Digital Commons Network^™

The Mythology Of Polymyositis, Suur Biliciler, Tahseen Mozaffar

Faculty, Staff and Student Publications

Polymyositis (PM) has been in the diagnostic armamentarium in medicine since the mid-nineteenth century. Medicine training puts a heavy emphasis on this diagnosis, and anyone with proximal muscle weakness with elevated serum creatinine kinase is assumed to be PM and a number of patients were rendered this diagnosis without additional testing. This article addresses the historical aspects of the diagnosis of PM and its evolution. We review this literature that addresses the rarity of this diagnosis and rightly puts in perspective in terms of its occurrence in relation to other inflammatory myositides.

Depression Polygenicity And Disease Activity And Disability Worsening In Multiple Sclerosis, Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff, Carol A Hitchon, Jan Hillert, Ingrid Kockum, Yi Lu, Fred D Lublin, Kyla Mckay, Tomas Olsson, Scott Patten, Amit Patki, Hayley Riel, Klementy Shchetynsky, Pernilla Stridh, Hemant K Tiwari, Jerry S Wolinsky, Kaarina Kowalec

Faculty, Staff and Student Publications

Objective: A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and …

Missing The Target: A Scoping Review Of The Use Of Percent Weight Loss For Obesity Management, Diana Sherifali, Megan Racey, Donna Fitzpatrick-Lewis, Michelle Greenway, Sanjeev Sockalingam, Jun Wada, Soo Huat Teoh, Ian Patton, David Macklin, Elizabeth F C Van Rossum, Luca Busetto, Deborah Bade Horn, J D Patricia Nece, Morgan Emile Gabriel Salmon Leguede, Nicole Pearce, Carel Le Roux, Jamy Ard, Angela S Alberga, Lee Kaplan, Arya M Sharma, Sean Wharton

Faculty, Staff and Student Publications

Introduction: To co-create comprehensive targets for obesity management, we need to understand the genesis and current use of percent weight loss targets in research. The goals of our scoping review are to (1) synthesize the literature on percent weight loss targets for adults with obesity and (2) discuss the percent weight loss targets in context with their health benefits.

Methods: We searched Cochrane, MEDLINE, and EMBASE for English language, pharmaceutical, and/or behavioral intervention studies in adults with obesity where the explicit aim of the study was weight reduction defined as a percent of body weight. Reviewers screened citations and extracted …

Revisiting The Genetics Of Hypophosphatasia., Priya S. Kishnani, Catherine Rehder, Keiichi Ozono, Jordi Pérez-López, Guillermo Del Angel, William R. Mowrey, Meena Balasubramanian, Wolfgang Högler, Eric T. Rush

Manuscripts, Articles, Book Chapters and Other Papers

Hypophosphatasia (HPP) is a rare, inherited monogenic disorder that is typically caused by variants in the tissue-nonspecific alkaline phosphatase (ALPL) gene. Genetic testing for ALPL variant(s) to confirm the diagnosis in patients with suspected HPP is a standard practice based on availability. This review attempts to improve the current understanding of the genetics of HPP as it addresses five key related topics: (1) HPP patterns of inheritance and the relationship between HPP genotype and phenotype, (2) how the disease can manifest (including specific genotypes) in heterozygotes, (3) potential reasons why some patients have persistently low alkaline phosphatase activity yet lack …

Cytochrome P450 2d6 *17 And *29 Allele Activity For Risperidone Metabolism: Advancing Precision Medicine Health Equity., Oyinlade Kehinde, Samuel E. Vaughn, Ogochukwu Amaeze, Paul Toren, Brandon Retke, Akinyemi Oni-Orisan, Laura Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

CYP2D6 alleles with low frequency in Eurocentrically biased study populations are often excluded from pharmacogenetic investigation and consequently may have misassigned activity values. This health inequity may be contributing to imprecise dose predictions for CYP2D6-metabolizing drugs. The objective of this study was to determine how sub-Saharan African-specific CYP2D6*17 and *29 alleles affect risperidone metabolism. To do this, we generated the largest real-world cohort of risperidone users in an African study population for pharmacogenetic studies. Risperidone users ≤ 18 years old were recruited from the Federal Neuro-Psychiatric Hospital. Health records were obtained by parent report and paper charts. CYP2D6 genotyping was …

Comparison Of Model-Predicted And Observed Evinacumab Pharmacokinetics And Efficacy In Children Aged < 5 Years With Homozygous Familial Hypercholesterolemia., Sébastien Bihorel, Robert Dingman, Jeanne Mendell, Katy C. Norman, Richard T. George, Xue-Qiao Zhao, Robert Pordy, Daniel Garcia, Wendy S. Putnam, Geetha Raghuveer, Brian W. Mccrindle, Elena Fornari, Ivo Baric, Shubha Srinivasan, Melissa Diamond, Eliot A. Brinton, John D. Davis, A Thomas Dicioccio, Lutz Harnisch

Manuscripts, Articles, Book Chapters and Other Papers

Evinacumab, an angiopoietin-like 3 inhibitor, significantly reduces low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). Herein, we report pharmacokinetic and efficacy analyses of evinacumab in <  5-year-old patients with HoFH. Population pharmacometric models characterizing evinacumab exposure and LDL-C response accounting for lipoprotein apheresis effect in ≥ 5-year-old patients were adapted for growth and maturation to predict and compare evinacumab and LDL-C concentrations across age/weight groups in virtual ≥ 6-month-old patients receiving 15 mg/kg evinacumab intravenous (iv) infusions every 4 weeks (q4w). As expected from allometric theory, weight-based dosing resulted in decreasing evinacumab exposures with declining body weight. Consistent with trends observed in > 5-year-old patients, the predicted percent change from LDL-C baseline (%∆LDL-C) was generally comparable or even higher in <  5-year-old patients (63.0%-68.5%) than in 5- to <  18-year-old patients (61.3%-67.8%) or adults (51.7%), with the predicted percentages of patients achieving %∆LDL-C > 50% also higher in <  5-year-old patients (82.0%-86.9%) versus 5- to <  18-year-old patients (72.0%-84.5%) and adults (54.8%). Through a managed access program, six 1- to <  5-year-old patients received between 5 and 23 iv infusions of 15 mg/kg evinacumab q4w. Rapid and clinically meaningful LDL-C reductions were observed, with %∆LDL-C at the last reported dose ranging from 41.3% to 77.3%. Based on the actual patient dosing and plasmapheresis history, model-predicted evinacumab and LDL-C concentrations were comparable to the observed data collected in the managed access program. Overall, this analysis provides evidence for the use of evinacumab 15 mg/kg iv q4w dosing regimen in 6-month-old to 5-year-old patients.

Redefining Central Nervous System Multiple Myeloma: From Rare Phenomenon To Emerging Entity, Ian Landry, Adam F. Binder, Marc Yorker, Sarah Ramirez

Department of Medical Oncology Faculty Papers

BACKGROUND: Central nervous system involvement in multiple myeloma (CNS-MM) is considered a rare but devastating manifestation of extra-medullary disease (EMD) associated with aggressive biology and dismal outcomes. Treatment advances over the past few decades have improved survival in patients with MM, however, it has not translated into a similar survival benefit for those with CNS-MM. Early recognition and targeted management of CNS-MM remain major clinical challenges.

OBJECTIVE: This literature review summarizes the current literature on epidemiology, risk factors, clinical features, diagnostic modalities, and therapeutic approaches to CNS-MM. It focuses on emerging biomarkers and new treatment options that may affect the …

Restricting Metabolic Plasticity Enhances Stress Adaptation Through The Modulation Of Pdh And Hif1a In Trap1-Depleted Colon Cancer, Hong-Yuan Tsai, Miao-Hsueh Chen, Jihye Yun, Lisa A Lai, John F Valentine, Mary P Bronner, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Student Publications

Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation. TRAP1-deficient cells showed tolerance to Oxidative Phosphorylation (OXPHOS) inhibitors and exhibited a higher extracellular acidification rate (ECAR). Additionally, TRAP1 depletion activated hypoxia response elements (HREs) and upregulated HIF1A target genes such as GLUT1 and MCT1. …

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 …

Inhibition Of Bmper Mitigates Pulmonary Hypertension By Modulating Lrp1-Yap Interaction In Smooth Muscle Cells, Hua Mao, Claire M Li, Bing Sun, Christopher S Ward, Alan R Waich-Cohen, Ivan O Rosas, Howard J Huang, Harry Karmouty-Quintana, Liang Xie, Lavannya M Pandit, Xinchun Pi

Faculty, Staff and Students Publications

Background: BMPER (bone morphogenetic protein-binding endothelial regulator) is a secreted protein that is highly expressed in endothelial cells. It regulates the BMP (bone morphogenetic protein) pathway during vascular development and adulthood. Mutations in the BMP pathway are recognized as risk factors for pulmonary arterial hypertension group 1 pulmonary hypertension (PH). However, the roles of BMPER in pulmonary arterial hypertension remain unknown.

Methods: We assessed BMPER expression in Group 1 pulmonary arterial hypertension patient samples and examined its role in vascular remodeling using in vivo and in vitro approaches.

Results: BMPER level was elevated in pulmonary arterial hypertension lungs and significantly …

Clonal Hematopoiesis And Subsequent Venous Thromboembolism Among Survivors Of Autologous Transplantation For Lymphoma, Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Alysia Bosworth, Elizabeth Ross, Liton Francisco, Purnima Singh, Melissa A Richard, Chengcheng Yan, Rashi Kalra, Changde Cheng, Saro H Armenian, Stephen J Forman, Ravi Bhatia, Smita Bhatia

Faculty, Staff and Students Publications

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median …

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 …

Perfluoroalkyl Substance Pollutants Disrupt Microglia Function And Trigger Transcriptional And Epigenomic Changes, Yating Cheng, Jian-Rong Li, Hangjin Yu, Shuang Li, Boranai Tychhon, Chao Cheng, Yi-Lan Weng

Faculty, Staff and Students Publications

Per- and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals", are widely utilized in various industries and consumer products worldwide. Their exposure has been associated with numerous diseases and malignancies, including neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying PFAS-induced adverse effects on the central nervous system (CNS) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic changes in microglia exposed to perfluorooctane sulfonate (PFOS), a prevalent PFAS compound. Our findings demonstrate that 24-hour PFOS exposure (25 and 50 µM) disrupts the microglial transcriptome and compromises their homeostatic state, marked by increased inflammation and impaired …

Targeting The Hippo Pathway For Cardiac Regeneration, Rich Gang Li, Fansen Meng, James F Martin

Faculty, Staff and Students Publications

Ischemic heart disease, which affects more than 200 million people worldwide, is caused by reduced blood flow to the heart and leads to widespread cardiomyocyte death. Due to the limited regenerative potential of cardiomyocytes, the lost tissue is replaced by a fibrotic scar, resulting in reduced cardiac function and progression to heart failure. Current therapeutic interventions aim to improve blood flow but cannot address the inability of cardiomyocytes to renew after injury. However, multiple studies have shown that modulating the Hippo signaling pathway to activate Yes-associated protein (YAP), a transcription coactivator, in adult murine and porcine cardiomyocytes induces robust cardiomyocyte …

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 …

Pharmacological Treatment For Patients With Obesity And Heart Failure: Focus On Glucagon-Like Peptide-1 Receptor Agonists. European Journal Of Heart Failure Expert Consensus Document, Luca Monzo, Gianluigi Savarese, Wilfried Mullens, Amr Abdin, Biykem Bozkurt, Ovidiu Chioncel, Seif El Hadidi, Thomas M Gorter, Riccardo M Inciardi, Mark C Petrie, Gabriele G Schiattarella, Davide Stolfo, Marco Metra, Nicolas Girerd

Faculty, Staff and Students Publications

There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and of the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP-1 RAs and GIP/GLP-1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body …

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, …

Albuminuria As A Diagnostic Criterion And A Therapeutic Target In Heart Failure And Other Cardiovascular Disease, Biykem Bozkurt, Patrick Rossignol, Joseph A Vassalotti

Faculty, Staff and Students Publications

The high disease burden and bidirectional relationship of chronic kidney disease (CKD), heart failure (HF) and other cardiovascular disease (CVD) necessitate the need for early diagnosis of these diseases. While current screening and detection methods are recommended by CKD and CVD guidelines, their adoption in practice is low. Urine albumin-to-creatinine ratio (uACR) is recognized as a diagnostic marker for CKD and a prognostic marker for CKD progression, HF and CVD outcomes, therefore albuminuria changes have been accepted as a surrogate outcome for kidney and cardiovascular endpoints. Furthermore, clinical trials investigating guideline-directed medical therapies have shown that uACR reductions are accompanied …

Neurodevelopmental Abnormalities Underlying Behavioral Deficits In A Model Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Michael R Williamson, Vaishnav Krishnan, Mahyar J Hedayatpour, Adam C Adler, Nandani Adyapak, Chris S Ward, Russell Ray, David Durgan, Farrah Kheradmand, Benjamin Deneen

Faculty, Staff and Students Publications

Rationale: Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.

Objectives: To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.

Methods: We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in 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, …

Targeting Rbm10-Repressed Rorb Activity In Liquid Condensates Inhibits Lysosomal Biogenesis And Neuroblastoma Progression Via Affecting Nf-Κb Signaling, Yanhua Guo, Xiaojing Wang, Chunhui Yang, Zhijie Wang, Xiaolin Wang, Xinyue Li, Jiaying Qu, Shunchen Zhou, Liduan Zheng, Qiangsong Tong

Faculty, Staff and Students Publications

Neuroblastoma (NB), a pediatric solid malignancy, is distinguished by hetergenous clinical characteristics, including tumor aggressiveness or spontaneous regression. Nevertheless, the regulatory mechanisms and therapeutic approaches underlying these processes are still mainly unknown. Herein, RAR-related orphan receptor B (RORB) as a transcription factor repressing nuclear factor kappa B (NF-κB) signaling involved in lysosomal biogenesis of NB. RORB attenuated the growth, invasiveness, and metastatic spread of NB cells are identified. From a mechanistic perspective, RORB increased the transcription of nuclear receptor subfamily 1 group D member 1 (NR1D1)- or RIO kinase 3 (RIOK3)- in a circadian clock-dependent manner, resulting in suppression of …

Call To Action-Pediatric Masld Requires Immediate Attention To Curb Health Crisis, Phillipp Hartmann, Marialena Mouzaki, Sara Hassan, Mohit Kehar, Krupa R Mysore, Erin Mauney, Dieudonne Nonga, Sara Karjoo, Shilpa Sood, Andrea Tou, Christine Brichta, Rachel E Herdes, Nikhil Pai, Donna K Garner, Mary E Rinella, Mazen Noureddin, Zobair Younossi, Alina M Allen, Arun Sanyal, Taisa Kohut, Rohit Kohli, Charina M Ramirez, Stavra Xanthakos, Miriam B Vos, Jeffrey B Schwimmer, Samar H Ibrahim, Jennifer Panganiban

Faculty, Staff and Students Publications

Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a …

Two Decades Of Diagnostic Safety Research: Advances, Challenges, And Next Steps, Sundas Khan, Andrea Bradford, Christina L Cifra, Hardeep Singh

Faculty, Staff and Students Publications

Since the National Academies of Sciences, Engineering, and Medicine (NASEM) report Improving Diagnosis in Health Care, various research efforts have accelerated progress to understand and improve diagnostic safety. In this opinion piece, we summarize two decades of progress in methods for identifying and learning from diagnostic errors and provide recommendations for future research. Multiple methods have been used to quantify diagnostic errors in various clinical settings, thereby facilitating a deeper understanding of the nature and magnitude of the problem and enabling studies of contributing factors. However, the use of standardized definitions of a diagnostic error and/or diagnostic safety event, …

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, …

Molecular Mechanisms In Masld/Mash-Related Hcc, Xiaobo Wang, Liang Zhang, Bingning Dong

Faculty, Staff and Students Publications

Liver cancer is the third leading cause of cancer-related deaths and ranks as the sixth most prevalent cancer type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, and its more severe manifestation, NASH or metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% of the population. The increased prevalence of metabolic dysfunction-associated steatotic liver disease and MASH is parallel to the increasing rates of obesity-associated metabolic diseases, including type 2 diabetes, insulin resistance, and fatty liver diseases. MASH can progress to MASH-related HCC (MASH-HCC) in about 2% of cases each year, influenced by various factors such …

From Pachymeningitis Hemorrhagica To Abusive Head Trauma: A Journey Through The Centuries, Oliver Berthold, Flora Blangis, Christopher Spencer Greeley

Faculty, Staff and Students Publications

The development of medical knowledge follows specific principles. These also apply to abusive head trauma. The seminal literature from the early 20th century is based on earlier research from Europe, which is fundamental to understand the evolution of understanding and nomenclature of abusive head trauma. A review of original medical literature on intracranial injuries in children, published in German, English, and French, was conducted using PubMed and Google Scholar for articles before 1950. The primary search focused on subdural hemorrhages and pachymeningitis in children, followed by a snowball search of references. Full texts of available manuscripts were reviewed. Primary literature …

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 …

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 …