Long-term health outcome and quality of life in children with multisystem inflammatory syndrome: findings from multidisciplinary follow-up at an Italian tertiary-care paediatric hospital.

Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001). CONLUSION: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial. WHAT IS KNOWN: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up. WHAT IS NEW: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being.

Long-term cytokine profile in multisystem inflammatory disease among children.

BACKGROUND: Multisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results. METHODS: Twenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1ß, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis. RESULTS: IP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6-12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1ß, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed. CONCLUSIONS: Our study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.

COVID-19-Associated Multisystem Inflammatory Syndrome in Children and Cardiovascular Autonomic Control: A Prospective Cohort Study Nine Months after SARS-CoV-2 Infection.

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a severe pediatric complication during the SARS-CoV-2 pandemic, with potential long-term cardiovascular repercussions. We hypothesized that heart rate and blood pressure control at rest and during postural maneuvers in MIS-C patients, months after the remission of the inflammatory syndrome, may reveal long-term autonomic dysfunctions. Methods: We assessed 17 MIS-C patients (13 males; 11.9 ± 2.6 years, m ± SD) 9 months after acute infection and 18 age- (12.5 ± 2.1 years) and sex- (13 males) matched controls. Heart rate and blood pressure variability, baroreflex function, and hemodynamic parameters were analyzed in supine and standing postures. Results: MIS-C patients exhibited reduced heart rate variability, particularly in parasympathetic parameters during standing (pNN50+: 6.1 ± 6.4% in controls, 2.5 ± 3.9% in MIS-C; RMSSD: 34 ± 19 ms in controls, 21 ± 14 ms in MIS-C, p < 0.05), with no interaction between case and posture. Blood pressure variability and baroreflex sensitivity did not differ between groups except for the high-frequency power in systolic blood pressure (3.3 ± 1.2 mmHg2 in controls, 1.8 ± 1.2 mmHg2 in MIS-C, p < 0.05). The MIS-C group also showed lower diastolic pressure-time indices (DPTI) and systolic pressure-time indices (SPTI), particularly in standing (DPTI: 36.2 ± 9.4 mmHg·s in controls, 29.4 ± 6.2 mmHg·s in MIS-C; SPTI: 26.5 ± 4.3 mmHg·s in controls, 23.9 ± 2.4 mmHg·s in MIS-C, p < 0.05). Conclusions: Altered cardiovascular autonomic control may persist in MIS-C patients with, however, compensatory mechanisms that may help maintain cardiovascular homeostasis during light autonomic challenges, such as postural maneuvers. These results highlight the importance of assessing long-term cardiovascular autonomic control in children with MIS-C to possibly identify residual cardiovascular risks and inform targeted interventions and rehabilitation protocols.

Circulating Mesenchymal Stromal Cells in Patients with Infantile Hemangioma: Evaluation of Their Functional Capacity and Gene Expression Profile.

We previously published that in patients with infantile hemangioma (IH) at the onset (T0) colony forming unit-fibroblasts (CFU-Fs) are present in in vitro cultures from PB. Herein, we characterize these CFU-Fs and investigate their potential role in IH pathogenesis, before and after propranolol therapy. The CFU-F phenotype (by flow cytometry), their differentiation capacity and ability to support angiogenesis (by in vitro cultures) and their gene expression (by RT-PCR) were evaluated. We found that CFU-Fs are actual circulating MSCs (cMSCs). In patients at T0, cMSCs had reduced adipogenic potential, supported the formation of tube-like structures in vitro and showed either inflammatory (IL1ß and ESM1) or angiogenic (F3) gene expression higher than that of cMSCs from CTRLs. In patients receiving one-year propranolol therapy, the cMSC differentiation in adipocytes improved, while their support in in vitro tube-like formation was lost; no difference was found between patient and CTRL cMSC gene expressions. In conclusion, in patients with IH at T0 the cMSC reduced adipogenic potential, their support in angiogenic activity and the inflammatory/angiogenic gene expression may fuel the tumor growth. One-year propranolol therapy modifies this picture, suggesting cMSCs as one of the drug targets.

Assessment of Epicardial Fat in Children: Its Role as a Cardiovascular Risk Factor and How It Is Influenced by Lifestyle Habits.

Epicardial adipose tissue (EAT) stands out as a distinctive repository of visceral fat, positioned in close anatomical and functional proximity to the heart. EAT has emerged as a distinctive reservoir of visceral fat, intricately interlinked with cardiovascular health, particularly within the domain of cardiovascular diseases (CVDs). The aim of our overview is to highlight the role of EAT as a marker for cardiovascular risk in children. We also explore the influence of unhealthy lifestyle habits as predisposing factors for the deposition of EAT. The literature data accentuate the consequential impact of lifestyle choices on EAT dynamics, with sedentary behavior and unwholesome dietary practices being contributory to a heightened cardiovascular risk. Lifestyle interventions with a multidisciplinary approach are therefore pivotal, involving a nutritionally balanced diet rich in polyunsaturated and monounsaturated fatty acids, regular engagement in aerobic exercise, and psychosocial support to effectively mitigate cardiovascular risks in children. Specific interventions, such as high-intensity intermittent training and circuit training, reveal favorable outcomes in diminishing the EAT volume and enhancing cardiometabolic health. Future clinical studies focusing on EAT in children are crucial for advancing our understanding and developing targeted strategies for cardiovascular risk management in this population.

Fetal Myocarditis Associated With Maternal SARS-CoV-2 Infection.

We report the first case of significant fetal myocardial involvement associated with maternal SARS-CoV-2 infection, in which restoration of cardiac function at birth was noted. The demonstration of previous infection was supported by the quantification of humoral response in child and mother, in particular the presence of anti-N antibodies and through the detection of specific antibodies against the BA.4/5 variant.

High-Sensitivity Cardiac Troponin and the Management of Congenital Heart Disease in Newborns and Infants.

BACKGROUND: Early cardiac interventions in newborns and infants suspected for congenital heart disease (CHD) decrease morbidity and mortality. After updating current evidence on the use of cardiac troponins (cTn) in the context of CHD for risk stratification at early ages, we discuss relevant issues, starting from the evidence that only the measurement of the cTnT form is useful in this population. CONTENT: In newborns/infants with CHD, the cTnT concentration increase is correlated with: (a) cardiac stress and hemodynamic parameters, but not with the type of CHD; (b) volume overload/right ventricular pressure overload; (c) postoperative hypoperfusion injury and mortality; and (d) effects of cardioprotective strategies. For infants with CHD, high-sensitivity cTnT (hs-cTnT) concentrations >25 ng/L are an independent predictor of poor outcomes. Transitioning from cTnT to hs-cTnT in newborns/infants improves the identification of: (a) physiopathological mechanisms and factors that increased hs-cTnT early after birth; (b) myocardial injury, even when subclinical; (c) identification of patients requiring immediate therapeutic interventions; and (d) 99th percentile upper reference limits (URLs). However, no reliable URLs are currently available to allow the detection of myocardial injury associated with CHD in newborns/infants. SUMMARY: Additional data evaluating the clinical value of hs-cTnT in the risk stratification of newborns/infants with CHD who may suffer myocardial injury is needed. Validating the measurement, possibly in amniotic fluid samples, and improving the interpretation of hs-cTnT concentrations in the prenatal period, at birth and within 1 year of age are crucial to change CHD mortality/morbidity trends in the pediatric population.

Prediction of atherosclerotic cardiovascular risk in early childhood.

Atherosclerotic lesions are present even in very young individuals and therefore, risk stratification for cardiovascular (CV) disease should be implemented in childhood to promote early prevention strategies. In this review we critically appraise clinical, biochemical and genetic biomarkers available for pediatric clinical practice, which might be integrated to build effective algorithms to identify children at risk of future CV events. The first critical issue is to characterize in children aged 2-5 years, those CV risk factors/clinical conditions associated with dramatically accelerated atherosclerosis. Presence of clinical conditions such as obesity, diabetes mellitus, Kawasaki disease, etc., or positive family history for premature CV disease should be evaluated. Subsequently, a complete lipid profile and Lipoprotein(a) determination are recommended for children with increased baseline CV risk. Individuals with altered lipid profile could then undergo genetic testing for monogenic dyslipidemias to identify children with high CV genetic risk, who will be directed to appropriate therapeutic options. In perspective, calculation of a polygenic risk score, based on the analysis of several common single-nucleotide polymorphisms, could be integrated for better risk assessment. We here emphasize the importance of a "holistic" strategy integrating biochemical, anamnestic and genetic data to stratify CV risk in early childhood.

Maternal hemodynamic evaluation in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.

BACKGROUND: Maternal cardiovascular adaptations are amplified in twin pregnancies to support the metabolic request of the feto-placental unit. Few studies have evaluated the maternal hemodynamics changes after routine use of laser surgery in the treatment of twin-twin transfusion syndrome. OBJECTIVE: The aim of our study was to evaluate hemodynamic changes in monochorionic twin pregnancies complicated by twin-twin transfusion syndrome before and after treatment with fetoscopic laser surgery. STUDY DESIGN: A prospective observational study from 2020 to 2022, included monochorionic twin pregnancies complicated with twin-twin transfusion syndrome undergoing laser surgery between 16 and 26 weeks of gestation. To assess placental function and perfusion, uterine artery pulsatility index, hemoglobin, hematocrit, and soluble fms-like tyrosine kinase-1/placental growth factor ratio sampling prelaser and 24 hours postlaser were measured. Echocardiography by a single cardiologist evaluated maternal hemodynamics at presurgery, 24 hours, and 1 week postlaser. Those data were crosswise compared with cardiovascular indices of uncomplicated monochorionic pregnancies recruited at the same gestational age using nonparametric tests. Moreover, we fitted random-intercept linear regression models to investigate maternal hemodynamic changes according to the amount of amniotic fluid drained during laser surgery. RESULTS: Forty-two twin-twin transfusion syndrome pregnancies with a median gestational age of 19.1 (17.4-20.9) weeks and 15 uncomplicated monochorionic pregnancies at the same gestational age were enrolled. Overall survival rate after laser was 72% with delivery at a median gestational age of 31.5 (27-34) weeks. Significant changes in blood chemistry and placental function were observed in the twin-twin transfusion syndrome group, along with alterations in arterial pressure, heart rate, cardiac output, and ventricular strain, eventually aligning with the uncomplicated group's values by 1 week postlaser. The amount of amniodrainage, with a 1000 ml cut-off, did not significantly impact hemodynamic parameters. Lastly, we detected a percentage of laser surgery complications in agreement with international literature and we did not record any maternal procedure-related problems. CONCLUSION: Our analysis highlighted that maternal cardiovascular status in monochorionic twin pregnancy complicated by twin-twin transfusion syndrome was more dynamic and; 1 week after fetoscopic laser ablation of placental anastomosis completed by amniodrainage, maternal hemodynamic parameters restored to values similar to uncomplicated monochorionic twin pregnancies.

A pediatric telecardiology system that facilitates integration between hospital-based services and community-based primary care.

INTRODUCTION: Telecardiology has emerged as a vital field within telemedicine, fostering collaboration between hospital and community medicine. This pilot study introduces an innovative pediatric telecardiology system, comprising a telecardiology system seamlessly integrated with a hospital telemedicine platform. A smooth flow of ECG execution, transmission, and reporting between Primary Care Pediatrician clinics and the hospital was tested as the primary objective. User experience surveys were also considered. METHODS: The study involved three Primary Care Pediatrician clinics, and the enrollment of children took place consecutively from January to July 2023. We integrated a digital electrocardiographic signal acquisition unit and online information transmission-capable tablets, that were provided to the pediatricians, with a telemedicine multitenant platform that facilitated the transmission of the patient's ECG data from the community to the Hospital Pediatric Cardiologist. RESULTS: A total of 158 children (80 M/78F, 8.9 ± 2.8 yrs) underwent ECG recording (78.5 % medical certificates, 21.5 % presence of symptoms) The transmission and reporting of ECGs were successfully completed in all cases, without technical issues. Normal findings on the ECG were demonstrated in 94.9 % of children. 70.8 % of respondents completed all parts of the survey. Respondents had a high level of education (90 %) and demonstrated excellent or good competence in using digital technologies (89 %). 51 % of respondents were not familiar with the term "Telemedicine" and 81 % of the cases had no previous telemedicine experience. 90 % of users were very satisfied or satisfied with the service. Connection problems (2.8 %) and concerns about the service's reliability compared to standard care (3.7 %) were mentioned as possible limitations of the telecardiology. CONCLUSIONS: Our pediatric telecardiology system offers a valuable diagnostic tool to enhance patient management in the community.

Cardiovascular Risk in Pediatrics: A Dynamic Process during the First 1000 Days of Life.

The early childhood period, encompassing prenatal and early stages, assumes a pivotal role in shaping cardiovascular risk factors. We conducted a narrative review, presenting a non-systematic summation and analysis of the available literature, focusing on cardiovascular risk from prenatal development to the first 1000 days of life. Elements such as maternal health, genetic predisposition, inadequate fetal nutrition, and rapid postnatal growth contribute to this risk. Specifically, maternal obesity and antibiotic use during pregnancy can influence transgenerational risk factors. Conditions at birth, such as fetal growth restriction and low birth weight, set the stage for potential cardiovascular challenges. To consider cardiovascular risk in early childhood as a dynamic process is useful when adopting a personalized prevention for future healthcare and providing recommendations for management throughout their journey from infancy to early adulthood. A comprehensive approach is paramount in addressing early childhood cardiovascular risks. By targeting critical periods and implementing preventive strategies, healthcare professionals and policymakers can pave the way for improved cardiovascular outcomes. Investing in children's health during their early years holds the key to alleviating the burden of cardiovascular diseases for future generations.

Paradigm shift in the treatment of tuberous sclerosis: Effectiveness of everolimus.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.

Long-Term Postnatal Follow-Up in Monochorionic TTTS Twin Pregnancies Treated with Fetoscopic Laser Surgery and Complicated by Right Ventricular Outflow Tract Anomalies.

Right ventricular outflow tract anomalies (RVOTAs), such as pulmonary stenosis (PS), pulmonary atresia (PA), and pulmonary insufficiency (PI), are typical cardiac anomalies in monochorionic twins, and they are complicated by twin-to-twin transfusion syndrome (TTTS). The aim of this study was to conduct a long-term postnatal cardiological evaluation of prenatal RVOTAs in monochorionic diamniotic twin pregnancies complicated by TTTS and treated with fetoscopic laser surgery (FLS) and to analyze possible prenatal predictors of congenital heart disease (CHD). Prenatal RVOTAs were retrospectively retrieved from all TTTS cases treated with FLS in our unit between 2009 and 2019. Twenty-eight prenatal cases of RVOTAs (16 PI, 10 PS, 2 PA) were observed out of 335 cases of TTTS. Four cases did not reach the postnatal period. CHD was present in 17 of the remaining 24 cases (70.8%), with 10 being severe (58.8%; 10/17); nine cases of PS required balloon valvuloplasty, and one case required biventricular non-compaction cardiomyopathy. The risk of major CHD increased with prenatal evidence of PS and decreased with the gestational age at the time of TTTS and with the prenatal normalization of blood flow across the pulmonary valve. Despite treatment with FLS, the majority of monochorionic diamniotic twin pregnancies complicated by TTTS with prenatal RVOTAs had CHD at long-term follow-up.

Effects of Endurance Exercise Intensities on Autonomic and Metabolic Controls in Children with Obesity: A Feasibility Study Employing Online Exercise Training.

Exercise is one of the major determinants of a healthy lifestyle, which is particularly important in childhood and serves as a powerful preventive tool. On the other hand, obesity and arterial hypertension rates are increasing in children, representing a huge risk for developing major cardiovascular and metabolic diseases in adult life. Of fundamental importance is the modality and volume of exercise required to obtain benefits. In this feasibility study, we considered a group of obese children, studied before and after a 12-week online exercise training program, and subdivided the participants into two groups considering the volume of exercise performed (above or below 1200 MET·min/week). This threshold level was applied in two different ways: subdivision A considered the total weekly physical activity volume (considering both time spent walking for at least 10 min consecutively and time spent performing structured exercise) and subdivision B considered only the weekly volume of structured exercise. We assessed autonomic and metabolic control and auxological and lifestyle parameters. We observed that the improved volume of structured exercise was associated with reduced arterial pressure percentile only in subdivision B and an improvement in markers of vagal and metabolic control was evident. Moreover, the 12-week online exercise training program, defined considering individual fitness level and progressively adapted as the goal was reached, proved to be sustainable from an economical and organizational point of view.

Longitudinal Anthropometry and Body Composition in Children With SARS-CoV-2-Associated Multisystem Inflammatory Syndrome.

OBJECTIVES: Acute coronavirus disease 2019 infection has been shown to negatively affect body composition among adult and malnourished or obesity children. Our aim is to longitudinally evaluate body composition in children affected by the Multisystem Inflammatory Syndrome (MIS-C). METHODS: In this cohort study, we recruited 40 patients affected by MIS-C, aged 2-18 years old, who were admitted in our clinic between December 2020 and February 2021. Physical examination for each participant included weight, height, body mass index (BMI) z score, circumferences, and skinfolds assessment. The same measurements were repeated during outpatient follow-up at 10 (T2), 30 (T3), 90 (T4), and 180 (T5) days after hospital discharge. Fat mass and fat free mass were calculated according to skinfolds predictive equations for children and adolescents. A control group was randomly selected among patients attending a pediatric nutritional outpatient clinic. RESULTS: BMI z score significantly decrease between preadmission and hospital discharge. Similarly, arm circumference z score, arm muscular area z score, and arm fat area z score significantly decreased, during hospital stay. Fat mass index (FMI) significantly increased over time, peaking at T3. Fat free mass index decreased during hospitalization. CONCLUSIONS: To the best of our knowledge, this is the first study to assess body composition in a numerically large pediatric MIS-C population from acute infection to 6 months after triggering event. FMI and anthropometric parameters linked to fat deposits were significantly higher 6 months after acute event. Thus, limiting physical activity and having sedentary lifestyle may lead to an accumulation of adipose tissue even in healthy children who experienced MIS-C and long hospitalization.

Benefits in Cardiac Function from a Remote Exercise Program in Children with Obesity.

Physical activity (PA) is a crucial factor in preventing and treating obesity and related complications. In this one-arm pre−post longitudinal prospective study, we evaluated the effects of a 12-week online supervised training program on cardiac morphology, function and blood pressure (BP) in children with obesity. The training program consisted of three sessions per week, each lasting 60 min. Advanced echocardiographic imaging (tissue Doppler and longitudinal strain analysis) was used to detect subclinical changes in heart function. Categorical variables were described as counts and percentages; quantitative variables as the mean and standard deviation (SD) as they were normally distributed (Shapiro−Wilks test). Pre−post comparisons were made with a paired t-test. A total of 27/38 (71%) enrolled patients (18M/9F, 11 ± 2 years) completed the training protocol and were considered in the analysis. At baseline, no hypertensive patient was noted; all echocardiographic variables were within the normal range. After training, we observed a significant reduction in BP parameters, including systolic BP values and Z-score, diastolic BP values, centiles and Z-score, and mean arterial pressure (all p < 0.05). Significant variations in echocardiographic interventricular septum (IVSd) thickness (p = 0.011), IVSd Z-score (p = 0.001), left ventricular (LV) end-diastolic diameter (p = 0.045), LV posterior wall thickness Z-score (p = 0.017), and LV global longitudinal strain (p = 0.016) were detected. No differences in LV diastolic function and right ventricular strain were noted. PA plays a decisive role in improving BP control and has benefits on left ventricle systolic function, representing a strategic approach to limit CV risk. Online exercise could be an excellent method of training in children with obesity.

Atrioventricular Block in Celiac Disease: An Unusual Clinical Presentation in a Child. A Case-Based Review.

Congenital or acquired atrioventricular block (AVB) is a rare disorder in the pediatric population, while celiac disease (CeD) is a common multisystemic autoimmune disorder that is characterized by intestinal manifestations as they are the typical clinical presentation. Sometimes CeD presents more complex multisystemic involvement which includes the heart. Cardiac involvement, such as dilated cardiomyopathy, myocarditis or conduction disease, have been mainly described in untreated adult patients with or without gastro-intestinal symptoms; rare cases of AVB and CeD have been also reported, particularly in association with extra-cardiac manifestations. We describe a case of a progressive acquired AVB block in a 4-year-old child, in which CeD was later diagnosed. A rapid and significantly improvement of the AVB grade has been obtained after the child started a strict gluten-free diet, and so we suggest including diagnostic exams for CeD in all of the children with acquired AVB.

SCN2A and arrhythmia: A potential correlation? A case report and literature review.

Variants in SCN2A, encoding the voltage-gated sodium channel Nav1.2, are commonly associated with developmental and epileptic encephalopathy. Although animal studies demonstrated a role for Nav1.2 in intraventricular conduction, heart anomalies have been only occasionally described in patients with SCN2A variants. In this report we trace the prenatal and neonatal history of a fetus/newborn with a de novo pathogenic variant in the SCN2A gene identified by prenatal trio whole-exome sequencing (WES). In addition to more typically SCN2A-associated neurological manifestations, the patient showed sustained tachyarrhythmia, potentially expanding the phenotypic spectrum associated with SCN2A variants and raising the question of whether cardiological assessment and prompt pharmacological intervention in SCN2A channelopathies to avoid heart complications might be beneficial. To the best of our knowledge, this represents the first clinical description of a SCN2A phenotype in a prenatal setting, as well as the first SCN2A diagnosis achieved by prenatal trio-WES approach.

Neurological Involvement in Multisystem Inflammatory Syndrome in Children: Clinical, Electroencephalographic and Magnetic Resonance Imaging Peculiarities and Therapeutic Implications. An Italian Single-Center Experience.

Objective: To describe neurological involvement in multisystem inflammatory syndrome in children (MIS-C) and to evaluate whether neurological manifestations are related to the degree of multiorgan involvement and inflammation. Methods: The authors conducted a retrospective analysis of clinical, electroencephalographic (EEG), neuroradiological (MRI), and CSF parameters in 62 children with MIS-C (45 M, age 8 months-17 years, mean age 9 years) hospitalized between October 1, 2020 and March 31, 2022. Results: Neurological involvement was documented in 58/62 (93.5%) patients. Altered mental status was observed in 29 (46.7%), focal neurological signs in 22 (35.4%), and non-specific symptoms in 54 (87%). EEG was performed in 26/62 children: 20 showed EEG slowing, diffuse or predominantly over the posterior regions. Ten patients underwent brain MRI: three showed a cytotoxic lesion of the corpus callosum. CSF analysis, performed in six patients, was normal. On the basis of the clinical and EEG findings, two profiles of neurological involvement were identified: 16/62 (26%) patients presented encephalitis with rapid-onset encephalopathy, focal neurological signs, and EEG slowing; 42/62 (68%) showed mild neurological involvement with mild or non-specific neurological signs. All patients received intravenous immunoglobulin and methylprednisolone (MTP), low-molecular-weight heparin, and therapeutic-dose anticoagulant treatment. Children with severe encephalopathy received intravenous MTP at 30 mg/kg/day for 3 days, obtaining rapid clinical and EEG improvement. Neurological assessment at discharge was normal in all cases. Children with encephalitis were younger than those without (median age 5 and 10 years, respectively); no differences between the two groups were found in the other parameters: comorbidities, fever, number of organs and systems involved, shock, hospitalization, pediatric intensive care unit admission, non-invasive ventilation, inotropic support, laboratory data. Conclusion: Neurological involvement in MIS-C is frequent but not serious in most cases: around two thirds of the affected children had mild and short-lasting symptoms. It seems to be related to age, but not to the degree of multiorgan involvement and inflammation. In children with acute immune-mediated encephalitis, the clinical picture was dominated by encephalopathy that disappeared with immunomodulatory therapy. Neurological assessment allowed timely diagnosis and treatment.

Effects of an Online Supervised Exercise Training in Children with Obesity during the COVID-19 Pandemic.

COVID-19 restrictions have dramatically reduced the active lifestyle and physical activity (PA) levels in the whole population, a situation that can contribute to weight gain and to develop obesity. To improve physical fitness (PF) in children with obesity during COVID-19 restrictions, sport specialists started to deliver physical training through tele-exercise. For these reasons, the aim of this study was to evaluate the effects of a 12-week online supervised training program in children with obesity on different PF components and PA levels. We enrolled a total of 40 Caucasian children (9 F/31 M; aged 11 ± 1.9 years) with obesity. The data collection consisted of a series of anthropometric measures, the PAQ-C questionnaire, and PF tests, valid and reliable tools to assess PF in children. We used a Wilcoxon's t-test and a Student's t-test, as appropriate, to assess the differences before and after the training protocol. A total of 37 patients completed the training protocol and were considered in the analysis. Our results show an improvement in all the PF tests, a reduction in the BMI z-score, the waist circumference, and in the waist-to-height ratio, and an increased PA level. In conclusion, the results of our study show that an online supervised training program is effective to promote PA, improving PF and reducing the BMI z-score in children with obesity.