Inova Children's Hospital

Circulating microRNAs are promising biomarkers of acute cellular rejection (ACR) and antibody-mediated rejection (AMR) in heart transplantation. The study objective was to assess the characteristics and diagnostic performance of previously identified microRNAs and clinical rejection scores (CRS) in distinct blood samples obtained at the time of an endomyocardial biopsy (EMB). In the 5-center, prospective, longitudinal cohort study, GRAfT (Genomic Research Alliance for Transplantation), microRNA sequencing was performed on blood samples. The previously identified microRNAs associated with ACR (n=12) and AMR (n=17) were used to fit a logistic regression model to the current cohort, and the scores were scaled from 0 to 100. Diagnostic performance of ACR and AMR microRNA panels was assessed by the area under the receiver-operating characteristic curve. An adjusted Cox proportional hazard model evaluated the effect of CRS on long-term outcomes. In 173 heart transplant recipients (29% female sex, 41% Black race, median follow-up 374 days after transplant), 922 blood samples were sequenced, 720 paired with EMB. Among 14 episodes of ACR, the median ACR CRS was 78 compared with 42 without ACR, P<0.001. Among 25 episodes of AMR, median AMR CRS was 75 compared with 53 without AMR, P<0.001. The area under the receiver-operating characteristics curve for the CRS was 0.93 for ACR and 0.92 for AMR. Using a CRS threshold of 65, the ACR CRS had 79% sensitivity, 97% specificity, and 100% negative predictive value; the AMR CRS had 84% sensitivity, 86% specificity, and 99% negative predictive value. The ACR and AMR CRS were both <65 in 589 (82%) of the tests. After adjustment, a 10-point increase in CRS was associated with >40% increase in the hazard of the composite outcome: subsequent ACR or AMR by EMB, allograft dysfunction, or death (ACR hazard ratio, 1.42 [95% CI, 1.20-1.69]; P<0.001; AMR hazard ratio, 1.45 [95% CI, 1.14-1.86]; P=0.003). Circulating microRNAs reliably identified ACR and AMR on EMB. An elevated microRNA CRS was associated with an increased risk of subsequent rejection, allograft dysfunction, or death. This biomarker, with further validation, can serve as a noninvasive test to screen and diagnose ACR and AMR without the need for an EMB. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

Introduction: Infants with congenital heart disease (CHD) face challenges with feeding and nutrition. These infants have an increased rate of gastroesophageal reflux, delayed gastric emptying, and requiring tube feeding, in particular those who undergo surgical palliation. Our primary aim was to evaluate anti-reflux and pro-motility medication use among hospitalized infants with CHD. Methods: This was a retrospective multicenter analysis of infants &lt;1 year of age with CHD at first admission to a center participating in the Pediatric Acute Care Cardiology Collaborative (PAC 3 ) registry. Patients with single ventricle (SV) and biventricular (BV) physiology were defined based on their surgical procedure codes for surgeries during the admission. Patients with extracardiac diagnoses relating to the gastrointestinal system were excluded. Groups were compared based on the use of the following medications at discharge: histamine H2 antagonists, proton pump inhibitors, antacids, metoclopramide, erythromycin ethylsuccinate, or amoxicillin/clavulanic acid. Summary and comparative statistics were performed. Results: From 2/2019 to 1/2025, 24,729 infants were included, of whom 9597 had undergone surgical intervention (16% SV, 84% BV). The overall frequency of anti-reflux or pro-motility medication use in this cohort of CHD patients was 38%. Patients discharged on these medications required elemental formula and tube-assisted feeds more frequently and had a longer acute care cardiology unit (ACCU) and total hospitalization length of stay (Table 1). SV patients were more likely to be on anti-reflux or pro-motility medications compared to BV patients. Similar findings were noted among SV patients receiving these medications at discharge compared to SV patients who were not (Table 2). SV patients discharged on anti-reflux or pro-motility medications had an increased growth velocity at the time of discharge compared to their counterparts. Conclusion: Patients with SV CHD, those on elemental formula, tube assisted feeding and those with longer length of stays are more likely to be discharged on anti-reflux or pro-motility medications. An interesting finding is the positive association of the use of these medications with growth velocity prior to discharge specifically among SV patients. This suggests that these infants may have additional benefit from utilization of these medications at discharge.

Sequencing reads are deposited in the Sequence Read Archive (SRA) under submission PRJNA1280936. This paper does not report original code. Data S1. Table S1. Table S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The initial approach to stable supraventricular tachycardia (SVT) in children is either adenosine or vagal maneuvers. While automatic tachycardias do not respond to such an approach, even reentrant arrythmias will fail to terminate with adenosine or vagal maneuvers. Little consensus exists on the ideal second line antiarrhythmic medication for stable SVT. This article reviews the current approach to stable SVT and early pediatric studies using intravenous (i.v.) sotalol. The development of i.v. sotalol has spawned enthusiasm for a novel antiarrhythmic for refractory reentrant SVT and other automatic atrial tachycardias. Retrospective pediatric multicenter studies have shown an excellent conversion (50-90%) of refractory SVT with a single dose of i.v. sotalol; generally, over 30 min. Cautioned should be exercised using i.v. sotalol in patients with ventricular dysfunction and dose adjustments need to be made based on creatinine clearance. In addition, i.v. sotalol has shown promising early results in slowing the ventricular rate in postoperative junctional ectopic tachycardia faster than i.v. amiodarone. Intravenous sotalol has shown promising results in refractory pediatric SVT. Protocol driven dosing with the help of hospital pharmacists should be established before i.v. sotalol is prescribed. Future prospective studies especially in postoperative patients, neonates and patients with congenital heart disease are needed.

Antibody-mediated rejection is one of the most significant risk factors for allograft dysfunction and failure in children and adolescents with kidney transplants, yet optimal treatment remains unidentified. To date, there are mixed findings regarding the use of Bortezomib, a plasma cell apoptosis inducer, as an adjunct therapy in the treatment of antibody-mediated rejection. In a retrospective single center study, we reviewed the efficacy and tolerability of bortezomib as adjunct therapy for treatment-refractory antibody-mediated rejection. Six patients with a median age of 14.6 years (range 6.9-20.1 years) received bortezomib at a mean of 71 months (range 15-83 months) post-kidney transplant. Four patients experienced decline in estimated glomerular filtration rate (eGFR) from 4% to 42%. One patient started bortezomib while on hemodialysis and did not recover graft function, and another patient progressed to hemodialysis 6 months after receiving bortezomib. Although DSA did not completely resolve, there was a statistically significant decline in DSA MFI pre and 12-months post-BZ (p = .012, paired t-test) for the subjects who were not on dialysis at the time of bortezomib. Chronic Allograft Damage Index (CADI) score of ≥3 was seen in all six subjects at their biopsy prior to therapy. No adverse effects were reported. Bortezomib was well tolerated and resulted in improvements in MFI of DSA among four pediatric subjects without allograft failure, although no effects were observed on eGFR trajectory. Further studies are needed to clarify whether earlier intervention with bortezomib could prevent renal failure progression.

IntroductionVirtual interviews (VI) are now a permanent part of pediatric emergency medicine (PEM) recruitment, especially given the cost and equity advantages. Yet inability to visit programs in person can impact decision-making, leading applicants to apply to more programs. Moreover, the cost advantages of VI may encourage applicants to apply to programs farther away than they might otherwise have been willing or able to travel. This could create unnecessary strain on programs. We conducted this study to determine whether PEM fellowship applicants would apply to a larger number of programs and in different geographic patterns with VI (2020 and 2021) as compared to in-person interviews (2018 and 2019).MethodsWe conducted an anonymous national survey of all PEM fellows comparing two cohorts: current fellows who interviewed inperson (applied in 2018/2019) and fellows who underwent VIs in 2020/2021 (current fellows and those recently matched in 2021). The study took place in March–April 2022. Questions focused on geographic considerations during interviews and the match. We used descriptive statistics, chi-square and t-tests for analysis.ResultsOverall response rate was 42% (231/550); 32% (n = 74) interviewed in person and 68% (n = 157) virtually. Fellows applied to a median of 4/6 geographic regions (interquartile range 2, 5). Most applied for fellowship both in the same region as residency (216, 93%) and outside (192, 83%). Only the Pacific region saw a statistically significant increase in applicants during VI (59.9% vs 43.2%, P = 0.02). There was no statistical difference in the number of programs applied to during in-person vs VI (mean difference (95% confidence interval 0.72, −2.8 – 4.2). A majority matched in their preferred state both during VI (60.4%) and in-person interviews (65.7%). The difference was not statistically significant (P = 0.45).ConclusionWhile more PEM fellowship applicants applied outside the geographic area where their residency was and to the Pacific region, there was no overall increase in the number of programs or geographic areas PEM applicants applied to during VI as compared to in-person interview seasons. As this was the first two years of VI, ongoing data collection will further identify trends and the impactof VI.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disorder characterized by episodes of polymorphic ventricular tachycardia. Clinically, patients who have CPVT present with juvenile sudden death or stress-induced syncope. We present a case of an 18-year-old girl with CPVT resistant to traditional pharmacotherapies. Instead of a typical stellate ganglion block (SGB), the patient underwent bilateral continuous proximal intercostal blocks that successfully inhibited arrhythmogenic events. This therapeutic method may provide an alternative to SGBs and demonstrates proof of concept for an early elective intervention to be included in the diagnostic and therapeutic algorithm for patients with CPVT.