Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study.

OBJECTIVES: The aim of our study was to investigate the role of serum calprotectin (SC) and muscle-skeletal ultrasound (MSUS) as predictive markers of relapse in patients with juvenile idiopathic arthritis (JIA). METHODS: Sixty non-systemic (ns) JIA patients in clinical remission were recruited to evaluate the risk of disease relapse. SC levels and JIA disease activity were assessed at every visit (3, 6, 12 and 18 months). Joint synovitis, characterised by both synovial effusion (SE) and synovial hyperplasia (SH), was measured by US score (sum of SE, SH, power Doppler and bone erosions) given to each examined joint and US ratio (US score/number of joints examined) at every visit. Associations of SC, US score and US ratio with relapse prevalence was studied longitudinally by using generalised estimating equations model. RESULTS: Thirty-one (51.6%) patients relapsed within 18 months. Patients with higher baseline US scores showed higher risk of relapse at 6 months (OR (95% confidence interval (CI)): 1.96 (1.09-3.52)). Additionally, patients with higher SC values at baseline showed higher risk of relapse at 18 months (1.66 (1.13-2.44)). Patients with higher baseline SC values showed an increased overall odds of relapse up to 18 months of follow-up (1.21 (1.08-1.36)). Furthermore, patients with higher US scores showed an increased overall odds of relapse up to 18 months of follow-up (1.96 (1.56-2.46)). Similarly, patients with higher US ratio showed an increased overall odds of relapse up to 18 months of follow-up (16.62 (7.17-38.54)). CONCLUSIONS: SC was able to identify JIA patients with unstable remission and increased risk of relapse. MSUS represents an interesting additional tool to the clinical evaluation, especially in predicting early relapse.

Kidney manifestations of pediatric Sjögren's syndrome.

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5-20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6-96.2%), and anti-Ro/SSA (36.4-84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature.

Rare genetic forms of obesity in childhood and adolescence: A narrative review of the main treatment options with a focus on innovative pharmacological therapies.

The prevalence of obesity in children and adolescents is increasing, and it is recognised as a complex disorder that often begins in early childhood and persists throughout life. Both polygenic and monogenic obesity are influenced by a combination of genetic predisposition and environmental factors. Rare genetic obesity forms are caused by specific pathogenic variants in single genes that have a significant impact on weight regulation, particularly genes involved in the leptin-melanocortin pathway. Genetic testing is recommended for patients who exhibit rapid weight gain in infancy and show additional clinical features suggestive of monogenic obesity as an early identification allows for appropriate treatment, preventing the development of obesity-related complications, avoiding the failure of traditional treatment approaches. In the past, the primary recommendations for managing obesity in children and teenagers have been focused on making multiple lifestyle changes that address diet, physical activity, and behaviour, with the goal of maintaining these changes long-term. However, achieving substantial and lasting weight loss and improvements in body mass index (BMI) through lifestyle interventions alone is rare. Recently the progress made in genetic analysis has paved the way for innovative pharmacological treatments for different forms of genetic obesity. By understanding the molecular pathways that contribute to the development of obesity, it is now feasible to identify specific patients who can benefit from targeted treatments based on their unique genetic mechanisms.  Conclusion: However, additional preclinical research and studies in the paediatric population are required, both to develop more personalised prevention and therapeutic programs, particularly for the early implementation of innovative and beneficial management options, and to enable the translation of these novel therapy approaches into clinical practice. What is Known: • The prevalence of obesity in the paediatric population is increasing, and it is considered as a multifaceted condition that often begins in early childhood and persists in the adult life. Particularly, rare genetic forms of obesity are influenced by a combination of genetic predisposition and environmental factors and are caused by specific pathogenic variants in single genes showing a remarkable impact on weight regulation, particularly genes involved in the leptin-melanocortin pathway. • Patients who present with rapid weight gain in infancy and show additional clinical characteristics indicative of monogenic obesity should undergo genetic testing, which, by enabling a correct diagnosis, can prevent the development of obesity-related consequences through the identification for appropriate treatment. What is New: • In recent years, advances made in genetic analysis has made it possible to develop innovative pharmacological treatments for various forms of genetic obesity. In fact, it is now achievable to identify specific patients who can benefit from targeted treatments based on their unique genetic mechanisms by understanding the molecular pathways involved in the development of obesity. • As demonstrated over the last years, two drugs, setmelanotide and metreleptin, have been identified as potentially effective interventions in the treatment of certain rare forms of monogenic obesity caused by loss-of-function mutations in genes involved in the leptin-melanocortin pathway. Recent advancements have led to the development of novel treatments, including liraglutide, semaglutide and retatrutide, that have the potential to prevent the progression of metabolic abnormalities and improve the prognosis of individuals with these rare and severe forms of obesity. However, extensive preclinical research and, specifically, additional studies in the paediatric population are necessary to facilitate the translation of these innovative treatment techniques into clinical practice.

Perinatal outcome in anti-NMDAr encephalitis during pregnancy-a systematic review with individual patients' data analysis.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. METHODS: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. RESULTS: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. CONCLUSIONS: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment.

Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Effects of COVID-19 time on the development of pre-impaired glucose tolerance state in children and adolescents with overweight and obesity.

OBJECTIVES: We aimed to characterize the effects of COVID-19 Pandemic on 2 h plasma glucose (2 h PG) values after an OGTT postulating a correlation between 2 h PG spectrum and the decline of ß-cell function. Particularly, we tried to evaluate the effects on the risk of showing 2 h plasma glucose values in the highest range of normal values in children and adolescent with obesity during COVID-19 Pandemic compared to those evaluated during the 13 years before. SUBJECTS/METHODS: Data from 532 children and adolescents with obesity and overweight (before COVID-19 Pandemic, 209M/262F, 2008-2019; during COVID-19 Pandemic, 40M/21F, 2020-2021) who had undergone a complete evaluation and had performed an OGTT were analyzed. The two groups were further divided into three sub-groups based on the 2 h PG, group 1 (2 h PG < 5.55 mmol/L), group 2 (5.56 < 2 h PG < 6.60 mmol/L), group 3 (6.61 < 2h PG < 7.72 mmol/L), respectively. The prevalence of 2 h PG values distribution in children was evaluated between before and during COVID-19 Pandemic period and the main differences between the two groups 3 of each period were analyzed. RESULTS: A significant difference (P = 0.01) in terms of distribution of the prevalence of 2h PG values was documented between the group before COVID-19 (35.6%, 45.9% and 18.5%) and the group during COVID-19 Pandemic (31.1%, 31.1% and 37.8%). A roughly doble higher prevalence of subjects with pre-IGT was documented in the COVID-19 group. In addition, group 3 of COVID-19 time showed significantly higher values for waist circumference (WC), Waist/Height ratio (WtHR), fasting glucose and HOMA-IR compared to the group 3 of the period before COVID-19 Pandemic (all P < 0.05). CONCLUSIONS: During COVID-19 time a higher percentage of children are in the highest range of normal 2 h PG values which is known to be associated with a significant impairment of ß-cell function and insulin sensitivity and have higher risk of developing IGT.

Long-term effectiveness of add-on perampanel in patients with Lennox-Gastaut syndrome: A multicenter retrospective study.

This retrospective study assessed long-term effectiveness of add-on perampanel (PER) in patients with Lennox-Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure-free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty-seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty-six patients (41.4%) were responders during a median follow-up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow-up. This study provides real-world evidence on the effectiveness of PER as adjunctive treatment in LGS patients.

Lessons and gaps in the prediction and prevention of type 1 diabetes.

Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the root cause of T1D development has yet to be determined, enough is known about the natural history of T1D pathogenesis to allow study of interventions that may delay or even prevent the onset of hyperglycemia and clinical T1D. Primary prevention aims to prevent the onset of beta cell autoimmunity in asymptomatic people at high genetic risk for T1D. Secondary prevention strategies aim to preserve functional beta cells once autoimmunity is present, and tertiary prevention aims to initiate and extend partial remission of beta cell destruction after the clinical onset of T1D. The approval of teplizumab in the United States to delay the onset of clinical T1D marks an impressive milestone in diabetes care. This treatment opens the door to a paradigm shift in T1D care. People with T1D risk need to be identified early by measuring T1D related islet autoantibodies. Identifying people with T1D before they have symptoms will facilitate better understanding of pre-symptomatic T1D progression and T1D prevention strategies that may be effective.

Early changes in S100B maternal blood levels can predict fetal intrauterine growth restriction.

OBJECTIVES: Intrauterine growth restriction (IUGR) represents one of the main causes of perinatal mortality and morbidity. Nowadays, IUGR early diagnosis is mandatory in order to limit the occurrence of multiorgan failure, especially the brain. Therefore, we investigated whether longitudinal S100B assessment in maternal blood could be a trustable predictor of IUGR. METHODS: We conducted a prospective study in 480 pregnancies (IUGR: n=40; small for gestational age, SGA: n=40; controls: n=400) in whom S100B was measured at three predetermined monitoring time-points (T1: 8-18 GA; T2: 19-23 GA; T3: 24-28 GA). RESULTS: Lower S100B in IUGR fetuses than SGA and controls (p<0.05, for all) at T1-T3. Receiver operating characteristic curve showed that S100B at T1 was the best predictor of IUGR (sensitivity: 100 %; specificity: 81.4 %) than T2, T3. CONCLUSIONS: The early lower S100B concentration in pregnant women lately complicated by IUGR support the notion that non-invasive early IUGR diagnosis and monitoring is becoming feasible. Results open the way to further studies aimed at diagnosing and monitoring fetal/maternal diseases at earliest time.

Rare genetic forms of obesity in childhood and adolescence, a comprehensive review of their molecular mechanisms and diagnostic approach.

Obesity represents a major health problem in the pediatric population with an increasing prevalence worldwide, associated with cardiovascular and metabolic disorders, and due to both genetic and environmental factors. Rare forms of obesity are mostly monogenic, and less frequently due to polygenic influence. Polygenic form of obesity is usually the common obesity with single gene variations exerting smaller impact on weight and is commonly non-syndromic.Non-syndromic monogenic obesity is associated with variants in single genes typically related to the hypothalamic leptin-melanocortin signalling pathway, which plays a key role in hunger and satiety regulation, thus body weight control. Patients with these genetic defects usually present with hyperphagia and early-onset severe obesity. Significant progress in genetic diagnostic testing has recently made for early identification of patients with genetic obesity, which guarantees prompt intervention in terms of therapeutic management of the disease. What is Known: • Obesity represents a major health problem among children and adolescents, with an increasing prevalence worldwide, associated with cardiovascular disease and metabolic abnormalities, and it can be due to both genetic and environmental factors. • Non-syndromic monogenic obesity is linked to modifications in single genes usually involved in the hypothalamic leptin-melanocortin signalling pathway, which plays a key role in hunger and satiety regulation. What is New: • The increasing understanding of rare forms of monogenic obesity has provided significant insights into the genetic causes of pediatric obesity, and our current knowledge of the various genes associated with childhood obesity is rapidly expanding. • A useful diagnostic algorithm for early identification of genetic obesity has been proposed, which can ensure a prompt intervention in terms of therapeutic management of the disease and an early prevention of the development of associated metabolic conditions.

Renal involvement in monogenic autoinflammatory diseases: A narrative review.

Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)-α, and proteins belonging to type I-interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low-molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro-inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non-amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type-I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement.

The benefits of physical therapy in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Recommended physiotherapy activity programs are essential for controlling JIA associated complications such as stiffness, deformity, muscle contractures, and cramps. It is uncertain if physiotherapy (PT) can significantly enhance prognosis and quality of life (QOL). In this review we focused on the specific effects of various PT on JIA manifestations. To conduct a literature review, the databases PubMed, Scopus, and DOAJ (last access in June 2023) were searched. The PubMed search returned a total of 952 articles, Scopus returned 108, and DOAJ returned no results. After screening, the final list included 18 papers on PT treatment for JIA patients. In children with JIA, targeted PT exercise may have the ability to improve strength, posture, aerobic conditioning, gait, functional mobility, and reduce pain.

Statins in Children, an Update.

Since lipid abnormalities tend to progress from childhood to adulthood, it is necessary to early identify and treat children and adolescents with dyslipidemia. This is important in order to reduce the cardiovascular risk, delay the development of fatty streaks, slow the progression of atherosclerosis and reverse atherosclerotic plaques. Together with therapeutic lifestyle changes, statins are the most common lipid-lowering drugs. By inhibiting the endogenous cholesterol synthesis in the liver, statins increase the catabolism of LDL-C, reduce VLDL-C, IDL-C and TG and modestly increase HDL-C. Regardless of their lipid-lowering effect, statins have also pleiotropic effects. Statins have increasingly been prescribed in children and adolescents and mounting evidence suggests their beneficial role. As with adults, in children, several studies have demonstrated that statin therapy is efficient at lowering lipid levels and reducing CIMT progression and cumulative estimated atherosclerotic burden in children. Statins are generally very well-tolerated in both adults and children and adverse events are quite uncommon. When evaluating the need and the timing for statin treatment, the presence of several factors (secondary causes, familial history, additional risk factors) should also be considered. Before initiating statins, it is imperative for clinical practitioners to consult patients and families and, as with any new medication therapy, to monitor patients taking statins. Despite being safe and effective, many children with lipid disorders are not on statin therapy and are not receiving the full potential benefit of adequate lipid-lowering therapies. It is therefore important that clinicians become familiar with statins.

MAFLD and Celiac Disease in Children.

Celiac disease (CD) is an immune-mediated systemic disorder elicited by the ingestion of gluten whose clinical presentation ranges from the asymptomatic form to clinical patterns characterized by multiple systemic involvement. Although CD is a disease more frequently diagnosed in patients with symptoms of malabsorption such as diarrhea, steatorrhea, weight loss, or failure to thrive, the raised rate of overweight and obesity among general pediatric and adult populations has increased the possibility to diagnose celiac disease in obese patients as well. Consequently, it is not difficult to also find obesity-related disorders in patients with CD, including "metabolic associated fatty liver disease" (MAFLD). The exact mechanisms linking these two conditions are not yet known. The going assumption is that a gluten-free diet (GFD) plays a pivotal role in determining an altered metabolic profile because of the elevated content of sugars, proteins, saturated fats, and complex carbohydrates, and the higher glycemic index of gluten-free products than gluten-contained foods, predisposing individuals to the development of insulin resistance. However, recent evidence supports the hypothesis that alterations in one of the components of the so-called "gut-liver axis" might contribute to the increased afflux of toxic substances to the liver triggering the liver fat accumulation and to the subsequent hepatocellular damage. The aim of this paper was to describe the actual knowledge about the factors implicated in the pathogenesis of hepatic steatosis in pediatric patients with CD. The presented review allows us to conclude that the serological evaluations for CD with anti-transglutaminase antibodies, should be a part of the general workup in the asymptomatic patients with "non-alcoholic fatty liver disease" (NAFLD) when metabolic risk factors are not evident, and in the patients with steatohepatitis when other causes of liver disease are excluded.

Endocrine Disruptor Chemicals and Children's Health.

We are all exposed to endocrine-disrupting chemicals (EDCs) starting from embryonic life. The fetus and child set up crucial developmental processes allowing adaptation to the environment throughout life: they are extremely sensitive to very low doses of hormones and EDCs because they are developing organisms. Considering the developmental origin of well-being and diseases, every adult organism expresses consequences of the environment in which it developed. The molecular mechanisms through which the main EDCs manifest their effects and their potential association with endocrine disorders, such as diabetes, obesity, thyroid disease and alteration of adrenal hormones, will be reviewed here. Despite 40 years having passed since the first study on EDCs, little is yet known about them; therefore, our purpose is to take stock of the situation to establish a starting point for further studies. Since there is plenty of evidence showing that exposure to EDCs may adversely impact the health of adults and children through altered endocrine function-suggesting their link to endocrinopathies-it is essential in this context to bear in mind what is already known about endocrine disruptors and to deepen our knowledge to establish rules of conduct aimed at limiting exposure to EDCs' negative effects. Considering that during the COVID-19 pandemic an increase in endocrine disruptor effects has been reported, it will also be useful to address this new phenomenon for better understanding its basis and limiting its consequences.

Drug-Induced Enterocolitis Syndrome in Children.

Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.

The Role of Serum Calprotectin in Defining Disease Outcomes in Non-Systemic Juvenile Idiopathic Arthritis: A Pilot Study.

Serum calprotectin (MRP8/14) is currently being studied as a promising biomarker of disease activity and outcome in patients with juvenile idiopathic arthritis (JIA) but the data in the literature are conflicting. The aim of our study was to investigate the potential role of serum calprotectin as biomarker of disease activity and flare/remission in a group of nsJIA patients during a follow-up period of 18 months. In this prospective longitudinal study, two groups of patients with ns-JIA (55 active patients and 56 patients in remission according to Wallace's criteria) and a control group (50 children) were recruited at baseline from January 2020 to September 2021. JIA patients were followed for up to 18 months at four timepoints: 3 months (T1), 6 months (T2), 12 months (T3) and 18 months (T4). At each timepoint, the following were recorded: JADAS27, blood counts, ESR, CRP, albumin, ferritin and serum calprotectin. To illustrate the performance of calprotectin, Kaplan-Meier curves were constructed from baseline to relapse/remission, dichotomizing patients at baseline in positive/negative on the basis progressive calprotectin cut-offs. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates. Comparing baseline clinical and laboratory data of the three groups (active vs. inactive JIA vs. controls), only serum calprotectin reached statistical significance (active patients vs. inactive (p = 0.0016) and vs. controls (p = 0.0012)). In the inactive group, during the 18 months of follow up, 31 patients (55.3%) had a relapse. Comparing the baseline data of relapsers vs. non-relapsers, serum calprotectin showed higher levels (p = 0.001) in relapsers. In survival analysis, a log rank test showed significant differences of up to 12 ng/mL (p = 0.045). Multivariate Cox regression confirmed that only baseline calprotectin levels were independently associated with disease recurrence. In the active group, in the 12 months of follow-up, 19 patients (38%) entered remission of the disease. In addition, in this group, the only statistical difference at the baseline was the value of MPR8/14 (p = 0.0001). Log rank test showed significant differences up to 10 ng/mL (p = 0.003). In the multivariate Cox regression, serum calprotectin levels at baseline were independently associated with remission. In conclusion, our study would suggest a dual role for calprotectin in predicting future relapse and treatment response in patients with nsJIA, thus influencing therapeutic decisions and management of these patients during follow up.

Genetic Background and Molecular Mechanisms of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in the paediatric population. JIA comprises a heterogeneous group of disorders with different onset patterns and clinical presentations with the only element in common being chronic joint inflammation. This review sought to evaluate the most relevant and up-to-date evidence on current knowledge regarding the pathogenesis of JIA subtypes to provide a better understanding of these disorders. Despite significant improvements over the past decade, the aetiology and molecular mechanisms of JIA remain unclear. It has been suggested that the immunopathogenesis is characterised by complex interactions between genetic background and environmental factors that may differ between JIA subtypes. Human leukocyte antigen (HLA) haplotypes and non-HLA genes play a crucial role in the abnormal activation of both innate and adaptive immune cells that cooperate in causing the inflammatory process. This results in the involvement of proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-10, IL-17, IL-21, IL-23, and others. These mediators, interacting with the surrounding tissue, cause cartilage stress and bone damage, including irreversible erosions. The purpose of this review is to provide a comprehensive overview of the genetic background and molecular mechanisms of JIA.

The bad rainbow of COVID-19 time: effects on glucose metabolism in children and adolescents with obesity and overweight.

BACKGROUND: COVID-19 restriction measurements have enhanced the obesity status in the pediatric population which might further contribute to obesity-related glucose-insulin metabolism alterations. Therefore, we retrospectively compared anthropometric and OGTT data on children with obesity during the 13 years before and during the COVID-19 pandemic. SUBJECTS/METHODS: Data from 741 children with obesity and overweight were retrieved and clustered into seven groups starting from year 2008-2009 until 2020-2021. Differences in anthropometric measurements and glucose/insulin metabolism were evaluated between the different groups. RESULTS: Children with overweight and obesity in the COVID-19 restriction group did not present increased values of SDS-Body Mass Index (BMI). Significantly higher values for Waist Circumference (WC), SDS-WC, Waist/Height ratio (WHtR), and body mass fat were detected in these children (all P < 0.01). Fasting glycaemia, glucose, and insulin excursions were significantly higher compared to pre- pandemic children (all P < 0.01). Insulin resistance was higher while insulin secretion was lower (all P < 0.01) determining a significantly higher percentage of impaired glucose tolerance in the COVID-19 restriction group (P < 0.002). Furthermore, High-Density Lipoprotein (HDL) cholesterol was significantly lower (P < 0.01) and SDS for systolic and diastolic blood pressure values were significantly higher (P = 0.03 and P = 0.02, respectively). CONCLUSIONS: COVID-19 restriction measurements determined profound alterations in glucose and insulin metabolism in children with obesity and overweight. Urgent strategies are needed in order to reverse COVID-19 restriction measures' effects on glucose and insulin metabolism.

Insulin resistance in children.

PURPOSE OF REVIEW: Insulin resistance (IR) is a clinical condition due to the decline in the efficiency of insulin promoting glucose uptake and utilization. The aim of this review is to provide an overview of the current knowledge on IR in children, focusing on its physiopathology, the most appropriate methods of measurement of IR, the assessment of risk factors, the effects of IR in children, and finally giving indications on screening and treatment. RECENT FINDINGS: IR has evolved more and more to be a global public health problem associated with several chronic metabolic diseases. SUMMARY: Detecting a correct measurement method and specific risk predictors, in order to reduce the incidence of IR, represents a challenging goal.