Cellular immune response to the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in pediatric autoimmune inflammatory rheumatic disease patients and controls.

This paper aims to compare the cellular immune response to the SARS-CoV-2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 and December 2022 at the Tel Aviv Medical Center. Children <18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6 ±â€…2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% of AIIRD children and 72.7% of controls had a breakthrough COVID-19 infection (P = 0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections.

Hyponatremia in childhood urinary tract infection.

Acute urinary tract infection (UTI) is the most common bacterial infection in childhood. Although hyponatremia was described in ~ 2/3 of these children, its clinical significance is still unclear. Herein, we evaluated the prevalence and clinical implications of hyponatremia in children hospitalized with a UTI. Medical records of previously healthy children hospitalized between January 2011 and December 2016 with UTI were retrospectively reviewed. Patients (median age 5.5 months) were divided into two groups according to their sodium levels: normonatremia (Na ≥ 135 mEq/L) and hyponatremia (Na < 135 mEq/L). Hyponatremia diagnosed on admission was found in 114/219 children (49%). Hyponatremic patients experienced a more severe disease manifested by a longer hospital stay (3.8 vs 3.4 days, p = 0.003), a higher prevalence of abnormal findings on renal ultrasound (10 vs 2, p = 0.01), higher C-reactive protein (CRP) levels (8.6 vs 3.4 mg/dl, p = <0.001), and a negative correlation between sodium levels and CRP (r = - 0.38, p < 0.001).Conclusion:Hyponatremia occurs frequently in children hospitalized with UTI and is associated with elevated inflammatory markers and a more severe disease course. What is Known: • Hyponatremia, one of the most common electrolyte abnormalities, occurs in approximately 1/3 of hospitalized children and in 2/3 of children with pyelonephritis. • In certain cases of various medical conditions, hyponatremia has been shown to correlate with disease severity. What is New: • Hyponatremia in hospitalized children with UTI correlates with elevated inflammatory markers and a more severe disease course.

Longitudinal safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in children aged 4-11 years with juvenile-onset autoimmune inflammatory rheumatic diseases: A prospective multicenter study.

This prospective, longitudinal, multicenter study assessed the safety and efficacy of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine among children 4-11 years-old with autoimmune inflammatory rheumatologic disease (AIIRD), compared to healthy controls. The study was conducted from 11/2021-12/2022 at 4 tertiary pediatric rheumatology units in Israel. Participants received at least 2 vaccine doses. Safety analysis included adverse events and disease activity measures. Efficacy was assessed by COVID-19 infection rates. Immunogenicity was evaluated in a subset of participants using anti- receptor binding domain antibody titers. Thirty-one children with AIIRD and 45 immunocompetent controls with similar baseline characteristics were included. Safety profile was favorable, with mild or no adverse events reported. The adverse event rates were similar in the AIIRD and control groups after the first (27 (60 %) vs. 14 (45.2 %), p = 0.2977) and the second vaccine doses (22 (49.0 %) vs. 18 (58.1 %), p = 0.5799), respectively. AIIRD activity remained stable and low after vaccination. Breakthrough COVID-19 infection rates were similar between groups, with 15 (48.4 %) in the AIIRD vs. 25 (55.6 %) in the control group (p = 0.7029). All reported COVID-19 infections in the AIIRD group and 18 (72 %) in the control group were symptomatic (p = 0.033), although symptoms were generally mild, with no severe disease. The safety of the BNT162b2 COVID-19 vaccine was excellent in children ages 4-11 years with AIIRD and healthy controls. Efficacy between groups was similar.

Efficacy and Safety of a Weight-based Dosing Regimen of Valganciclovir for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients.

BACKGROUND: Valganciclovir has been widely used for cytomegalovirus (CMV) prophylaxis in solid-organ transplant recipients. However, the optimal dosing protocol and target exposure in children are still unclear. Specific data as to the efficacy and safety of low-dose/low-exposure regimens are lacking and urgently needed. METHODS: During 2010 to 2015, the clinical efficacy and safety of a weight-based regimen of valganciclovir of 17 mg/kg/day, with a stratified dose reduction for impaired creatinine clearance, given as a CMV prophylaxis for 3 to 6 months, was retrospectively evaluated among pediatric kidney and liver transplant recipients, 12 months posttransplantation. Incidence of CMV infection was assessed by periodic measurements of viral load; adverse events were evaluated. RESULTS: Eighty-three children who had undergone 86 transplantations and were treated with 17 mg/kg of valganciclovir were included. Median age was 9.77 years (range, 0.6 to 18.9). Twelve (14%) developed CMV infection: 1 during prophylaxis and 11 during follow-up. These events comprised 6 cases of asymptomatic viremia and 6 cases of a clinically significant disease without occurrences of tissue-invasive disease. Treatment-related adverse effects occurred in 7 patients (8%), mostly hematological, resulting in premature drug cessation. CONCLUSIONS: Our results support the use of 17 mg/kg of valganciclovir for CMV prophylaxis in liver and kidney transplanted children as it showed satisfactory long-term efficacy and a good safety profile.

Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes.

BACKGROUND: Benign childhood epilepsy with centrotemporal spikes is benign childhood epilepsy, presenting between 4 and 10 years of age, characterized by typical clinical and EEG findings. Despite excellent prognosis, there are reports of mild cognitive, language, fine motor and behavioral difficulties. In its atypical form - electrical status epilepticus during slow wave sleep, continuous epileptiform activity during sleep lead to severe neurocognitive deterioration. Our objective was to investigate the influence of abundant sleep epileptiform activity, not fulfilling the criteria for electrical status epilepticus during Slow Wave Sleep, discovered randomly in children without overt intellectual impairment. METHODS: We retrospectively reviewed the charts and EEG's of 34 children with benign childhood epilepsy with centrotemporal spikes, who underwent neurocognitive evaluation. The neurocognitive battery included items in the following domains: attention span, memory, language, fine motor and behavior. Patients were divided into two groups according to the spike wave index on sleep EEG, with a cut-off point of 50%. The groups were compared regarding to neurocognitive performance. OUTCOMES: Children with epileptiform activity of more than 50%, were diagnosed at a significantly younger age (5.13 ± 1.94 years vs. 7.17 ± 2.45, p = 0.014 T test), had less controlled seizures and received more antiepileptic drugs. However, there was no difference in neurocognitive performance, except in fine motor tasks (Pegboard), where children with more abundant activity were scored lower (-0.79 ± 0.96 vs. 0.20 ± 1.05, p = 0.011, T test). CONCLUSION: Our study did not show negative cognitive effect of abundant epileptiform activity discovered randomly in children with benign childhood epilepsy with centrotemporal spikes, warranting aggressive treatment.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study.

BACKGROUND: Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens. METHODS: The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated. RESULTS: Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given. CONCLUSIONS: The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.