Children's Hospital of The King's Daughters

OBJECTIVE:To assess whether submucosal ablation of turbinates (SAT) at the time of adenotonsillectomy (AT) confers benefit in the reduction of nasal obstruction compared to AT alone. STUDY DESIGN:A randomized, single-blinded study between 2014 and 2017. Children between 3 and 17 years with sleep-disordered breathing (SDB) and nasal obstruction were eligible. Patients had turbinate hypertrophy at baseline and were scheduled to undergo AT for SDB. The sinus and nasal quality of life survey (SN-5) and the visual analog scale (VAS) were measured. SETTING:Tertiary Children's Hospital. METHODS:Children were randomized to AT (control group) or AT with SAT. The study was powered to assess for changes in the SN-5 at 3 and 12 months. RESULTS:In total, 51 patients were randomly assigned: 18 in the control group and 33 in the AT with SAT group. The SAT group had higher preoperative SN-5 scores compared to the control group. Both groups experienced improvement in SN-5 scores at 3 and 12 months. There was no statistically significant difference in the reduction of the total SN-5 score at 3 months (51% vs 50.1%, P = .707) and 12 months (52.1% vs 43.6%, P = .225) between the AT with SAT group and the AT alone group. CONCLUSION:Children with nasal obstruction that undergo AT and SAT experience improvement in SN-5 scores. It remains uncertain whether SAT performed at the time of AT confers additional improvement in nasal symptoms compared to AT alone. Future research should include an assessment of SDB symptom burden to allow for a definitive determination of the role of turbinate surgery in children with SDB.

Acute liver injury (ALI) is a recognized adverse event with adeno-associated virus (AAV)-based gene therapies, including delandistrogene moxeparvovec, an AAVrh74-based gene therapy for Duchenne muscular dystrophy. Progression of ALI to acute liver failure (ALF) is rare. In clinical trials, ALF was defined as an international normalized ratio ≥1.5 with encephalopathy and/or ascites, occurring <26 weeks since product/treatment exposure, and in the absence of identified preexisting liver disease as assessed by the treating investigator. The two cases presented here represent the only known instances of ALF following delandistrogene moxeparvovec to date, both resulting in fatal outcomes. Both cases occurred in nonambulatory patients (ages 15 and 16 years). Both patients exhibited abrupt elevations in aminotransferases from baseline approximately 4 weeks after delandistrogene moxeparvovec administration. Over the subsequent weeks and despite interventions, aminotransferases, including gamma-glutamyl transferase (GGT), declined concurrently with a continued rise in total bilirubin, consistent with severe hepatocellular injury and a harbinger of ALF. An interdisciplinary expert panel was convened and concluded that no single biomarker or clinical feature consistently predicted the rapid progression of severe ALI to ALF. Advisors recommended basing treatment intervention for severe ALI on the rate and magnitude of changes from baseline in liver biomarkers (e.g., 2-3× increase in alanine aminotransferase within ≤1 week). For these severe cases, most advisors recommended intravenous methylprednisolone as the initial treatment whereas typical ALI may be managed with oral corticosteroid adjustment or may resolve with time, as seen in the clinical trial experience. Advisors hypothesized that delandistrogene moxeparvovec-related ALI is T-cell-mediated and discussed the potential of additional immunosuppression. Advisors also recommended enhancing baseline evaluation for hepatic comorbidities with lipid profiling, transient elastography, and abdominal ultrasound to further study potential risk factors for ALI progressing to ALF. Finally, there was strong support for generating additional real-world evidence and conducting prospective clinical trials to inform clinical management of ALI in practice.

Delandistrogene moxeparvovec is a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene therapy that addresses the absence of functional dystrophin in Duchenne muscular dystrophy (DMD). EMBARK is a phase 3, two-part, crossover, randomized, placebo-controlled trial assessing the safety and efficacy of delandistrogene moxeparvovec (single intravenous dose 1.33 × 1014 vector genomes/kg) in ambulatory male patients with DMD aged 4 to < 8 years; N = 125. One-year results demonstrated the manageable safety of delandistrogene moxeparvovec, consistent with previous clinical trials. The primary endpoint (change from baseline in North Star Ambulatory Assessment [NSAA] total score at 52 weeks compared with placebo) did not meet statistical significance. However, key secondary endpoints, comprising timed function tests, suggested slowing or stabilization of disease progression with delandistrogene moxeparvovec, which could become increasingly evident over longer periods of time. We report 2-year follow-up of safety and functional outcomes in patients receiving delandistrogene moxeparvovec in EMBARK part 1. As a result of the crossover study design, 2-year functional outcomes of patients receiving delandistrogene moxeparvovec in part 1 of EMBARK were compared, by pre-specified analysis, with a matched propensity score-weighted external control (EC). At 2 years, EMBARK patients showed statistically significant benefit versus the EC cohort in functional outcomes prognostic for delaying loss of ambulation (NSAA, Time to Rise, 10-m Walk/Run), demonstrating sustained stabilization or slowing of disease progression. Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization were maintained over 64 weeks. No new safety signals were observed between week 52 and week 104. Between baseline and week 104, there were no treatment-related deaths, study discontinuations due to adverse events, or clinically significant complement-mediated adverse events. At 2 years, stabilization or slowing of DMD disease progression was observed in ambulatory male patients with DMD aged 4 to < 8 years receiving delandistrogene moxeparvovec versus a matched EC cohort. Safety was consistent with EMBARK 1-year data and manageable with appropriate monitoring. NCT05096221.

Families sometimes worry that donating a child’s tumor tissue after death might conflict with their religious beliefs. Similarly, clinicians may hesitate to raise this topic with their patients over concerns about causing undue distress or misunderstanding. This study reviewed official teachings from major U.S. faith traditions—Catholicism, Protestantism, Judaism, and Islam—and found that most support donation when it helps reduce suffering and advance medical research. By sharing these positions, we hope to ease concerns, encourage informed conversations, and make it easier for families who wish to donate. These donations are vital for developing new treatments and improving outcomes for children with brain tumors.

Introduction:Preventing ambulatory central line-associated bloodstream infections (A-CLABSIs) is challenging due to inconsistent education, follow-up, and home care practices. Pediatric intestinal failure (IF) patients are particularly vulnerable. This institution aimed to decrease its IF A-CLABSI rate by 25% within 2 years through a standardized, step-by-step central line care education program. Methods:Using the Toyota problem-solving method, the team reviewed data and performed a root cause analysis of the prioritized problem, implementing a 2-phase education program. Phase 1 delivered in-hospital education using videos, handouts, and hands-on teaching with skill demonstration. The existing pediatric central line skills class was expanded and offered to partnering home health agencies. Phase 2 included postdischarge follow-up via phone calls or clinic visits to address questions and identify needs. Family feedback was collected through surveys. Results:The average IF A-CLABSI rate decreased from 3.66 per 1,000 ambulatory line days to 1.85, representing a 49.5% reduction (P = 0.1479). One hundred percent of families surveyed at 7 days postdischarge reported confidence in providing central line care at home and found follow-up phone calls very helpful. Among 44 home health staff trained, the mean percent improvement in pre- to posttest scores was 47%. Families and home health personnel especially valued the hands-on learning component. Conclusions:The standardized education program substantially reduced the rate of IF A-CLABSIs and improved confidence and satisfaction among families and home health nurses. It also enhanced collaboration among families, home health agencies, and the health system, fostering trust and continuity of care.