Digital Commons Network^™

An Annotated Biobank Of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve And Longitudinal Samples During Neoadjuvant Chemotherapy, Amanda L Rinkenbaugh, Yuan Qi, Shirong Cai, Jiansu Shao, Faiza Baameur Hancock, Sabrina L Jeter-Jones, Xiaomei Zhang, Emily Powell, Lei Huo, Rosanna Lau, Chunxiao Fu, Rebekah Gould, Petra Den Hollander, Elizabeth E Ravenberg, Jason B White, Gaiane M Rauch, Banu Arun, Clinton Yam, Alastair M Thompson, Gloria V Echeverria, Stacy L Moulder, W Fraser Symmans, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing …

Orphan Nuclear Receptor 4a1 (Nr4a1) And Nr4a2 Are Endogenous Regulators Of Cd71 And Their Ligands Induce Ferroptosis In Breast Cancer, Arafat Rahman Oany, Srijana Upadhyay, Wai Ning Tiffany Tsui, Amanuel Hailemariam, Sarah Latka, John D Landua, Sandra D Scherer, Alana L Welm, Hugo Villanueva, Michael T Lewis, Stephen Safe

Faculty, Staff and Students Publications

Ferroptosis is an iron-dependent cell death pathway that involves multiple genes, including the transferrin receptor (TFRC/CD71), glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11). This study is based on the hypothesis that orphan nuclear receptor 4A1 (NR4A1) and NR4A2 maintain low levels of ferroptosis in triple negative breast cancer (TNBC) cells and bis-indole derived (CDIM) compounds act as NR4A1/2 ligands that induce ferroptosis by enhancing CD71 expression. 1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs were investigated for their cytotoxicity and effects on NR4A1 and NR4A2 regulated genes and induction of ferroptosis. Several assays also determined enhanced lipoperoxidation, reactive oxygen species and malondialdehyde formation in …

Availability Of Multidisciplinary Treatment Modalities And Outcomes Among Patients With Resected Early-Stage Non-Small Cell Lung Cancer, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Ana A Baumann, Theodore S Thomas, Steven Tohmasi, Nikki Rossetti, Daniel Kreisel, Ruben G Nava, Bryan F Meyers, Benjamin D Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Comprehensive, multidisciplinary care is crucial for managing early-stage non-small cell lung cancer (NSCLC), typically treated via lung resection or stereotactic body radiation therapy (SBRT). We evaluated how variable access to on-site SBRT may be associated with clinical outcomes for patients with stage I NSCLC receiving surgical resection within an integrated health-care system.

METHODS: We performed a retrospective cohort study of patients with stage I NSCLC treated with lung resection at Veterans Health Administration (VHA) facilities between 2006 and 2016. The VHA provides thoracic surgery at approximately 100 facilities, whereas lung SBRT is currently available at approximately 20 facilities. We …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Changes In Walking Performance Under Dual Task Conditions Across Pregnancy – A Case Study, Nikola Chmura, Wanda Forczek-Karkosz

ISBS Proceedings Archive

In recent years there is a growing literature on the walking pattern during pregnancy in the context of preventing falls as pregnancy progresses (Błaszczyk et al. 2016). The study examines the impact of pregnancy on walking under dual-task conditions. A 27-year-old participant was assessed in her first and third trimester for gait parameters and cognitive function changes. Results showed slower walking speed, prolonged double support phase, and a wider base of support, especially when performing an additional task. The DIVA test revealed impaired attention and increased errors.Findings highlight the effect of cognitive load on stability in pregnant women, potentially increasing …

Prenatal Metabolomics Analysis And Fetal Congenital Anomalies And Genetic Conditions: A Review Of Current Literature, Sarah Araji, Onur Turkoglu, Mohamad Ali Maktabi, Tracy Ashby, Ignatia B Van Den Veyver

Library Staff Publications

Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we …

Insights Into Early Adoption And Physician Learning Curve Of Pulsed Field Ablation In The United States., Amin Al-Ahmad, Daniela Hincapie-Tabares, Paul C Zei, Andrea Natale, David Kessler, Joe Gallinghouse, Weeranun Bode, Jose Osorio, Jonathan W Dukes, Robert Eckart, Anish Amin, Yoel Vivas, Luis Mora, Amit Thosani, Joshua Silverstein, Anil Rajendra, Gustavo Morales, Michael Manogue, Joseph Donnelly, Frank Cuoco, Darren Sidney, Robert Brewer, Jason Meyers, Mark D Metzl, Guru Mohanty, Michael Rehorn, Paari Dominic, John D Day, Nischala Nannapaneni, John Costello

OhioHealth Research Institute Articles

BACKGROUND: Pulsed field ablation (PFA) has been available in Europe since 2021. In the United States, PFA became commercially available in 2024, and practice patterns are expected to differ from those in Europe. The objective of this study was to describe acute procedural efficiency and safety outcomes, clinical workflow patterns, and the physician learning curve associated with PFA for paroxysmal and nonparoxysmal atrial fibrillation in the first US real-world registry.

METHODS: DISRUPT-AF (A Registry Based Collaborative to Measure Efficiency, Effectiveness, and Safety of Farapulse PFA Technology for AF) is a prospective, multicenter registry capturing patient-level data on first-time PFA procedures …

Neurometabolic And Vascular Dysfunction As An Early Diagnostic For Alzheimer's Disease And Related Dementias., Juan Antonio K Chong Chie, Scott A Persohn, Ravi S Pandey, Gregory W. Carter, Olivia R Simcox, Paul Salama, Paul R Territo, The Alzheimer’S Disease Neuroimaging Initiative

Faculty Research 2025

INTRODUCTION: Recent studies suggest that the brain undergoes anatomical and functional restructuring, resulting in neurometabolic and vascular dysregulation (MVD) prior to amyloid beta accumulation, which begins at an early age and leads to the onset of Alzheimer's disease (AD).

METHODS: Using a retrospective clinical population (n = 403) from the Alzheimer's Disease Neuroimaging Initiative, cerebral perfusion and metabolism changes across 59 brain regions were evaluated from clinical studies. Results were verified by transcriptomic signatures and clinical cognitive assessments.

RESULTS: Our findings suggest that disease progression follows a stage-dependent MVD pattern that can identify at-risk regions. Although each region progresses at …

New Onset Of Comorbidities In People With Epilepsy In A National Healthcare Claims Database., Edward Faught, Emily Klatte, Clarence T Wade, Sean Stern, Wesley T Kerr

Neuroscience Articles

PURPOSE: This study evaluated the rate of new occurrence of select comorbidities in adults after events of uncontrolled epilepsy versus controlled epilepsy.

METHODS: The HealthVerity Marketplace Inovalon healthcare claims database was used. Adults (≥18 years) with an epilepsy diagnosis (ICD-10-CM G40*) prescribed at least one antiseizure medication (ASM) between January 1, 2015, and December 31, 2021, were included. Patients were categorized as having either a first-filled or third-filled ASM. The first ASM filled was defined as no ASMs filled for at least 1 year of enrollment. Uncontrolled epilepsy events within 1 year of new ASM initiation were: seizure-related inpatient or …

J. Robert Gladden Orthopaedic Society Research Grants: What Is The Return On Invesments, Lancelot Benn, Susan Stephens, Mark Ehioghae, Rishi Balkissoon, Brendan A. Williams, Shaina Lipa, David N. Bernstein, Gbolabo Sokunbi, Barrett I. Woods, Wakenda Tyler, Jaysson Brooks, Randall C. Morgan, Kwadwo Owusu-Akyaw, Wayne Johnson, Eric Carson, George V. Russell, Addisu Mesfin

Rothman Institute Papers

INTRODUCTION: The J. Robert Gladden Orthopaedic Society (JRGOS) aims to increase diversity in orthopaedic surgery and promote high-quality musculoskeletal care for all. Through targeted research funding, JRGOS supports projects aligned with its mission. Despite awarding over $300,000 in research grants since 2011, the return on investment (ROI) of this program has not been analyzed. This study evaluates the ROI of JRGOS research grants from 2011 to 2023.

METHODS: We conducted a retrospective review of all JRGOS research grants awarded between 2011 and 2023. Data included recipient demographics, grant titles, award year, institution, and amount. PubMed and Google Scholar were used …

Differences In Patient And Parent Preferences For Prognostic Communication Across Disease Milestones In Advanced Childhood Cancer, Rachel A Kentor, Shoshana Mehler, Caroline Christianson, Harmony Farner, Tara M Brinkman, Justin N Baker, Pamela S Hinds, Jennifer W Mack, Erica C Kaye

Faculty, Staff and Students Publications

Background: Navigating prognostic communication is challenging for clinicians caring for adolescents and young adults (AYAs) with poor-prognosis cancer. Presently, little is known about how AYA and parent preferences for prognostic disclosure evolve over time. This study explored communication preferences at key illness milestones of disease progression to inform individualized, person-centered approaches to optimize prognostic disclosure.

Procedure: Sixty-five participants, including 25 AYAs aged 12-25 years and 40 parents, were recruited at distinct illness timepoints-diagnosis, relapse/progression, Phase I/II trial enrollment, and bereavement-to participate in semi-structured interviews about their preferences for timing, style, and content of prognostic communication. Rapid analysis was conducted to …

High Risk Of Persistence And Risk Of Dysplasia After Diagnosis Of Ultrashort Barrett's Esophagus, Wasseem Skef, Jasmine Haydel, Ashwin Rao, Ronan Allencherril, Rollin George, Gyanprakash A Ketwaroo, Aaron P Thrift, Hashem B El-Serag, Theresa Nguyen Wenker

Faculty, Staff and Students Publications

Introduction: The management of ultrashort (< 1 cm) Barrett's esophagus (BE) remains unclear. We aimed to determine the prevalence of ultrashort BE (USBE) at index diagnosis, identify factors associated with persistent BE after USBE diagnosis, and identify risk of dysplasia after initial USBE in a population of US veterans.

Methods: This was a retrospective cohort study at the Veterans Affairs hospital in Houston, TX, of consecutive patients with new BE diagnosis from November 1990 to June 2022 with follow-up through April 2023. Using a pathology database, we identified patients with a new USBE diagnosis and any subsequent follow-up esophagogastroduodenoscopy (EGD). We examined the association of sociodemographic and clinical risk factors of persistent USBE cohort compared with longer-length segment BE and those with a negative follow-up EGD after index USBE with χ 2 tests and logistic regression models. Last, we calculated the prevalence and …

Management Of Patients With Heart Failure At High Risk Of Hyperkalaemia: The Care-Hk In Hf Registry, Stephen J Greene, Andrew J Sauer, 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, Victoria Donachie, Solenn Fabien, Sandra Waechter, Maria G Crespo-Leiro, Martin Hülsmann, Tibor Kempf, Otmar Pfister, Anne-Catherine Pouleur, Manish Saxena, Martin Schulz, Maurizio Volterrani, Stefan D Anker, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Aims: Patients with heart failure (HF) at high risk for hyperkalaemia are underrepresented in prospective HF registries. The CARE-HK in HF registry sought to characterize prospectively the clinical profile, management, and outcomes for patients with HF at high risk of hyperkalaemia.

Methods and results: CARE-HK in HF was a multinational prospective registry of outpatients with HF (regardless of left ventricular ejection fraction [LVEF]) treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI) and either receiving or potential candidate for a mineralocorticoid receptor antagonist (MRA). All patients were at increased risk of hyperkalaemia, defined as hyperkalaemia at baseline, …

Ambulatory Acute Kidney Injury In Patients With Cirrhosis Is Common And Burdensome, Kavish R Patidar, Ruben Hernaez, Yan Liu, George Cholankeril, Jennifer R Kramer, Thom Taylor, Prasun Jalal, Tzu-Hao Lee, Avegail G Flores, Giuseppe Cullaro, Andrew S Allegretti, Pere Gines, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: Little is known about ambulatory acute kidney injury (A-AKI), which develops in an outpatient setting.

Methods: We conducted a retrospective cohort study of patients diagnosed with cirrhosis between January 1, 2018, and December 31, 2019 from 130 hospitals in the Veterans Affairs healthcare system. Patients were classified as having incident A-AKI if they met the International Club of Ascites AKI criteria in an outpatient setting. We used multivariable regression models to identify factors associated with A-AKI development within 1 year of cirrhosis diagnosis. We also conducted a structured implicit review of patients' medical charts to determine the …

Low Socioeconomic Status Adversely Influences Outcomes After Coronary Artery Bypass Grafting, Paige E Brlecic, Christopher B Sylvester, Katie J Hogan, Qianzi Zhang, Joseph S Coselli, Marc R Moon, Todd K Rosengart, Subhasis Chatterjee, Ravi K Ghanta

Faculty, Staff and Students Publications

Objectives: Although socioeconomic status (SES) is believed to affect patient outcomes after coronary artery bypass grafting (CABG), readmission data are sparse. In a national cohort, we analyzed the influence of SES on readmission, resource utilization, and mortality after CABG.

Methods: We queried the Nationwide Readmissions Database to identify patients who underwent isolated CABG from January 2016 through December 2018. We derived low, middle, and high SES from International Classification of Diseases, 10th Revision, Clinical Modification codes, patient demographics, and neighborhood-level factors. The effect of SES on risk-adjusted outcomes was assessed with multivariable analysis.

Results: Of 523,042 patients who underwent CABG, …

Ocular Bacterial Microbiome Analysis By Next-Generation Sequencing In Patients With Stevens-Johnson Syndrome And Sjögren’S Disease: Associations With Dry Eye Indices, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Ana Luisa Hofling-Lima, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

The ocular surface microbiome plays a crucial role in maintaining immune homeostasis, and its disruption may contribute to mucosal inflammation and autoimmunity. This pilot exploratory study investigated and compared the ocular surface bacterial microbiome in patients with Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), and healthy controls using next-generation sequencing (NGS) and correlated these findings with dry eye parameters. Conjunctival swabs were collected from sixteen individuals: ten with SJS, three with SjD, and three healthy controls. Dry eye parameters were employed to evaluate the dry eye disease. Microbiome profiles were determined by the NGS of the 16S V3-V4 region and analyzed …

Association Of Preoperative Nocturnal Hypoxaemia Nadir And Fentanyl Ventilatory Sensitivity In Children With Obstructive Sleep Apnoea Undergoing General Anaesthesia: A Multicentre Clinical Cohort Study, Adam C Adler, Elaina E Lin, Anna H Messner, Tara L Rosenberg, Shelly Pecorella, Aidan Keleghan, Spencer Faircloth, T Wesley Templeton, Lynnette Harris, Sabina A Khan, Greesha S Pednekar, Duc T Nguyen, Arvind Chandrakantan, Britta S Von Ungern-Sternberg

Faculty, Staff and Students Publications

Background: Obstructive sleep apnoea (OSA) has been thought to increase the risk of respiratory depression from opioids. The primary aim of this study was to assess whether preoperative hypoxaemia by sleep study pulse oximetry imparts greater opioid sensitivity.

Methods: A multicentre observational cohort study with in-cohort dose randomisation was performed in children 2-8 yr of age with OSA undergoing adenotonsillectomy. Ninety patients were assigned to one of two Spo2 cohorts by preoperative sleep study Spo2 nadir of < or ≥85% to receive fentanyl 1.0 or 1.5 μg kg-1 (maximum 25 μg) after sevoflurane induction. The primary outcome was the extent of opioid-induced central ventilatory depression over time by Spo2 status as defined by the differences in tidal volume, respiratory rate, end-tidal CO2, and minute ventilation for 10 min after fentanyl administration when compared with pre-fentanyl baseline values. Secondary outcomes included assessment of body mass index, fentanyl dose, sex, age, and race on opioid-induced central ventilatory depression. Intention-to-treat and per protocol analysis were performed.

Results: Ninety patients underwent in-cohort randomisation (Spo2 < 85%; n=47 and Spo2 ≥85%; n=43). Final per protocol analysis included 73 subjects, fentanyl 1.0 μg kg-1 (Spo2 < 85%; n=36 and Spo2 ≥85%; n=37) and 15 subjects, fentanyl 1.5 μg kg-1 (Spo2 < 85%; n=9 and Spo2 ≥85%; n=6). Multivariable mixed effect model for the primary outcomes (tidal volume, respiratory rate, end-tidal CO2, and minute ventilation) from baseline to 10 min (as % change per minute) were not different between groups by Spo2 nadir (< or ≥85%) and fentanyl dose for the intention-to-treat and per protocol analyses.

Conclusions: Single-dose fentanyl ventilatory effects in paediatric OSA patients during sevoflurane anaesthesia were not associated with …

Predictors Of Decannulation Success In Tracheostomy: A 10-Year Analysis Of The Global Tracheostomy Collaborative Database, Charissa J Zaga, Carly E Milliren, Brendan A Mcgrath, Christina J Yang, Bradley A Schiff, Stephen J Warrillow, Jennifer K Henningfeld, Prudence A Gregson, Joshua R Bedwell, Karen M Beaudet, Michael J Brenner, Vinciya Pandian

Faculty, Staff and Students Publications

Objective: Decannulation is a critical milestone in functional recovery after tracheostomy, but standardized guidelines are lacking. This study examined factors associated with tracheostomy decannulation success, comparing hospital utilization, adverse events, and survival outcomes between decannulated and non-decannulated patients.

Study design: Retrospective, observational study.

Setting: Data were collected from 25 hospitals participating in the Global Tracheostomy Collaborative (GTC) in the United States, Australia, and the United Kingdom.

Methods: Prospectively collected data from adult patients who underwent tracheostomy from 2013 to 2022 were analyzed. Outcomes included decannulation success, hospital utilization metrics (intensive care unit [ICU] admissions, mechanical ventilation use, tracheostomy duration, and …

Factors Influencing 25-Year Survival In Pediatric Liver Transplant Recipients, Garrett Wortham, Megan Crawford, John Miggins, Chun-Sing Huang, John A Goss, Abbas Rana, Nhu Thao Galván

Faculty, Staff and Students Publications

Background: This study assesses the impact of cholestatic liver disease, including biliary atresia, on 25-year survival post-transplantation and additional factors influencing long-term outcomes after pediatric liver transplantation.

Methods: We conducted a retrospective analysis of pediatric liver transplant recipients (1987-1998) using de-identified data from the OPTN 2023 Liver Database. After exclusions for multi-organ transplants (n = 222), prior transplants (n = 2256), and deaths within 1 year (n = 526), 2429 patients remained, including 645 with cholestatic disease. Univariate and multivariate analyses identified factors associated with 25-year survival.

Results: A primary diagnosis of cholestatic disease was associated with improved 25-year survival …

Beyond Seizures As An Outcome Measure: A Global Severity Scoring System For Cdkl5 Deficiency Disorder, Peter Jacoby, Eric D Marsh, Scott Demarest, Jacinta M Saldaris, Helen Leonard, Heather E Olson, Joni N Saby, Elia Pestana-Knight, Rajsekar Rajaraman, Dana Price, Judith Weisenberg, Bernhard Suter, Jenny Downs, Tim A Benke

Faculty, Staff and Students Publications

Background: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease-modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.

Methods: The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment-Clinician and -Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance …

A Rare Molecular Diagnosis In A Patient With Hepatocerebral Syndrome Contributes To The Expansion Of The Phenotypic Spectrum Of Polg2 -Related Mitochondrial Disorder, Vittoria Rossi, Dan Brooks, Hongzheng Dai, Elizabeth Mizerik, Karla Salazar, Daniel Davila-Williams, Yishay Ben-Moshe, Seema R Lalani, Sarah H Elsea, Charul Gijavanekar, Daryl A Scott, Keren Machol, Mir Reza Bekheirnia, Fernando Scaglia

Faculty, Staff and Students Publications

POLG2 encodes an accessory subunit in DNA polymerase gamma that is required for mitochondrial DNA synthesis. Monoallelic pathogenic variants in POLG2 are associated primarily with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant type 4 (PEOA4, MIM #610131). We report a rare case of severe infantile hepatocerebral syndrome associated with biallelic variants in POLG2. The proband, a 5-week-old female infant, presented with seizures and acute liver failure. Extensive metabolic workup, including untargeted metabolomics analysis and elevated plasma growth differentiation factor 15, was suggestive of mitochondrial dysfunction. Rapid trio genome sequencing identified compound heterozygous variants, a likely pathogenic variant and …

Can Interpersonal Trust Predict And Account For Symptom Change During Group Cognitive Processing Therapy For Ptsd? An Investigation Of The Iterated Trust Game, M Wright Williams, Christopher Hunt, David P Graham, Matt Estey, Lia Smith, Katherine Mccurry, Brooks King-Casas, Pearl Chiu

Faculty, Staff and Students Publications

Objective: Group cognitive processing therapy (GCPT) is frequently utilized to treat PTSD within the VA healthcare system, but its mechanisms are not well understood. Interpersonal trust could be an important change process in GCPT given its relevance to group-based therapy and its role in CPT, but self-report measures are inadequate for capturing the dynamic interplay that defines interpersonal trust. Here, we examined the degree to which interpersonal could predict and account for PTSD symptom change in GCPT using the iterated trust game (ITG)-a behavioral task used to approximate real-world trust behavior.

Methods: Participants were Veterans with PTSD who participated in …

Real-World Effectiveness And Safety Of Upadacitinib In Crohn's Disease: A Multicenter Study, Jalpa Devi, Anthony Xu, Molly Stone, Anish Patel, Abdul Khan, Nikhil Reddy, Jeremy Klein, Navreet Chowla, Caroline Benson, Bryan Christopher Luu, Katherine Huang, Fnu Jaiprada, Marc Fenster, Ryan Ungaro, Joel Pekow, Amanda M Johnson, Andres J Yarur, Richa Shukla, Julia Huecker, Shrinivas Bishu, Reboot Ibd Consortium, Parakkal Deepak

Faculty, Staff and Students Publications

Background & aims: We aimed to describe the real-world effectiveness and safety of upadacitinib (UPA), an oral Janus kinase 1 inhibitor, in patients with Crohn's disease (CD).

Methods: A retrospective analysis was conducted across 9 centers in the United States, focusing on adults with CD treated with UPA, 45 mg, as induction therapy for active luminal disease. The coprimary end points were clinical remission at 12 weeks (Harvey Bradshaw Index ≤4 or absence of symptoms on physician's global assessment) and endoscopic remission at 6 months (Simplified Endoscopic Mucosal Assessment for Crohn's Disease score of 0-1 or absence of ulcers). Secondary …

Using Video Ethnography And Stimulated Recall Interviews To Describe The Diagnostic Process In The Emergency Department, Milisa Manojlovich, Caitlin Cassady, Sarah J Parker, Ellie Davis, Charlotte Ahr, David Ryamukuru, Anna Wang, Kalyan Pasupathy, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: Understanding how physicians make diagnoses is challenging because cognitive processes are unobservable and partly unconscious, making it difficult for physicians to describe how they arrived at a diagnosis. Physicians who work in emergency departments (EDs) are especially vulnerable to making diagnostic errors because the ED is a fast-paced, dynamic setting where complex decision-making occurs under severe time, information, and resource constraints. The purpose of our study was to describe how the diagnostic process evolves for ED clinicians in both pediatric and adult ED settings.

Methods: We used a qualitative, video ethnography study design to capture in situ, real-time ED …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Centrally Inserted Central Catheter Placement Using A Novel, Handheld, Image-Guided, Robotic Device: Results Of Initial Feasibility Trial In Patients, James P Herlihy, William E Cohn, Adrian Ebner

Faculty, Staff and Students Publications

Background: Central venous access devices (CVADs) are an essential and widely used tool for the treatment of the critically ill, patients undergoing major surgery, and for many patients requiring hemodialysis. Automation of centrally inserted central catheters (CICCs) could potentially make CVAD placement safer, more effective, and more accessible. A new device that uses ultrasound image-guided, robotic needle placement, in addition to traditional Seldinger technique, to place a CICC is described.

Objective: The device was used in a small, first-in-human, trial for placing non-tunneled hemodialysis catheters (NTHDCs), in order to determine feasibility of clinical use.

Methods: Consecutive patients requiring a NTHDC, …

Pathogenic Xpo1 Variants Cause A Dominant Neurodevelopmental Disorder, Amber S E Van Oirsouw, Pavla Nedbalova, Miroslava Hancarova, Jan Prchal, Darina Prchalova, Marketa Vlckova, Sarka Bendova, Kristin G Monaghan, Lisa M Dyer, Yanmin Chen, Deanna Alexis Carere, Emma A M Te Bogt, Heather Fisher, Angela E Scheuerle, Stephanie Riley, Mahim Jain, Weiyi Mu, Joann N Bodurtha, Albertien M Van Eerde, Marijn F Stokman, Nicola Longo, Meena Balasubramanian, Michael Spiller, Gregory Costain, Charlotte Von Der Lippe, Kristian Tveten, Marianne Jortveit, Øystein L Holla, Bertrand Isidor, Benjamin Cogné, Kevin E Glinton, Blake Vuocolo, Roberta Ann Sierra, Brad Angle, Kelly Bontempo, Klaas Koop, Rachel Rabin, John Pappas, David A Staffenberg, Pascal Joset, Peter Miny, Isabel Filges, Abdulrazak Alali, Kara Vitalone, Jill A Rosenfeld, Weimin Bi, Samuel Bradbrook, Renee Perrier, Subhadra Ramanathan, June-Anne Gold, María Palomares Bralo, María Ángeles Gómez-Cano, Ann Haskins Olney, Shelly Nielsen, Alban Ziegler, Dominique Bonneau, Clément Prouteau, Ange-Line Bruel, Charlotte Caille-Benigni, Laëtitia Lambert, Andrea C Yu, Nathaniel H Robin, Dana Goodloe, Jan Fischer, Joseph Porrmann, Yvonne D Hennig, Rami Abou Jamra, Isabella Herman, Ivy R Johnson, Lucas Hérissant, Guillaume Jouret, Koen L I Van Gassen, Ellen Van Binsbergen, Bert Van Der Zwaag, Alwin Kamermans, Renske Oegema, Zdenek Sedlacek, Michaela Fenckova, Richard H Van Jaarsveld

Faculty, Staff and Students Publications

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date.

Methods: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning.

Results: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We …

Information Theory Analysis Of Ctx Shows Consistent Clinical Presentation, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is a rare, metabolic disorder caused by pathogenic variants in CYP27A1. The classic clinical presentation includes infantile-onset chronic diarrhea, juvenile-onset bilateral cataracts, with development of tendon xanthomas and progressive neurological dysfunction. These multisystem clinical features typically appear in different decades of life often confounding diagnosis of CTX. Further complicating diagnosis is the generally held belief that the clinical presentation of CTX varies highly between individuals and even within families. We applied information theory analyses to CTX patient data to quantitatively assess clinical variability in CTX. We conducted a systematic review of the literature to identify all CTX …

Mutations In The Key Autophagy Tethering Factor Epg5 Link Neurodevelopmental And Neurodegenerative Disorders Including Early-Onset Parkinsonism, Hormos Salimi Dafsari, Celine Deneubourg, Kritarth Singh, Reza Maroofian, Zita Suprenant, Ay Lin Kho, Neil J Ingham, Karen P Steel, Preethi Sheshadri, Franciska Baur, Lea Hentrich, Birgit Gerisch, Mina Zamani, Cesar Alves, Ata Siddiqui, Haidar S Dafsari, Mehri Salari, Anthony E Lang, Michael Harris, Alice Abdelaleem, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Gholamreza Shariati, Alireza Sedaghat, Jawaher Zeighami, Daniel Calame, Dana Marafi, Ruizhi Duan, Adrian Boehnke, Gary D Clark, Jill A Rosenfeld, Carrie A Mohila, Dora Steel, Saurabh Chopra, Suvasini Sharma, Nicolai Kohlschmidt, Steffi Patzer, Afshin Saffari, Darius Ebrahimi-Fakhari, Büşra Eser Çavdartepe, Irene J Chang, Erika Beckman, Renate Peters, Andrew Paul Fennell, Bernice Lo, Luisa Averdunk, Felix Distelmaier, Martina Baethmann, Frances Elmslie, Kairit Joost, Sheela Nampoothiri, Dhanya Yesodharan, Hanna Mandel, Amy Kimball, Antonie D Kline, Cyril Mignot, Boris Keren, Vincent Laugel, Katrin Õunap, Kalpana Devadathan, Frederique M C Van Berkestijn, Arpana Silwal, Saskia Koene, Sumit Verma, Mohammed Yousuf Karim, Chahynez Boubidi, Majid Aziz, Gehad Elghazali, Lauren Mattas, Mohammad Miryounesi, Farzad Hashemi-Gorji, Shahryar Alavi, Nayereh Nouri, Mehrdad Noruzinia, Saeideh Kavousi, Arveen Kamath, Sandeep Jayawant, Russell Saneto, Nourelhoda A Haridy, Pinar Ozkan Kart, Ali Cansu, Madeleine Joubert, Claire Beneteau, Kyra E Stuurman, Martina Wilke, Tahsin Stefan Barakat, Homa Tajsharghi, Annarita Scardamaglia, Sadeq Vallian, Semra Hız, Ali Shoeibi, Reza Boostani, Narges Hashemi, Meisam Babaei, Norah Saleh Alsaleh, Julie Porter, Tania Attié-Bitach, Pauline Marzin, Dorota Wicher, Jessica I Gold, Elisabeth Schuler, Amna Kashgari, Rakan F Alanazi, Wafaa Eyaid, Marc Engelen, Mirjam Langeveld, Burkhard Stüve, Yun Li, Gökhan Yigit, Bernd Wollnik, Mariana H G Monje, Dimitri Krainc, Niccolò E Mencacci, Somayeh Bakhtiari, Michael Kruer, Emanuela Argilli, Elliott Sherr, Yalda Jamshidi, Ehsan Ghayoor Karimiani, Yiu Wing Sunny Cheung, Ivan Karin, Giovanni Zifarelli, Peter Bauer, Wendy K Chung, James R Lupski, Manju A Kurian, Jörg Dötsch, Jürgen-Christoph Von Kleist-Retzow, Thomas Klopstock, Matias Wagner, Calvin Yip, Andreas Roos, Rita Carsetti, Carlo Dionisi-Vici, Mathias Gautel, Michael R Duchen, Adam Antebi, Henry Houlden, Manolis Fanto, Heinz Jungbluth

Faculty, Staff and Students Publications

Objective: Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.

Methods: We investigated clinical, radiological, and molecular features from the largest cohort of EPG5-related patients identified to date, complemented by experimental investigation of cellular and animal models of EPG5 defects.

Results: Through worldwide collaboration, we identified 211 patients, 97 …

Cognitive Reserve Predicts Baseline Tau Burden In The Us Pointer Trial Imaging Cohort, Valory N Pavlik, Chris J Weber, Joseph C Masdeu, Laura D Baker, Melissa M Yu, Michele York, Rachel A Whitmer, Susan M Landau, Theresa M Harrison, Tomas M Holland, Laura Lovato

Faculty, Staff and Students Publications

Introduction: Higher cognitive reserve (CR) is associated with reduced dementia risk. We hypothesized that higher CR is associated with less baseline Alzheimer's disease (AD) pathology in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort.

Methods: A subsample of participants underwent amyloid beta and tau positron emission tomography imaging. Regression analysis was used to model the association between educational attainment (EA) as a CR proxy measure, amyloid positivity, and entorhinal cortex (ERC) and meta-temporal region of interest (meta-ROI) tau standardized uptake value ratio (SUVR).

Results: In 911 participants with complete imaging data, higher …