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Conventional belief is that high-intensity (HI) exercise inhibits immune function; however, recent work challenges this position. The purpose of this was to quantify changes in T cell proliferative capacity following either a HI or moderate-intensity (MI) exercise. Sixteen males were randomly selected to a HI or MI exercise group. Blood was obtained baseline and immediately, 1-, 4-, and 6-hours post-exercise for analyses of CD3+ T cell proliferation (co-stimulation via PHA or CD3+CD28). The proliferative response increased in T cells in the HI group and remained significantly elevated up to 6-hours post-exercise in both co-stimulation conditions. In contrast, the MI group saw no change proliferative ability following exercise. Analyses of serum stress hormones, and immunomodulatory cytokines failed to reveal any correlated variations that could clarify the T cell findings. We suggest the increase in proliferative capacity following HI exercise is indicative of an exercise-induced activation that provides for enhanced functional responses to stimuli. Moreover, this study shows that HI exercise increases T cell processes, effectively priming them for activation in response to stimuli. This study is registered with ClinicalTrials.gov (NCT06638684).

Context: Limited data exists about care received by children with complex chronic conditions (CCCs) in the final years of their disease and end-of-life (EOL)., Objective: To examine hospital performance on EOL quality measures and to describe healthcare services during the last two years of life for children with CCCs who died in-hospital., Methods: Retrospective automated electronic health record review of children with ≥1 CCC ICD-10 diagnosis code, who died inpatient between October 2020 and March 2023 at a single quaternary U.S. children's hospital. Quality was assessed based on performance on 15 measures across five domains: healthcare utilization, interprofessional supports, medical intensity, symptom management, and communication. Quality EOL care and healthcare services in the last two years of life were determined overall by age group and per patient. Descriptive statistics were used to evaluate demographic differences by age., Results: 266 children with CCCs died in the study timeframe; 45% were infants (n = 120), 52% (n = 137) were male, 42% (n = 113) were white, 64% (n = 170) were non-Hispanic, and 59% (n=156) had public insurance. Children had a median of three CCCs (IQR 2.4; range 1-8). On average, children met 69% (SD 13%) of EOL quality measures for which they were eligible. In the two years prior to death, 98% (n = 261) had an ICU admission, 75% (n = 200) had a procedure requiring sedation, and 29% (n = 79) had received cardiopulmonary resuscitation. 86% (n = 229) died in the ICU., Conclusion: In this study, children with CCCs met 69% of quality measures and received high-intensity healthcare in the last two years of life., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The financial burden of bronchiolitis-related hospitalizations in the United States surpasses $700 million annually. Procalcitonin (PCT) has garnered recent interest in pediatrics and has demonstrated the potential to decrease antibiotic usage in other illnesses. This study assessed PCT utilization trends in bronchiolitis, hypothesizing an annual increase in PCT testing., Methods: We conducted a multicenter, retrospective cross-sectional study utilizing the Pediatric Health Information Systems database. Infants aged 2 to 23 months presenting with bronchiolitis from January 1, 2016, to December 31, 2022, were included. Encounters with and without PCT testing were compared using χ2 testing and Wilcoxon rank-sum testing as appropriate. Temporal trends in PCT testing and correlations with hospital-level proportions of PCT use, antibiotic administration, and admission proportion were assessed using Spearman's ρ., Results: There were 366 643 bronchiolitis encounters among 307 949 distinct patients across 38 hospitals during the study period. Of those, 1.5% (5517 of 366 643) had PCT testing performed. PCT usage increased more than 14-fold between 2016 and 2022 (0.2% in 2016 vs 2.8% in 2022, ρ > 0.99, P < .001). PCT use ranged from 0.01% to 8.29% across hospitals. The hospital-level proportion of PCT testing was not associated with admissions (ρ = 0.13, P = .42) or antibiotic use (ρ = 0.31, P = .06)., Conclusions: PCT testing in patients with bronchiolitis increased 14-fold between 2016 and 2022 and was not associated with decreased antimicrobial prescriptions. Further studies are needed to determine the diagnostic yield of PCT in bronchiolitis., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Background Stigma towards sexually active young people presents profound barriers to uptake of sexual and reproductive health (SRH) services, including HIV testing and contraception. Yet, few studies have examined adolescent SRH stigma trajectories over time. To address this knowledge gap, we examined associations between social-ecological factors and trajectories of adolescent SRH stigma among urban refugee youth in Kampala, Uganda. Methods This longitudinal cohort study with refugee youth in Kampala collected data on adolescent SRH stigma at four time-points between 2022 and 2024. We used latent class growth analyses to examine distinct trajectories of adolescent SRH stigma, and examined baseline social-ecological and socio-demographic factors associated with class membership using multivariable logistic regression. Results Among the participants (n =164 with n =668 observations; mean age 19.9 years, standard deviation2.5 years; 52.8% cisgender women), we categorised two distinct adolescent SRH stigma trajectories: consistently high (n =496; 74.2%) and sustained low (n =172; 25.8%). In multivariable analyses, living in Uganda ≥1year at baseline assessment (1-5years: adjusted odds ratio [aOR]5.28, confidence interval [CI]2.29-12.19, P P 10years: aOR3.89, CI1.56-9.68, P P P P P Conclusions Social-ecological and socio-demographic factors were associated with consistently high levels of adolescent SRH stigma over 2years. Multi-level strategies can meaningfully engage youth in developing stigma reduction strategies for SRH service delivery.

Background and Objectives: The authors of previous work have associated the Childhood Opportunity Index (COI) with increased hospitalizations for ambulatory care sensitive conditions (ACSC). The burden of this inequity on the health care system is unknown. We sought to understand health care resource expenditure in terms of excess hospitalizations, hospital days, and cost., Methods: We performed a retrospective cross-sectional study of the Pediatric Health Information Systems database, including inpatient hospitalizations between January 1, 2016 and December 31, 2022 for children <18 years of age. We compared ACSC hospitalizations, mortality, and cost across COI strata., Results: We identified 2 870 121 hospitalizations among 1 969 934 children, of which 44.5% (1 277 568/2 870 121) were for ACSCs. A total of 49.1% (331 083/674 548) of hospitalizations in the very low stratum were potentially preventable, compared with 39.7% (222 037/559 003) in the very high stratum (P < .001). After adjustment, lower COI was associated with higher odds of potentially preventable hospitalization (odds ratio 1.18, 95% confidence interval [CI] 1.17-1.19). Compared with the very high COI stratum, there were a total of 137 550 (95% CI 134 582-140 517) excess hospitalizations across all other strata, resulting in an excess cost of $1.3 billion (95% CI $1.28-1.35 billion). Compared with the very high COI stratum, there were 813 (95% CI 758-871) excess deaths, with >95% from the very low and low COI strata., Conclusions: Children with lower neighborhood opportunity have increased risk of ACSC hospitalizations. The COI may identify communities in which targeted intervention could reduce health care utilization and costs., (Copyright © 2024 by the American Academy of Pediatrics.)

A 12-year-old female with active pediatric juvenile systemic lupus erythematosus presented to the emergency department because of episodes of oppressive central thoracic pain associated with pallor, sweating, and muscle weakness that persisted for >30 minutes. During the last episode, the electrocardiogram revealed alterations in cardiac repolarization coincident with progressive troponin T elevation. An angio computed tomography revealed a 20 mm long complete segmental obstruction of the proximal anterior descending artery that was confirmed by angiography. Because this extensive occlusion did not permit a noninvasive procedure, an off-pump coronary bypass of the internal mammary artery to the anterior descending artery was performed without complication. Six months after the procedure, myocardial function was good. To our knowledge, this is the first case report of an adolescent girl with acute coronary syndrome complicating juvenile systemic lupus erythematosus that was treated with a surgical procedure., (Copyright © 2024 by the American Academy of Pediatrics.)

Introduction: The endocannabinoid system (ECS) mediates the actions of cannabis and has been implicated in playing critical roles in key developmental events, including axon guidance. Although several recent studies have demonstrated ECS involvement in neurodevelopment, an emphasis on its putative role in axon guidance has not been reviewed comprehensively. Objective: The purpose of this literature review is to evaluate the interrelationships between the ECS and axon guidance. Methodology: This literature review analyzes existing literature demonstrating the normal role of endocannabinoid (eCB) signaling in axon guidance, with evidence from diverse animal models. Studies were obtained from a search strategy involving terms related to the ECS and axon guidance, and cross-checking cited literature to ensure a complete evaluation. Discussion: Cannabinoid receptors, as well as eCB synthesis and degradation machinery, appear necessary for normal axon guidance during neurodevelopment. Genetic and/or pharmacological disruption of eCB signaling results in axon growth and guidance errors, implying high sensitivity to exogenous cannabinoids. Conclusion: Overall, this review highlights the intricate connections between the ECS and axon guidance in normal neurodevelopment. The mechanistic evidence discussed suggests that alterations of the ECS through genetic and pharmacological interference disrupt its normal functioning and by extension its normal role in regulating neural circuitry formation. A comprehensive understanding of this topic will be valuable in potentially uncovering the mechanisms responsible for the neurodevelopmental defects associated with pre-natal cannabis use.

Objectives: Hospital at home (HAH) replaces acute inpatient hospital care for selected patients by providing care in their homes. We sought to describe the characteristics, management, and complications of patients with osteoarticular infections (OAIs) treated in an HAH program and its economic impact., Methods: We conducted a retrospective observational study evaluating an HAH program in a pediatric hospital in Spain, describing the characteristics of patients with confirmed OAIs requiring intravenous antibiotic therapy admitted to this program between January 2019 and December 2022. The program operates as a virtual ward with possible daily visits by physicians and nurses and 24/7 telephone contact., Results: A total of 88 patients (median age, 4.1 years; interquartile range [IQR], 1.7-10.6) with OIAs were admitted to the HAH program. Osteomyelitis (57%) and septic arthritis (29%) were the most frequent infections. Cefuroxime (42%) and cefazolin (39%) were the most frequently prescribed antibiotics. Caregiver self-administration was performed in 99%, allowing multiple daily doses of antimicrobial therapy, 80% by peripheral line. Thirteen patients (15%) had drug-related adverse events, only 3 requiring drug modification. Two patients (2%) were readmitted during HAH, and 1 was readmitted within 30 days of HAH discharge. The median HAH stay was 7 days (IQR, 4-8.75). For osteomyelitis, hospital days lowered from 8.5 days (IQR, 4.5-12) to 4 days (IQR, 3-7) after HAH implementation (P = .005) with 68% per-patient estimated cost savings., Conclusions: HAH treatment of OAIs is effective and cost-efficient. Patient support by medical and nursing staff, adequate family training, and regular communication are essential to ensure safe home admission., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: To examine 2 hospital oxygen saturation target policies and clinical outcomes in infants hospitalized with bronchiolitis., Methods: This multicenter cohort study used data collected from a randomized clinical trial of infants aged 4 weeks to 24 months, hospitalized with bronchiolitis at children's and community hospitals from 2016 to 2019. We modeled the association between hospital oxygen saturation target policy, either 90% while awake and 88% while asleep (90%/88%) or 90% while awake and asleep (90%/90%), and clinical outcomes., Results: A total of 162 infants were enrolled at 4 hospitals using a 90%/88% oxygen saturation target and 67 infants at 2 hospitals using a 90%/90% target policy. No significant differences between the 90%/88% group and 90%/90% groups were observed for time to discharge (adjusted hazard ratio, 0.83; 95% confidence interval [CI], 0.61-1.14; P = .25), initiation of supplemental oxygen (adjusted odds ratio [aOR], 0.98; 95% CI, 0.47-2.02; P = .95), time to discontinuation of supplemental oxygen (adjusted hazard ratio, 0.75; 95% CI, 0.44-1.27; P = .28), revisits (aOR, 1.38; 95% CI, 0.52-3.71; P = .52), and parent days missed from work (aOR, 2.41; 95% CI, 0.90-6.41; P = .08). Three infants in the 90%/88% group and none in the 90%/90% group were transferred to the ICU., Conclusions: Among infants hospitalized with bronchiolitis, clinical outcomes were similar between a hospital oxygen saturation target policy of 90% while awake and 88% while asleep compared with 90% while awake and asleep. These findings may inform the design of future trials of oxygen saturation targets in bronchiolitis hospital care., (Copyright © 2024 by the American Academy of Pediatrics.)

Introduction: Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions., Methods: In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017., Results: Across 34 sites, all reported tunneled central venous catheters, including Broviac ® and Hickman ® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration., Discussion/conclusion: Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion., Competing Interests: JR has consulted for Novartis. CBo has patents pending on the use of engineered cellular therapies for cancer, and has research support provided by BMS, Merck, and Kiadis pharma. CC has served as the C.M.C. reports honorarium for advisory boards from Bayer, Elephas, Nektar Therapeutics, Novartis and WiCell Research Institute, all of whom had no input in the study design, analysis, manuscript preparation or decision to submit for publication. VH has grant funding from Servier. TL has consulted for Advanced Microbubbles, AI Therapeutics, Bayer, GentiBio, Jazz Pharmaceuticals, MassiveBio, Menarini, Novartis, Pyramid Biosciences, and Treeline Bio. VF has consulted for Adaptimmune. LS served on advisory board for Novartis and CARGO therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eylon, Prabhu, John, King, Bhatt, Curran, Erickson, Karras, Phillips, Satwani, Hermiston, Southworth, Baumeister, Talano, MacMillan, Rossoff, Bonifant, Myers, Rouce, Toner, Driscoll, Katsanis, Salzberg, Schiff, De Oliveira, Capitini, Pacenta, Pfeiffer, Shah, Huynh, Skiles, Fraint, McNerney, Quigg, Krueger, Ligon, Fabrizio, Baggott, Laetsch and Schultz.)

Purpose: The study evaluates the effects on sero-immunity, health status and quality of life of children and adolescents after the upsurge of the Omicron variant in Germany., Methods: This multicenter cross-sectional study (IMMUNEBRIDGE Kids) was conducted within the German Network University Medicine (NUM) from July to October 2022. SARS-CoV-2- antibodies were measured and data on SARS-CoV-2 infections, vaccinations, health and socioeconomic factors as well as caregiver-reported evaluation on their children's health and psychological status were assessed., Results: 497 children aged 2-17 years were included. Three groups were analyzed: 183 pre-schoolchildren aged 2-4 years, 176 schoolchildren aged 5-11 years and 138 adolescents aged 12-18 years. Positive antibodies against the S- or N-antigen of SARS-CoV-2 were detected in 86.5% of all participants (70.0% [128/183] of pre-schoolchildren, 94.3% of schoolchildren [166/176] and 98.6% of adolescents [136/138]). Among all children, 40.4% (201/497) were vaccinated against COVID-19 (pre-schoolchildren 4.4% [8/183], schoolchildren 44.3% [78/176] and adolescents 83.3% [115/138]). SARS-CoV-2 seroprevalence was lowest in pre-school. Health status and quality of life reported by the parents were very positive at the time of the survey (Summer 2022)., Conclusion: Age-related differences on SARS-CoV-2 sero-immunity could mainly be explained by differences in vaccination rates based on the official German vaccination recommendations as well as differences in SARS-CoV-2 infection rates in the different age groups. Health status and quality of life of almost all children were very good independent of SARS-CoV-2 infection and/or vaccination., Trial Registration: German Registry for Clinical Trials Identifier Würzburg: DRKS00025546 (registration: 11.09.2021), Bochum: DRKS00022434 (registration:07.08.2020), Dresden: DRKS 00022455 (registration: 23.07.2020)., (© 2023. The Author(s).)

A 20-year-old female with depression presented to the emergency department with chronic weight loss, weakness, fatigue, hair loss, rash, palpitations, and 2 weeks of cough. Initial history revealed that she had disordered eating habits with dietary restriction, experienced a 50-pound unintentional weight loss over 2 years despite reported adherence to nutritional supplementation, and had a normal gastrointestinal workup. On examination, she was markedly cachectic with a BMI of 10.3kg/m2 and hypotensive (84/69 mmHg). Her cardiovascular examination revealed a regular rate and rhythm without a murmur. Her breath sounds were diminished in the upper lobes bilaterally. A skin examination showed diffuse hair loss, skin breakdown, and peeling with a tender, erythematous, papular rash over the bilateral ankles, and nonpitting edema. A chest radiograph showed a right upper lobe opacity and lucent lesions in the left proximal humerus. A focused assessment with sonography for trauma examination showed a large pericardial effusion. Chest computed tomography revealed a right upper lobe opacity with an associated cavitation. Though she began improving with rifampin, isoniazid, pyrazinamide, ethambutol, levofloxacin, azithromycin, and nutritional rehabilitation, her clinical course was complicated by an acute worsening nearly 1 month into her hospitalization with persistent high fevers, worsening cough, development of a murmur, and worsening consolidation on chest computed tomography. Adolescent Medicine, Infectious Diseases, Gastroenterology, and Allergy and Immunology were consulted to guide the diagnostic evaluation and management of this patient's complex clinical course., (Copyright © 2023 by the American Academy of Pediatrics.)

Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26 +6 weeks' gestation born and/or admitted <24 hours postnatal age were included. As compared with standard neonatal care for control subjects (January 2010-December 2017), patients admitted in the second epoch (October 2018-April 2022) were exposed to HS using targeted neonatal echocardiography at 12-18 hours. Measurements and Main Results: A primary composite outcome of death or severe intraventricular hemorrhage was decided a priori using a 10% reduction in baseline rate to calculate sample size. A total of 423 control subjects and 191 screening patients were recruited with a mean gestation and birth weight of 24.7 ± 1.5 weeks and 699 ± 191 g, respectively. Infants born at 22-23 weeks represented 41% ( n  = 78) of the HS epoch versus 32% ( n  = 137) of the control subjects ( P  = 0.004). An increase in perinatal optimization (e.g., antepartum steroids) but with a decline in maternal health (e.g., increased obesity) was seen in the HS versus control epoch. A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.

Objectives: Osteoarticular infections (OAIs) in children pose significant risks if incorrectly managed. We introduced a clinical practice guideline (CPG) to decrease use of broad-spectrum and intravenous (IV) antibiotics for OAI treatment. The primary aims of our project were to decrease the percent of patients with empirical broad cephalosporin use to 10% and decrease IV antibiotic therapy on discharge to 20% while increasing narrow-spectrum oral antibiotic use to 80% within 24 months., Methods: We used quality improvement methodology to study patients diagnosed with OAIs. Interventions included multidisciplinary workgroup planning, CPG implementation, education, information technology, and stakeholder feedback. Outcome measures were the percentage of patients prescribed empirical broad-spectrum cephalosporins, percent discharged on IV antibiotics, and percent discharged on narrow-spectrum oral antibiotics. Process measures included percent of patients hospitalized on medicine service and infectious diseases consultation. Balancing measures included rates of adverse drug reactions, disease complications, length of stay, and readmission within 90 days. The impact of the interventions was assessed with run and control charts., Results: A total of 330 patients were included over 96 months. The percentage of patients with empirical broad cephalosporin coverage decreased from 47% to 10%, percent discharged on IV antibiotics decreased from 75% to 11%, and percent discharged on narrow-spectrum oral antibiotics increased from 24% to 84%. Adverse drug reactions decreased from 31% to 10%. Rates of complications, readmissions, and length of stay were unchanged., Conclusions: Through development and implementation of a CPG for OAI management, we demonstrated decreased use of empirical broad-spectrum antibiotics and improved definitive antibiotic management., (Copyright © 2023 by the American Academy of Pediatrics.)

Introduction: Tuberous sclerosis complex (TSC) is a common genetic cause of epilepsy. Infantile epileptic spasm syndrome (IESS) is often the presenting neurologic feature, progressively evolving into refractory epilepsy. Vigabatrin (VGB) is often used in clinical practice as a first-line therapy in TSC with IESS. This systematic review aims to collect and analyze the efficacy data about VGB in TSC cases with IESS, in order to evaluate the strength of evidence in the literature., Methods: A systematic search of trials, observational studies, and case series involving patients with TSC and IESS treated with VGB was performed using MEDLINE, CENTRAL, and the US NIH Clinical Trials Registry. Single case studies, animal and non-English language studies were excluded. Seventeen studies were selected, of which 3 were RCTs and 14 were observational studies., Results: An overall response rate of 67% (231/343 responders) resulted from the analysis, with a spasm-free rate restricted to RCTs of 88% (29/33 subjects)., Conclusions: Although all the studies analyzed reported beneficial effects of VGB in TSC patients with IESS, with higher response rates in comparison to non-TSC subjects with IESS, a low level of evidence and high heterogeneity do not guarantee sufficient strength for therapeutic recommendations.

Objectives: To assess the performance of pediatric residents in recognizing a decompensating patient with impending respiratory failure and appropriately escalating care using a virtual reality (VR) simulated case of an infant with bronchiolitis after an extended period of decreased clinical volumes during the coronavirus disease 2019 (COVID-19) pandemic., Methods: Sixty-two pediatric residents at a single academic pediatric referral center engaged in a 30-minute VR simulation on respiratory failure in a 3-month-old admitted to the pediatric hospital medicine service with bronchiolitis. This occurred in a socially distant manner across the Zoom platform during the COVID-19 pandemic (January-April 2021). Residents were assessed on their ability to (1) recognize altered mental status (AMS), (2) designate clinical status as "(impending) respiratory failure," and (3) escalate care. Statistical differences between and across postgraduate year (PGY) levels were examined using χ2 or Fisher's exact test, followed by pairwise comparison and posthoc multiple testing using the Hochberg test., Results: Among all residents, 53% successfully recognized AMS, 16% identified respiratory failure, and 23% escalated care. No significant differences were seen across PGY levels for recognizing AMS or identifying respiratory failure. PGY3+ residents were more likely to escalate care than PGY2 residents (P = .05)., Conclusions: In the setting of an extended period with decreased clinical volumes during the COVID-19 pandemic, pediatric residents across all PGY levels demonstrated challenges with identifying (impending) respiratory failure and appropriately escalating care during VR simulations. Though limited, VR simulation may serve as a safe adjunct for clinical training and assessment during times of decreased clinical exposure., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: Patients and families preferring languages other than English (LOE) often experience inequitable communication with their health care providers, including the underutilization of professional interpretation. This study had 2 aims: to characterize resident-perceived communication with families preferring LOE and to evaluate the impact of language preference on frequency of resident interactions with hospitalized patients and families., Methods: This was a cross-sectional study at a quaternary care children's hospital. We developed a questionnaire for residents regarding their interactions with patients preferring LOE. We concurrently developed a communication tracking tool to measure the frequency of resident communication events with hospitalized patients. Data were analyzed with logistic and Poisson regression models., Results: Questionnaire results demonstrated a high level of resident comfort with interpretation, though more than 30% of residents reported "sometimes" or "usually" communicating with families preferring LOE without appropriate interpretation (response rate, 47%). The communication tracking tool was completed by 36 unique residents regarding 151 patients, with a 95% completion rate. Results demonstrated that patients and families preferring LOE were less likely to be present on rounds compared with their counterparts preferring English (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.07-0.39). Similarly, patients and families preferring LOE were less likely to receive a resident update after rounds (adjusted odds ratio, 0.29; 95% CI, 0.13-0.62) and received fewer resident updates overall (incidence rate ratio, 0.45; 95% CI, 0.30-0.69)., Conclusions: Hospitalized patients and families preferring LOE experience significant communication-related inequities. Ongoing efforts are needed to promote equitable communication with this population and should consider the unique role of residents., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: An extended newborn critical congenital heart disease (CCHD) screening program using oximetry has been implemented in Taipei, Taiwan since April 2014. This study was conducted to investigate the test accuracy and efficiency of this screening protocol., Methods: This study analyzed data from 30 birthing facilities representing 87.9% of live births in Taipei. Positive screening was defined as oxygen saturation <95% in either extremity or a preductal-postductal oxygen saturation difference of >3%. This study cohort was used to retrospectively estimate outcomes on the basis of different CCHD screening protocols., Results: During the study period, 93 058 of 94 204 (98.8%) infants who had no prenatal suspicion were screened. The referral rate was 0.17% (156/93 058), and up to 90% of test-positive infants were referred within 48 hours of life. Forty-two CCHD cases without prenatal suspicion were detected and 97.6% were diagnosed within 72 hours of life. Of the screened newborns, 4 CCHD cases passed the screening. The false positive and false negative rates were 0.12% and 0.04%, respectively. In addition, applying our database to Spanish and updated American Academy of Pediatrics screening strategies led to more CCHD case detection., Conclusions: The Taipei protocol provided an efficient and effective screening referral system in a community setting. For optimal efficiency, we advocated the updated American Academy of Pediatrics algorithm/Spanish recommendation with a modification of immediate referral if oxygen saturation ≤90% in either extremity. The updated protocol would be practicable for nationwide screening in Taiwan and could also be applied to other regions with similar medical care systems., (Copyright © 2023 by the American Academy of Pediatrics.)

A well-conducted prenatal visit remains of paramount importance because it allows the preservation of mother and child health by reducing the rates of morbidity and mortality for them. However, the quality of prenatal visits remains a serious problem in our environment, and a new approach is urgently needed to improve the quality of prenatal visits in our environment., Competing Interests: The authors declare no conflicts of interest., (© 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

New antifungal therapies are needed for both systemic, invasive infections as well as superficial infections of mucosal and skin surfaces as well as biofilms associated with medical devices. The resistance of biofilm and biofilm-like growth phases of fungi contributes to the poor efficacy of systemic therapies to non-systemic infections. Here, we describe the identification and characterization of a novel keto-alkyl-pyridinium scaffold with broad spectrum activity (2-16 µg/mL) against medically important yeasts and moulds, including clinical isolates resistant to azoles and/or echinocandins. Furthermore, these keto-alkyl-pyridinium agents retain substantial activity against biofilm phase yeast and have direct activity against hyphal A. fumigatus . Although their toxicity precludes use in systemic infections, we found that the keto-alkyl-pyridinium molecules reduce C. albicans fungal burden in a rat model of vascular catheter infection and reduce Candida auris colonization in a porcine ex vivo model. These initial pre-clinical data suggest that molecules of this class may warrant further study and development.

Objectives: The first aim was to develop a nomogram for the area of the right atrium (ARA) of the fetal heart in uncomplicated singleton pregnancies. The second aim was to assess diagnostic indices of ARA to distinguish between tricuspid regurgitation (TR) with and without concomitant congenital heart defect (CDH)., Methods: The study was conducted between 2014 and 2019. Fetal echocardiography was performed on fetuses with and without TR. For the first aim, ARA was measured in 460 fetuses without proven structural and chromosomal abnormalities, and for the second aim, ARA was measured in 1077 fetuses with TR., Results: A nomogram for the ARA of fetuses with normal hearts was developed. TR was observed in 4.5% (1077/23,771) of euploid fetuses; 4.3% (1020/23,771) of fetuses had TR without a concomitant CHD, and 0.2% (57/23,771) fetuses had TR with a concomitant CHD. No significant differences in ARAs were found between fetuses with normal hearts without TR ( n  = 22,694) and fetuses with TR without CHD ( n  = 1020; p  = .751). Fetuses with TR and CHDs had different ARA than fetuses with normal hearts without TR and fetuses with TR without CHD ( p  < .0005 in both cases)., Conclusions: ARA seems to be an auxiliary marker to distinguish the presence of CHD in fetuses with TR.

Background and Objectives: Hospitalized children with medical complexity (CMC) are at high risk of medical errors. Their families are an underutilized source of hospital safety data. We evaluated safety concerns from families of hospitalized CMC and patient/parent characteristics associated with family safety concerns., Methods: We conducted a 12-month prospective cohort study of English- and Spanish-speaking parents/staff of hospitalized CMC on 5 units caring for complex care patients at a tertiary care children's hospital. Parents completed safety and experience surveys predischarge. Staff completed surveys during meetings and shifts. Mixed-effects logistic regression with random intercepts controlling for clustering and other patient/parent factors evaluated associations between family safety concerns and patient/parent characteristics., Results: A total of 155 parents and 214 staff completed surveys (>89% response rates). 43% (n = 66) had ≥1 hospital safety concerns, totaling 115 concerns (1-6 concerns each). On physician review, 69% of concerns were medical errors and 22% nonsafety-related quality issues. Most parents (68%) reported concerns to staff, particularly bedside nurses. Only 32% of parents recalled being told how to report safety concerns. Higher education (adjusted odds ratio 2.94, 95% confidence interval [1.21-7.14], P = .02) and longer length of stay (3.08 [1.29-7.38], P = .01) were associated with family safety concerns., Conclusions: Although parents of CMC were infrequently advised about how to report safety concerns, they frequently identified medical errors during hospitalization. Hospitals should provide clear mechanisms for families, particularly of CMC and those from disadvantaged backgrounds, to share safety concerns. Actively engaging patients/families in reporting will allow hospitals to develop a more comprehensive, patient-centered view of safety., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD., Methods: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained., Results: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up., Conclusions: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Disorganized morphogenesis of arteries, veins, capillaries, and lymphatic vessels results in vascular malformations. Most individuals with isolated vascular malformations have postzygotic (mosaic), activating pathogenic variants in a handful of oncogenes within the PI3K-RAS-MAPK pathway (Padia et al., Laryngoscope Investig Otolaryngol 4: 170-173 [2019]). Activating pathogenic variants in the gene PIK3CA , which encodes for the catalytic subunit of phosphatidylinositol 3-kinase, are present in both lymphatic and venous malformations as well as arteriovenous malformations in other complex disorders such as CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformations, epidermal anevi, scoliosis) (Luks et al., Pediatr Dev Pathol 16: 51 [2013]; Luks et al., J Pediatr 166: 1048-1054.e1-5 [2015]; Al-Olabi et al., J Clin Invest 128: 1496-1508 [2018]). These vascular malformations are part of the PIK3CA -related overgrowth spectrum, a spectrum of entities that have regionalized disordered growth due to the presence of tissue-restricted postzygotic PIK3CA pathogenic variants (Keppler-Noreuil et al., Am J Med Genet A 167A: 287-295 [2015]). Cerebrofacial vascular metameric syndrome (CVMS; also described as cerebrofacial arteriovenous metameric syndrome, Bonnet-Dechaume-Blanc syndrome, and Wyburn-Mason syndrome) is the association of retinal, facial, and cerebral vascular malformations (Bhattacharya et al., Interv Neuroradiol 7: 5-17 [2001]; Krings et al., Neuroimaging Clin N Am 17: 245-258 [2007]). The segmental distribution, the presence of tissue overgrowth, and the absence of familial recurrence are all consistent with CVMS being caused by a postzygotic mutation, which has been hypothesized by previous authors (Brinjiki et al., Am J Neuroradiol 39: 2103-2107 [2018]). However, the genetic cause of CVMS has not yet been described. Here, we present three individuals with CVMS and mosaic activating pathogenic variants within the gene PIK3CA We propose that CVMS be recognized as part of the PIK3CA -related overgrowth spectrum, providing justification for future trials using pharmacologic PIK3CA inhibitors (e.g., alpelisib) for these difficult-to-treat patients., (© 2021 Sheppard et al.; Published by Cold Spring Harbor Laboratory Press.)

Families and physicians alike benefit from the advances and ease of the Internet. Similarly, both can be unaware of harmful misinformation circulating the Web. In this article, we describe the presentation of 2 unrelated infants, within 1 week of each other, with vitamin D deficiency rickets and severe extraskeletal manifestations of hypocalcemia, including seizures and cardiac arrest, from homemade, vegan formula found through Pinterest (San Francisco, CA). Despite good parental intentions this formula did not meet macronutrient and micronutrient standards, particularly regarding vitamin D, phosphorus, and calcium content, and led to rare, life-threatening complications in both cases. Before presentation, both patients followed appropriately with their pediatrician and discussed feeding in detail, although neither family disclosed the use of homemade formula. Pediatricians must be aware of these dangerous homemade alternative formulas, consider the manner and depth of their feeding history questioning, and continue to counsel against homemade formula to prevent further harm to children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Graber is a contributing author to Merck Manuals. Drs Vieira, Kube, van Helmond, Hanley, Bialo, and Slamon have disclosed no financial relationships relevant to this article., (Copyright © 2021 by the American Academy of Pediatrics.)

Tacrolimus-induced immune thrombocytopenia (ITP) is a rare entity that can occur years after initiation of tacrolimus therapy following solid organ transplantation, and platelet recovery can be substantially delayed following discontinuation of tacrolimus. Romiplostim, a thrombopoietin receptor agonist approved by the FDA in 2018 for the treatment of chronic ITP in children, may be a useful therapy to hasten platelet recovery in the acute ITP setting in place of immunomodulating agents. We present a case of tacrolimus-induced ITP successfully treated with romiplostim in a child following cardiac transplantation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

This article was migrated. The article was marked as recommended. Background: Education in social determinants of health (SDH) has become an important part of medical curricula, facilitated increasingly through students' experiential learning with communities. The Community and Workplace Centred Learning Experience (CWCLE) module of the University of Saskatchewan, Canada, intends to integrate and extend second-year medical students' attitudes, skills, and knowledge about SDH and community resources. We aimed to: 1) Solicit students' self-evaluation of their ability to perform module learning objectives, 2) Assess module impact on student attitudes toward SDH, 3) Obtain feedback from community partners and students about their community experiences, and 4) Use feedback to collaboratively develop recommendations to enhance the CWCLE module. Methods: We used a mixed-method approach to combine quantitative data with stories and personal experiences. We developed an online survey for two cohorts of students who had completed the module, soliciting students to self-evaluate their perceived abilities to perform the module's learning objectives and evaluating students' attitudes towards SDH. We invited representatives from community agencies involved in the CWCLE module to participate in focus groups. We also held separate focus groups with students who participated in the online survey to elaborate on their survey comments. Results: In total, 145 students participated in the online survey (response rate=72.5%). Eleven community agency representatives and seven students participated in five focus groups. Our results demonstrate that medical students benefit from community-based experiential learning of SDH and community resources. We trace evaluations and discussions in the ongoing development of this community-based experiential learning module from its initial, primarily medical-school driven designs, towards a substantial involvement of community-based organizations in its operation and continuing redevelopment. Conclusions: Our mixed method offered us a better understanding of module impact and opportunities for improvement. This module evaluation and reform generated opportunities for community partners to influence decisions in medical education and led to a collaborative evolution of a community-centred learning experience. Medical schools should actively engage community partners in teaching behavioural and social components of the curriculum and acknowledge their partners' expertise to promote community engagement and social accountability in medical education., (Copyright: © 2021 Gao Y et al.)

Competing Interests: Conflict of Interest None declared.

Abstract: We had earlier reported about the increase in the prevalence of atrial fibrillation (AF) among residents in the evacuation zone of Fukushima Prefecture after the Great East Japan Earthquake. In the present investigation, we explored the association between the prevalence of AF and white blood cell (WBC) count after the earthquake through an observational cross-sectional study.A total of 14,800 participants (6427 men and 8373 women) were included in the Fukushima Health Management Survey. For the present study, 12-lead electrocardiogram tracings and the WBC count and its subtypes were obtained and analyzed. The odds ratios (ORs) of AF after the earthquake and the 95% confidence intervals (CIs) for one standard deviation of differential WBC count were calculated after adjustments for age and other potential confounding factors using the logistic regression model.Our results revealed a prevalence of AF of 1.8% (269 participants) after the earthquake. Monocyte count and neutrophil/lymphocyte ratio exhibited a significant association with the prevalence of AF in the multivariable-adjusted model. The adjusted ORs of monocyte count and neutrophil/lymphocyte ratio for AF were 1.21 (95% CI, 1.05-1.40, P = .01) and 1.22 (95% CI, 1.01-1.44, P < .05), respectively.The prevalence of AF was associated with increased monocyte count and neutrophil/lymphocyte ratio among residents in the evacuation zone in Fukushima Prefecture, suggesting that inflammation and psychological stress could be important factors mediating the development of AF after the earthquake., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA . Here we investigated the prevalence and diversity of ehxA in 239 STEC isolates from human clinical samples. In total, 199 out of 239 isolates (83.26%) were ehxA positive, and ehxA was significantly overrepresented in isolates carrying stx 2a + stx 2c ( p < 0.001). The presence of eae ( p < 0.001). The presence of ehxA was significantly associated with BD and serotype O157:H7. Five ehxA subtypes were identified, among which, ehxA subtypes B, C, and F were overrepresented in eae -positive isolates. All O157:H7 isolates carried ehxA subtype B, which was related to BD and HUS. Three ehxA groups were observed in the phylogenetic analysis, namely, group Ⅰ ( ehxA subtype A), group Ⅱ ( ehxA subtype B, C, and F), and group Ⅲ ( ehxA group Ⅰ was associated with non-bloody stool and individuals ≥10 years of age. The presence of ehxA group Ⅱ, while ehxA group Ⅰ was associated with non-bloody stool and individuals ≥10 years of age. The presence of ehxA + eae was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA + eae + stx 2 was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA among clinical STEC isolates. The ehxA genotypes (subtype B and phylogenetic group Ⅱ) could be used as risk predictors, as they were associated with severe clinical symptoms, such as BD and HUS. Furthermore, ehxA , together with stx and eae, can be used as a risk predictor for HUS in STEC infections.

Objective: To discuss the skin microbiome modulates immunity by interactions between skin immunology with keratinocytes to combat pathogens. Allergic disorders are classified by immunoglobulin E sensitivity and aberrant T H 2 cell responses, and an increasing number of studies have described the associations with skin microbiome fluctuations. In this review, we discuss commensal-epidermal homeostasis and its influence on allergic disease., Data Sources: All included references were obtained from the PubMed database., Study Selections: Studies addressing relevant aspects of commensal-epidermal homeostasis, skin microbiome dysbiosis, microbiome-targeted therapeutics, and prevention in allergy were included., Results: Homeostasis between the commensal microbiome and the epidermis is important in protecting against allergic disease. Commensals promote antiallergic T H 1 and T H 17 immunophenotypes within the skin and induce keratinocytes to secrete antimicrobial peptides and alarmins that enhance barrier function and antagonize proallergic organisms. Perturbations in this homeostasis, however, is associated with allergic disease development. Atopic dermatitis is associated with decreases in skin commensals and increases in the pathogen, Staphylococcus aureus. Fluctuations in the skin microbiome contributes to decreased barrier dysfunction, allergic sensitization, and T H 2 cytokine secretion. Little is known about how the skin microbiome affects food allergy, allergic rhinitis, and asthma, and it is poorly understood how cutaneous inflammation influences systemic allergic responses. Therapies are targeted toward maintenance of the skin barrier, replacement of healthy commensals, and anti-T H 2 biologic therapy., Conclusion: Although the effects of commensal-epidermal homeostasis on allergy within the skin are becoming increasingly clear, future studies are necessary to assess its effects on extracutaneous allergic disorders and explore potential therapeutics targeting the skin microbiome., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Inherited bone marrow failure (IBMF) syndromes are rare blood disorders characterized by hematopoietic cell dysfunction and predisposition to hematologic malignancies. Despite advances in the understanding of molecular pathogenesis of these heterogeneous diseases, genetic variant interpretation, genotype-phenotype correlation, and outcome prognostication remain difficult. As new IBMF and other myelodysplastic syndrome (MDS) predisposition genes continue to be discovered (frequently in small kindred studies), there is an increasing need for a systematic framework to evaluate penetrance and prevalence of mutations in genes associated with IBMF phenotypes. To address this need, we analyzed population-based genomic data from >125 000 individuals in the Genome Aggregation Database for loss-of-function (LoF) variants in 100 genes associated with IBMF. LoF variants in genes associated with IBMF/MDS were present in 0.426% of individuals. Heterozygous LoF variants in genes in which haploinsufficiency is associated with IBMF/MDS were identified in 0.422% of the population; homozygous LoF variants associated with autosomal recessive IBMF/MDS diseases were identified in only .004% of the cohort. Using age distribution of LoF variants and 2 measures of mutational constraint, LOEUF ("loss-of-function observed/expected upper bound fraction") and pLI ("probability of being loss-of-function intolerance"), we evaluated the pathogenicity, tolerance, and age-related penetrance of LoF mutations in specific genes associated with IBMF syndromes. This analysis led to insights into rare IBMF diseases, including syndromes associated with DHX34, MDM4, RAD51, SRP54, and WIPF1. Our results provide an important population-based framework for the interpretation of LoF variant pathogenicity in rare and emerging IBMF syndromes., (© 2020 by The American Society of Hematology.)

Rationale: Anorexia nervosa (AN) is a serious eating disorder associated with a distorted body image. Hypercholesterolemia has been found in patients with AN but the mechanism of hyperlipidemia in AN remains little known. Ascites in patients with AN has been attributed to hypoalbuminemia and liver diseases, but massive ascites without the aforementioned etiologies has never been reported in AN., Patient Concerns: An 11-year-old girl was admitted for exclusion of organic underlying diseases due to severe body weight loss (18% within 3 weeks), poor appetite, and hypercholesterolemia (274 mg/dL). She complained of heartburn sensation, nausea, vomiting, constipation, and postprandial dull abdominal pain with fullness., Diagnoses: The patient's condition met with all 3 of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for diagnosing AN. On admission, her total cholesterol level was 337 mg/dL and hypocomplementemia (C3 55.5 mg/dL) was also found. Abdominal sonography and computed tomography scans showed massive ascites. However, neither proteinuria nor hypoalbuminemia was found. Upper gastroduodenal endoscopy showed chronic superficial gastritis and colonoscopy revealed negative findings. Ascites obtained by paracentesis demonstrated a transudate without bacterial infection, tuberculosis, or pancreatitis. Exploratory laparoscopy showed nonpurulent ascites. However, biopsies from the small intestine, mesentery, and liver showed chronic inflammation and fibrosis., Interventions: The intensive nutritional therapy by increasing total energy intake stepwise with a combination of high-energy formula and her favorite foods., Outcomes: Her hypercholesterolemia, hypocomplementemia, and massive ascites resolved after her weight was restored. She developed binge eating with continuous weight gain after discharge. Her weight significantly increased to an obese level (body mass index [BMI] 25.9 kg/m) after loss to follow-up for 4 years until she returned to our emergency room due to suicide attempt., Conclusion: Diagnostic crossover between subtypes in anorexia nervosa might be a potential risk factor for illness severity and poor prognosis. AN can manifest as massive ascites with normal albumin concentrations that could possibly be due to chronic inflammation of the intestinal serosa, mesentery, and peritoneal surface of the liver.

Right ventricle (RV) has frequently been described as the forgotten ventricle in the circulation. However, its importance in various cardiac diseases is now unquestioned. This recognition has led to improved risk stratification and development of algorithms for intervention, which incorporate measurements of RV function as key components of the assessment of many conditions. The diastolic function plays an important role in determining ventricular filling and stroke volume. Abnormal left ventricular (LV) diastolic function has been recognized in many cardiovascular diseases and is associated with worse outcomes, including total mortality and hospitalizations due to heart failure. In this review, we define what global RV diastolic function is, and how to measure it. This article indicates the validation of kinematic model parameters for assessing RV diastolic function. J. Med. Invest. 67 : 11-20, February, 2020.

Cystic fibrosis (CF) is caused by mutations of the gene encoding the CF transmembrane conductance regulator. It remains unclear whether the abnormal immune response in CF involves extrinsic signals released from the external or internal environment. We sought to characterize the peripheral immune signatures in CF and its association with clinical phenotypes. Healthy peripheral blood mononuclear cells (PBMCs) were cultured with plasma from CF probands (CFPs) or healthy control subjects (HCs) followed by nCounter gene and microRNA (miRNA) profiling. A discovery cohort of 12 CFPs and 12 HCs and a validation cohort of 103 CFPs and 31 HCs (our previous microarray data [GSE71799]) were analyzed to characterize the composition of cultured immune cells and establish a miRNA‒mRNA network. Cell compositions and miRNA profiles were associated with clinical characteristics of the cohorts. Significantly differentially expressed genes and abundance of myeloid cells were downregulated in PMBCs after culture with CF plasma ( P  < 0.05). Top-ranked miRNAs that increased in response to CF plasma (adjusted P  < 0.05) included miR-155 and miR-146a, which target many immune-related genes, such as IL-8. Pseudomonas aeruginosa infection was negatively associated with abundance of monocytes and the presence of those regulatory miRNAs. Extrinsic signals in plasma from patients with CF led to monocyte inactivation and miRNA upregulation in PBMCs. An improved understanding of the immune effects of extrinsic factors in CF holds great promise for integrating immunomodulatory cell therapies into current treatment strategies in CF.

Both breast cancer and autoimmune diseases (ADs) are predominant in women. NSAIDs are common medications for AD. Evidence on the association between NSAIDs use and breast cancer risk is controversial. We investigated the association between NSAIDs exposure and breast cancer risk in female patients with AD. AD patients older than 18 years of age were enrolled from Taiwan Longitudinal Health Insurance Database 2005. The NSAID users were defined as AD patients who had ever taken NSAIDs for at least 3 months between 2000 and 2009. All individuals were followed from the date of first diagnosis of AD to the end of 2013 to evaluate the risk of breast cancer. We estimated the adjusted hazard ratio (HR) using Cox proportional hazard regression after adjusting for age, comorbidities and medications. A total of 12 331 NSAID users and 12 331 non-NSAID users were included in this study after 1: 1 individual matching. The NSAID users were less likely to develop breast cancer than the non-NSAID users (adjusted HR: 0.37; 95% confidence interval: 0.27-0.50; P < 0.001), even if they used NSAIDs with low cumulative defined daily doses (adjusted HR: 0.42; 95% confidence interval: 0.34-0.53; P < 0.001). The incidence of new-onset breast cancer in NSAID users was significantly decreased in users taking selective cyclooxygenase 2 inhibitors, diclofenac, ibuprofen and piroxicam. Lower cumulative hazard rates were found in the AD patients who used NSAIDs (P < 0.001). NSAID exposure is associated with a decreased risk of breast cancer in female AD patients.

Objectives: The use of ventricular assist devices for pediatric patients with heart failure is increasing, but is associated with significant morbidity and mortality. Our objectives were to describe the admission outcomes and resource utilization of pediatric patients supported with ventricular assist devices, utilizing a multicenter database., Data Sources: Pediatric Health Information System database (comprising 49 nonprofit children's hospitals)., Study Selection: Retrospective cohort analysis of the database from January 2006 to September 2015 for all admissions less than or equal to 21 years old with ventricular assist device implantation., Data Extraction: The primary outcome was hospital mortality. The secondary outcomes were hospital length of stay and adjusted cost., Data Synthesis: We analyzed 744 ventricular assist device implantations (740 patients), 422 (57%) males, and 363 (49%) non-Hispanic white. Median age at admission was 5.9 years (interquartile range, 0.9-13.5 yr), and median length of stay was 69 days (interquartile range, 36-122 d). The overall hospital mortality was 188 (25%), whereas 395 (53%) were transplanted and 141 (19%) were discharged on ventricular assist device. Extracorporeal membrane oxygenation was used, in addition to ventricular assist device, in 340 (46%). The majority of ventricular assist device implantations (453, 61%) were from 2011 to 2015 (compared to 2006-2010). More patients discharged on ventricular assist device from 2011 to 2015 (23% vs 13% in 2006-2010; p = 0.001). There was no difference in median age, mortality, length of stay, or adjusted costs between these time periods. On multivariable analysis, underlying congenital heart disease, renal failure, liver congestion, sepsis, cerebrovascular accident, and extracorporeal membrane oxygenation were associated with hospital mortality. Sepsis and ventricular assist device replacement/repair were associated with higher adjusted cost and longer length of stay., Conclusions: The pediatric ventricular assist device experience continues to grow, with a significant increase in the number of patients undergoing ventricular assist device implantation and a higher proportion being discharged from hospital on ventricular assist device support in recent years. Underlying congenital heart disease, renal failure, sepsis, cerebrovascular accident, and extracorporeal membrane oxygenation are significantly associated with hospital mortality.

Purpose of Review: Outcomes after cardiac transplantation have improved over past decades, but long-term graft survival remains limited in part because of uncertainty regarding clinical implications of donor-specific antibodies (DSAs). The purpose of this review is to consolidate recent advances in knowledge on the topic of DSA and their potential to impact long-term prognosis after heart transplantation., Recent Findings: The presence of persistent DSA increases the risk of poor outcome after heart transplantation, including development of antibody-mediated rejection (AMR), graft failure, cardiac allograft vasculopathy, and mortality. Importantly, different DSA vary in clinical significance. DSA capable of activating the complement cascade portend a higher risk of developing AMR. human leukocyte antigen class I and class II antigens are expressed differently within the heart, and so, clinical manifestations of class I and class II DSA vary accordingly. Further, compared with class I, class II DSA carry an increased risk of graft loss and mortality. When comparing preexisting DSA with formation of de-novo DSA, de-novo DSA are associated with worse outcome., Summary: DSAs are generally associated worse long-term prognosis after heart transplantation but vary in their clinical significance. Recognition of specific risk profiles is essential for guiding posttransplant antibody management.

Objective: To study the effect of zinc supplementation in children under 5 years of age rom low- and middle-income countries (LMICs) on anthropometry and prevalence of malnutrition., Design: Systematic review of randomized controlled trials and cluster randomized trials., Setting: Low- and middle-income countries., Participants: 63 trials with zinc supplementation, incorporating data on 27372 children. Trials conducted exclusively in specifically diseased participants and in children with severe acute malnutrition were excluded., Intervention: Zinc supplementation, provided either as medicinal supplementation or through food fortification., Outcome Measures: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference, head circumference; (ii) Prevalence of malnutrition., Results: There was no evidence of effect on height-for-age Z score at the end of supplementation period (25 trials; 9165 participants; MD= 0.00 Z; 95% CI -0.07, 0.07; P=0.98; moderate quality evidence) with significant heterogeneity (I² = 57%; P<0.001) related to dose and duration of zinc between trials. There was little or no effect on change in height-for-age Z score (13 trials; 8852 participants; MD= 0.11 Z; 95% CI -0.00, 0.21; P=0.05), but the heterogeneity was considerable (I²=94%; P<0.001). There was no evidence of effect on length (6303 participants; MD= 1.18 cm; 95% CI -0.63, 2.99 cm, P=0.20; moderate quality evidence; considerable heterogeneity, I²=99%) but a little positive effect on change in length (19 trials; 10783 participants; MD= 0.43 cm; 95% CI 0.16, 0.70, P=0.002; moderate quality evidence; considerable heterogeneity, I²=93%). There was no evidence of effect on weight-for-age Z score or change in weight-for-age Z score but a little positive effect on weight (19 trials; 8851 study participants; MD= 0.23 kg; 95% CI 0.03, 0.42; P=0.02; considerable heterogeneity, I²=91%) and change in weight (kg) (23 trials; 10143 study participants; MD= 0.11 kg; 95% CI 0.05, 0.17, P<0.001, substantial heterogeneity, I²=80%). There was no evidence of effect on weight-for-height Z score, and mid upper arm circumference at the end of supplementation period, but there was a little positive effect on change in MUAC from baseline (8 trials; 1724 participants; MD = 0.09 cm; 95% CI 0.01, 0.16; P=0.03; no heterogeneity, I²=0%). Head circumference in zinc supplemented group was marginally higher compared to control (2966 study participants; MD= 0.39 cm; 95% CI 0.03, 0.75; P=0.03; substantial heterogeneity, I²=67%). There was no evidence of benefit in stunting (10 trials; 11838 study participants; RR= 1.0; 95% CI 0.95, 1.06; P=0.89; Moderate Quality Evidence; no significant heterogeneity, I²=11%), wasting (7 trials; 8988 study participants; RR= 0.94; 95% CI 0.82, 1.06; P=0.31; Moderate Quality Evidence; no significant heterogeneity, I²=13%) or underweight (7 trials; 8677 study participants; RR= 1.08; 95% CI 0.96, 1.21; P=0.19; Moderate Quality Evidence; substantial heterogeneity, I²=73%)., Conclusion: Available evidence suggests that zinc supplementation probably leads to little or no improvement in anthropometric indices and malnutrition (stunting, underweight and wasting) in children under five years of age in LMICs. Advocating zinc supplementation as a public health measure to improve growth, therefore appears unjustified in these settings with scarce resources.

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population., Methods: A case-case-control study of patients (0-22 years) at 3 tertiary-care Chicago-area medical centers, 2008-2015, was conducted. Case group 1 children possessed KPC-CRE infections; case group 2 harbored carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls had negative cultures. Case-control matching was 1:1:3 by age, infection site and hospital. Statistical and molecular analyses were performed., Results: Eighteen KPC-CRE infections were identified; median patient age was 16.5 years. Of 4 available KPC-CRE, 2 were unrelated, non-ST258 KP strains harboring blaKPC-2, one was a ST258 KP harboring blaKPC-3, and the last was an E. coli containing blaKPC-2. KPC-CRE and CSE-infected patients had more multidrug-resistant organisms infections, long-term care facility admissions and lengths of stay (LOS) > 7 days before culture. KPC-CRE and CSE patients had more gastrointestinal comorbidities (odds ratios [Ors], 28.0 and 6.4) and ≥ 3 comorbidities (Or 15.4 and 3.5) compared with controls; KPC-CRE patients had significantly more pulmonary and neurologic comorbidities (both ORs 4.4) or GI and pulmonary devices (ORs, 11.4 and 6.1). Compared with controls, CSE patients had more prior fluoroquinolone use (OR, 7.4); KPC-CRE patients had more carbapenem or aminoglycoside use (ORs, 10.0 and 8.0). Race, gender, LOS and mortality differences were insignificant., Conclusions: Pediatric patients with KPC-CRE infection suffer from high multi-system disease/device burdens and exposures to carbapenems and aminoglycosides. Different from adult reports, non-ST258 KP strains were more common, and LOS and mortality rates were similar in all groups. Pediatric CRE control in should focus on modifiable risk factors including antibiotic and device utilization.

Objective: To evaluate the effect of withholding feeds during transfusion on transfusion associated acute gut injury (TRAGI)., Study Design: Data were collected on 125 preterm infants before and after the practice of withholding feeds for 12-24 h during transfusion was instituted. Logistic regression was used to examine effects of withholding feeds on TRAGI rates., Results: A total of 19 (15%) infants developed NEC; 6/19 (32%) had TRAGI. Postnatal hydrocortisone use was associated with TRAGI (OR 8.97; 95% CI 1.17-68.46, p = 0.034). There was no difference in NEC rates (15.8 vs. 14.7%) and the proportions (22.2 vs. 40%) of TRAGI in the two time periods before and after instituting the standardized feeding regimen and practice of holding feeds during transfusion., Conclusion: No significant decrease was noted in the rates of TRAGI after feeds were withheld during transfusion. Further studies are warranted to explore the relationship between feeds during transfusion and NEC.

Parents' understanding/expectations regarding genetic testing for children with developmental disorders were explored. Within a month of testing, interviews were conducted with 57 parents. Many (74%) could not recall the nature of testing. Parents expected genetic testing to have positive impacts for the child (93%) and the family (98%), mainly to find the etiology and/or an intervention. Many parents (40%) reported not knowing their child's clinical diagnosis. They expected genetic testing would establish the diagnosis. Parents anticipated potential negative impacts of testing for children (78%) and families (87%), mainly finding another illness or not finding potential interventions. Abnormal results explaining the disorder were found in 9% of children. In summary, genetic results for developmental disorders are unlikely to meet parental expectations.