the overall survival (OS) of colorectal cancer (CRC) patients treated with either cetuximab or bevacizumab. We performed enrichment analysis for specific consensus molecular subtypes (CMS) of CRC and evaluated differential expression of identified genes using paired tumor and normal tissue from an external cohort. …

Impact Of Screening For Human Papillomavirus-Positive Oropharyngeal Cancers: A Microsimulation-Based Modeling Study, Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi

Faculty, Staff and Student Publications

Background: We estimated the impact of screening on morbidity and mortality of human papillomavirus (HPV)16-positive oropharyngeal cancer among US men aged 45-79 years.

Methods: We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed 4 progression speeds across cancer stages (very slow, slow, fast, and very fast) and 4 screening frequencies.

Results: Among US men aged 45-79 years in 2021 (n = 54 …

Association Of Sirt6 Expression With Risk Of Pneumonitis Induced By Radiotherapy In Cancer Patients, Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Miaowei Wen, Bingying Zhao, Zhezhe Xu, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song

Faculty, Staff and Student Publications

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients …

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

Functional Vs Structural Cortical Deficit Pattern Biomarkers For Major Depressive Disorder, Peter Kochunov, Bhim M Adhikari, David Keator, Daniel Amen, Si Gao, Nicole R Karcher, Demetrio Labate, Robert Azencott, Yewen Huang, Hussain Syed, Hongjie Ke, Paul M Thompson, Danny J J Wang, Braxton D Mitchell, Jessica A Turner, Theo G M Van Erp, Neda Jahanshad, Yizhou Ma, Xiaoming Du, William Burroughs, Shuo Chen, Tianzhou Ma, Jair C Soares, L Elliot Hong

Faculty, Staff and Student Publications

Importance: Major depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern-based biomarker for MDD that is linked to the underlying pathophysiology.

Objective: To examine whether cortical ReHo patterns provide a replicable biomarker for MDD that is more sensitive than reduced cortical thickness and evaluate whether the ReHo MDD deficit pattern reflects regional cerebral blood flow (RCBF) deficit patterns in MDD and whether a regional vulnerability index (RVI) thus …

Home-Based Transcranial Direct Current Stimulation For Major Depressive Disorder: 6-Month Follow-Up From Randomised Sham-Controlled Trial And Open-Label Treatment Phases, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Peter J Lagerberg, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, Cynthia H Y Fu

Faculty, Staff and Student Publications

Transcranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our double-blind randomised controlled trial (RCT) (n = 174; UK and USA), a 10-week course of home-based tDCS demonstrated clinical efficacy (clinical response: 58.3 % active treatment arm and 37.8 % sham (p = 0.017). tDCS was delivered in a bifrontal montage, with anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC. Each session was 30 min, with active stimulation at 2 mA and sham at 0 mA, incorporating brief ramp-up and ramp-down phased. Following the 10-week RCT, all participants were …

The Burden Of Burnout: Understanding Its Prevalence And Organizational Drivers In Medical Physics, Deborah Schofield, C Lynn Chevalier, Laurence Court, William Harmsen, Akiva Turner

Faculty, Staff and Student Publications

Background: Burnout is a work-related syndrome characterized by increased levels of emotional exhaustion (EE) and depersonalization (DP) along with decreased levels of personal achievement. In the healthcare setting, higher burnout levels have been associated with negative impacts on personnel, an increased risk of errors, and a decrease in the quality of delivered care.

Purpose: The purpose of this study was to assess the prevalence of burnout among medical physicists working in the United States. Additionally, the impact of personal and organizational features on burnout risk was examined.

Methods: The anonymous survey was distributed to 1962 full members of the American …

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), …

Blockade Of A2ar Improved Brain Perfusion And Cognitive Function In A Mouse Model Of Alzheimer’S Disease, Mariana Sayuri Berto Udo, Julia Zaccarelli-Magalhães, Garrett Alan Clemons, Cristiane Teresinha Citadin, Julia Langman, Drew James Smith, Luiz Henrique Matuguma, Vesna Tesic, Hung Wen Lin

Faculty, Staff and Student Publications

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects more than 6.2 million Americans aged 65 and older, particularly women. Along with AD’s main hallmarks (formation of β-amyloid plaques and tau neurofibrillary tangles), there are vascular alterations that occurs in AD pathology. Adenosine A2 receptor (A2AR) is one of the key factors of brain vascular autoregulation and is overexpressed in AD patients. Our previous findings suggest that protein arginine methyltransferase 4 (PRMT4) is overexpressed in AD, which leads to decrease in cerebral blood flow in aged female 3xTg mice. We aimed to investigate the mechanism behind A2AR signaling in the …

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 …

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 …

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 …

Conduction System Pacing Compared With Biventricular Pacing For Cardiac Resynchronization Therapy In Patients With Heart Failure And Mildly Reduced Left Ventricular Ejection Fraction: Results From International Collaborative Lbbap Study (I-Clas) Group, Pugazhendhi Vijayaraman, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit Sharma, Manuel Molina-Lerma, Marek Jastrzębski, Zachary Whinnett, Kevin Vernooy, Rajeev K Pathak, Roderick Tung, Gaurav Upadhyay, Karol Curila, Dipen Zalavadia, Nischay Shah, Lina Marcantoni, Mohamed Gad, Ramez Morcos, Pawel Moskal, Akriti Naraen, Mishal Mumtaz, Jamario R Skeete, Praneet S Katrapati, Jeffrey Kolominsky, Johan Van Koll, Mihail G Chelu, Kenneth A Ellenbogen, Oscar Cano

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) is a guideline-recommended therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF, 36%-50%) and left bundle branch block or indication for ventricular pacing. Conduction system pacing (CSP) using left bundle branch area pacing or His bundle pacing has been shown to be a safe and physiologic alternative to biventricular pacing (BVP).

Objective: The aim of this study was to compare the clinical outcomes between BVP and CSP for patients with HFmrEF undergoing CRT.

Methods: Consecutive patients who underwent BVP or CSP with HFmrEF between January 2018 and June 2023 at 16 international …

Neuroanatomical Features Of Naa10 And Naa15-Related Neurodevelopmental Syndromes, Rahi Patel, Rikhil Makwana, Carolina Christ, Elaine Marchi, Christina Y Miyake, Fabricio Guimaraes Goncalves, Gholson J Lyon, Matthew T Whitehead

Faculty, Staff and Students Publications

Background: NAA10-related and NAA15-related neurodevelopmental (ND) syndromes present with intellectual disability, hypotonia, cardiac abnormalities, and delayed development. While data exists on the clinical manifestations of these conditions, there are few reports describing the neuroanatomical abnormalities present on imaging.

Objective: We aim to provide neuroimaging analyses for a subset of probands with NAA10- and NAA15-related neurodevelopmental symptoms and assess the severity and number of neuroanatomical anomalies and their associated functional impairments to better understand the pathophysiology of these disease processes.

Materials and methods: Neuroimaging studies were obtained from 26 probands (18 with pathogenic variants in NAA10, 8 with pathogenic variants in …

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 …

Plasma Microbial Cell-Free Dna Sequencing For The Detection Of Kingella Kingae Pediatric Spinal Infections, Asim A Ahmed, Sarah Y Park, Matthew J Smollin, Martin S Lindner, Adriana Sarmiento Clemente, Ana Del Valle Penella, P Marcelo Laufer, Carolina Sanchez-Vegas, Manuel R Cotilla, Marian E Melish, Connie Trieu, Nazia A Kabani, Joshua Cooper, Audrey R Lloyd, David W Kimberlin, John C Arnold, Alejandro Jordan-Villegas, Lori E Patterson, Catherine E Foster, Pablo Yagupsky

Faculty, Staff and Students Publications

Background: Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe's fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae .

Methods: Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age < 18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction).

Results: Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11-23 months). All case-patients had vertebral osteomyelitis …

Ophthalmology Examinations In Children With Skull Fractures And Underlying Focal Hemorrhage, Karli Breeden, Cindy W Christian, Joanne N Wood, Gil Binenbaum, Daniel M Lindberg, Angela Bachim, Colleen J Bressler, Lori Frasier, Terra Frazier, Nicole R Johnson, Natalie Laub, Megan M Letson, Tagrid Ruiz-Maldonado, Matthew Valente, Jenna Kiely, Jan Leonard, M Katherine Henry

Faculty, Staff and Students Publications

Objectives: To assess the frequency and yield of retinal examination in children below 2 years old undergoing abuse evaluations in the setting of skull fracture(s) and small underlying intracranial hemorrhage.

Methods: This cross-sectional study used CAPNET, a multicenter child physical abuse network, to identify children below 2 years with a skull fracture(s) and intracranial injury limited to an underlying small focal intracranial hemorrhage undergoing subspeciality child abuse evaluations. Our outcomes of interest were (1) the performance of a retinal examination, (2) the identification of retinal hemorrhages, and (3) associations of clinical factors and CAPNET site with the performance of retinal …

Linking Symptom Inventories Using Semantic Textual Similarity, Eamonn Kennedy, Shashank Vadlamani, Hannah M Lindsey, Kelly S Peterson, Kristen Dams O'Connor, Ronak Agarwal, Houshang H Amiri, Raeda K Andersen, Talin Babikian, David A Baron, Erin D Bigler, Karen Caeyenberghs, Lisa Delano-Wood, Seth G Disner, Ekaterina Dobryakova, Blessen C Eapen, Rachel M Edelstein, Carrie Esopenko, Helen M Genova, Elbert Geuze, Naomi J Goodrich-Hunsaker, Jordan Grafman, Asta K Håberg, Cooper B Hodges, Kristen R Hoskinson, Elizabeth S Hovenden, Andrei Irimia, Neda Jahanshad, Ruchira M Jha, Finian Keleher, Kimbra Kenney, Inga K Koerte, Spencer W Liebel, Abigail Livny, Marianne Løvstad, Sarah L Martindale, Jeffrey E Max, Andrew R Mayer, Timothy B Meier, Deleene S Menefee, Abdalla Z Mohamed, Stefania Mondello, Martin M Monti, Rajendra A Morey, Virginia Newcombe, Mary R Newsome, Alexander Olsen, Nicholas J Pastorek, Mary Jo Pugh, Adeel Razi, Jacob E Resch, Jared A Rowland, Kelly Russell, Nicholas P Ryan, Randall S Scheibel, Adam T Schmidt, Gershon Spitz, Jaclyn A Stephens, Assaf Tal, Leah D Talbert, Maria Carmela Tartaglia, Brian A Taylor, Sophia I Thomopoulos, Maya Troyanskaya, Eve M Valera, Harm Jan Van Der Horn, John D Van Horn, Ragini Verma, Benjamin S C Wade, Willian C Walker, Ashley L Ware, J Kent Werner, Keith Owen Yeates, Ross D Zafonte, Michael M Zeineh, Brandon Zielinski, Paul M Thompson, Frank G Hillary, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Students Publications

An extensive library of symptom inventories has been developed over time to measure clinical symptoms of traumatic brain injury (TBI), but this variety has led to several long-standing issues. Most notably, results drawn from different settings and studies are not comparable. This creates a fundamental problem in TBI diagnostics and outcome prediction, namely that it is not possible to equate results drawn from distinct tools and symptom inventories. Here, we present an approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories by ranking item text similarities according to their conceptual likeness. We tested …

Psychometric Properties Of The Spanish Yale-Brown Obsessive-Compulsive Scale - Second Edition, Eric A Storch, Jessica Sc Cheng, Miranda Higham, Josselyn S Muñoz, Vanessa Zavala Cruz, Dayan Berrones, Diana P Obando, Jacey L Anderberg, Renee M Frederick, Vissente Tapia-Cuevas, Macarena Churruca Muñoz, Constanza Uribe Villar, Pablo R Moya, Marcos E Ochoa-Panaifo, Mayra C Martinez Mallen, Andrew D Wiese, Caitlin M Pinciotti, Melisa N Sagarnaga, Joseph F Mcguire, Ogechi C Onyeka, María B Moyano, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), Wayne K Goodman, James J Crowley

Faculty, Staff and Students Publications

The Yale-Brown Obsessive-Compulsive Scale, Second Edition (Y-BOCS-II) is an evidence-based clinician-rated measure for assessing the presence and severity of obsessive-compulsive symptoms. The Spanish version of the Y-BOCS-II has not yet been validated. The present study examines the psychometric properties of the Spanish Y-BOCS-II (Spanish-Y-BOCS-II) in adults with obsessive-compulsive disorder (OCD) who are of Hispanic/Latino ancestry. The Spanish-Y-BOCS-II was administered to 1805 adults with OCD. Participants also completed a battery of measures assessing OCD, depression, and anxiety symptoms. The internal consistency for the Symptom Checklist (Kuder-Richardson-20=0.92), Obsession Severity (α=0.87), Compulsion Severity (α=0.86), and Total Severity (α=0.92) were high. The inter-rater reliability …

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 …

Detection Of Enterovirus Rna In Pancreas And Lymphoid Tissues Of Organ Donors With Type 1 Diabetes, Jutta E Laiho, Sami Oikarinen, Sofia Morfopoulou, Maarit Oikarinen, Ashlie Renner, Daniel Depledge, Matthew C Ross, Ivan C Gerling, Judith Breuer, Joseph F Petrosino, Vincent Plagnol, Alberto Pugliese, Antonio Toniolo, Richard E Lloyd, Heikki Hyöty, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. The aim of the current work was to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and without type 1 diabetes.

Methods: We analysed pancreas, spleen, pancreatic lymph nodes and duodenum samples from the following groups: (1) donors with type 1 diabetes (n=71) with (n=35) or without (n=36) insulin-containing islets; (2) donors with single or …

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 …

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 …