Epidemiology of respiratory syncytial virus in a large pediatric hospital in Central Italy and development of a forecasting model to predict the seasonal peak.

BACKGROUND: Respiratory Syncytial Virus (RSV) is responsible for the majority of acute lower respiratory infections in infants and can affect also older age groups. Restrictions linked to the emergence of the SARS-CoV-2 pandemic and their subsequent lifting caused a change in the dynamics of RSV circulation. It is therefore fundamental to monitor RSV seasonal trends and to be able to predict its seasonal peak to be prepared to the next RSV epidemics. METHODS: We performed a retrospective descriptive study on laboratory-confirmed RSV infections from Bambino Gesù Children's Hospital in Rome from 1st January 2018 to 31st December 2022. Data on RSV-positive respiratory samples (n = 3,536) and RSV-confirmed hospitalizations (n = 1,895) on patients aged 0-18 years were analyzed. In addition to this, a SARIMA (Seasonal AutoRegressive Integrated Moving Average) forecasting model was developed to predict the next peak of RSV. RESULTS: Findings show that, after the 2020 SARS-CoV-2 pandemic season, where RSV circulation was almost absent, RSV infections presented with an increased and anticipated peak compared to pre-pandemic seasons. While mostly targeting infants below 1 year of age, there was a proportional increase in RSV infections and hospitalizations in older age groups in the post-pandemic period. A forecasting model built using RSV weekly data from 2018 to 2022 predicted the RSV peaks of 2023, showing a reasonable level of accuracy (MAPE 33%). Additional analysis indicated that the peak of RSV cases is expected to be reached after 4-5 weeks from case doubling. CONCLUSION: Our study provides epidemiological evidence on the dynamics of RSV circulation before and after the COVID-19 pandemic. Our findings highlight the potential of combining surveillance and forecasting to promote preparedness for the next RSV epidemics.

Transvenous lead advancement in pediatric pacing to overcome growth-induced lead straightening and stretching.

BACKGROUND: The stretching of the lead caused by somatic growth may lead to complications (dislodgement, fracture, failure) of transvenous leads implanted in pediatric patients. Atrial loop and absorbable ligatures may prevent it. Periodical lead advancement with lead pushing from the pocket may be an option to growth-induced stretching. Our aim was to analyze retrospectively the outcome of periodical transvenous lead advancement in children with pacemaker (PM). METHODS: A procedure of lead advancement was performed in patients with a single-chamber PM implanted for isolated congenital complete atrioventricular block or sinus node dysfunction with growth-induced lead straightening/stretching. The PM pocket was opened, the lead was released from subcutaneous adherences and was gently advanced to shape again a loop/semi-loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are described as median (25th-75th centiles). RESULTS: 14 patients with 13 VVIR and 1 AAIR PM implanted at 6.8 (5.9-8.0) years of age, 23 (19-26) kg, 118 (108-124) cm, underwent 30 advancement procedures, 1.5 (1.0-2.3) per patient, during follow-up [45 (35-63) months]. Delta between procedures was: 18 (14-25) months, 11 (7-13) cm, 6 (4-9) kg; 90% of leads were successfully advanced without complications. Three unsuccessful procedures occurred with longer times [30 (14-37) months]. Electrical lead parameters did not show significant differences pre-/post-procedures. CONCLUSION: the advancement of transvenous leads in children seems safe and effective. This procedure may be another possible choice to preserve transvenous lead position and function until growth has completed.

Adrenocortical function in patients with Single Large Scale Mitochondrial DNA Deletions: a retrospective single centre cohort study.

OBJECTIVE: Single Large Scale Mitochondrial DNA Deletions (SLSMDs), Pearson Syndrome (PS) and Kearns-Sayre Syndrome (KSS), are systemic diseases with multiple endocrine abnormalities. The adrenocortical function has not been systematically investigated with a few anecdotal reports of overt adrenal insufficiency (AI). The study aimed to assess the adrenocortical function in a large cohort of SLSMDs. DESIGN AND METHODS: A retrospective monocentric longitudinal study involved a cohort of 18 SLSMDs patients. Adrenocortical function was evaluated by baseline adrenocorticotrophic hormone (ACTH) and cortisol measurements and by high- (HDT) and low-dose (LDT) ACTH stimulation tests and compared with 92 healthy controls (HC). RESULTS: Baseline adrenocortical function was impaired in 39% of patients and by the end of the study, 66% of PS and 25% of KSS showed an insufficient increase after ACTH stimulation, with cortisol deficiency due to primary AI in most PS and subclinical AI in KSS. Symptomatic AI was recorded in 44% of patients. Peak cortisol levels after ACTH stimulation tests were significantly lower in patients than in HC (P < .0001), with a more reduced response to LDT vs HDT (P < .05). CONCLUSIONS: Our study highlights that cortisol deficiency due to primary AI represents a relevant part of the clinical spectrum in SLSMDs, with more severe impairment in PS than in KSS. Basal and after-stimulus assessment of adrenocortical axis should be early and regularly investigated to identify any degree of adrenocortical dysfunction. The study allowed the elaboration of a diagnostic process designed for the diagnosis, treatment, and follow-up of adrenocortical abnormalities in SLSMDs.

Insulin Clearance at the Pubertal Transition in Youth with Obesity and Steatosis Liver Disease.

No data are available on insulin clearance (ClI) trends during the pubertal transition. The aim of this study was to investigate in 973 youths with obesity whether ClI in fasting and post-oral glucose challenge (OGTT) conditions varies at the pubertal transition in relation to the severity of obesity and the presence of steatosis liver disease (SLD). The severity of obesity was graded according to the Centers for Disease Control. SLD was graded as absent, mild and severe based on alanine amino transferase levels. ClI was defined as the molar ratio of fasting C-peptide to insulin and of the areas under the insulin to glucose curves during an OGTT. In total, 35% of participants were prepubertal, 72.6% had obesity class II, and 52.6% had mild SLD. Fasting ClI (nmol/pmol × 10-2) was significantly lower in pubertal [0.11 (0.08-0.14)] than in prepubertal individuals [0.12 (0.09-0.16)] and higher in class III [0.15 (0.11-0.16)] than in class I obesity [0.11 (0.09-0.14)]. OGTT ClI was higher in boys [0.08 (0.06-0.10)] than in girls [0.07 (0.06-0.09)]; in prepubertal [0.08 (0.06-0.11)] than in pubertal individuals [0.07 (0.05-0.09)]; in class III [0.14 (0.08-0.17)] than in class I obesity [0.07 (0.05-0.10)]; and in severe SLD [0.09 (0.04-0.14)] than in no steatosis [0.06 (0.04-0.17)]. It was lower in participants with prediabetes [0.06 (0.04-0.07)]. OGTT ClI was lower in youths with obesity at puberty along with insulin sensitivity and greater secretion. The findings suggest that the initial increase in ClI in youth with severe obesity and SLD is likely to compensate for hyperinsulinemia and its subsequent decrease at the onset of prediabetes and other metabolic abnormalities.

Left ventricular endocardial activation maps during right ventricular pacing in pediatric patients.

BACKGROUND: Cardiac pacing from right ventricular (RV) sites may cause electromechanical ventricular dyssynchrony. Invasive and noninvasive mapping studies showed left ventricular (LV) activation sequence in adults. Aim of this study was to seek out the LV endocardial activation (LVEA) in pediatric patients who underwent RV pacing. METHODS: Single-center, prospective study conducted on pediatric patients who underwent left sided catheter ablation of accessory pathways with the Carto Univu mapping system. After successful ablation procedures, LVEA was recorded by the ablation catheter during sinus rhythm (SR) and during para-hisian (PHP), midseptum (MSP), and apical (RVAP) pacing. RESULTS: Seventeen patients, 13 males, aged 12 (10-15) years, registered LV activation maps and times (LVAT). SR showed significantly shorter LVAT than during pacing. LVAT of PHP was shorter than MSP, while there were not significant differences among PHP and MSP versus RVAP. In SR initial LV endocardial activation occurred in two midseptum sites, inferior-posterior and superior-anterior. During PHP, initial activation occurred at parahisian basal septum, rapidly followed by midseptum as in SR. During MSP and RVAP initial activation occurred at midseptum and apex, respectively. From all initial sites, the excitation spreads toward the base of the lateral LV free wall. A mild linear correlation was found between QRS duration and LVAT for MSP and for PHP. CONCLUSIONS: In pediatric patients LVEA maps during RV pacing showed that the shortest LVAT was obtained with PHP. The LV activation pattern seemed similar in sinus rhythm, PHP and MSP, from midseptum to LV lateral base.

Decreased incidence of late-onset sepsis during the SARS-CoV-2 pandemic in Italy: a multicentric study on a cohort of infants requiring major surgery.

Changes in the organization of the clinical care wards, requested by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, have influenced the environmental circulation of other pathogens. The implementation of prevention procedures may have led to a decrease in the incidence of healthcare-associated infections. We aimed to investigate the impact of prevention and control measures for preventing the COVID-19 spread on the incidence of bacterial sepsis and invasive fungal infections in neonates and infants requiring major surgery. We compared the incidence of bacterial and fungal sepsis and their risk factors observed before the SARS-CoV-2 pandemic (from 01/10/2018 to 29/02/2020) with those observed during the pandemic (from 01/03/2020 to 07/05/2021) in 13 level III Neonatal Intensive Care Units in Italy, through a secondary analysis of data, collected during a prospective multicenter study (REF). The patients enrolled were infants within three months of life, hospitalized in the two periods in the participating centers to undergo major surgery. Among 541 enrolled patients, 324 (59.9%) were born in the pre-pandemic period and 217 (40.1%) during the pandemic. The incidence density (ID) of any infection in the pre-pandemic period was 16.0/1000 patient days versus 13.6/1000 patient days in the pandemic period (p < 0.001). One hundred and forty-five (145/324; 44.8%) patients developed at least one episode of bacterial sepsis in the pre-pandemic period, versus 103/217 (31.8%) patients, during the pandemic (p = 0.539). Concerning fungal sepsis, 12 (3.7%) patients had one episode in the pre-pandemic period versus 11 (5.1%) patients during the pandemic (p = 0.516). The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics pre-surgery, and that of proton pump inhibitors during the SARS-CoV-2 pandemic compared with the previous period. CONCLUSIONS: In our cohort of patients with major surgical needs, the reduction of CVC days, pre-surgery antibiotics administration, and current use of proton pump inhibitors, during the SARS-CoV-2 pandemic, led to a decrease in the incidence of late-onset sepsis. WHAT IS KNOWN: • Most cases of late-onset sepsis in neonates are referred to as central line-associated bloodstream infections. • In adults, the COVID-19 outbreak negatively influenced healthcare-associated infection rates and infection clusters within hospitals. WHAT IS NEW: • In neonates and infants undergoing major surgery the incidence density of infections was lower in the pandemic period than before. • The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics before surgery, and that of proton pump inhibitors during the pandemic compared with previously.

Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy.

BACKGROUND: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation. METHODS: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women. RESULTS: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff -1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff -0.9; p = 0.03), C22:0 (coeff -0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff -86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 × 10-5), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06). CONCLUSIONS: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes.

Age and memory B cells at baseline are associated with risk of relapse and memory B-cell reappearance following anti-CD20 treatment in pediatric frequently-relapsing/steroid-dependent nephrotic syndrome.

B-cell depleting anti-CD20 monoclonal antibodies, such as rituximab, have proven efficacy in children with frequently-relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). However, drug-free remission is variable and specific baseline markers predictive of relapse after anti-CD20 treatment are still being defined. To clarify these, we performed a bicentric observational study in a large cohort of 102 children and young adults with FR/SDNS treated with anti-CD20 monoclonal antibodies (rituximab and ofatumumab). Sixty-two patients (60.8%) relapsed during a 24-month period (median [interquartile range] relapse-free survival, 14.4 months [7.9-24.0]). A lower risk of relapse was significantly associated with an older age (over 9.8 years, hazard ratio, 0.44; 95% confidence interval, 0.26-0.74) and a higher risk of relapse was significantly associated with higher circulating levels of memory B cells (1.14; 1.09-1.32) at time of anti-CD20 infusion, independent of time elapsed from onset, previous anti-CD20 treatment, type of administered anti-CD20 monoclonal antibodies, and previous or maintenance oral immunosuppression. Patients younger than 9.8 years at anti-CD20 infusion had a subsequent higher recovery of total, transitional, mature-naïve and memory B-cell subsets independent of previous anti-CD20 treatment and maintenance immunosuppression. Significantly, younger age and higher circulating levels of memory B cells at time of anti-CD20 infusion were also independently associated with the recovery of memory B cells by linear mixed-effects modelling. Thus, both younger age and higher circulating levels of memory B cells at time of infusion are independently associated with a higher risk of relapse and an earlier recovery of memory B cells following anti-CD20 treatment in children with FR/SDNS.

Acute respiratory infection emergency access in a tertiary care children hospital in Italy, prior and after the SARS-CoV-2 emergence.

Background: The COVID-19 pandemic has changed the epidemiology of acute respiratory infections (ARIs) in children. The aims of the present study were to describe the epidemiological trend of ARI emergency visits and virology results prior and after the SARS-CoV-2 emergence and to estimate the association of ARI emergency department (ED) visits with respiratory viruses. Methods: This study was conducted at the Bambino Gesù Children's Hospital, a tertiary care children's hospital in the Lazio Region, Italy. The demographic and clinical information of children who accessed the ED and were diagnosed with ARI from January 1, 2018 to June 30, 2022 was retrospectively extracted from the electronic health records. The observed temporal trends in viruses diagnosed from respiratory samples were compared with the number of ARI ED visits over the same period through a multivariable linear regression model. Results: During the study period, there were 72,959 ED admissions for ARIs and 33,355 respiratory samples resulted positive for viruses. Prior to the pandemic, respiratory syncytial virus (RSV) and influenza had a clear seasonal pattern, which was interrupted in 2020. In 2021-2022, RSV reached the highest peak observed during the study period, whereas influenza activity was minimal. The peaks of ARI ED visits corresponded to peaks of influenza, RSV, and rhinovirus in the 2018-2019 and 2019-2020 seasons, to SARS-CoV-2 and rhinovirus in 2020, and to RSV and parainfluenza in 2021-2022. Conclusions: ARI resulting in ED visits should be included in the ARI disease burden measurement for a more accurate measure of the impact of preventive measures.

Three-dimensional-mapping-guided permanent conduction system pacing in paediatric patients with congenitally corrected transposition of the great arteries.

AIMS: In congenitally corrected transposition of the great arteries (CCTGA) the right ventricle (RV) is systemic. Atrioventricular block (AVB) and systolic dysfunction are frequently observed. Permanent pacing of the subpulmonary left ventricle (LV) may worsen RV dysfunction. The aim of this study was to seek out if LV conduction system pacing (LVCSP) guided by three-dimensional-electroanatomic mapping systems (3D-EAMs) can preserve RV systolic function in paediatric CCTGA patients with AVB. METHODS AND RESULTS: Retrospective analysis of CCTGA patients who underwent 3D-EAM-guided LVCSP. Three-dimensional-pacing map guided lead implantation towards septal sites with narrower paced QRS. Electrocardiograms (ECGs), echocardiograms, and lead parameters (threshold, sensing, and impedance) were compared at baseline (pre-implantation) and at 1-year follow-up. Right ventricle function was evaluated by 3D ejection fraction (EF), fractional area change (FAC), RV global longitudinal strain (GLS). Data are reported as median (25th-75th centiles). Seven CCTGA patients aged 15 (9-17) years, with complete/advanced AVB (4 with prior epicardial pacing), underwent 3D-guided LVCSP (5 DDD, 2 VVIR). Baseline echocardiographic parameters were impaired in most patients. No acute/chronic complications occurred. Ventricular pacing was >90%. At 1-year follow-up QRS duration showed no significant changes compared with baseline; however, QRS duration shortened in comparison with prior epicardial pacing. Lead parameters remained acceptable despite ventricular threshold increased. Systemic RV function was preserved: FAC and GLS improved significantly, and all patients showed normal RV EF (>45%). CONCLUSION: Three-dimensional-EAM-guided LVCSP preserved RV systolic function in paediatric patients with CCTGA and AVB after short-term follow-up.

Preliminary Evaluation of Sedentary Lifestyle in Italian Children after Solid Transplant: What Role Could Physical Activity Play in Health? It Is Time to Move.

BACKGROUND: Advances in the medical-surgical field have significantly increased survival after solid organ transplantation in the pediatric population. However, these patients are predisposed to the development of long-term complications (e.g., cardiovascular disease). The therapeutic role of physical activity (PA) to counteract these complications is well known. The purpose of the study was to investigate the level of PA in a pediatric population after solid organ transplantation. METHODS: In the first 4 weeks at the beginning of the school year, the Physical Activity Questionnaire for Older Children and Adolescents was administered to young patients who had previously undergone solid transplants at our institute. RESULTS: Questionnaires of 49 patients (57.1% female, mean age 13.2 ± 3.5 years) were analyzed and 32.7% of subjects did not perform any exercise during school physical education classes. Only 24% practiced a moderate quantity of exercise in the previous week (2-3 times/week) and 72% engaged in sedentary behaviors during weekends. CONCLUSIONS: Preliminary data confirmed that young recipients are still far from meeting the minimum indications of the World Health Organization on PA and sedentary behavior. It will be necessary to increase their involvement in PA programs in order not only to increase their life expectancy but also to improve their quality of life.

To go left or right? Driving towards the best direction in paediatric pacing.

BACKGROUND: Permanent pacing in children with isolated congenital complete atrioventricular block may cause left ventricular dysfunction. To prevent it, alternative pacing sites have been proposed: left ventricular epicardial or selective right ventricular endocardial pacing. AIMS: To compare the functional outcome (left ventricular systolic function and synchrony) in paediatric patients with congenital complete atrioventricular block and left ventricular apical epicardial or right ventricular transvenous mid-septal pacing. METHODS: Retrospective study. Epicardial leads were implanted by standard surgical technique, transvenous leads by 3D electroanatomic mapping systems. 3D mapping acquired 3D right ventricular local pacing map and defined the narrowest paced QRS site. 3D mapping guided screw-in bipolar leads on that ventricular site. Electrocardiogram (ECG) (QRS duration) and echocardiographic data (synchrony: interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index; contractility: global longitudinal strain, ejection fraction) were recorded. Data are reported as median [interquartile ranges]. p < 0.05 was significant. RESULTS: There were 19 transvenous systems (age 8.8 [6-14] years; right ventricular mid-septum) and 17 epicardial systems (0.04 [0.001-0.6] years; left ventricular apex). Post-implantation QRS significantly widened either in endocardial or in epicardial patients. Most patients reached 4-year follow-up. One-year and 4-year ejection fraction and global longitudinal strain were mostly within normal limits and did not show significant differences between the two groups and between the same endocardial/epicardial group. Synchrony parameters were within normal limits in the two groups. CONCLUSIONS: Left ventricular apical epicardial pacing and 3D mapping-guided right ventricular mid-septal pacing preserved left ventricular contractility and synchrony in children and adolescents with congenital complete atrioventricular block at short-/mid-term follow-up, without relevant significant differences between the two groups.

The burden of central line-associated bloodstream infections in children with medical complexity.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) are significant cause of complications in pediatric intensive care units (PICUs). An emerging challenge are CLABSIs in children with medical complexity (CMC) admitted to PICU. CMC are patients with chronic conditions with or without neurological impairment needing for tracheostomy and/or home mechanical or non-invasive ventilation and/or gastrostomy/jejunostomy. We evaluate CLABSI incidence in a PICU with high prevalence of CMC. METHODS: This was a retrospective study in the PICU of the Bambino Gesù Children Hospital from January 2017 to December 2020. The medical records were reviewed and demographic, clinical and microbiological data were extracted. CLABSI were defined according to the Center for Disease Control and Prevention's National Healthcare Safety Networks (NHSN) surveillance. RESULTS: A total of 101 children with 125 central lines (CLs) were included; 79/101 (78%) patients were CMC and 50/101 (50%) had a thracheostomy. CLABSI incidence was 2.75/1000 CL-days (9 cases/3269 CL-days); incidence was 0 in patients without underling conditions and 3.14/1000 in CMC (p < 0.001). CLABSI were due to gram negative bacteria in five patients, Candida spp in three and Staphylococcus hominis in one. CLs were removed in eight cases while in the later one, with CLABSI due to Pseudomonas aeruginosa, a conservative strategy was adopted cause of unavailable alternative venous access and removed at discharge with negative culture. All patients recovered. CONCLUSIONS: A target 0% CLABSI was possible in critically ill children without underling condition while a high incidence was reported in CMC and sustained by a peculiar CLABSI ecology. This ecology should be considered when a CLABSI was suspected in CMC for prompt antibiotics stewardship.

Escalation of care in children at high risk of clinical deterioration in a tertiary care children's hospital using the Bedside Pediatric Early Warning System.

BACKGROUND: Escalation and de-escalation are a routine part of high-quality care that should be matched with clinical needs. The aim of this study was to describe escalation of care in relation to the occurrence and timing of Pediatric Intensive Care Unit (PICU) admission in a cohort of pediatric inpatients with acute worsening of their clinical condition. METHODS: A monocentric, observational cohort study was performed from January to December 2018. Eligible patients were children: 1) admitted to one of the inpatient wards other than ICU; 2) under the age of 18 years at the time of admission; 3) with two or more Bedside-Paediatric-Early-Warning-System (BedsidePEWS) scores ≥ 7 recorded at a distance of at least one hour and for a period of 4 h during admission. The main outcome -the 24-h disposition - was defined as admission to PICU within 24-h of enrolment or staying in the inpatient ward. Escalation of care was measured using an eight-point scale-the Escalation Index (EI), developed by the authors. The EI was calculated every 6 h, starting from the moment the patient was considered eligible. Analyses used multivariate quantile and logistic regression models. RESULTS: The 228 episodes included 574 EI calculated scores. The 24-h disposition was the ward in 129 (57%) and the PICU in 99 (43%) episodes. Patients who were admitted to PICU within 24-h had higher top EI scores [median (IQR) 6 (5-7) vs 4 (3-5), p < 0.001]; higher initial BedsidePEWS scores [median (IQR) 10(8-13) vs. 9 (8-11), p = 0.02], were less likely to have a chronic disease [n = 62 (63%) vs. n = 127 (98%), p < 0.0001], and were rated by physicians as being at a higher risk of having a cardiac arrest (p = 0.01) than patients remaining on the ward. The EI increased over 24 h before urgent admission to PICU or cardiac arrest by 0.53 every 6-h interval (CI 0.37-0.70, p < 0.001), while it decreased by 0.25 every 6-h interval (CI -0.36-0.15, p < 0.001) in patients who stayed on the wards. CONCLUSION: Escalation of care was related to temporal changes in severity of illness, patient background and environmental factors. The EI index can improve responses to evolving critical illness.

Differences and Similarities in Adaptive Functioning between Children with Autism Spectrum Disorder and Williams-Beuren Syndrome: A Longitudinal Study.

BACKGROUND: The last decade has seen a growing number of comparative studies on adaptive profiles between individuals with autism spectrum disorder (ASD) and Williams-Beuren syndrome (WBS), showing shared and syndrome-specific adaptive trajectories. Studies have revealed similarities in global adaptive profiles across conditions, while some differences have been found in preschoolers on the specific sub-domains of communication and socialization. However, the majority of studies that have focused on the differences in adaptive functioning across these two conditions used a cross-sectional design. To the best of our knowledge, there are no studies exploring the differences and similarities of adaptive functioning over time. METHODS: We compared longitudinal data of adaptive functioning measured by Vineland Adaptive Behavior Scales (VABS) between two samples of children and adolescents with ASD and WBS, matched for chronological age and cognitive/developmental level at the time of the first evaluation. RESULTS AND CONCLUSIONS: We did not find any difference on the global adaptive level, both at the first evaluation and over time. However, significant differences emerged on the socialization and communication levels at the time of recruitment. Longitudinal data show that only the socialization domain remains different over time, with individuals with WBS having better functioning than those with ASD. The results on shared and distinct patterns of adaptive functioning between disorders are discussed from a developmental perspective, thus contributing to the implementation of age-specific interventions.

Late outcome of extracardiac Fontan patients: 32 years of follow-up.

OBJECTIVES: We sought to evaluate the long-term survival and risk factors for morbidity and mortality in our cohort of patients after extracardiac (EC) Fontan. METHODS: We collected and analysed follow-up data until September 2020 for all patients who underwent EC Fontan operation at our institution from November 1988 to November 2015. RESULTS: Out of 406 patients treated with EC Fontan at a mean age of 5.4 ± 4.5 years, 372 (91.6%) were discharged home; 15% were lost to follow-up. The median follow-up was 14.6 years (interquartile range 8.7-20.3). Two hundred patients (54%) had a good long-term outcome, with an event-free long-term survival, but late adverse events of any kind needing interventional or surgical reoperations were reported in 128 patients (34%). Forty-four patients (12%) developed late Fontan failure. Thirty-seven survivors (10%) had late arrhythmias, with the need for pacemaker implantation. Obstruction of the cavopulmonary pathway occurred in 49 patients (13%), but just 8 patients needed conduit surgical replacement. At 32 years, the survival probability was 84%. The risk of orthotopic heart transplant, considering death as a competing event (showed as cumulative incidence), was 12.5%. A preoperative diagnosis of hypoplastic left heart syndrome was an independent risk factor for the need for heart transplant. CONCLUSIONS: The EC Fontan shows satisfactory long-term survival and low incidence of adverse events and late failure. Conduit replacement is rare, and its longevity may not represent a substantial issue in these patients. However, as with other technical variants, the need for reoperations during long-term follow-up is a significant challenge.

ICD Outcome in Pediatric Cardiomyopathies.

BACKGROUND: Pediatric patients with cardiomyopathies are at risk of malignant arrhythmias and sudden cardiac death (SCD). An ICD may prevent SCD. The aim of this study was to evaluate ICD implantation outcomes, and to compare transvenous and subcutaneous ICDs (S-ICDs) implanted in pediatric patients with cardiomyopathies. METHODS: The study is single center and retrospective, and includes pediatric patients with cardiomyopathies who required ICD implantation (2010-2021). Outcomes were recorded for appropriate/inappropriate ICD therapy and surgical complications. Transvenous ICD and S-ICD were compared. Data are presented as median values (25th-75th centiles). RESULTS: Forty-four patients with cardiomyopathies (hypertrophic 39%, arrhythmogenic 32%, dilated 27%, and restrictive 2%) underwent transvenous (52%) and S-ICD (48%) implantation at 14 (12-17) years of age, mostly for primary prevention (73%). The follow-up period was 29 (14-60) months. Appropriate ICD therapies were delivered in 25% of patients, without defibrillation failures. Lower age at implantation and secondary prevention were significant risk factors for malignant ventricular arrhythmias that required appropriate ICD therapies. ICD-related complications were surgical complications (18%) and inappropriate shocks (7%). No significant differences in outcomes were recorded, either when comparing transvenous and S-ICD or comparing the different cardiomyopathies. CONCLUSIONS: In pediatric patients with cardiomyopathy, ICD therapy is effective, with a low rate of inappropriate shocks. Neither ICD type (transvenous and S-ICDs) nor the cardiomyopathies subgroup revealed divergent outcomes.

Prevalence of prediabetes in children and adolescents by class of obesity.

BACKGROUND: To evaluate prevalence of prediabetes (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; and high glycated haemoglobin, h-HbA1c) in children and adolescents in relation to class of age and obesity; to appraise association with estimates of insulin metabolism, cardiovascular risk factors and alanine aminotransferase (ALT) levels. METHODS: Study of marginal prevalence (i.e., as function of sex, age and obesity class) of isolated and combined IFG, IGT and h-HbA1c in children (age 4-9.9 years) and adolescents (age 10-17.9 years) and association to blood pressure (BP), total, HDL and non-HDL cholesterol, triglycerides, ALT and insulin sensitivity/secretion indexes. RESULTS: Data of 3110 participants (51% males, 33% children; 33% overweight, 39% obesity class I, 20.5% class II, 7.5% class III) were available. Unadjusted prevalence of prediabetes was 13.9% in children (2.1% IFG, 6.7% IGT, 3.9% h-HbA1c, IFG-IGT 0.06%) and 24.6% in adolescents (3.4% IFG, 9.4% IGT, 5.5% h-HbA1c, IFG-IGT 0.09%). Combined h-HBA1c was found in very few adolescents. Prevalence of prediabetes increased significantly by class of obesity up to 20.5% in children and 31.6% in adolescents. Phenotypes of prediabetes were differently but significantly associated with increased systolic and diastolic BP (by 2-7.3 and ~8 mmHg, respectively), triglycerides (by 23-66 mg/dl), and ALT levels (by 10-22 UI/L) depending on the prediabetes phenotype. CONCLUSION AND RELEVANCE: It is worth screening prediabetes in children aged <10 years old with obesity classes II and III and in adolescents. In those with prediabetes, monitoring of blood pressure, triglycerides and ALT levels must be encouraged.

A decade of insertable cardiac monitors with remote monitoring in pediatric patients.

BACKGROUND: Remote monitoring-enabled insertable cardiac monitors (ICMs) are useful tools for arrhythmias and symptom management. This study sought to evaluate the outcome of ICM implantation in a large, heterogeneous cohort of pediatric and young adult patients. METHODS: Single centre, retrospective analysis of patients who underwent ICM implantation in 2010-2019. Patients were analysed according to age, symptoms, arrhythmias and underlying heart disease. RESULTS: A total of 200 consecutive patients (58% male), aged 11.5 ± 5.8 years at ICM implantation, were included. Follow-up was 31 ± 18 months. Electrophysiologic study (EPS) was initially performed in 123 patients and was negative in 85%. Patients had no heart disease (57.5%), congenital heart defects (21%), channelopathies (14.5%), cardiomyopathies/heart tumors (8%). The commonest symptoms were syncope/presyncope (45.5%) and palpitations (12.5%). A definite diagnosis was made in 63% of patients (positive diagnosis in 25%, negative in 38%) after 8 (2-19) months of monitoring. EPS results and the presence/absence of an arrhythmia before ICM implantation had no impact on the diagnostic yield. Symptomatic patients as well as patients without structural heart disease showed higher diagnostic yield. Patients with a positive diagnosis underwent pacemaker/implantable cardioverter-defibrillator implantation (13%), pharmacological treatment (10.5%), or catheter ablation (1.5%). CONCLUSIONS: In a large cohort of 200 children and young adults, ICMs with remote monitoring showed a high diagnostic yield (63%), especially in symptomatic patients and in patients without structural heart disease.

Estimated insulin sensitivity, cardiovascular risk, and hepatic steatosis after 12 years from the onset of T1D.

AIM: To test the hypothesis that intensive insulin treatment and optimal glycaemic control are not fully protective against reduction of insulin sensitivity in children with type 1 diabetes. MATERIAL AND METHODS: Cohort study of 78 normal-weight patients with prepubertal onset (T0 ) and follow-up waves at 1 (T1 ), 5 (T5 ), 10 (T10 ), and 12 (T12 ) years; matched for age and sex to 30 controls at T12 . Estimated insulin sensitivity (eIS) by three formulae; ultrasound evaluation of para and perirenal fat thickness; hepatic steatosis (HS); carotid intima media thickness (cIMT) at T12 . RESULTS: At T12, the 36 patients (46%) who had constantly or prevalently haemoglobin A1c (HbA1c) < 58 mmol/l during follow-up showed better eIS indexes (p = 0.049 to <0.0001); lipid profile (p = 0.042 to <0.0001), reduced fat mass (p = 0.012) and required lower insulin dose (p = 0.032) than the 42 patients (54%) with HbA1c ≥ 58 at T12. Patients (N = 25) with eISEDC  < 8.77 mg kg-1  min-1 showed higher cIMT (p < 0.0001). HS was found in 6 patients (∼8%). In patients and normal-weight controls, fat mass (p = 0.03), age (p = 0.03), cIMT (p = 0.05) predicted HS; eIS indexes (p from 0.04 to <0.0001) predicted cIMT. Body mass index, perirenal fat, fat mass, and triglycerides to high density lipoprotein cholesterol ratio were associated with eIS indexes (p from 0.03 to <0.0001). CONCLUSIONS: Young T1D patients have reduced insulin sensitivity and higher cIMT. Adiposity, glucose, and lipid control over follow-up are likely to influence both. Enhanced adiposity seems of paramount relevance for the onset of HS in T1D patients alike in healthy youths.