Medical Specialties Commons^™

Outcome Of Corynebacterial Bloodstream Infection In Patients With Cardiac Implantable Electronic Devices: A Brief Report And Systematic Review, Supavit Chesdachai, Larry M Baddour, M Rizwan Sohail, Bharath Raj Palraj, Malini Madhavan, Hussam Tabaja, Michele T Mcginnis, Madiha Fida, Douglas W Challener, Daniel C Desimone

Faculty, Staff and Students Publications

Cardiac implantable electronic device infection in the context of corynebacterial bloodstream infection (BSI) remains poorly understood. From 2012 to 2023 at Mayo Clinic, 4 of 12 patients with corynebacterial BSI had cardiac implantable electronic device infection: 1 patient was diagnosed during a relapsing BSI episode. Undefined source, persistent BSI, and the presence of a prosthetic cardiac valve were common characteristics.

Something Seems Fishy: Hepatic Abscess Due To Foreign Body Ingestion In A Pediatric Patient, James Rhodes, Amanda Macias, Emma Cooke, Joel Jacob, Ashley Devoll, Chelsea Young, Bradford Nguyen

Faculty, Staff and Students Publications

Pediatric hepatic abscesses are uncommon in children. They are usually preceded by intra-abdominal infections or caused by acute or chronic biliary disease. Cases of hepatic abscesses secondary to foreign body ingestion are even rarer but are most reported in countries such as China, where ingestion of fish and chicken bones is common. We report a rare case of an adolescent patient who developed a hepatic abscess after ingestion of a fishbone foreign body. He presented to the emergency department with emesis, abdominal pain, and subjective fevers of unknown etiology. Initial imaging of the abdomen was pertinent for a heterogeneous hepatic …

Infant Anaphylaxis And Epinephrine Use: Can We Improve Acute Management?, Aikaterini Anagnostou, Matthew Greenhawt, S Shahzad Mustafa, Jay A Lieberman, Marcus Shaker

Faculty, Staff and Students Publications

Background: Anaphylaxis is a serious systemic hypersensitivity reaction that is rapid in onset and may cause death.

Methods: The true prevalence of infant anaphylaxis is unknown, but such cases may be increasing in presentation of these patients to emergency departments, with studies that evaluate health-care utilization after implementation of early introduction guidelines that report an increase in the use of emergency department for food-related visits as well as an increase in epinephrine prescriptions for infants.

Results: Reasons for these increases may include early food introduction as well as therapeutic interventions such as early life or preschool oral immunotherapy.

Conclusion: Infant …

Cerebellar Functions Beyond Movement And Learning, Linda H Kim, Detlef H Heck, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

The cerebellum has a well-established role in controlling motor functions, including coordination, posture, and the learning of skilled movements. The mechanisms for how it carries out motor behavior remain under intense investigation. Interestingly though, in recent years the mechanisms of cerebellar function have faced additional scrutiny since nonmotor behaviors may also be controlled by the cerebellum. With such complexity arising, there is now a pressing need to better understand how cerebellar structure, function, and behavior intersect to influence behaviors that are dynamically called upon as an animal experiences its environment. Here, we discuss recent experimental work that frames possible neural …

Complement C3ar Signaling: Immune And Metabolic Modulation And Its Impact On Alzheimer’S Disease, Manasee Gedam, Hui Zheng

Center on Aging Staff Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly population. Despite its widespread prevalence, our comprehension of the intricate mechanisms governing the pathogenesis of the disease remains incomplete, posing a challenge for the development of efficient therapies. Pathologically characterized by the presence of amyloid β plaques and neurofibrillary tau tangles, AD is also accompanied by the hyperactivation of glial cells and the immune system. The complement cascade, the evolutionarily conserved innate immune pathway, has emerged as a significant contributor to AD. This review focuses on one of the complement components, the …

Chick Embryo Chorioallantoic Membrane As A Platform For Assessing The In Vivo Efficacy Of Chimeric Antigen Receptor T-Cell Therapy In Solid Tumors, Allison J Nipper, Emilie A K Warren, Kershena S Liao, Hsuan-Chen Liu, Chieko Michikawa, Caroline E Porter, Gabrielle A Wells, Mariana Villanueva, Fabio Henrique Brasil Da Costa, Ratna Veeramachaneni, Hugo Villanueva, Masataka Suzuki, Andrew G Sikora

Faculty, Staff and Student Publications

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied …

Secondary Endpoint Utilization And Publication Rate Among Phase Iii Oncology Trials, Esther J Beck, Alexander D Sherry, Marcus A Florez, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Roshal R Patel, Fumiko Chino, Victoria Serpas Higbie, Christine M Parseghian, Michael J Overman, Bruce D Minsky, Charles R Thomas, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

UNLABELLED: Secondary endpoints (SEP) provide crucial information in the interpretation of clinical trials, but their features are not yet well understood. Thus, we sought to empirically characterize the scope and publication rate of SEPs among late-phase oncology trials. We assessed SEPs for each randomized, published phase III oncology trial across all publications and ClinicalTrials.gov, performing logistic regressions to evaluate associations between trial characteristics and SEP publication rates. After screening, a total of 280 trials enrolling 244,576 patients and containing 2,562 SEPs met the inclusion criteria. Only 22% of trials (62/280) listed all SEPs consistently between ClinicalTrials.gov and the trial protocol. …

Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian

The Texas Heart Institute Journal

Despite substantial advances in the management of hypertrophic cardiomyopathy, advanced heart failure remains a major cause of morbidity in this patient population. This narrative review presents the case of a patient with hypertrophic obstructive cardiomyopathy who underwent alcohol septal ablation to frame a discussion of modern therapies for hypertrophic cardiomyopathy. The current treatment landscape includes medications, both old and new, and surgical and procedural interventions to relieve mechanical obstruction. Several promising new modalities for relieving obstruction are in the nascent stages of development.

Systematic Transcriptome Profiling Of Hpsc-Derived Osteoblasts Unveils Corin’S Mastery In Governing Osteogenesis Through Cebpd Modulation, Dandan Zhu, Mo-Fan Huang, An Xu, Xueqin Gao, Yu-Wen Huang, Trinh T T Phan, Linchao Lu, Ting-Yen Chi, Yulin Dai, Lon Kai Pang, Julian A Gingold, Jian Tu, Zijun Huo, Danielle A Bazer, Rachel Shoemaker, Jun Wang, Catherine G Ambrose, Jingnan Shen, Jun Kameoka, Zhongming Zhao, Lisa L Wang, Yang Zhang, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect human pluripotent stem cell-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide chromatin …

2023 American College Of Rheumatology (Acr)/American College Of Chest Physicians (Chest) Guideline For The Treatment Of Interstitial Lung Disease In People With Systemic Autoimmune Rheumatic Diseases, Sindhu R Johnson, Elana J Bernstein, Marcy B Bolster, Jonathan H Chung, Sonye K Danoff, Michael D George, Dinesh Khanna, Gordon Guyatt, Reza D Mirza, Rohit Aggarwal, Aberdeen Allen, Shervin Assassi, Lenore Buckley, Hassan A Chami, Douglas S Corwin, Paul F Dellaripa, Robyn T Domsic, Tracy J Doyle, Catherine Marie Falardeau, Tracy M Frech, Fiona K Gibbons, Monique Hinchcliff, Cheilonda Johnson, Jeffrey P Kanne, John S Kim, Sian Yik Lim, Scott Matson, Zsuzsanna H Mcmahan, Samantha J Merck, Kiana Nesbitt, Mary Beth Scholand, Lee Shapiro, Christine D Sharkey, Ross Summer, John Varga, Anil Warrier, Sandeep K Agarwal, Danielle Antin-Ozerkis, Bradford Bemiss, Vaidehi Chowdhary, Jane E Dematte D'Amico, Robert Hallowell, Alicia M Hinze, Patil A Injean, Nikhil Jiwrajka, Elena K Joerns, Joyce S Lee, Ashima Makol, Gregory C Mcdermott, Jake G Natalini, Justin M Oldham, Didem Saygin, Kimberly Showalter Lakin, Namrata Singh, Joshua J Solomon, Jeffrey A Sparks, Marat Turgunbaev, Samera Vaseer, Amy Turner, Stacey Uhl, Ilya Ivlev

Faculty, Staff and Student Publications

Objective: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs).

Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations.

Results: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong …

Selecting Patients For Food Allergy Therapy, Aikaterini Anagnostou

Faculty, Staff and Students Publications

Background: Food allergies pose a significant burden on the daily life of individuals with food allergy, including dietary, psychosocial, and economic impact. The management of food allergy has shifted recently from previous passive avoidance approaches to current active therapeutic interventions.

Objective: This article aims to discuss selection of patients with food allergies for different therapies.

Methods: Published literature on risks and benefits of various therapies as well as articles on shared decision-making were reviewed for this article. Key papers are included.

Results and conclusion: In addition to the two U.S. Food and Drug Administration approved therapies currently available (for oral …

De Novo Variants In Immune Regulatory Genes In Down Syndrome Regression Disorder, Saba Jafarpour, Abhik K Banerjee, Mellad M Khoshnood, Benjamin N Vogel, Natalie K Boyd, Lina Nguyen, Rebecca Partridge, Stephanie L Santoro, Grace Y Gombolay, Kristen S Fisher, Diego Real De Asua, Maria Carmen Del Ortega, Cathy Franklin, Michael S Rafii, Jonathan D Santoro

Faculty, Staff and Students Publications

Background: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD.

Methods: This study included individuals with …

Impact Of Pretreatment Body Mass Index On The Survival Of Head And Neck Cancer Patients, Zheng Yang, Jobran Mansour, Peng Sun, Peng Wei, Kristina R Dahlstrom, Mark Zafereo, Guojun Li, Neil D Gross

Faculty, Staff and Student Publications

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite.

Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival.

Results: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI …

Fine-Tuning Ampk In Physiology And Disease Using Point-Mutant Mouse Models, Naghmana Ashraf, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that monitors the cellular energy status to adapt it to the fluctuating nutritional and environmental conditions in an organism. AMPK plays an integral part in a wide array of physiological processes, such as cell growth, autophagy and mitochondrial function, and is implicated in diverse diseases, including cancer, metabolic disorders, cardiovascular diseases and neurodegenerative diseases. AMPK orchestrates many different physiological outcomes by phosphorylating a broad range of downstream substrates. However, the importance of AMPK-mediated regulation of these substrates in vivo remains an ongoing area of investigation to better understand its precise …

De Novo Variants In The Rnu4-2 Snrna Cause A Frequent Neurodevelopmental Syndrome, Yuyang Chen, Ruebena Dawes, Hyung Chul Kim, Alicia Ljungdahl, Sarah L Stenton, Susan Walker, Jenny Lord, Gabrielle Lemire, Alexandra C Martin-Geary, Vijay S Ganesh, Jialan Ma, Jamie M Ellingford, Erwan Delage, Elston N D'Souza, Shan Dong, David R Adams, Kirsten Allan, Madhura Bakshi, Erin E Baldwin, Seth I Berger, Jonathan A Bernstein, Ishita Bhatnagar, Ed Blair, Natasha J Brown, Lindsay C Burrage, Kimberly Chapman, David J Coman, Alison G Compton, Chloe A Cunningham, Precilla D'Souza, Petr Danecek, Emmanuèle C Délot, Kerith-Rae Dias, Ellen R Elias, Frances Elmslie, Care-Anne Evans, Lisa Ewans, Kimberly Ezell, Jamie L Fraser, Lyndon Gallacher, Casie A Genetti, Anne Goriely, Christina L Grant, Tobias Haack, Jenny E Higgs, Anjali G Hinch, Matthew E Hurles, Alma Kuechler, Katherine L Lachlan, Seema R Lalani, François Lecoquierre, Elsa Leitão, Anna Le Fevre, Richard J Leventer, Jan E Liebelt, Sarah Lindsay, Paul J Lockhart, Alan S Ma, Ellen F Macnamara, Sahar Mansour, Taylor M Maurer, Hector R Mendez, Kay Metcalfe, Stephen B Montgomery, Mariya Moosajee, Marie-Cécile Nassogne, Serena Neumann, Michael O'Donoghue, Melanie O'Leary, Elizabeth E Palmer, Nikhil Pattani, John Phillips, Georgia Pitsava, Ryan Pysar, Heidi L Rehm, Chloe M Reuter, Nicole Revencu, Angelika Riess, Rocio Rius, Lance Rodan, Tony Roscioli, Jill A Rosenfeld, Rani Sachdev, Charles J Shaw-Smith, Cas Simons, Sanjay M Sisodiya, Penny Snell, Laura St Clair, Zornitza Stark, Helen S Stewart, Tiong Yang Tan, Natalie B Tan, Suzanna E L Temple, David R Thorburn, Cynthia J Tifft, Eloise Uebergang, Grace E Vannoy, Pradeep Vasudevan, Eric Vilain, David H Viskochil, Laura Wedd, Matthew T Wheeler, Susan M White, Monica Wojcik, Lynne A Wolfe, Zoe Wolfenson, Caroline F Wright, Changrui Xiao, David Zocche, John L Rubenstein, Eirene Markenscoff-Papadimitriou, Sebastian M Fica, Diana Baralle, Christel Depienne, Daniel G Macarthur, Joanna M M Howson, Stephan J Sanders, Anne O'Donnell-Luria, Nicola Whiffin

Faculty, Staff and Students Publications

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of …

Cardiomyopathy, An Uncommon Phenotype Of Congenital Disorders Of Glycosylation: Recommendations For Baseline Screening And Follow-Up Evaluation, Roni Zemet, Kyle D Hope, Andrew C Edmondson, Rameen Shah, Maria Patino, Abigail M Yesso, Justin H Berger, Kyriakie Sarafoglou, Austin Larson, Christina Lam, Eva Morava, Fernando Scaglia

Faculty, Staff and Students Publications

Introduction:

Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG. Cardiomyopathy is an important phenotype in CDG. The clinical manifestations and progression of cardiomyopathy in CDG patients have not been well characterized. This study aims to delineate common patterns of cardiomyopathy across a range of …

Sinus Arrest Related To Dexmedetomidine Infusion In An Infant; A Case Report And Review Of Current Literature, Alexandra Dennee, Thomas P Fogarty, Taylor S Howard, Ryan Brandon Hunter

Faculty, Staff and Students Publications

Background: Dexmedetomidine, an alpha 2 agonist, has emerged as a desirable sedative agent in the pediatric intensive care unit due to its minimal effect on respiratory status and reduction in delirium. Bradycardia and hypotension are common side effects, however there are emerging reports of more serious cardiovascular events, including sinus arrest and asystole. These case reports have been attributed to high vagal tone or underlying cardiac conduction dysfunction.

Objectives: To describe the development of sinus arrest during sedation with dexmedetomidine in a patient without clinical features of high vagal tone, underlying cardiac conduction dysfunction, or intervening episodes of bradycardia.

Case …

Developmental Delay Can Precede Neurologic Regression In Early Onset Metachromatic Leukodystrophy, Laura Ann Adang, Samuel Groeschel, Chloe Grzyb, Russell D'Aiello, Francesco Gavazzi, Omar Sherbini, Nowa Bronner, Akshilkumar Patel, Ariel Vincent, Anjana Sevagamoorthy, Sylvia Mutua, Kayla Muirhead, Johanna Schmidt, Amy Pizzino, Emily Yu, Danielle Jin, Florian Eichler, Jamie L Fraser, Lisa Emrick, Keith Van Haren, Jean-Martin Boulanger, Maura Ruzhnikov, Michel Sylvain, Cam-Tu Émilie Nguyen, Ana Potic, Stephanie Keller, Ali Fatemi, Eloise Uebergang, Michele Poe, Pouneh Amir Yazdani, John Bernat, Kristen Lindstrom, Joshua L Bonkowsky, Genevieve Bernard, Chloe A Stutterd, Paul Orchard, Ashish O Gupta, Merete Ljungberg, Sabine Groenborg, Alberto Zambon, Sara Locatelli, Francesca Fumagalli, Saskia Elguen, Christiane Kehrer, Ingeborg Krägeloh-Mann, Justine Shults, Adeline Vanderver, Maria L Escolar

Faculty, Staff and Students Publications

Objective: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau. With the advent of presymptomatic screening platforms and transformative therapies, it is essential to define the onset of neurologic disease.

Methods: The specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative …

Long-Term Prospective Outcomes Of Intensity Modulated Radiotherapy For Locally Advanced Lung Cancer: A Secondary Analysis Of A Randomized Clinical Trial, Stephen G Chun, Chen Hu, Ritsuko U Komaki, Robert D Timmerman, Steven E Schild, Jeffrey A Bogart, Michael C Dobelbower, Walter Bosch, Vivek S Kavadi, Samir Narayan, Puneeth Iyengar, Clifford Robinson, Jan Rothman, Adam Raben, Mark E Augspurger, Robert M Macrae, Rebecca Paulus, Jeffrey D Bradley

Faculty, Staff and Students Publications

Importance: The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of intensity-modulated radiotherapy (IMRT) is important.

Objective: To compare long-term prospective outcomes of patients receiving IMRT and 3-dimensional conformal radiotherapy (3D-CRT) with concurrent carboplatin/paclitaxel for locally advanced NSCLC.

Design, setting, and participants: A secondary analysis of a prospective phase 3 randomized clinical trial NRG Oncology-RTOG 0617 assessed 483 patients receiving chemoradiotherapy (3D-CRT vs IMRT) for locally advanced NSCLC based on stratification.

Main outcomes and measures: Long-term outcomes were analyzed, including overall survival (OS), progression-free survival (PFS), time to local …

Mechanisms Of Neurodevelopmental Toxicity Of Topiramate, John W Steele, Vaishnav Krishnan, Richard H Finnell

Faculty, Staff and Students Publications

Prescriptions for antiseizure medications (ASMs) have been rapidly growing over the last several decades due, in part, to an expanding list of clinical indications for which they are now prescribed. This trend has raised concern for potential adverse neurodevelopmental outcomes in ASM-exposed pregnancies. Recent large scale population studies have suggested that the use of topiramate (TOPAMAX, Janssen-Cilag), when prescribed for seizure control, migraines, and/or weight management, is associated with an increased risk for autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD) in exposed offspring. Here, we critically review epidemiologic evidence demonstrating the neurobehavioral teratogenicity of topiramate and speculate …

Frontiers In Congenital Disorders Of Glycosylation Consortium, A Cross-Sectional Study Report At Year 5 Of 280 Individuals In The Natural History Cohort, Christina Lam, Fernando Scaglia, Gerard T Berry, Austin Larson, Kyriakie Sarafoglou, Hans C Andersson, Evgenia Sklirou, Queenie K G Tan, Rodrigo T Starosta, Mustafa Sadek, Lynne Wolfe, Seishu Horikoshi, May Ali, Rita Barone, Teresa Campbell, Irene J Chang, Kiaira Coles, Edward Cook, Erik A Eklund, Nicole M Engelhardt, Mary Freeman, Jennifer Friedman, Debbie Y T Fu, Grace Botzo, Brandy Rawls, Christien Hernandez, Christin Johnsen, Kierstin Keller, Sara Kramer, Bryce Kuschel, Angela Leshinski, Ivan Martinez-Duncker, Gina L Mazza, Saadet Mercimek-Andrews, Bradley S Miller, Karthik Muthusamy, Juanita Neira, Marc C Patterson, Natalie Pogorelc, Lex N Powers, Elizabeth Ramey, Michaela Reinhart, Audrey Squire, Jenny Thies, Jerry Vockley, Hayden Vreugdenhil, Peter Witters, Mehdi Youbi, Aziza Zeighami, Roni Zemet, Andrew C Edmondson, Eva Morava

Faculty, Staff and Students Publications

Objective: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study.

Methods: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023. …

Extrapyramidal System/Symptoms/Signs Should Be Retired, Abhishek Lenka, Joseph Jankovic

Faculty, Staff and Students Publications

The term "extrapyramidal system/symptoms/signs" and the acronym "EPS" have been abundantly used in neurology and psychiatry literature for more than a century. However, EPS has been increasingly criticized, especially by movement disorder neurologists, for its lack of clinical, anatomical, and physiologic definition. Contrary to traditional assumptions, pyramidal and extrapyramidal systems are not mutually exclusive. The acronym EPS, commonly used to denote drug-induced movement disorders, lacks specificity in conveying the nature and severity of these and other movement disorders. Consequently, we propose that the term is retired from scientific literature and that clinicians use specific phenomenologic descriptors for the various hypokinetc …

Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg

Faculty, Staff and Students Publications

IMPORTANCE: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes.

OBJECTIVE: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November …

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh

Faculty, Staff and Students Publications

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.

Derivation And Validation Of An Optimal Neutrophil Gelatinase-Associated Lipocalin Cutoff To Predict Stage 2/3 Acute Kidney Injury (Aki) In Critically Ill Children, Stuart L Goldstein, Ayse Akcan-Arikan, Natasha Afonso, David J Askenazi, Abby M Basalely, Rajit K Basu, Hostensia Beng, Julie C Fitzgerald, Katja Gist, Sarah Kizilbash, David Kwiatkowski, Christopher W Mastropietro, Shina Menon, Megan Soohoo, Avram Z Traum, Christopher A Bird

Faculty, Staff and Students Publications

INTRODUCTION: Acute kidney injury (AKI) defined by changes in serum creatinine (SCr), or oliguria is associated with increased morbidity and mortality in children who are critically ill. We derived and validated a clinical cutoff value for urine neutrophil gelatinase-associated lipocalin (NGAL), in a prospective multicenter study of children who were critically ill. We report the clinical performance of urine NGAL (uNGAL) to aid in pediatric AKI risk assessment.

METHODS: Eligible subjects were aged ≥ 90 days to < 22 years, admitted to an intensive care unit (ICU), and had 1 or more of the following: mechanical ventilation, vasoactive medication administration, solid organ or bone marrow transplantation, or hypotension within 24-hours of admission. uNGAL was assessed within 24-hours of admission. The primary outcome was SCr-based stage 2/3 AKI presence at 48- to 72-hours.

RESULTS: Twenty-five (12.3%) derivation study patients had stage 2/3 AKI at 48- to 72-hours. uNGAL concentration of 125 ng/ml was the optimal cutoff. …

Eculizumab For Management Of Hyperhemolysis Syndrome In Pediatric Patients With Sickle Cell Disease: A Single-Center Case Series, Ajibike Lapite, Saleh Bhar, Titilope Fasipe

Faculty, Staff and Students Publications

Chronic hemolytic anemia and vascular occlusion are hallmarks of sickle cell disease (SCD). Blood transfusions are critical for supportive and preventive management of SCD complications. Patients with SCD are at risk for hyperhemolysis syndrome (HHS), a subtype of delayed hemolytic transfusion reactions. HHS management includes intravenous immunoglobulin, corticosteroids, and avoidance of further transfusions. Not all patients respond to first-line agents. Eculizumab, which blocks terminal complement activation, has been proposed as second-line management of HHS. We describe two patients who received eculizumab for refractory HHS. In our experience, eculizumab is a safe and effective option for refractory pediatric HHS.

Hypoxaemia And Risk Of Death Among Children: Rethinking Oxygen Saturation, Risk-Stratification, And The Role Of Pulse Oximetry In Primary Care, Hamish R Graham, Carina King, Trevor Duke, Salahuddin Ahmed, Abdullah H Baqui, Tim Colbourn, Adegoke G Falade, Helena Hildenwall, Shubhada Hooli, Yewande Kamuntu, Rami Subhi, Eric D Mccollum

Faculty, Staff and Students Publications

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO2] 90–93%) and severe hypoxaemia (ie, …

Predicting Wait Time For Pediatric Kidney Transplant: A Novel Index, Alexandra Alvarez, Ashley Montgomery, Nhu Thao Nguyen Galván, Eileen D Brewer, Abbas Rana

Faculty, Staff and Students Publications

BACKGROUND: Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors.

METHODS: A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS …

Impact Of Frailty On Outcomes And Readmissions After Transcatheter And Surgical Aortic Valve Replacement In A National Cohort, Travis J Miles, Christopher T Ryan, Katie J Hogan, Bhavesh S Sayal, Christopher B Sylvester, Todd K Rosengart, Joseph S Coselli, Marc R Moon, Ravi K Ghanta, Subhasis Chatterjee

Faculty, Staff and Students Publications

OBJECTIVE: We examined the effect of frailty on in-hospital mortality, readmission rates, and hospitalization costs after transcatheter and surgical aortic valve replacement in a population-level cohort.

METHODS: The Nationwide Readmissions Database was queried for patients who underwent transcatheter or surgical aortic valve replacement during 2016-2018. Multivariate logistic regression was used to discern independent effects of frailty on outcomes. Kaplan-Meier time-to-event analysis was used to evaluate the effect of frailty on freedom from readmission.

RESULTS: A total of 243,619 patients underwent aortic valve replacement: 142,786 (58.6%) transcatheter aortic valve replacements and 100,833 (41.4%) surgical aortic valve replacements. Frail patients constituted 16,388 …

Use Of Pancreatic Endotherapy In Patients With Chronic Pancreatitis: Results From A Multicenter Cohort Study In The United States, Samuel Han, Darwin L Conwell, Jeffrey J Easler, Yunlong Yang, Dana K Andersen, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Steven J Hughes, Liang Li, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort.

METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after …