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Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and lifethreatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied. Objective: This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management. Methods: A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria. Results: A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups. Conclusion: A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and lifethreatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied. Objective: This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management. Methods: A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria. Results: A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups. Conclusion: A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes. [ABSTRACT FROM AUTHOR]

Evidence about the impact of advanced hybrid closed loop (AHCL) on body mass index (BMI) and eating habits in children with type 1 diabetes (T1D) is lacking. This real-world study aimed at evaluating glycemic control, BMI, meals and basal/bolus distribution in young subjects with T1D treated by AHCL. Glycemic metrics, HbA1c, basal/bolus distribution, meals/day, BMI, total daily dose (TDD), and carbohydrates/kg (CHO/kg) have been evaluated in 83 subjects, aged 13 ± 4.5 years, in manual mode, 3 and 6 months after auto-mode. Time in range (TIR) increased after 3 months, exceeding the target of 70% and was maintained at 6 months. While coefficient of variation (CV) did not change, the glucose management indicator (GMI) decreased in auto-mode (6.7 ± 0.3 vs. 7.1 ± 0.5%; p < 0.001), as well as HbA1c. Basal proportion decreased in favor of boluses (38.3 ± 7.3 vs. 43.6 ± 10.9%; p < 0.001). Meals increased at 3 and 6 months (4.4 ± 1.2 vs. 5.0 ± 1.5, p 0.002 and 5.1 ± 1.7, p < 0.001), as well as TDD/kg, without changes in BMI and CHO consumed. No differences in meal composition have arisen from food diaries. In conclusion, AHCL ensured the achievement and maintenance of target TIR in young T1D subjects. The number of meals, TDD, and insulin bolus proportion increased over time, but BMI remained stable. [ABSTRACT FROM AUTHOR]

Background: Few studies have assessed the differences of patterns of Long COVID (L-COVID) with regards to the pathogenetic SARS-CoV-2 strains. Objectives: To investigate the relationship between demographic and clinical characteristics of acute phase of infection and the persistence of L-COVID symptoms and clinical presentation across different SARS-CoV-2 strains. Methods: In this observational-multicenter study we recorded all demographic and clinical characteristics, severity of infection, presence/persistence of symptoms of fatigue, dyspnoea and altered quality of life (QoL) at baseline and after 6 months, in a sample of Italian patients from Liguria between March 2020 and March 2022. Results: 308 patients (mean age 63.2 years; 55.5% men) with previous COVID were enrolled. Obese patients were 21.2% with a significant difference in obesity prevalence across the second and third wave (p = 0.012). Treatment strategies differed between waves (p < 0.001): more patients required invasive mechanical ventilation in the first wave, more patients were treated with high-flow nasal cannula/non-invasive ventilation in the in the second and more patients were treated with oxygen-therapy in the fourth wave. At baseline, a high proportion of patients were symptomatic (dyspnoea and fatigue), with impairment in some QoL indicators. A higher prevalence of patients with pain, were seen in the first wave compared to later infections (p = 0.01). At follow-up, we observed improvement of dyspnoea, fatigue and some dimensions of QoL scale evaluation such as mobility, usual activities, pain evaluations; instead there was no improvement in remaining QoL scale indicators (usual care and anxiety-depression). Conclusions: There were no significant differences in the prevalence of the most frequent L-COVID symptoms, except for QoL pain domain that was especially associated with classical variant. Our results show substantial impact on social and professional life and usual care activities. These findings highlight the importance of multidisciplinary post COVID follow-up care including mental health support and rehabilitation program. [ABSTRACT FROM AUTHOR]

Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulinlike growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism (CH) is a relatively frequent congenital endocrine disorder, caused by defective production of thyroid hormones (THs) at birth. Because THs are essential for the development of normal neuronal networks, CH is also a common preventable cause of irreversible intellectual disability (ID) in children. Prolonged hypothyroidism, particularly during the THs-dependent processes of brain development in the first years of life, due to delays in diagnosis, inadequate timing and dosing of levothyroxine (l-thyroxine or l-T4), the non-compliance of families, incorrect follow-up and the interference of foods, drugs and medications affecting the absorption of l-T4, may be responsible for more severe ID. In this review we evaluate the main factors influencing levels of THs and the absorption of l-T4 in order to provide a practical guide, based on the existing literature, to allow optimal follow-up for these patients. [ABSTRACT FROM AUTHOR]

Objective: over the last few decades there has been a progressive decline in the average age of onset of pubertal development stages in both sexes. The increase in the prevalence of childhood obesity seems to play an important role in this phenomenon. Design: we undertook a retrospective, longitudinal evaluation of the average age of thelarche and menarche to evaluate the relationship between BMI and weight change during the first years of life and the timing and tempo of puberty. Methods: we evaluated data for 577 Italian girls born between 1995 and 2003. We collected the main auxological and clinical parameters, including age at B2 and at menarche, BMI SDS at B2 and menarche, gestational age and birth weight and Z-score change from birth weight (BW) to BMI at B2 and menarche. Results: the mean age of B2 was 10.06 ± 1.03 years and the mean age of menarche was 12.08 ± 1.02 years. Age at B2 and menarche were inversely correlated with BMI SDS (p < 0.0001). Both age at menarche and at thelarche have an inverse relationship with the Z-score change from birth weight and BMI at menarche and thelarche respectively (p < 0.0001). Conclusions: our data confirm a significant relationship between BMI and age of B2 and menarche. We observed a clear relationship among weight change during the first years of life, age at thelarche and menarche and the duration of puberty, demonstrating the importance of weight and weight gain in determining the timing and tempo of pubertal changes and growth. [ABSTRACT FROM AUTHOR]

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The purpose of this study is to assess psychosocial risk across several pediatric medical conditions and test the hypothesis that different severe or chronic pediatric illnesses are characterized by disease specific enhanced psychosocial risk and that risk is driven by disease specific connectivity and interdependencies among various domains of psychosocial function using the Psychosocial Assessment Tool (PAT). In a multicenter prospective cohort study of 195 patients, aged 5–12, 90 diagnosed with acute lymphoblastic leukemia (ALL), 42 with epilepsy and 63 with asthma, parents completed the PAT2.0 or the PAT2.0 generic version. Multivariate analysis was performed with disease as factor and age as covariate. Graph theory and network analysis was employed to study the connectivity and interdependencies among subscales of the PAT while data-driven cluster analysis was used to test whether common patterns of risk exist among the various diseases. Using a network modelling approach analysis, we observed unique patterns of interconnected domains of psychosocial factors. Each pathology was characterized by different interdependencies among the most central and most connected domains. Furthermore, data-driven cluster analysis resulted in two clusters: patients with ALL (89%) mostly belonged to cluster 1, while patients with epilepsy and asthma belonged primarily to cluster 2 (83% and 82% respectively). In sum, implementing a network approach improves our comprehension concerning the character of the problems central to the development of psychosocial difficulties. Therapy directed at problems related to the most central domain(s) constitutes the more rational one because such an approach will inevitably carry over to other domains that depend on the more central function. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Galego de Literatura is the property of Universidad de Santiago de Compostela, Servicio de Publicaciones and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although the number of research reactors (RRs) is steadily decreasing, more than half of the operational RRs are still heavily underutilized, and in most cases, underfunded. The decreasing and rather old fleet of RRs needs to ensure the provision of useful services to the community, in some cases with adequate revenue generation for reliable, safe and secure facility management and operations. Enhancement of low and medium power research reactor (RR) utilization is often pursued by increasing the neutron activation analysis (NAA) activities. In this paper we will present the strategy and concrete actions how NAA as one of the most popular RR applications can contribute to the above goals in particular through (a) RR coalitions and networks, (b) implementation of automation in different stages of NAA, (c) QA/QC, including skills improvement of involved personnel, (d) dedicated proficiency tests performed by a number of targeted analytical laboratories. We also show that despite the IAEA's efforts, some of the NAA laboratories still perform badly in proficiency tests, do not have formal QA/QC procedures implemented, have not implemented automation to process large number of samples or lack of clear marketing strategies. Some concrete actions are proposed and outlined to address these issues in the near future. [ABSTRACT FROM AUTHOR]

Background: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. Aims: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). Patients and Methods: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years' standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5–15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4–15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. Results: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). Conclusions: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome. [ABSTRACT FROM AUTHOR]

Oxidative stress is the result of an imbalance in the redox state in a cell or a tissue. When the production of free radicals, which are physiologically essential for signaling, exceeds the antioxidant capability, pathological outcomes including oxidative damage to macromolecules, aberrant signaling, and inflammation can occur. Down syndrome (DS) and Williams-Beuren syndrome (WBS) are well-known and common genetic conditions with multi-systemic involvement. Their etiology is linked to oxidative stress with important causative genes, such as SOD-1 and NCF-1, respectively, of the diseases being primarily involved in the regulation of the redox state. Early aging, dementia, autoimmunity, and chronic inflammation are some of the main characteristics of these conditions that can be associated with oxidative stress. In recent decades, there has been a growing interest in the possible role of oxidative stress and inflammation in the pathology of these conditions. However, at present, few studies have investigated these correlations. We provide an overview of the current literature concerning the role of oxidative stress and oxidative damage in genetic syndromes with a focus on Down syndrome and WBS. We hope to provide new insights to improve the management of complications related to these diseases. [ABSTRACT FROM AUTHOR]

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus emerged in December 2019 and then spread globally. Little is still known about the impact of COVID-19 on pregnant women and neonates. A review of the literature was performed according to the PRISMA guideline recommendations, searching the MEDLINE and EMBASE databases. Studies' quality assessments were performed using the JBI Critical Appraisal Checklist. A total of 37 studies were included, involving 275 pregnant women with COVID-19 and 248 neonates. The majority of pregnant women presented with mild to moderate symptoms, only 10 were admitted in the ICU, and one died. Two stillbirths were reported and the incidence of prematurity was 28%. Sixteen neonates were tested positive for SARS-CoV-2 by RT-PCR, and nine of them were born from mothers infected during pregnancy. Neonatal outcomes were generally good: all the affected neonates recovered. RT-PCR for SARS-CoV-2 yielded negative results on amniotic fluid, vaginal/cervical fluids, placenta tissue, and breast milk samples. SARS-CoV-2 infection in pregnant women appeared associated with mild or moderate disease in most cases, with a low morbidity and mortality rate. The outcomes of neonates born from infected women were mainly favorable, although neonates at risk should be closely monitored. Further studies are needed to investigate the possibility of vertical transmission. [ABSTRACT FROM AUTHOR]

Summary at a glance: On the hypothesis that psychological distress might interfere with airway reactivity in patients suffering of mild to moderate COPD through a cholinergic-mediated-bronchial reflex. [ABSTRACT FROM AUTHOR]