Diseases Commons^™

Midterm Outcomes Of Pediatric Mitral Valvuloplasty For Moderate To Severe Mitral Valve Regurgitation And Associated Risk Factors For Postoperative Deterioration, Hongyuan Fu, Aijun Liu, Ming Yang, Zeyu Liu, Junwu Su

The Texas Heart Institute Journal

BACKGROUND: Mitral valvuloplasty is considered the best treatment for pediatric mitral valve regurgitation. The objective of this analysis was to identify risk factors for postoperative mitral valve regurgitation progression and evaluate valvuloplasty effectiveness.

METHODS: This retrospective, single-center study investigated the clinical efficacy of mitral valvuloplasty and identified factors that affect prognosis. Pediatric patients with moderate or severe mitral valve regurgitation who had undergone mitral valvuloplasty between September 2016 and August 2023 were included. Kaplan-Meier survival analysis was used to assess freedom from both mitral valve deterioration and cardiovascular death. Univariate and multivariate Cox regression analyses were performed to identify potential …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Disparities In Cardiovascular Disease Outcomes And Economic Burdens Among Minorities In Southeastern Virginia, Ismail El Moudden, Asra Amidi, Reem Sharaf Alddin, Michael Bittner, Qi Zhang

Department of Obstetrics & Gynecology Faculty Publications

Background

Cardiovascular diseases are the leading cause of mortality in the United States, presenting significant public health challenges and financial burdens, particularly in Southeastern Virginia, where African American and Hispanic (AA&H) populations are disproportionately affected.

Methods

This retrospective observational study analyzed data from 30,855 hospital discharges of AA&H patients across Southeastern Virginia from 2016 to 2020, focusing on individuals aged 18 to 85 with cardiovascular diseases. Utilizing the Virginia Health Information database, we examined demographic information, clinical data, and healthcare utilization patterns through hypothesis tests and regression models to explore associations between these variables and the economic impacts of cardiovascular …

The Camden Study - A Pregnancy Cohort Study Of Pregnancy Complications And Birth Outcomes In Camden, New Jersey, Usa., Stephanie Shiau, Xinhua Chen, Ayana April-Sanders, Ellen C Francis, Shristi Rawal, Megan Hansel, Kehinde Adeyemi, Zorimar Rivera-Núñez, Emily S Barrett

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Pregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.

METHODS: From 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the US. The cohort reflects a population under-represented in perinatal cohort studies (45% Hispanic, 38% non-Hispanic Black, 17% White …

The Study Of The Epidemiology Of Pediatric Hypertension Registry (Superhero): Rationale And Methods, Andrew M South, Victoria C Giammattei, Kiri W Bagley, Christine Y Bakhoum, William H Beasley, Morgan B Bily, Shupti Biswas, Aaron M Bridges, Rushelle L Byfield, Jessica Fallon Campbell, Rahul Chanchlani, Ashton Chen, Lucy D'Agostino Mcgowan, Stephen M Downs, Gina M Fergeson, Jason H Greenberg, Taylor A Hill-Horowitz, Elizabeth T Jensen, Mahmoud Kallash, Margret Kamel, Stefan G Kiessling, David M Kline, John R Laisure, Gang Liu, Jackson Londeree, Caroline B Lucas, Sai Sudha Mannemuddhu, Kuo-Rei Mao, Jason M Misurac, Margaret O Murphy, James T Nugent, Elizabeth A Onugha, Ashna Pudupakkam, Kathy M Redmond, Sandeep Riar, Christine B Sethna, Sahar Siddiqui, Ashley L Thumann, Stephen R Uss, Carol L Vincent, Irina V Viviano, Michael J Walsh, Blanche D White, Robert P Woroniecki, Michael Wu, Ikuyo Yamaguchi, Emily Yun, Donald J Weaver

Faculty, Staff and Students Publications

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th …

Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

OBJECTIVE: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

DERIVATION COHORT: Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).

VALIDATION COHORT: Internal validation occurred in a testing group of patients from the dataset (20%).

PREDICTION MODEL: Retrospective international …

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Cutaneous Adverse Effects From Diabetes Devices In Pediatric Patients With Type 1 Diabetes Mellitus: Systematic Review, Alicia Podwojniak, Joseph Flemming, Isabella J Tan, Hira Ghani, Zachary Neubauer, Anne Jones

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusions (CSIIs) are the current standard treatment devices for type 1 diabetes (T1D) management. With a high prevalence of T1D beginning in pediatrics and carrying into adulthood, insufficient glycemic control leads to poor patient outcomes. Dermatologic complications such as contact dermatitis, lipodystrophies, and inflammatory lesions are among those associated with CGM and CSII, which reduce glycemic control and patient compliance.

OBJECTIVE: This systematic review aims to explore the current literature surrounding dermatologic complications of CGM and CSII as well as the impact on patient outcomes.

METHODS: A systematic review of the …

Identification Of Atypical Pediatric Diabetes Mellitus Cases Using Electronic Medical Records, Marcela F Astudillo, William E Winter, Liana K Billings, Raymond Kreienkamp, Ashok Balasubramanyam, Maria J Redondo, Mustafa Tosur

Faculty, Staff and Students Publications

INTRODUCTION: There are no established methods to identify children with atypical diabetes for further study. We aimed to develop strategies to systematically ascertain cases of atypical pediatric diabetes using electronic medical records (EMR).

RESEARCH DESIGN AND METHODS: We tested two strategies in a large pediatric hospital in the USA. Strategy 1: we designed a questionnaire to rule out typical diabetes and applied it to the EMR of 100 youth with diabetes. Strategy 2: we built three electronic queries to generate reports of three atypical pediatric diabetes phenotypes: unknown type, type 2 diabetes (T2D) diagnosed(AbNegT1D).

RESULTS: Strategy 1 identified six cases …

Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …

A Phase 1 Study Of Abi-009 (Nab-Sirolimus) In Combination With Temozolomide And Irinotecan In Pediatric Patients With Recurrent Or Refractory Solid Tumors, Including Cns Tumors-A Children's Oncology Group Pediatric Early Phase Clinical Trial Network Study Advl1514, Stuart L Cramer, Alyssa Terry Reddy, Charles Gene Minard, Stephan Voss, Elizabeth Fox, Xiaowei Liu, Kristina Denic, Joel M Reid, Brenda J Weigel

Faculty, Staff and Students Publications

BACKGROUND: Nab-sirolimus (ABI-009, nab-rapamycin; Aadi Bioscience Inc. [Aadi]) is a human albumin-bound form of sirolimus nanoparticles, a potent mTOR inhibitor. This phase I trial was conducted to define dose-limiting toxicities (DLT), maximum tolerated or recommended phase II dose (MTD/RP2D), and pharmacokinetics of Nab-sirolimus in combination with temozolomide and irinotecan.

METHODS: Using a rolling 6 design, Nab-sirolimus was administered intravenously (IV) on days (D) 1 and 8 of cycle (C) 1. In subsequent cycles, Nab-sirolimus was administered D1 and D8 in combination with temozolomide (125 mg/m

RESULTS: Thirty-three patients were enrolled, 32 were eligible. Dose determination included 17 evaluable patients, median …

A Comparison Of The Diagnostic Capability Of Kato-Katz And Real-Time Pcr For The Assessment Of Treatment Efficacy Of Ivermectin And Albendazole Combination Against T Trichiura Infections, Gabriela Matamoros, Ana Sanchez, Ruben Cimino, Alejandro Krolewiecki, Rojelio Mejia

Faculty, Staff and Students Publications

BACKGROUND: Trichuris trichiura is humans' second most prevalent soil-transmitted helminth (STH) infection after Ascaris lumbricoides, affecting approximately 460 million people worldwide. Despite its sub-optimal sensitivity, especially in low prevalence and infection intensity settings, the modified Kato-Katz (K-K) is still recommended as a diagnostic method by the World Health organization (WHO) guidelines.

METHODOLOGY/PRINCIPAL FINDINGS: Within a randomized clinical trial (RCT) comprising four treatment arms with two different anthelmintics, the present study reports an important secondary research objective to determine the diagnostic agreement between K-K and real-time PCR evaluating treatment efficacy against T. trichiura. The parasitological results were analyzed, including cure rates …

Trends In Gaps Of Care For Patients With Congenital Heart Disease: Implications For Social Determinants Of Health And Child Opportunity Index, Abbas H. Zaidi, Adam Alberts, Devyani Chowdhury, Claude Beaty, Benjamin Brewer, Ming Hui Chen, Sarah D. De Ferranti

Department of Surgery Faculty Papers

BACKGROUND: Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood.

METHODS AND RESULTS: This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such …

Institutional Experience Of Lymphoproliferative Disorders With Initial Diagnosis Made Via Fine Needle Aspiration At Otolaryngology Clinic, Alaa S. Hrizat, Jerald Gong, Stacey M. Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: This study characterizes lymphomas presenting as palpable head and neck masses and evaluates the role of fine needle aspiration (FNA) and flow cytometry (FC) in diagnosis.

DESIGN: A 5-year retrospective review of FNAs performed by pathologists in an ENT clinic identified cases with a predominant lymphoid population that lacked an epithelial component. Cytology, FC, and subsequent surgical pathology diagnoses were correlated.

RESULTS: Of 821 FNAs, 154 (19%) met selection criteria. Reactive lymph nodes accounted for 43% (67/154), with most diagnosed as 'negative for malignancy,' except one 'atypical' (ATY) case. Lymphoma was confirmed in 57% (87/154) of cases, categorized as …

Exposure To Per- And Polyfluoroalkyl Substances And Alterations In Plasma Microrna Profiles In Children, Yijie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Haotian Wu, Shelley H Liu, Hongxu Wang, Emily Beglarian, Scott M Bartell, Sandrah Proctor Eckel, Douglas Walker, Damaskini Valvi, Michele Andrea La Merrill, Thomas H Inge, Todd Jenkins, Justin R Ryder, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Marina Vafeiadi, Aikaterini Margetaki, Theano Roumeliotaki, Max Aung, Rob Mcconnell, Andrea Baccarelli, David Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans.

OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children.

METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and …

Long-Term Efficacy And Safety Of Cannabidiol In Patients With Tuberous Sclerosis Complex: 3-Year Results From The Cannabidiol Expanded Access Program, Arie Weinstock, E Martina Bebin, Daniel Checketts, Gary D Clark, Jerzy P Szaflarski, Laurie E Seltzer, Elizabeth A Thiele, Farhad Sahebkar

Faculty, Staff and Students Publications

OBJECTIVE: The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC.

METHODS: Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. …

Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello

Faculty, Staff and Students Publications

BACKGROUND: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity.

METHODS AND RESULTS: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in …

Decoding Complex Inherited Phenotypes In Rare Disorders: The Decipherd Initiative For Rare Undiagnosed Diseases In Chile, M Cecilia Poli, Boris Rebolledo-Jaramillo, Catalina Lagos, Joan Orellana, Gabriela Moreno, Luz M Martín, Gonzalo Encina, Daniela Böhme, Víctor Faundes, M Jesús Zavala, Trinidad Hasbún, Sara Fischer, Florencia Brito, Diego Araya, Manuel Lira, Javiera De La Cruz, Camila Astudillo, Guillermo Lay-Son, Carolina Cares, Mariana Aracena, Esteban San Martin, Zeynep Coban-Akdemir, Jennifer E Posey, James R Lupski, Gabriela M Repetto

Faculty, Staff and Students Publications

Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the "diagnostic odyssey" for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international …

Human Papillomavirus Vaccination And Human Papillomavirus-Related Cancer Rates, Victor Adekanmbi, Itunu Sokale, Fangjian Guo, Jessica Ngo, Thao N Hoang, Christine D Hsu, Abiodun Oluyomi, Abbey B Berenson

Faculty, Staff and Students Publications

IMPORTANCE: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs).

OBJECTIVE: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

Mitral Annular Disjunction And Its Progression During Childhood In Marfan Syndrome, Tam T Doan, Alejandra Iturralde Chavez, Santiago O Valdes, Justin D Weigand, James C Wilkinson, Anitha Parthiban, Sara B Stephens, Ricardo H Pignatelli, Shaine A Morris

Faculty, Staff and Students Publications

AIMS: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

METHODS AND RESULTS: We included patientsMFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different …

Pre-Existing Immunocompromising Conditions And Outcomes Of Acute Covid-19 Patients Admitted For Pediatric Intensive Care, Courtney M Rowan, Brenna Labere, Cameron C Young, Laura D Zambrano, Margaret M Newhams, Suden Kucukak, Elizabeth R Mcnamara, Elizabeth H Mack, Julie C Fitzgerald, Katherine Irby, Aline B Maddux, Jennifer E Schuster, Michele Kong, Heda Dapul, Stephanie P Schwartz, Melania M Bembea, Laura L Loftis, Amanda R Kolmar, Christopher J Babbitt, Ryan A Nofziger, Mark W Hall, Shira J Gertz, Natalie Z Cvijanovich, Matt S Zinter, Natasha B Halasa, Tamara T Bradford, Gwenn E Mclaughlin, Aalok R Singh, Charlotte V Hobbs, Kari Wellnitz, Mary A Staat, Bria M Coates, Hillary R Crandall, Mia Maamari, Kevin M Havlin, Adam J Schwarz, Christopher L Carroll, Emily R Levy, Kristin L Moffitt, Angela P Campbell, Adrienne G Randolph, Janet Chou

Faculty, Staff and Students Publications

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care.

METHODS: Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients(PICU) or high-acuity unit for acute COVID-19 were included.

RESULTS: Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were …

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 …

In Utero Exposure To Antihistamines And Risk Of Hepatocellular Carcinoma In A Multigenerational Cohort, Caitlin C Murphy, Karim Seif El Dahan, Amit G Singal, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records …

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.

Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups In The Navigator Study, Tara F Carr, Wendy C Moore, Monica Kraft, Guy Brusselle, Mario Castro, Geoffrey L Chupp, Michael E Wechsler, Gillian Hunter, Andrew W Lindsley, Jean-Pierre Llanos, Luke K Burke, Shradha Chandarana, Christopher S Ambrose

Faculty, Staff and Student Publications

INTRODUCTION: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.

METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses …

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After Sars-Cov-2 Infection, Elizabeth R. Unger, Jin-Mann S. Lin, Lauren E. Wisk, Huihui Yu, Michelle L'Hommedieu, Helen Lavretsky, Juan Carlos C. Montoy, Michael A. Gottlieb, Kristin L. Rising, Nicole L. Gentile, Michelle Santangelo, Arjun K. Venkatesh, Robert M. Rodriguez, Mandy J. Hill, Rachel E. Geyer, Efrat R. Kean, Sharon Saydah, Samuel A. Mcdonald, Ryan Huebinger, Ahamed H. Idris, Jocelyn Dorney, Bala Hota, Erica S. Spatz, Kari A. Stephens, Robert A. Weinstein, Joann G. Elmore

Department of Emergency Medicine Faculty Papers

IMPORTANCE: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

OBJECTIVE: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 …

Risk Of Anthracycline-Induced Cardiac Dysfunction In Adolescent And Young Adult (Aya) Cancer Survivors: Role Of Genetic Susceptibility Loci, Lily K Stafford, Xiaohui Tang, Amanda Brandt, Jianzhong Ma, Jose Banchs, J Andrew Livingston, Michael E Roth, Alanna C Morrison, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

There is a known genetic susceptibility to anthracycline-induced cardiac dysfunction in childhood cancer survivors, but this has not been adequately shown in adolescent and young adult (AYA) patients. Our aim was to determine if the previously identified variants associated with cardiac dysfunction in childhood cancer patients affect AYA cancer patients similarly. Forty-five variants were selected for analysis in 253 AYAs previously treated with anthracyclines. We identified four variants that were associated with cardiac dysfunction: SLC10A2:rs7319981 (p = 0.017), SLC22A17:rs4982753 (p = 0.019), HAS3:rs2232228 (p = 0.023), and RARG:rs2229774 (p = 0.050). HAS3:rs2232228 and SLC10A2:rs7319981 displayed significant effects in our AYA …