Digital Commons Network^™

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 …

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 …

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 …

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 …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …

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 …

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 …

Predictors Of Response To Emergent Therapies In Paediatric Immune Thrombocytopenia, Candelaria O'Farrell, Taylor M Luckie, Matthew J Willis, Susan E Kirk, Brandon R Lucari, Michael E Scheurer, Xiaotian Gao, Amanda B Grimes

Faculty, Staff and Students Publications

Emergent therapies (ET), which include intravenous immunoglobulin (IVIG), corticosteroids and intravenous anti‐Rho(D) immunoglobulin, are used to treat acute episodes of bleeding in children with immune thrombocytopenia (ITP). There are currently no known biomarkers or clinical features predictive of treatment response to any specific ET. Thus, the treatment of ITP remains largely trial and error, exposing patients to potentially ineffective medications, which are often expensive and associated with adverse effects. We therefore sought to identify the predictors of treatment response through comparison of clinical characteristics in paediatric patients with ITP responsive to ET versus those non‐responsive to ET. We identified high …

Reprogrammed Glucose Metabolism In Vascular Smooth Muscle Cells And Its Implications For Vascular Diseases, Qian Ma, Yongfeng Cai, Qiuhua Yang, Wendy Zhang, Suowen Xu, Yuqing Huo

Faculty, Staff and Students Publications

Vascular smooth muscle cells (VSMCs) play a pivotal role in maintaining vascular homeostasis and are critical contributors to the pathogenesis of various vascular diseases, including atherosclerosis, calcification, aneurysms, and pulmonary hypertension. Emerging evidence highlights the significance of glucose metabolism in regulating VSMC phenotypic transitions during these pathologies. This review provides a comprehensive overview of the major glucose metabolic pathways in VSMCs, glycolysis, the pentose phosphate pathway (PPP), and the hexosamine biosynthetic pathway (HBP), and their roles in disease development. We summarize the molecular mechanisms linking glucose metabolic reprogramming to VSMC dysfunction, focusing on key regulatory enzymes and signaling pathways. Additionally, …

Endothelial Adenosine Receptor 2a Loss Alleviates Diabetic Vascular Calcification By Blocking Creb1-Snai1-Driven Endmt, Yaqi Zhou, Dingwei Zhao, Qian Ma, Jiean Xu, Yongfeng Cai, Qiuhua Yang, Qingen Da, Kian Sheridan, Chunxiang Zhang, Clint L Miller, Rajeev Malhotra, Suowen Xu, Mei Hong, Yuqing Huo

Faculty, Staff and Students Publications

Vascular calcification (VC), a common complication associated with diabetes mellitus (DM), substantially increases the risk of cardiovascular diseases and is associated with elevated mortality in individuals with DM. Endothelial-to-mesenchymal transition (EndMT) imparts phenotypic plasticity to vascular endothelial cells (VECs), granting them the potential for osteogenic differentiation, which is a crucial mechanism in regulating VC. Notably, adenosine-ADORA2A-mediated endothelial dysfunction plays a pivotal regulatory role in cardiovascular diseases. However, the specific role of endothelial ADORA2A in diabetic VC remains to be elucidated. In this study, we found that ADORA2A was upregulated in the endothelium of diabetic mice and cultured human aortic endothelial …

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 …

Targeting Adenosine 2a Receptor Signaling Suppresses Vascular Calcification By Restraining Smooth Muscle Osteogenic Differentiation, Yaqi Zhou, Dingwei Zhao, Qian Ma, Sujin Lee, Kangsan Roh, Yongfeng Cai, Jiean Xu, Qiuhua Yang, Qingen Da, Zhiping Liu, Kunfu Ouyang, Eric J Belin De Chantemele, Mei Hong, Clint L Miller, Rajeev Malhotra, Chunxiang Zhang, Suowen Xu, Yuqing Huo

Faculty, Staff and Students Publications

Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality, particularly in patients with chronic kidney disease (CKD). Adenosine 2 A receptor (ADORA2A) is highly expressed in vascular cells and implicated in cardiovascular disease; however, its specific role in VC pathogenesis remains unclear. Here, we investigated the role of ADORA2A using in vitro (vascular smooth muscle cells; VSMCs), ex vivo (mouse aortic rings), and in vivo (5/6th nephrectomy with high phosphate and cholecalciferol) models of VC. The ADORA2A expression was significantly upregulated in calcified human and murine aortic tissues, as well as in VSMCs, under osteogenic conditions. Genetic …

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 …

Urinary Markers In Heart Failure – Types, Timing And Thresholds. European Journal Of Heart Failure Expert Consensus Document, Masatake Kobayashi, Biykem Bozkurt, Peder Langeland Myhre, Juan Carlos Lopez Azor, Mateusz Guzik, Gracjan Iwanek, Guillaume Baudry, Marta Cobo-Marcos, Òscar Miró, Jeroen Dauw, Piotr Ponikowski, Wilfried Mullens, Alberto Palazzuoli, Marco Metra, Jan Biegus

Faculty, Staff and Students Publications

Several urinary markers reflect disease severity and have the potential to support the management of heart failure (HF). Collecting urine samples is easy and inexpensive, and urine sample composition can be altered not only by underlying kidney impairments (i.e. filtration barrier damage and tubular injury) but also via neurohormonal and inflammatory activation, ageing, comorbidities, other medical conditions and pharmacological interventions. For instance, urinary sodium may help to predict the response to loop diuretic therapy in acute HF, while albuminuria is used as a risk marker and therapeutic target for the progression of cardiovascular and kidney diseases in chronic HF, especially …

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 …

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 …

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 …

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 …

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 …

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 …

Early Outcomes Of Endovascular Repair Of Aortic Arch Lesions In Zone 0/1 With A Thoracic Branched Endoprosthesis, Matthew P Sweet, Ali Azizzadeh, Gustavo S Oderich, William Brinkman, Jon S Matsumura, Takao Ohki, Sara Zettervall, Shinji Miyamoto, Himanshu J Patel, Michael D Dake

Faculty, Staff and Students Publications

Objective: The pivotal trial 30-day outcomes of the GORE TAG Thoracic Branch Endoprosthesis in patients with endovascular repair of the aortic arch or descending thoracic aorta using a zone 0 or 1 landing zone were evaluated.

Methods: In this nonrandomized, multicenter, prospective study, the primary, clinically driven outcome was a composite of the following through 1 month: technical success (successful device deployment with maintenance of side-branch patency and the absence of aortic rupture), lesion-related mortality, disabling stroke, permanent paraplegia or paraparesis, new onset renal failure requiring permanent dialysis, and protocol-defined unanticipated reintervention.

Results: The 77 study patients enrolled had aneurysm …

Physician Perceptions Of The Evaluation And Management Of Incarcerated Patients In The Emergency Department, Michelle Suh, Anita N Chary, Melanie F Molina, Caitlin M Farrell, Mark B Mycyk, Vidya Eswaran

Faculty, Staff and Students Publications

Background: Incarcerated patients in the United States are frequently seen in the emergency department. Although other specialties have reported differential care for patients who are incarcerated, little is known about the emergency physicians' evaluation and management of patients who are incarcerated.

Objective: The aim of our study was to characterize emergency physician (EP) perceptions of the emergency department (ED) care of incarcerated patients.

Methods: We surveyed emergency medicine resident and attending physicians at three academic safety-net EDs that regularly treat incarcerated patients from May to June 2023. We conducted thematic analysis of responses about perceptions of ED evaluation and management …

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 …

A Computer Vision And Machine Learning Approach To Classify Views In Distal Radius Radiographs, Rohan Vemu, Dion Birhiray, Bassem Darwish, Raven Hollis, Sai Unnam, Srikhar Chilukuri, Lorenzo Deveza

Faculty, Staff and Students Publications

Advances in computer vision and machine learning have augmented the ability to analyze orthopedic radiographs. A critical but underexplored component of this process is the accurate classification of radiographic views and localization of relevant anatomical regions, both of which can impact the performance of downstream diagnostic models. This study presents a deep learning object detection model and mobile application designed to classify distal radius radiographs into standard views-anterior-posterior (AP), lateral (LAT), and oblique (OB)- while localizing the anatomical region most relevant to distal radius fractures. A total of 1593 deidentified radiographs were collected from a single institution between 2021 and …

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 …