Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Early initiation of inhaled corticosteroids does not decrease acute chest syndrome morbidity in pediatric patients with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of mortality in patients with sickle cell disease (SCD). Systemic corticosteroids decrease ACS severity, but the risk of readmission for vaso-occlusive crises (VOC) has limited their use. The efficacy of inhaled corticosteroids (ICS) as a safer alternative is currently unknown. An observational, historic cohort study compared patients with SCD with ACS who received ICS at admission (ICS) to those who did not (non-ICS). Outcome measures included rates of transfusion, oxygen requirement, BiPAP initiation, PICU transfer, intubation, readmission, hospital cost, and length of stay. One hundred twenty patients with SCD (55 non-ICS, 65 ICS) were included. A significantly higher proportion of the non-ICS group had bilateral infiltrates, but fewer had asthma. More children in the ICS group had BiPAP initiated, however transfer to the PICU, intubation, transfusion rates, oxygen requirement, hospital cost, length of stay, and readmission rates did not differ between groups. Regression analysis did not reveal any differences in outcomes, nor were outcomes changed when patients were separated based on the presence or absence of asthma. In this observational cohort study, ICS did not demonstrate a significant reduction in ACS morbidity, though ICS use should be studied in a prospective manner.

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV.

Standardization of Postoperative Transitions of Care to the Pediatric Intensive Care Unit Enhances Efficiency and Handover Comprehensiveness.

INTRODUCTION: To determine the impact of standardization of postoperative transitions of care to the pediatric intensive care unit on handover efficiency and the quality of healthcare data exchange. METHODS: This was a prospective, pre-post observational study after standardization of postoperative transitions in a 44-bed pediatric intensive care unit in a 313-bed tertiary care pediatric hospital from April to July 2015. Standardization was completed using a multidisciplinary handover checklist. Primary outcomes were efficiency expressed as mean handover duration and the comprehensiveness of healthcare data exchange. RESULTS: Forty-seven postoperative transitions were observed of which 23 were preintervention and 24 were postintervention. After standardization, efficiency improved from 10.5 ± 5.4 to 7.8 ± 2.7 minutes (P < 0.05). Healthcare data exchanged between surgical, anesthesia, and critical care providers were more robust including intraoperative, historical, and anticipatory guidance (all P < 0.05). After intervention, attendance through completion of handover for surgical services increased from 13% to 88% (P < 0.05). CONCLUSIONS: Standardization of postoperative transitions improved efficiency, healthcare data exchange, and anticipatory planning. Future research is required to link standardization of transitions to improved patient outcomes and measure the development of shared mental models.

Quantification of in vitro and in vivo Cryptosporidium parvum infection by using real-time PCR.

Established methods for quantifying experimental Cryptosporidium infection are highly variable and subjective. We describe a new technique using quantitative real-time PCR (qPCR) that can be used to measure in vitro and in vivo laboratory infections with Cryptosporidium. We show for the first time that qPCR permits absolute quantification of the parasite while simultaneously controlling for the amount of host tissue and correlates significantly with established methods of quantification in in vitro and in vivo laboratory models of infection.

An early intestinal mucosal source of gamma interferon is associated with resistance to and control of Cryptosporidium parvum infection in mice.

Resistance to and control of Cryptosporidium parvum infection in mice in the absence of adaptive immunity appears to be gamma interferon (IFN-gamma) dependent. Using an IFN-gamma-neutralizing antibody in a murine model, we demonstrated increased susceptibility to infection within 24 h. We correlated this early resistance and control with increased mucosal expression of IFN-gamma and demonstrate that CD8+ T-cell receptor alphabeta intestinal intraepithelial lymphocytes express and secrete this cytokine shortly after infection. The rapid kinetics of IFN-gamma expression and secretion by naive CD8+ T cells in response to a protozoan pathogen have not previously been demonstrated.