Immune and TRG repertoire signature of the thymus in Down syndrome patients.

BACKGROUND: Patients with Down syndrome (DS) are at increased risk for infections and autoimmune disorders. Although several immunological abnormalities were previously found, differences in T cell receptor repertoire have never been shown. Thus we compared the T cell receptor gamma (TRG) repertoire in DS and non-syndromic pediatric patients by next-generation sequencing, in addition to other immunological markers. METHODS: Genomic DNA was extracted from thymuses of pediatric patients who underwent heart surgery, where six were with DS and six were non-syndromic patients. Peripheral blood counts, T cell subpopulations, thymus TCR excision circles (TRECs), spectratyping, and next-generation sequencing for TRG were analyzed. RESULTS: The mean age of the patients was 7 months and the mean lymphocyte count was slightly lower in patients with DS, whereas thymus TREC results were similar to non-syndromic patients (p = 0.197). The TRG repertoire analysis showed that patients with DS had a significantly larger number of unique TRG sequences, together with decreased clonal expansion. Lastly, the V and J gene usages in the thymus were similar in DS and non-syndromic patients. CONCLUSIONS: Patients with DS showed increased TRG repertoire diversity with decreased clonal expansion compared to non-syndromic patients. IMPACT: Alterations in T cell receptor gamma repertoire were found in patients with Down syndrome using next-generation sequencing (NGS) technique. Patients showed increased repertoire diversity and decreased clonal expansion compared to controls. These findings add to previous reports on abnormalities of other immune system components in patients with Down syndrome. NGS technique may point out differences not seen by previous methods. Repertoire abnormalities may contribute to those patients' predisposition to infections and autoimmune diseases.

Increased risk for early hypertriglyceridemia in small for gestational age preterm infants.

Small for gestational age preterm are at increased risk for future metabolic syndrome. Early indication for the disrupted metabolism may be found in the perinatal period. We aimed to evaluate whether small for gestational age preterm infants are at increased risk for hypertriglyceridemia when treated with lipid emulsions, and to investigate the association between triglyceride levels and morbidity. Small for gestational age infants ≤ 34 weeks' gestation age born during 2013-2016 were matched and compared with appropriate for gestational age counterparts. Triglyceride concentration > 250 mg/dL during treatment with parenteral nutrition was considered high. The study included 71 pairs of preterm infants. Hypertriglyceridemia was documented among 22.5% of the small for gestational age infants vs. 5.6% of the appropriate for gestational age infants (p = 0.007). Mean triglyceride levels were 194.4 ± 192.3 mg/dL and 99.9 ± 82.8 mg/dL, respectively (p < 0.001). Small for gestational age was predictive of hypertriglyceridemia (OR = 6.41; 95% CI 1.8-22.9). No significant association was found between triglyceride levels and morbidities in multivariate analysis.Conclusion: Small for gestational age preterm infants receiving lipid emulsions might be at a higher risk for hypertriglyceridemia. Routine monitoring of triglyceride levels will enable identification of the necessity for a slower increase in lipid emulsion therapy. What is Known: • Moderate and very preterm infants are routinely treated with lipid emulsions. • Small for gestational age (SGA) infants may have different metabolism, as they demonstrate higher risk for metabolic syndrome. What is New: • • SGA infants had a higher mean triglyceride level and more commonly had early hypertriglyceridemia (triglycerides > 250 mg/dL) compared with appropriate for gestational age infants treated with the same intravenous lipid dose. Small for gestational age was predictive of hypertriglyceridemia. • No significant association was found between triglyceride levels and morbidities in multivariate analysis.

Foscarnet-related Hypercalcemia During CMV Treatment in an Infant With SCID: A Case Report and Review of Literature.

Foscarnet is a main treatment for disseminated cytomegalovirus infection in immunocompromised patients. One of its documented side effects is hypocalcemia. Hypercalcemia, in contrast, was described anecdotally before, almost exclusively in adults with human immunodeficiency virus infection or posttransplantation. We describe a case of severe hypercalcemia during foscarnet treatment in an infant with IL-7 Rα deficient severe combined immunodeficiency, resolved after treatment cessation. We speculate that this unusual side effect is caused by foscarnet binding to the inorganic matrix of bone.

An Outbreak of Coxsackievirus B Type 2 Acute Meningoencephalitis in Children, Israel, July-September 2022.

During July-September 2022, 14 children suffering from meningoencephalitis tested positive for Coxsackievirus B2 (8 cerebrospinal fluid, 9 stool samples). Mean age 22 months (range 0-60 months); 8 were males. Seven of the children presented with ataxia and 2 had imaging features of rhombencephalitis, not previously described in association with Coxsackievirus B2.

The Long-Term Effectiveness and Safety of Cannabidiol-Enriched Oil in Children With Drug-Resistant Epilepsy.

BACKGROUND: Several retrospective studies on pediatric epilepsy reported positive effects of cannabidiol-enriched artisanal cannabis oil and pure cannabidiol oil on seizure reduction. METHODS: This is a retrospective study of children and adolescents with refractory epilepsy caused by various etiologies who were treated with artisanal cannabis oil during January 2014 to June 2019, with at least one year follow-up. RESULTS: Of 114 patients, 84 (73.3%) reported some improvement in seizure frequency at some point during treatment. Fifty-one (59%) of the 86 patients who continued treatment for at least one year showed >50% improvement in seizure frequency. Seizure etiology, seizure type, and patients' age and sex were not found to be associated with the response to cannabidiol-enriched cannabis oil. Side effects were minor, and positive effects beyond seizure reduction were noted. CONCLUSIONS: Artisanal cannabidiol-enriched cannabis may be an effective and safe long-term treatment for refractory epilepsy.

Felbamate for pediatric epilepsy-should we keep on using it as the last resort?

Introduction: Concerns regarding felbamate adverse effects restrict its widespread use in children with drug-resistant epilepsy. We aimed to examine the efficacy and safety of felbamate in those children and identify the ones who may benefit most from its use. Methods: We retrospectively reviewed the medical files of all patients who were treated with felbamate in a tertiary pediatric epilepsy clinic between 2009-2021. Drug efficacy was determined at the first 3 months of treatment and thereafter. Therapeutic response and adverse reactions were monitored throughout the course of treatment. Results: Our study included 75 children (age 8.9 ± 3.7 years), of whom 53 were treated with felbamate for seizures, 16 for electrical status epilepticus during sleep and 6 for both. The median follow-up time was 16 months (range 1-129 months). The most common cause for epilepsy was genetic (29%). The median number of previous anti-seizure medications was six [4-8]. A therapeutic response ≥50% was documented in 37 (51%) patients, and a complete response in 9 (12%). Nineteen patients (25%) sustained adverse reactions, including three cases of elevated liver enzymes and one case of neutropenia with normal bone marrow aspiration. In all cases, treatment could be continued. All children with intractable epilepsy following herpes encephalitis showed a response to felbamate. Conclusion: Felbamate is an efficacious and safe anti-seizure medication in the pediatric population.

Acute schistosomiasis in paediatric travellers and comparison with their companion adults.

BACKGROUND: Schistosomiasis in non-immune travellers can cause acute schistosomiasis, a multi-systemic hypersensitivity reaction. Little is known regarding acute schistosomiasis in children. We describe acute schistosomiasis in paediatric travellers and compare them with adult travellers. METHODS: A retrospective study of paediatric travellers (0-18 years old) diagnosed with schistosomiasis at Sheba Medical Center. Patients' findings are compared with those of adult travellers from the same travel groups. RESULTS: in total, 18 children and 24 adults from five different trips to Tanzania, Uganda, Nigeria and Laos were infected (90% of the exposed travellers). The median bathing time of the infected children was 30 min (interquartile range (IQR) 15-30 min). The most common presentations were respiratory symptoms in 13 (72%), eosinophilia in 13 (72%) and fever in 11 (61%). Acute illness included a median of 2.5 symptoms. Three children required hospitalization and three were asymptomatic. Fatigue was significantly less common in children compared with similarly exposed adults (33% vs 71%, P = 0.03). Rates of hospitalization and steroid treatment were similar. The median eosinophil count in children was 1045 cells/µl (IQR 625-2575), lower than adults [2900 cells/µl (IQR 1170-4584)], P = 0.02. CONCLUSIONS: Children may develop acute schistosomiasis following short exposure to contaminated freshwater, demonstrating a high infection rate. Severity seems to be similar to adults, although children report fatigue less commonly and show lower eosinophil counts. The disease should be suspected in children with multi-systemic illness and in asymptomatic children with relevant travel history.

COVID-19 in the Pediatric Population-Review and Current Evidence.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) pandemic has major health and economic impacts. We review disease characteristics in children. RECENT FINDINGS: Children comprise 1-2% of the diagnosed cases, and typically suffer mild disease. The median age of infected children is 3.3-11 years, and male/female ratio is 1.15-1.55. Common symptoms in children include upper respiratory symptoms (26-54%), cough (44-54%), fever (32-65%), and gastrointestinal (15-30%) symptoms. Substantial proportion (4-23%) are asymptomatic. Death rates are up to 0.7%. Risk factors associated with severe disease are neonatal age group, male gender, lower respiratory tract disease, and pre-existing medical conditions. Vertical transmission was reported. Multisystem inflammatory syndrome (MIS), characterized by fever, multisystem organ involvement, and laboratory markers of inflammation, causes critical illness in > 50% of cases and is increasingly reported from endemic countries. Indirect effects of the coronavirus epidemic include higher rates of psychiatric morbidities, education loss, unhealthy lifestyle changes, and increased child neglect. Vaccines are in clinical trials and immunogenicity has not yet been shown in children. SUMMARY: Overall, COVID-19 has lower incidence and causes milder disease in children compared with adult patients. MIS is a rare severe complication more common in children. More data on the efficacy and safety of antivirals in children are needed.

Age-Related Clinical Presentation of MOG-IgG Seropositivity in Israel.

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce. Aim: To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event. Methods: MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records. Results: Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1-66 years, with increased prevalence in children (19% compared to 6.7% in adults) (p < 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31-40 years (16.6%). Conclusions: MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age.

Morbidity among Israeli paediatric travellers.

BACKGROUND: International travel, particularly to developing countries, is becoming increasingly common among the Israeli population, including an increase in the number of travelling children. Since children are a distinct travellers' population, data about their post-travel morbidity are needed. METHODS: A retrospective study which examined all children (0-19 years old) who presented to our centre after international travel from 1999 to 2015. RESULTS: About 314 children were seen. The mean age was 10 years (SD ± 5.8). Most of the patients (80.6%) were tourists, and the rest were expatriates. The main destinations visited were South-Asia (46.5%), Sub-Saharan Africa (33.4%), Latin-America (7%) and Europe (6.4%). Overall, the most common diagnoses were gastrointestinal (GI) (mainly chronic) disorders (30.6%), followed by febrile diseases (26.4%), among which 18.1% of patients were diagnosed with dengue fever and 12% with malaria. Dermatologic conditions accounted for 25.2%. Additional diagnoses were schistosomiasis (6.4%) and neuropsychiatric symptoms (2.2%). A substantial part, 10.8%, had eosinophilia, either symptomatic or asymptomatic. Travellers to Asia, compared to travellers to Africa, presented more commonly with GI illness (OR 2.02, 95% confidence interval 1.13-3.61), and dermatologic conditions (OR 1.94, 95% confidence interval 1.05-3.61). Morbidity was associated with a variety of transmission modes, such as food-borne illnesses (30.9%), bite and sting wounds (10.2%), mosquito-borne infections (8%), freshwater contact (6.7%) and tick-borne infections (2.2%). CONCLUSION: The main conditions seen in paediatric returning travellers were GI, febrile and dermatologic illnesses, some may be rare in their country of origin. Targeting care for the suspected pathogens based on updated knowledge of epidemiology and thorough travel history is essential.