BK polyomavirus DNAemia, allograft rejection, and de novo donor-specific antibodies after lowering target tacrolimus levels in pediatric kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and tacrolimus is often the first immunosuppressive medication adjusted upon the diagnosis of BKV DNAemia. This study aimed to evaluate the impact of a new institutional protocol with lower target tacrolimus levels on BKV DNAemia, allograft rejection, and de novo donor-specific antibodies (dnDSA) among pediatric KT recipients. METHODS: We conducted a retrospective chart review of all KT episodes between January 2013 and December 2018. The new protocol with lower target tacrolimus levels was implemented in March 2015. One hundred twenty-seven patients were included in primary analysis. All patients received induction with basiliximab and methylprednisolone and were maintained on a steroid-based immunosuppressive regimen. RESULTS: In the post-intervention cohort, cumulative incidence of BKV DNAemia at 100 days (13.4% vs. 17.8%, p = .605) and 18 months post-KT (34.1% vs. 26.7%, p = .504) was not significantly different from the pre-intervention cohort. Biopsy-proven rejection rate did not change. However, we observed a trend toward earlier development of dnDSA in the post-intervention cohort using the Kaplan-Meier survival analysis (log-rank p = .06). Younger recipient age at the time of transplant was found to slightly increase the risk of BKV DNAemia (OR: 1.09, 95% CI [1.01, 1.16], p = .024). There was an association between BKV DNAemia and biopsy-proven rejection of any type (adjustedOR: 2.77, 95% CI [1.26, 6.23], p = .012), especially acute T-cell-mediated rejection grade 1A and above (adjustedOR: 2.95, 95% CI [1.06, 8.30], p = .037), after adjusted for recipient age at the time of transplant. CONCLUSIONS: Targeting lower tacrolimus levels did not decrease the incidence of BKV DNAemia within 100 days or 18 months post-KT, nor did it increase the risk of biopsy-proven rejection among pediatric KT recipients in our center. However, there was a trend toward earlier development of dnDSA, which may portend worse long-term graft outcome post-KT. Our findings highlight the need for individualized immunosuppressive regimens based on immunologic and infectious risk factors and the importance of implementing innovative biomarkers to guide therapy and improve outcomes.

The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium.

OBJECTIVE: Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. DESIGN: Retrospective study, July 1, 2017-May 31, 2022. SETTING: Tertiary children's hospital. PATIENTS: Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). CONCLUSIONS: The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Short-Term Outcomes, Functional Status, and Risk Factors for Requiring Extracorporeal Life Support After Norwood Operation: A Single-Center Retrospective Study.

Patients requiring extracorporeal life support (ECLS) post-Norwood operation constitute an extremely high-risk group. We retrospectively described short-term outcomes, functional status, and assessed risk factors for requiring ECLS post-Norwood operation between January 2010 and December 2020 in a high-volume center. During the study period, 269 patients underwent a Norwood procedure of which 65 (24%) required ECLS. Of the 65 patients, 27 (41.5%) survived to hospital discharge. Mean functional status scale (FSS) score at discharge increased from 6.0 on admission to 8.48 (p < 0.0001). This change was primary in feeding (p < 0.0001) and respiratory domains (p = 0.017). Seven survivors (26%) developed new morbidity, and two (7%) developed unfavorable functional outcomes. In the regression analysis, we showed that patients with moderate-severe univentricular dysfunction on pre-Norwood transthoracic echocardiogram (odds ratio [OR] = 6.97), modified Blalock Taussig Thomas (m-BTT) shunt as source of pulmonary blood flow (OR = 2.65), moderate-severe atrioventricular valve regurgitation on transesophageal echocardiogram (OR = 8.50), longer cardiopulmonary bypass time (OR = 1.16), longer circulatory arrest time (OR = 1.20), and delayed sternal closure (OR = 3.86), had higher odds of requiring ECLS (p < 0.05). Careful identification of these risk factors is imperative to improve the care of this high-risk cohort and improve overall outcomes.

Outcome measures in pediatric chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION/AIMS: Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. METHODS: This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. RESULTS: Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. DISCUSSION: Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.

Intraoperative and postoperative findings in children with myringotomy tubes (MT) undergoing cochlear implantation (CI).

OBJECTIVE: To evaluate and compare children undergoing cochlear implantation (CI) with myringotomy tubes (MT) placed preoperatively or intraoperatively to those without MT . METHODS: This was a retrospective review of pediatric patients undergoing CI between 2015 to 2020 at a tertiary care pediatric hospital. CI patients with and without MT were reviewed for the following outcomes: intraoperative findings, intraoperative and postoperative complications, and surgical time. Descriptive and bivariable statistical analysis was performed. RESULTS: 192 cochlear implant surgeries were included: 116 without MT tubes and 76 with a history of MT. Twenty-six patients had MT present at the time of CI surgery. No statistical difference existed between patients with MT (CI + MT group) and those without MT (CI - MT group) with regard to intraoperative complications (P = 0.760) and intraoperative findings (P = 0.545). MT association with total post-operative complications (GEE) showed no statistical significance (OR 2.45, 95% CI 0.83-7.22, P-value 0.105). CI + MT patients were significantly more likely to have inflamed middle ear mucosa at time of surgery (P = 0.003). CI + MT patients did not have a longer length of surgery compared to the CI - MT group (3.47 h vs 3.3 h, respectively, P = 0.342). CONCLUSION: Our data confirms it is safe to perform CI in ears with myringotomy tubes, although the surgeon should be aware of possibly encountering increased middle ear inflammation during the surgery.

Early Intervention Provider-Reported NDBI Use and Relationships with Provider- to System-Level Implementation Determinants.

An expanding evidence base has advocated for delivery of naturalistic developmental behavioral interventions (NDBIs) within community systems, thus extending the reach of these practices to young autistic children. The current study examined provider-reported use of NBDIs within a Part C Early Intervention (EI) system and the extent to which provider background, attitudes, and perceived organizational support predicted NDBI use. Results from 100 EI providers representing multiple disciplines indicated reported use of NDBI strategies within their practice despite inconsistent reported competency with manualized NDBI programs. Although NDBI strategy use was not predicted by provider experiences or perceived organizational support, provider openness to new interventions predicted the reported use of NDBI strategies. Future directions include mixed methods data collection across and within EI systems to better understand NDBI use and ultimately facilitate NDBI implementation.

Short-Course Empiric Antibiotics in Children Undergoing Allogeneic Hematopoietic Cell Transplantation.

Fever is common in children undergoing hematopoietic cell transplantation (HCT). Empiric antibiotic (EA) therapy is initiated and often continued until neutrophil engraftment. Prolonged antibiotic exposure reduces microbiome diversity and causes overgrowth of pathogenic organisms, leading to such complications as infections from antibiotic-resistant organisms and Clostridium difficile colitis. Shorter courses of EA therapy have been studied in adults undergoing HCT without significant safety concerns, but data in children are lacking. We instituted a single-center preintervention/ postintervention quality improvement (QI) project to assess the feasibility of short-course EA therapy for first fever in patients undergoing HCT. We aimed to reduce the median duration of broad-spectrum antibiotic use in eligible patients from 20 days in 2020 to 10 days in 2021. Patients were eligible for the intervention, limiting EAs to 7 days for first fever, if they were admitted for their first allogeneic HCT, were afebrile for >24 hours, had no infection requiring systemic treatment, and were hemodynamically stable. Outcome measures included days of EA therapy for first fever and total broad-spectrum antibiotic use during the period of hospitalization, defined as the time from the start of conditioning to 30 days after HCT or hospital discharge, whichever occurred first. Balancing measures included bloodstream infection (BSI), fever, and intensive care (ICU) admission within 3 days of stopping EA therapy. Project criteria were applied retrospectively to patients who underwent HCT in 2020 to construct a preintervention short-course-eligible cohort. During the intervention period, 41 patients underwent allogeneic HCT, of whom 17 (41%) were eligible for short-course EA therapy. Among eligible patients, the median age was 5.3 years, 47% had an underlying malignancy, and 88% received myeloablative conditioning. There were no differences in demographic or HCT characteristics between patients eligible for short-course EA during the intervention and preintervention period (n = 24). The short-course EA schedule was adhered to by 14 of the 17 eligible patients (82%). The duration of EA for first fever and total broad-spectrum antibiotic use was significantly decreased in the short-course EA-eligible patients compared to the preintervention cohort, from a median of 17 days to 8 days and from 20 days to 10 days, respectively (P < .01). Of the 14 patients adhering to short-course EA, 2 experienced a balancing measure of recurrent fever requiring resumption of EA, but no infection was identified. There were no BSIs, ICU admissions, or deaths during the hospitalization period in patients who received short-course EA. In this single-center QI project, short-course EA for initial fever was successfully applied to children undergoing allogeneic HCT using strict criteria and led to a significant decrease in broad-spectrum antibiotic use during hospitalization. These results should be validated in a prospective clinical trial to include the impact of short-course EA on antibiotic-resistant organisms, the intestinal microbiome, and HCT outcomes.

Prognostic Value of Plasma Biomarkers S100B and Osteopontin in Pediatric TBI: A Prospective Analysis Evaluating Acute and 6-Month Outcomes after Mild to Severe TBI.

Blood based traumatic brain injury (TBI) biomarkers offer additional diagnostic, therapeutic, and prognostic utility. While adult studies are robust, the pediatric population is less well studied. We sought to determine whether plasma osteopontin (OPN) and S100B alone or in combination predict mortality, head Computed tomography (CT) findings, as well as 6-month functional outcomes after TBI in children. This is a prospective, observational study between March 2017 and June 2021 at a tertiary pediatric hospital. The sample included children with a diagnosed head injury of any severity admitted to the Emergency Department. Control patients sustained trauma-related injuries and no known head trauma. Serial blood samples were collected at admission, as well as at 24, 48, and 72 h. Patient demographics, acute clinical symptoms, head CT, and 6-month follow-up using the Glasgow outcome scale, extended for pediatrics (GOSE-Peds), were also obtained. The cohort included 460 children (ages 0 to 21 years) and reflected the race and sex distribution of the population served. Linear mixed effect models and logistic regressions were utilized to evaluate the trajectory of biomarkers over time and predictors of dichotomous outcomes. Both OPN and S100B correlated with injury severity based on GCS. S100B and OPN showed lower AUC values (0.59) in predicting positive head CT. S100B had the largest AUC (0.87) in predicting mortality, as well as 6-month outcomes (0.85). The combination of the two biomarkers did not add meaningfully to the model. Our findings continue to support the utility of OPN as a marker of injury severity in this population. Our findings also show the importance of S100B in predicting mortality and 6-month functional outcomes. Continued work is needed to examine the influence of age-dependent neurodevelopment on TBI biomarker profiles in children.

Changes in pediatric injuries sustained while engaged in activities where helmet usage is recommended during the COVID-19 pandemic.

BACKGROUND: Unintentional injuries, including traumatic brain injuries (TBI), are the leading cause of pediatric morbidity and mortality in the USA. Helmet usage can reduce TBI incidence and severity; however, the epidemiology of pediatric TBI and helmet use is ever evolving. With lifestyle changes potentially accelerated by the pandemic, we predicted a decrease in helmet utilization with an associated increase in TBI during the pandemic compared to the pre-pandemic period. RESULTS: There were 1093 patients that presented with AWHUR injuries from 2018 to 2020 with an annual increase from 263 patients in 2018 up to 492 in 2020. The most frequently implicated mechanisms included bicycles (35.9%), ATVs (20.3%), skateboards (11.6%), scooters (8.3%), and dirt bikes (7.4%). Unhelmeted patients increased from 111 (58.7%) in 2018 to 258 (64.8%) in 2020. There was not a significant difference in the proportion of injuries that were unhelmeted from 38.9% in 2018-2019 to 35.2% in 2020 (p = 0.30), as well as the proportion of head injuries from 2018 to 2019 (24.3%) to 2020 (29.3%) (p = 0.07). A significant increase was seen in neurosurgical consultation from 17 (6.5%) in 2018 to 87 (17.7%) in 2020 (p = 0.02). Notably, there was an increase in the percentage of publicly insured patients presenting with injuries from AWHUR during 2020 (p < 0.001); this group also had suboptimal helmet usage. CONCLUSION: This study found an increase in patients presenting with injuries sustained while engaged in AWHUR in relation to the COVID-19 pandemic. Concerningly, there was a trend toward decreased helmet utilization and increased injury severity markers. Further analysis is needed into the communities impacted the most by AWHUR injuries.

Role of PGC-1α mediated synaptic plasticity, mitochondrial function, and neuroinflammation in the antidepressant effect of Zi-Shui-Qing-Gan-Yin.

Depression is the most prevalent psychiatric disorder, which needs deeper mechanism research studies and effective therapy. Zi-Shui-Qing-Gan-Yin (ZSQGY) is a traditional Chinese medicine decoction that has been widely used in China in the treatment of depressive symptoms. The aim of the study was to examine the anti-depressive effects of ZSQGY and the possible mechanism of action in the monosodium glutamate (MSG)-induced depressive model and the corticosterone (CORT)-induced PC12 cell model. Liquid chromatography-mass spectrometry (LC-MS) was performed to determine the major compounds in the water extract of ZSQGY. The depressive behaviors were evaluated by the field swimming test (FST), the sucrose preference test (SPT), and the open field test (OFT). Golgi staining and transmission electron microscopy (TEM) were performed to display the alterations of synaptic ultrastructure. The mitochondrion function and inflammatory factors were also quantified. The changes in peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) expression were evaluated. The results of this study demonstrated that ZSQGY significantly improved depressive behaviors. ZSQGY also reversed the changes in synaptic plasticity, improved mitochondrion function, and reduced the levels of inflammatory factors. The neuroprotective effects were accompanied by the increased expression of PGC-1α. However, the beneficial changes were reversed after the inhibition of PGC-1α. These results indicated that ZSQGY effectively could improve depressive behaviors via the mechanisms that regulate synaptic structural plasticity, improve mitochondrion function, and alleviate neuroinflammation, which could, or partly, attribute to the regulation of PGC-1α.

Appropriateness of cardiovascular computed tomography and magnetic resonance imaging in patients with conotruncal defects.

BACKGROUND: To promote the rational use of cardiovascular imaging in patients with congenital heart disease, the American College of Cardiology developed Appropriate Use Criteria (AUC), but its clinical application and pre-release benchmarks have not been evaluated. We aimed to evaluate the appropriateness of indications for cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) in patients with conotruncal defects and to identify factors associated with maybe or rarely appropriate (M/R) indications. METHODS: Twelve centers each contributed a median of 147 studies performed prior to AUC publication (01/2020) on patients with conotruncal defects. To incorporate patient characteristics and center-level effects, a hierarchical generalized linear mixed model was used. RESULTS: Of the 1753 studies (80% CMR, and 20% CCT), 16% were rated M/R. Center M/R ranged from 4 to 39%. Infants accounted for 8.4% of studies. In multivariable analyses, patient- and study-level factors associated with M/R rating included: age <1 year (OR 1.90 [1.15-3.13]), truncus arteriosus (vs. tetralogy of Fallot, OR 2.55 [1.5-4.35]), and CCT (vs. CMR, OR 2.67 [1.87-3.83]). None of the provider- or center-level factors reached statistical significance in the multivariable model. CONCLUSIONS: Most CMRs and CCTs ordered for the follow-up care of patients with conotruncal defects were rated appropriate. However, there was significant center-level variation in appropriateness ratings. Younger age, CCT, and truncus arteriosus were independently associated with higher odds of M/R rating. These findings could inform future quality improvement initiatives and further exploration of factors resulting in center-level variation.

Exercise testing in patients with multisystem inflammatory syndrome in children-related myocarditis versus idiopathic or viral myocarditis.

BACKGROUND: While most children with multisystem inflammatory syndrome in children have rapid recovery of cardiac dysfunction, little is known about the long-term outcomes regarding exercise capacity. We aimed to compare the exercise capacity among patients with multisystem inflammatory syndrome in children versus viral/idiopathic myocarditis at 3-6 months after initial diagnosis. METHODS: We performed a retrospective cohort study among patients with multisystem inflammatory syndrome in children in June 2020 to May 2021 and patients with viral/idiopathic myocarditis in August 2014 to January 2020. Data from cardiopulmonary exercise test as well as echocardiographic and laboratory data were obtained. Inclusion criteria included diagnosis of multisystem inflammatory syndrome in children or viral/idiopathic myocarditis, exercise test performed within 3-6 months of hospital discharge, and maximal effort on cardiopulmonary exercise test as determined by respiratory exchange ratio >1.10. RESULTS: Thirty-one patients with multisystem inflammatory syndrome in children and 25 with viral/idiopathic myocarditis were included. The mean percent predicted peak VO2 was 90.84% for multisystem inflammatory syndrome in children patients and 91.08% for those with viral/idiopathic myocarditis (p-value 0.955). There were no statistically significant differences between the groups with regard to percent predicted maximal heart rate, metabolic equivalents, percent predicted peak VO2, percent predicted anerobic threshold, or percent predicted O2 pulse. There was a statistically significant correlation between lowest ejection fraction during hospitalisation and peak VO2 among viral/idiopathic myocarditis patients (r: 0.62, p-value 0.01) but not multisystem inflammatory syndrome in children patients (r: 0.1, p-value 0.6). CONCLUSIONS: Patients with multisystem inflammatory syndrome in children and viral myocarditis appear to, on average, have normal exercise capacity around 3-6 months following hospital discharge. For patients with viral/idiopathic myocarditis, those with worse ejection fraction during hospitalisation had lower peak VO2 on cardiopulmonary exercise test.

USP9X promotes lipopolysaccharide-stimulated acute lung injury by deubiquitination of NLRP3.

Alveolar epithelial cells (AECs) function as a vital defense barrier avoiding the invasion of exogenous agents and preserving the functional and structural integrity of lung tissues, while damage/breakdown of this airway epithelial barrier is frequently associated with the pathogenesis of acute lung injury (ALI). NOD-like receptor family, pyrindomain-containing 3 (NLRP3) inflammasome activation-associated pyroptosis is involved in the development of ALI. Yet, how the activity of NLRP3 inflammasome is regulated in the context of ALI remains unknown. Herein we hypothesized that USP9X, an important deubiquitinase, participates in modulating the activation of NLRP3 inflammasome, thereby affecting the phenotypes in a lipopolysaccharide (LPS)-stimulated AEC model. Human pulmonary AECs were subjected to LPS/adenosine triphosphate (ATP) treatment to induce NLRP3 inflammasome activation and cell pyroptosis. Knockdown and overexpression of USP9X were applied to validate the function of USP9X. Inhibitors of proteinase and protein synthesis, as well as approach of co-immunoprecipitation coupled with Western blot, were utilized to explore the molecular mechanism. LPS/ATP challenge resulted in pronouncedly increased pyroptosis of AECs, activation of NLRP3 inflammasome and release of interleukin (IL)-1ß and IL-18 cytokines, while downregulation of USP9X could reverse these alterations. USP9X was found to have marked impact on NLRP3 protein instead of mRNA level. Furthermore, increased ubiquitination of NLRP3 was observed upon downregulating USP9X. Additionally, the inhibitory effect of USP9X downregulation was reversed by NLRP3 overexpression, while the promoting impact of USP9X overexpression was dampened by NLRP3 inhibitor in terms of cell pyroptosis and cytokine secretion. USP9X modulated the activity of NLRP3 inflammasome and pyroptosis of AECs via its deubiquitination function.

Virtual cardiac fitness training in pediatric heart transplant patients: A pilot study.

BACKGROUND: Cardiac fitness training in pediatric heart transplant recipients can improve functional capacity. Widespread implementation has been limited mostly due to logistical constraints, specifically related to travel. The aim of this study was to implement and assess a virtual cardiac fitness program for pediatric heart transplant patients. METHODS: Participants were between the age of 10 and 20 years old. All subjects completed an initial 6MWT, strength/flexibility assessment, and QOL assessment with the PROMIS measurement. Participants then underwent a 16-week intervention with exercise sessions twice weekly for 30 min with a trained exercise physiologist over a virtual platform. At the end of the intervention period, participants repeated a 6MWT, strength/flexibility assessment, and PROMIS measurement. Throughout the study, patients wore a FitBit accelerometer to monitor daily activity levels. RESULTS: Thirteen individuals were enrolled. Mean age was 15.4 years (SD =3.4) with a mean post-transplant period of 9.7 years (SD = 4.3). Session attendance was 83%. Post-intervention measurements showed improvements in 6MWT (median, +21 m, p = .02), push-up repetitions (median, +5 rep, p = .0005), wall-sit duration (median, +10 s, p = .001), plank duration (median, +9 s, p = .03), sit-up repetitions (median, +7 rep, p = .002), and sit and reach distance (median, +5 cm, p = .04). PROMIS measurement showed significant improvements in self-reported fatigue (Δz-score, -7.7, p = .008) and sleep impairment (Δz-score, -5.9, p = .002). Average daily step count increased 1464 steps per day per patient (p = .008). CONCLUSION: We have demonstrated the successful implementation of a virtual cardiac fitness with excellent adherence and improvement in physical fitness and QOL metrics.

Long-Term Organ Function After HCT for SCD: A Report From the Sickle Cell Transplant Advocacy and Research Alliance.

Hematopoietic cell transplantation (HCT) is an established cure for sickle cell disease (SCD) supported by long-term survival, but long-term organ function data are lacking. We sought to describe organ function and assess predictors for dysfunction in a retrospective cohort (n = 247) through the Sickle cell Transplant Advocacy and Research alliance. Patients with <1-year follow-up or graft rejection/second HCT were excluded. Organ function data were collected from last follow-up. Primary measures were organ function, comparing pre- and post-HCT. Bivariable and multivariable analyses were performed for predictors of dysfunction. Median age at HCT was 9.4 years; the majority had HbSS (88.2%) and severe clinical phenotype (65.4%). Most received matched related (76.9%) bone marrow (83.3%) with myeloablative conditioning (MAC; 57.1%). Acute and chronic graft-versus-host disease (GVHD) developed in 24.0% and 24.8%. Thirteen patients (5.3%) died ≥1 year after HCT, primarily from GVHD or infection. More post-HCT patients had low ejection or shortening fractions than pre-HCT (0.6% â†’ 6.0%, P = .007 and 0% â†’ 4.6%, P = .003). The proportion with lung disease remained stable. Eight patients (3.2%) had overt stroke; most had normal (28.3%) or stable (50.3%) brain magnetic resonance imaging. On multivariable analysis, cardiac dysfunction was associated with MAC (odds ratio [OR] = 2.71; 95% confidence interval [CI], 1.09-6.77; P = .033) and severe acute GVHD (OR = 2.41; 95% CI, 1.04-5.62; P = .041). Neurologic events were associated with central nervous system indication (OR = 2.88; 95% CI, 2.00-4.12; P < .001). Overall organ dysfunction was associated with age ≥16 years (OR = 2.26; 95% CI, 1.35-3.78; P = .002) and clinically severe disease (OR = 1.64; 95% CI, 1.02-2.63; P = .043). In conclusion, our results support consideration of HCT at younger age and use of less intense conditioning.

Social-environmental factors as mediators of IQ and achievement differences across race groups in adolescents with high risk congenital heart disease.

An increasing number of neuropsychologists are evaluating children with congenital heart disease (CHD). When conceptualizing results, the provider must consider medical risks such as abnormal neuroimaging and comorbidities, along with social risks such as socioeconomic status. The aim of the current study was to examine the influence of parent income and education on IQ and achievement across race groups in adolescents with CHD, while also accounting for medical risk (e.g., gestational age, number of ventricles, neuroimaging). This is a single-center cross-sectional study, including 92 children ages 12-19 years (median 14.9 years; 59% male; 71% White; 29% Black) with high risk CHD (i.e., cardiac surgery <12 months) who were referred for a neuropsychological evaluation. Retrospective data were retrieved from a larger clinical registry. Patients completed an intellectual assessment (WISC-V; WAIS-IV; WASI-II), Word Reading and Math Calculation tests. Parents completed questionnaires assessing the family environment [income, parent education]. Results revealed significant differences in IQ when comparing children who were Black versus White (11.4 point IQ difference); however, around 70% of this variance was explained by parent income and education. Medical variables accounted for 12% of the variance in IQ. For academics, parent income and education accounted for 91.5% and 78.8% of the variance in race group differences for reading and math, respectively. Medical risk and sex explained 11.7% and 14.7% of the variance in reading and math, respectively. Findings suggest that sociodemographic factors should be weighed heavily during the neuropsychological evaluation, including prioritizing risk, making recommendations, and facilitating referrals.

Georgia state spinal muscular atrophy newborn screening experience: Screening assay performance and early clinical outcomes.

The purpose of this study is to provide the results of the newborn screening (NBS) program for Spinal Muscular Atrophy (SMA) in the state of Georgia to determine disease incidence, time to diagnosis and treatment, and early outcomes. NBS for SMA was performed using real time PCR assays from February 2019 through February 2020 in a pilot phase of screening. This method continued as part of our official state panel, and here we describe the pilot period as well as the first year of standard screening through February 2021. Medical records of infants with a positive NBS were reviewed for time to confirmation and neurologic evaluation, SMN2 copy number, clinical information, and treatment. Descriptive statistics were applied. Of the 301,418 samples screened, there were 15 true positive (eight males) and 24 false positive cases. One patient was missed due to human error early in the pilot phase and presented after symptom onset. The incidence of SMA in Georgia is approximately 1 in 18,840 births per year. After the pilot phase, the false positive rate was found to be so low that all patients who test positive were immediately referred to neurology for further care. Four patients died prior to intervention. Ten patients received intervention. Gene therapy was the preferred treatment. One patient was lost to follow-up; another was clinically followed. In conclusion, trends for treated patients show improved or stable motor function. Long-term follow-up will help determine the durability of treatment.

Neurological Complications in Children Hospitalized With Seizures and Respiratory Infections: A Comparison Between SARS-CoV-2 and Other Respiratory Infections.

BACKGROUND: Children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can experience neurological symptoms, but limited data are available on neurological symptoms associated with other respiratory infections. We compared proportions of neurological symptoms in children hospitalized with seizures and respiratory infections, including SARS-CoV-2, influenza, and endemic coronaviruses. METHODS: A retrospective cohort study was performed on children admitted for seizures who had positive respiratory polymerase chain reactions for SARS-CoV-2, coronavirus NL63, coronavirus OC34, influenza (A and B), adenovirus, Mycoplasma pneumoniae, or parainfluenza 3 or 4. Primary outcomes were rates of new neurological diagnoses and mortality. RESULTS: A total of 883 children were included. Mortality rates ranged from 0% with M. pneumoniae to 4.9% with parainfluenza 4. Strokes were observed with all infections except for coronavirus OC43 and M. pneumoniae, with the highest rates in parainfluenza 4 (4.9%) and SARS-CoV-2 (5.9%). Compared with other infections, children with SARS-CoV-2 were older, had higher rates of stroke, and lower rates of intubation. The most common brain magnetic resonance imaging (MRI) abnormality was diffusion restriction. Abnormal MRI rates were lower in SARS-CoV-2, compared with patients with other coronavirus (OC). However, rates of stroke, encephalopathy, hypoxic-ischemic encephalopathy, and meningoencephalitis were similar between SARS-CoV-2 and influenza cohorts. CONCLUSIONS: In children hospitalized with seizures, higher rates of stroke were observed in SARS-CoV-2 versus OC. Similar rates of neurological symptoms were observed in patients with SARS-CoV-2 and those with influenza. Strokes can occur in children with these viral infections, particularly SARS-CoV-2.

Comparing Eosinophilic Esophagitis in a Black and Non-Black Pediatric Cohort.

OBJECTIVES: To compare presenting symptoms, comorbidities, disease, and treatment characteristics of a black pediatric eosinophilic esophagitis (EoE) group to a non-black pediatric EoE group. METHODS: A retrospective chart review consisting of pediatric patients diagnosed with EoE between the years of 2010 and 2018 at a single urban pediatric hospital system comprising 143 black pediatric patients compared with 142 non-black pediatric patients with similar distribution of age and sex. RESULTS: Both groups were majority male, and the median age of diagnosis between the black and non-black group was 5.1 and 6.7 years old, respectively. Comorbidities more commonly seen in the black group included food allergies, atopic dermatitis, asthma, and allergic rhinitis. Black patients were more likely to present with failure to thrive (FTT)/poor growth, whereas non-black patients were more likely to present with abdominal pain. There was no statistically significant difference between the groups in achieving remission using current therapies. The black group had higher rates of nonadherence to medical therapies. CONCLUSIONS: This is the largest study to date comparing a black versus non-black pediatric EoE population. The black population had more atopic comorbidities and FTT at presentation and had significantly more issues with nonadherence. This new knowledge describing EoE in a minority population will hopefully improve awareness, diagnosis, and management of EoE in this population.

Mandibular Distraction in Neonatal Pierre Robin Sequence: Is Immediate Extubation Both Feasible and Safe?

BACKGROUND: The timing of extubation following placement of mandibular distractors in the setting of Pierre Robin sequence is variable across institutional algorithms. Postoperative maintenance of intubation allows for an improvement in airway dimension and tongue positioning before extubation, theoretically decreasing the impact of postoperative airway edema. Maintenance of intubation, however, is not without risk. The authors analyze their institutional experience with neonatal mandibular distraction followed by immediate extubation to assess feasibility and safety profiles. METHODS: A 4-year retrospective review of patients diagnosed with Pierre Robin sequence who underwent mandibular distraction within the first 3 months of life was performed. Patients intubated preoperatively were excluded. RESULTS: Fifty-two patients met inclusion criteria. Thirty-eight patients (73 percent) were extubated immediately, whereas 14 patients (27 percent) remained intubated. No differences between these groups were found when comorbidities, cleft pathology, preoperative respiratory support, or grade of view on direct laryngoscopy were analyzed. Case duration greater than 120 minutes, operation start time after 3 pm, and the subjective designation of a difficult airway by the anesthesiologist were associated with maintaining intubation (p < 0.05). Eight patients (21 percent) in the extubated group required an increase in respiratory support in the postoperative interval. Four of these patients (11 percent) required reintubation. Increased postoperative respiratory support was more likely in patients with certain comorbidities and higher preoperative respiratory support requirements (p < 0.05). CONCLUSIONS: The authors' data suggest that immediate extubation following neonatal mandibular distraction is feasible in patients who are not intubated preoperatively. Careful consideration should be given to patients who require significant respiratory support preoperatively and in those with certain comorbidities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.