Children's Hospital Los Angeles

BACKGROUND Poor cerebrovascular reactivity is associated with a higher risk of cerebrovascular disease. The most common method to study cerebrovascular reactivity in aging adults, transcranial Doppler ultrasound, yields measurements in large intracranial arteries, but not in regional brain parenchyma that may be more impaired in some disease processes. Measurements derived from transcranial Doppler ultrasound suggest that there are sex differences in cerebrovascular reactivity for aging adults. We investigated the association between age and sex on cerebrovascular reactivity using blood oxygen level dependent (BOLD) magnetic resonance imaging in a representative group of aging adults. METHODS This cross-sectional study investigated BOLD cerebrovascular reactivity to CO 2 in a representative group of aging adults, 51 to 83 years old. We manipulated end-tidal carbon dioxide with breathing exercises and evaluated changes in 6 brain regions: whole brain, white matter, cortical gray matter, subcortical gray matter, left hippocampus, and right hippocampus. We used 1 linear regression per region to investigate the effects of age, sex, and their interaction on BOLD cerebrovascular reactivity. RESULTS We report an age-by-sex interaction for all brain regions ( P ≤0.050), except cortical gray matter ( P =0.062). For white matter and subcortical gray matter, female participants trended toward an age-related BOLD cerebrovascular reactivity increase ( P ≤0.058), while male participants did not change with age ( P >0.580). In the whole brain and bilateral hippocampi, the age trends for each sex were in opposite directions but not significant ( P >0.211). We report a main effect of sex (female greater than male participants) for subcortical gray matter and the right hippocampus ( P ≤0.048) and no main effect of age in any model. CONCLUSIONS We present the first report of age-related BOLD cerebrovascular reactivity increases in older female participants and higher BOLD cerebrovascular reactivity in older female compared with male participants. Sex and age-by-sex-based differences seem to be driven by changes in white matter, subcortical gray matter, and bilateral hippocampi.

Objectives Clusters of severe acute hepatitis in children were reported worldwide beginning in October 2021. Although most children recovered, some progressed to liver failure leading to death or liver transplantation. Herein, we characterize the clinical characteristics, and outcomes of this group of children through an international collaborative effort. Methods Participation was solicited via a global listserv to pediatric gastroenterologists worldwide. Patients <18 years, alanine aminotransferase >500 U/L, without chronic liver disease or acetaminophen ingestion were eligible. Data were submitted by individual sites into a Research Electronic Data Capture registry created in July 2022. Results Two hundred and seven cases were collected, with a peak incidence of 28 in April 2022. The median age was 40 months, 52.7% were male, 63.3% were white, and 44% were Hispanic. At presentation, 80% reported gastrointestinal symptoms followed by fever (27.7%). The median duration of hospitalization was 5.5 days with 51 patients requiring intensive care. Adenovirus serum/whole blood DNA was detected in 28/133 (21%) and seven patients were treated with cidofovir. Liver biopsies, performed in 76 patients revealed portal and lobular inflammation with none identifying a viral etiology. Eleven patients underwent liver transplantation, four were adenovirus positive, all of whom survived. There were four reported deaths. Conclusions In this large data set of pediatric patients with severe acute hepatitis, the majority did not have a singular definitive etiology but did recover spontaneously. Continued community surveillance and close cooperation are critical toward understanding the etiology of such clusters in pediatrics.

Background and Objectives Mononuclear cell (MNC) collection is critical for paediatric patients undergoing cellular therapies such as chimeric antigen receptor T‐cell and haematopoietic stem cell transplantation. In children, extracorporeal volume (ECV) often exceeds 15% of total blood volume (TBV), traditionally necessitating red blood cell (RBC) priming to reduce the risk of haemodynamic instability. However, RBC priming introduces allogenic blood exposure and related complications. This study evaluated the safety and feasibility of unprimed MNC collection in paediatric patients with ECV/TBV ratios greater than 15%. Materials and Methods We retrospectively reviewed two paediatric patients with B‐cell acute lymphoblastic leukaemia (B‐ALL) who underwent MNC collection using the Spectra Optia system in continuous mononuclear cell collection mode. Both patients had ECV/TBV ratios of 16% and 17%, respectively. Vital signs and laboratory parameters were monitored throughout and after the procedures to assess for adverse events, haemodynamic instability, and need for transfusion. Results Both patients completed MNC collection without adverse reactions, interruptions, or clinically significant changes in vital signs. Post‐procedural haemoglobin and platelet counts showed no major declines, and neither patient required transfusion. Collection efficiency met institutional standards, and no symptoms of hypovolemia or citrate toxicity were observed. Conclusion Unprimed MNC collection can be safely performed in paediatric patients even when the ECV/TBV ratio exceeds 15%. With careful monitoring and procedural planning, this conservative strategy may reduce allogenic blood exposure without compromising safety or collection efficiency.

Background While breastfeeding benefits early child neurocognition, its influences into adolescence, a period of intense brain remodeling and heightened mental health risk, remain unclear. Methods Breastfeeding and neurocognitive longitudinal associations were explored over a two-year period in the Adolescent Brain Cognitive Development (ABCD) Study® ( n baseline = 5098, ages 9–10, 49% female; n follow-up = 3810, ages 11–12, 48% female). Breastfeeding duration was reported as never breastfed (15.8%), 1–6 months (34.6%), 7–12 months (26.4%), and >12 months (23.1%). MRI-derived estimates of cortical thickness, surface area, and cortical myelin were calculated across 148 brain regions alongside fluid cognition measures. Linear mixed-effects models tested the influence of breastfeeding duration and its interaction with age on neurocognitive outcomes. Significant cortical thickness and surface area associations were explored for cortical myelin differences. Parallel mediation analyses examined whether cortical features mediated the breastfeeding-fluid cognition relationship. Results Breastfeeding duration was positively associated with cortical thickness (31 regions), surface area (45 regions), and fluid cognition (all p values < 0.05), and with greater cortical myelin in four regions and increases by follow-up in 12 regions (all p values < 0.05). Surface area mediated the breastfeeding-fluid cognition link ( β = 0.008, CI boot 95% = 0.005, 0.012). Conclusions These findings emphasize the importance of extending breastfeeding practices for optimal adolescent neurocognition. Impact Does breastfeeding influence neurocognition during early adolescence, and does it impact neurocognitive development at this stage? In this longitudinal study, breastfeeding demonstrated dose-dependent, lasting positive influences on neurocognition that remained stable over a 2-year period spanning late childhood to early adolescence. Specifically, individuals who were breastfed longer showed increased cortical thickness, surface area, cortical myelin, and fluid cognition, predictors of positive outcomes in later life, including physical and mental health. Our findings highlight the importance of breastfeeding and support its extended practice for optimal neurodevelopment and potential late-life benefits.

Objectives Congenital heart disease (CHD) patients with single ventricle physiology (SVP) have heterogeneous characteristics that challenge cohort classification. We aim to develop a phenotyping algorithm that accurately identifies SVP patients using electronic health record (EHR) data. Materials and Methods We used ICD-9 and ICD-10 codes for initial classification, then enhanced the algorithm with domain expertise, imaging reports, and progress notes. The algorithm was developed using a cohort of 1020 patients who underwent magnetic resonance imaging scans and tested in a separate cohort of 2500 CHD patients with adjudication. Validation was performed in a holdout group of 22 500 CHD patients. We evaluated performance using accuracy, sensitivity, precision, and F1 score, and compared it to a published algorithm for SVP using the same dataset. Results In the 2500-testing cohort, our algorithm based on specialty-defined features and International Classification of Diseases (ICD) codes achieved 99.24% accuracy, 94.12% precision, 85.11% sensitivity, and 89.39% F1 score. In contrast, the published method achieved 95.20% accuracy, 43.23% precision, 88.30% sensitivity, and 58.04% F1 score. In the 22 500-validation cohort, our algorithm achieved 93.82% precision, while the published method achieved 43.00%. Discussion and Conclusions Our automated phenotype algorithm, combined with physician adjudication, outperforms a published method for SVP classification. It effectively identifies false positives by cross-referencing clinical notes and detects missed SVP cases that were due to absent or erroneous ICD codes. Our integrated phenotyping algorithm showed excellent performance and has the potential to improve research and clinical care of SVP patients through the automated development of an electronic cohort for prognostication, monitoring, and management.

Objective Family‐Based Treatment (FBT) is the gold standard outpatient eating disorder treatment for children and adolescents with eating disorders. Especially within the past decade, higher levels of care (HLOC) programs including inpatient medical settings and partial hospitalisation programs have incorporated elements of FBT to improve the effectiveness of their treatments. The present study aimed to systematically review the state of the research on FBT adaptations in HLOC and describe the outcomes of those treatment programs. Method Articles were identified via a systematic search of three databases (PsycINFO, PubMed, Cochrane Database of Randomized Controlled Trials) according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses. Results Forty articles were identified including 35 studies and 5 programme descriptions, representing 17 inpatient and 23 partial hospitalisation and/or intensive outpatient programs. Thirty quantitative studies and five qualitative studies were included. Findings supported suitability and effectiveness of treatments in improving weight, eating disorder and mental health symptoms and family functioning. Conclusions Burgeoning research supports the effectiveness of FBT adapted to HLOC, with the most evidence for improving weight and eating disorder symptoms. The present review identifies further areas of research needed to expand on the current evidence, such as with controlled trials with sufficient follow‐up data.

Background Velopharyngeal insufficiency (VPI) can be effectively treated surgically with palatal lengthening or pharyngeal procedures. There is limited data on long-term national trends in their use and associated outcomes. This study evaluates 10 years of trends and outcomes in VPI-correcting procedures. Methods We conducted a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program Pediatric database, identifying cases with CPT codes corresponding to VPI-correction procedures. Patients 6 to 18 years old were included. Outcomes included operative characteristics and postoperative complications. Results Of 5957 cases, 45% were palatal lengthening, and 55% were pharyngeal procedures (63% pharyngeal flap and 37% sphincter pharyngoplasties). Palatal procedures had longer operative ( P < 0.001) and anesthesia ( P < 0.001) durations compared to pharyngeal procedures. Pharyngeal flaps had longer operative ( P < 0.001) and anesthesia ( P < 0.001) durations compared to sphincter pharyngoplasties. Palatal-lengthening surgeries had higher rates of wound dehiscence ( P = 0.001) but no significant difference in major complications compared to pharyngoplasties. No differences in complication rates between pharyngeal flaps and sphincter pharyngoplasties were observed. Discussion Low complication rates across palatal lengthening and pharyngeal procedures suggest that VPI surgical planning should prioritize factors such as patient anatomy, existing comorbidities, and the potential risks associated with prolonged operative and anesthesia times.

Purpose Surgical invasiveness indices have been used in adult spine surgery to characterize the invasiveness of complex procedures and for risk stratification. This has not been studied in the pediatric population. The purpose of this study was to develop and validate a surgical invasiveness index for pediatric spinal deformity surgery. Methods The National Surgical Quality Improvement Program (NSQIP) Pediatric database was queried between the years 2016–2022. Patients were included if they were <18 years of age, received posterior or anterior-posterior spinal fusion surgery, and had a diagnosis of spinal deformity. The study cohort was divided into a derivation cohort and a validation cohort. A multivariable linear regression analysis was performed to identify surgical components associated with operative time. Surgical components of interest included number of posterior fusion levels, number of anterior fusion levels, pelvic instrumentation, posterior column osteotomies, three-column osteotomies, and prior spinal deformity surgery. Statistically significant variables were used to establish a pediatric spinal deformity surgical invasiveness index. The score was assessed and validated using linear and logistic regression analysis and receiver operating characteristic curve analysis on operative time and allogeneic transfusion. Results There were 37,658 patients included (Derivation cohort: 26,372; Validation cohort: 11,286). In the linear regression analysis, more posterior fusion levels (7–12 levels: 0.54, p<0.001;>12 levels: 1.40, p<0.001), anterior fusion 1–3 levels (2.42, p<0.001), anterior fusion ≥4 levels (2.93, p<0.001), pelvic instrumentation (0.79, p<0.001), and previous spinal deformity surgery (0.44, p<0.001) were associated with longer operative time. Each level of posterior column osteotomy (0.13, p<0.001) and three-column osteotomy (0.61, p<0.001) were associated with increased operative time. Points were assigned to each surgical component: 7–12 posterior fusion levels (4 pts), >12 posterior fusion levels (11 pts), anterior fusion 1-3 levels (19 pts), anterior fusion ≥4 levels (23 pts), pelvic instrumentation (6 pts), previous spinal deformity surgery (3 pts), posterior column osteotomy (1 pt per level), and three-column osteotomy (5 pts per level). In the derivation cohort, each point was associated with an increase in operative time by 0.13 hours (R ² =0.16, p<0.001). In the validation cohort, each point was associated with an increase in operative time by 0.12 hours (R ² =0.15, p<0.001). In the derivation cohort, the area under the curve (AUC) for operative time ≥8 hours and allogeneic transfusion were 0.74 and 0.71, respectively. In the validation cohort, the AUC for operative time ≥8 hours and allogeneic transfusion were 0.74 and 0.70, respectively. Conclusion A pediatric spinal deformity surgical invasiveness index was created and predictive of prolonged operative time and allogeneic transfusion. This is the first quantitative tool to measure the extent of surgical interventions in pediatric spine surgery.

Aims The PANORAMA‐HF trial demonstrated significant N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) reductions in paediatric patients with left ventricular systolic dysfunction with sacubitril/valsartan or enalapril treatment over 52 weeks. This post hoc analysis aims to correlate changes in NT‐proBNP levels with clinical outcomes in PANORAMA‐HF patients receiving either sacubitril/valsartan or enalapril. Additionally, NT‐proBNP reductions in the paediatric population were compared with a subset of adult heart failure with reduced ejection fraction (HFrEF) patients from the PARADIGM‐HF trial. Methods and results This post hoc analysis utilized data from Part 2 of the PANORAMA‐HF trial. Associations between baseline NT‐proBNP levels, changes post‐baseline and the risk of HF clinical events in paediatric patients on sacubitril/valsartan or enalapril were assessed. The paediatric HF population from PANORAMA‐HF was categorized into age groups (AG): AG1 (aged 6 to <18 years), AG2a (aged 2 to <6 years) and AG3a (aged 1 month to <2 years). The Cox proportional hazard model evaluated the relationship between NT‐proBNP and clinical outcomes. Analysis of 361 paediatric patients (sacubitril/valsartan, n = 179; enalapril, n = 182) demonstrated overall higher baseline NT‐proBNP levels in younger AGs. At Week 52, both treatment groups exhibited reduced NT‐proBNP levels across all AGs. Reductions were comparable between sacubitril/valsartan and enalapril, with a numerically greater reduction observed in adult patients versus children. Strong associations between NT‐proBNP levels and HF clinical outcomes were observed in paediatric populations in PANORAMA‐HF and in adult DCM patients with HFrEF in PARADIGM‐HF. Doubling of NT‐proBNP levels was associated with a ≥1.7‐fold increased risk of HF clinical events, while halving of the levels correlated with a 52% reduction in the risk of clinical events. Conclusions This is the first prospective, randomized large‐scale study to demonstrate a strong correlation between NT‐proBNP levels and risks of HF clinical events in paediatric patients with HF.

Non-coronary artery systemic arterial aneurysms (SAAs) are rare and an under-reported sequelae of Kawasaki disease (KD). We hypothesize that practices regarding SAA screening and management vary widely among experts and published literature. A survey was sent to members of the International KD Registry regarding their experiences and practices with SAAs in KD patients. For comparison, a systematic scoping review was conducted using PRISMA methodology, from which 25 reports with 83 patients were included. Results from each were compared. Surveys were completed by 48 (56%) of 86 IKDR investigators; 35 (73%) respondents had > 10 years of experience caring for KD patients. However, 33% of respondents had not cared for a patient with SAA. Features prompting assessment for SAA included demographics, presence and degree of coronary artery (CA) involvement, and clinical features, including prolonged/persistent fever, progressing/persistent elevation of inflammatory markers, and resistance to standard treatment. Features prompting screening were somewhat concordant with the characteristics of patients with SAA identified in the scoping review. From the survey, the initial preferred assessment included computed tomographic angiography (48%), ultrasound (29%), and magnetic resonance imaging (24%). In contrast, assessment of patients with SAA from the scoping review commonly used multiple imaging modalities. SAA often regressed, but associated complications included thrombosis, calcification, stenosis, occlusion, and collateral formation. While SAA is a known but rare complication of acute KD, there remains a gap in evidence regarding which patients are at risk, best practices for screening and management, and outcomes. Prospective cohort studies are needed.

Transgender and gender diverse (TGD) youth and their caregivers, seeking gender affirming treatment (GAT) such as puberty blockers or hormone therapy, must understand complex medical information to participate in shared decision making. Decision aids are one method to provide treatment-based information and enhance shared decision making. This pilot study aimed to develop and evaluate the effect of a web-based decision aid on GAT in a pediatric gender care clinic. This cross-sectional, pre-, and postintervention design study included treatment-naive TGD youth aged 13–25 years or caregivers ( N = 10). Participants were evaluated for their knowledge, fertility attitudes, decisional conflict, and acceptability of the intervention. All participants had high mean GAT knowledge (7.8 [SD = 1.3] vs. 7.4 [SD = 1.8], p = .509) and low mean decisional conflict (18.1 [SD = 19.9] vs. 10.9 [SD = 12.9], p = .187) scores pre- and postintervention. The decision aid reduced decisional conflict in both youth and caregivers but had no change in knowledge scores. Many youth did not want children (66.7%) but felt it was important to learn about the effects of GAT on future fertility (100%). Most participants (80%) found that the decision aid was helpful for their decision-making process. Future testing is needed to evaluate its usefulness in a larger, more diverse sample.

Anesthesiology has a longstanding commitment to patient safety, characterized by innovative research, quality improvement, multidisciplinary collaboration, and engineering-based approaches to care systems. The field has been instrumental in advancing technological developments across the perioperative continuum, contributing to the ongoing mission of harm reduction and risk mitigation. However, modern challenges in health care, including increasingly complex patient conditions, workforce shortages, burnout, and the overwhelming volume of health data generated, have created a more urgent and multifaceted landscape for patient safety efforts. Furthermore, with the expanding perioperative continuum, from prehabilitation to postoperative acute care at home, anesthesiology teams must now adapt to a broader role in patient care. To continue enhancing patient safety, anesthesiology must integrate emerging technologies into clinical workflows, scaling their presence and effectiveness. The 2023 Anesthesia Patient Safety Foundation Stoelting Conference highlighted the necessity for anesthesiology to embrace these innovations while recognizing the challenges they pose. Three key technological domains were emphasized: wearables and the Internet of Medical Things; big data and artificial intelligence; and clinical decision support systems coupled with advanced alarm systems. These technologies offer opportunities to improve patient safety but require careful integration into clinical practice. This report explores the potential of these technologies to reshape anesthesiology and perioperative care while focusing on their application across 4 key phases: the preanesthesia phase at home; the intraoperative phase within health systems; postanesthesia recovery; and recovery at home. By leveraging these technologies, anesthesiology can enhance decision-making, improve outcomes, and continue advancing the mission of patient safety in a rapidly evolving health care landscape.

Experimental evolution studies that feature selection on life-history characters are a proven approach for studying the evolution of aging and variation in rates of senescence. Recently, the incorporation of genomic and transcriptomic approaches into this framework has led to the identification of hundreds of genes associated with different aging patterns. However, our understanding of the specific molecular mechanisms underlying these aging patterns remains limited. Here, we incorporated extensive metabolomic profiling into this framework to generate mechanistic insights into aging patterns in Drosophila melanogaster. Specifically, we characterized metabolomic change over adult lifespan in populations of D. melanogaster where selection for early reproduction has led to an accelerated aging phenotype relative to their controls. Using these data we: i) evaluated evolutionary repeatability across the metabolome; ii) assessed the value of the metabolome as a predictor of “biological age” in this system; and iii) identified specific metabolites associated with accelerated aging. Generally, our findings suggest that selection for early reproduction resulted in highly repeatable alterations to the metabolome and the metabolome itself is a reliable predictor of “biological age”. Specifically, we find clusters of metabolites that are associated with the different rates of senescence observed between our accelerated aging population and their controls, adding new insights into the metabolites that may be driving the accelerated aging phenotype.