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

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

Sex-Related Differences in Cardiovascular Risk in Adolescents with Overweight or Obesity.

Background: Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB). Methods: The main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls). Results: The three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011). Conclusions: Adolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.

The impact of vitamin D status on lipid profiles and atherogenic dyslipidemia markers in children and adolescents with obesity.

BACKGROUND AND AIM: Adequate serum vitamin D levels correlate with a more favorable lipid profile compared to deficient levels. Despite the well-established prevalence of vitamin D deficiency in children with obesity, studies investigating its influence on lipid profiles in this population are scarce. We explored the impact of vitamin D status on lipid profiles and markers of atherogenic dyslipidemia in a cohort of children and adolescents with obesity. METHODS AND RESULTS: A total of 271 Caucasian children and adolescents with overweight/obesity and a control group of 54 pediatric patients with normal weight. All participants underwent outpatient visits for the assessment of clinical parameters and venous blood collection for biochemical analysis such as triglycerides (TG)/HDL-C ratio, LDL-C/HDL-C ratio, atherogenic index of plasma AIP), vitamin D level. Individuals with obesity displayed severe vitamin D deficiency (25-OH-D ≤10 ng/ml) at a higher frequency compared to those with normal weight (p = 0.03). In patients with overweight/obesity and low 25-OH-D levels show higher values of glycemia (p = 0.001), insulin resistance (HOMA-IR and TRYG p < 0.001), TG (p < 0.001), TG/HDL-C (p = 0.001), AIP (p < 0.001), SBP (p = 0.01), and DBP (p = 0.04). In normal-weight individuals with low 25-OH- D levels an increased values of glycemia (p = 0.01), insulin resistance (HOMA-IR p = 0.01 and TRYG p = 0.002), TG (p = 0.01), TG/HDL-C (p = 0.02), AIP (p = 0.01). A direct correlation between 25-OH-D levels and metabolic parameters is observed. CONCLUSIONS: A correlation between vitamin D levels and the lipid/atherosclerotic profile was recorded. Vitamin D deficiency may represent a preventable and easily treatable cardiometabolic risk factor, emphasizing the importance of early intervention and preventive measures.

Association of HDL-Cholesterol, hypertension and left ventricular hypertrophy in youths with overweight or obesity.

BACKGROUND AND AIM: To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional multicenter study was performed in 1469 youths (age 6-16 years) with OW/OB observed in the period 2016-2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56 > 51, Q3: ≤51 > 45, Q4: ≤45 > 41, Q5: ≤41 > 39, Q6: <39 mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33-3.16) (P < 0.01) in Q2, 1.67 (1.10-2.55) (P < 0.05) in Q3 and 1.59 (1.05-2.41) (P < 0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15-10.24) (P < 0.05) in Q2, 4.16 (1.58-10.91) (P < 0.05) in Q3 and 3.60 (1.44-9.02) (P < 0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. CONCLUSION: Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease.

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

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

The digital readiness of future physicians: nurturing the post-pandemic medical education.

BACKGROUND: The COVID-19 pandemic has accelerated the integration of digital technologies in the healthcare sector. Telemedicine has notably emerged as a significant tool, offering a range of benefits. However, various barriers, such as healthcare professionals' insufficient technological skills and competencies, can hinder its effective implementation. Scholars have examined the readiness of future physicians, with some studies exploring their readiness before or during the COVID-19 crisis. There is, however, a noteable gap in the literature concerning the post-pandemic period. This study aims to identify gaps in current medical education programs by examining two primary aspects: (1) technical readiness (encompassing general and health-related digital competencies) and (2) behavioural readiness, which includes prior experiences and future intentions related to telemedicine education and implementation among medical students and residents. METHODS: A cross-sectional study was conducted using a web-based questionnaire administered to medical students and residents at a major Northern Italian university. The survey responses were analyzed to ascertain whether their distributions varied across demographic variables such as gender and level of education. RESULTS: The most commonly owned technologies were laptops and smartphones, with smartphones perceived as the easiest to use, while desktop computers presented more challenges. Approximately 38% of respondents expressed apprehension about applying digital health information in decision-making processes. There was a significant lack of both personal and academic experience, with only 16% of students and residents having used telemedicine in a university setting. Despite this, 83% of participants expressed a desire for training in telemedicine, and 81% were open to experimenting with it during their academic journey. Moreover, 76% of respondents expressed interest in incorporating telemedicine into their future clinical practice. CONCLUSIONS: This study highlights the need for medical students and residents to receive specific education in digital health and telemedicine. Introducing curricula and courses in this domain is critical to addressing the challenges of digital healthcare.

Mastication and oral myofunctional status in excess weight children and adolescents: A cross-sectional observational study.

BACKGROUND: Masticatory function seems to play a role in the aetiology of obesity. However, literature on the association between oral myofunctional status and overweight and obesity in children and adolescents is scarce and contrasting. OBJECTIVE: To compare masticatory performance, orofacial myofunctional status and tongue strength and endurance between children and adolescents with overweight and obesity and those with normal weight. METHODS: Thirty children and adolescents with overweight and obesity and 30 subjects with normal weight matched for age and sex were recruited. All subjects were evaluated with the Test of Masticating and Swallowing Solids in Children (TOMASS-C) for masticatory performance and with the Italian Orofacial Myofunctional Evaluation with Scores (I-OMES) for the orofacial myofunctional status. Anterior and posterior maximum tongue pressures and tongue endurance were measured. Parents-reported (PRO) duration of meals was recorded. Data were compared between the groups through the paired samples t-test or the Wilcoxon signed-rank test. RESULTS: Children and adolescents with overweight showed significantly lower number of bites (p = .033), lower I-OMES scores (p < .05), and shorter meal duration (p = .005) compared to their peers with normal weight. No significant differences were found between the two groups for the number of swallows, the number of masticatory cycles and the total time of the TOMASS-C, and none of the tongue pressure measurements. CONCLUSIONS: Eating in children and adolescents with overweight and obesity is characterised by a larger bolus sizes and shorter PRO meal duration. Additionally, overweight and obesity seem to be associated with poorer orofacial skills and structures in the paediatric population.

Lipodystrophies in non-insulin-dependent children: Treatment options and results from recombinant human leptin therapy.

Lipodystrophy is a general definition containing different pathologies which, except for those observed in insulin-treated subjects falling outside the scope of this paper, are characterized by total or partial lack of body fat, that, according to the amount of missing adipose tissue, are divided in generalized or partial lipodystrophy. These diseases are characterized by leptin deficiency, which often leads to metabolic derangement, causing insulin resistance, dyslipidemia, and increasing cardiovascular risk. In this narrative review, we presentend the clinical presentation of different types of lipodystrophies and metabolic unbalances related to disease in children and adolescents, focusing on the main treatment options and the novel results from recombinant human leptin (metreleptin) therapy. Milestones in the management of lipodystrophy include lifestyle modification as diet and physical activity, paired with hypoglycemic drugs, insulin, hypolipidemic drugs, and other drugs with the aim of treating lipodystrophy complications. Metreleptin has been recently approved for pediatric patients with general lipodystrophy (GL)> 2 years of age and for children with partial lipodystrophy (PL)> 12 years of age not controlled with conventional therapies. New therapeutic strategies are currently being investigated, especially for patients with PL forms, specifically, liver-targeted therapies. Further studies are needed to achieve the most specific and precise treatment possible.

Dual biological therapy and small molecules in pediatric inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) including Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U) are chronic inflammatory disorders which can affect the gastrointestinal tract. Anti-tumor necrosis factors antibodies (anti-TNFα) such as infliximab (IFX) and adalimumab (ADA) are the first line biological therapy for severe or complicated IBDs in pediatric age. Second line therapeutic options as vedolizumab (VDZ) and ustekinumab (UST) are currently used off-label in pediatric age. Furthermore, despite optimization of biologics, a great proportion of patients may fail to respond to biologic agents (up to 30%) or lose response over the time (around 50%) hence these patients may be left without another valid therapeutic option. Consequently, several efforts have been made in the last years in order to develop new drugs and to contrive new therapeutic strategies. Small molecule drugs (SMDs) and combination therapy with either two biologic agents or with a SMD and a biological agent have recently been proposed. Data on safety and efficacy of these new therapeutic options are limited. The objective of the present review is to summarize the most up-to-date available literature in pediatric IBD.

Bioactive compounds in childhood obesity and associated metabolic complications: Current evidence, controversies and perspectives.

Obesity represents the most frequent chronic disease among children worldwide, with a significant global burden on society. Metabolically unhealthy obesity (MUO) can affect children since their first years of life, and novel therapeutic strategies to tackle metabolic complications are under investigation. This review focuses on bioactive compounds and their possible beneficial effects on obesity, particularly omega-3, docosahexaenoic acid, vitamin D, biotics, polysaccharide macromolecules, polyphenols, inositols, alpha lipoic acid, and bromelaine. Our aim is to summarize current evidence about bioactive compounds in the treatment of obesity, highlighting recent findings on their use in children and adolescents. Most studied molecules are omega-3 and vitamin D, despite the heterogeneity between the studies. Moreover, given the emerging interest in the gut-brain axis in the link between metabolic health and microbiota, various studies on prebiotics, probiotics, synbiotics, postbiotics and polysaccharide macromolecules have been considered. Some preclinical studies seem to highlight a possible role of the polyphenols, even if their clinical evidence is still discussed. Lastly, we describe possible effects of inositols and alpha-lipoic acid. Despite some dietary supplements seem to be promising in overweight subjects, only in a few of them a dose/response efficacy has been found in the pediatric age. Innovative, well-designed and targeted clinical trials are then needed to prove the beneficial effects of these compounds that could support the standard behavioral therapy for obesity.

Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.

We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.

Reference intervals for thyroid biomarkers to enhance the assessment of thyroid status in childhood and adolescence.

OBJECTIVES: The determination of assay-dependent upper and lower reference limits (URL, LRL) of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) during childhood and adolescence, is challenging. METHODS: Thyroid hormones were measured via the Abbott Alinity system in 502 euthyroid children partitioned in the following age groups: ≤2, 2.1-10, and 10.1-18 years. The 97.5th and 2.5th percentiles (URL and LRL) were derived according to CLSI EP28- A3c guidelines. Quantile regression models were used to assess: (a) 90% confidence intervals of the URL and LRL, (b) the effect of age on URL and LRL within each age class and on overall age range, (c) the difference between the URLs and LRLs estimated for each age partition with an estimate of the confidence interval divided by the reference interval being derived (CI/RI). RESULTS: The CI/RI for the LRLs are smaller as compared to the URLs, except for FT4 for the 2.1-10 years age group. Considering the CI/RI and the overlap between CIs across the three age groups, one single LRL might be considered for TSH, FT3 and FT4 between 0 and 18 years. However, for the URL, there was a noticeable decrease in the URL over the 3 age groups for all three biomarkers, with there being no overlap in CIs for the URL between the ≤2 vs. the 10.1-19 years age groups. CONCLUSIONS: A common LRL for TSH, FT4 and FT3 for patients aged ≤18 years may be utilized when these biomarkers are measured with the Alinity system. For the URLs the use of age-specific URLs for these biomarkers is recommended.

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

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

Medical treatment of weight loss in children and adolescents with obesity.

Obesity remains one of the biggest health problems both in adults and children. Lifestyle modification, including diet and exercise, continues to be the mainstay of obesity prevention and treatment. Unfortunately, lifestyle modifications are often unsuccessful. Pharmacological treatment of obesity in pediatric patients can be applied in selected cases, and not before evidence of failure of the multidisciplinary lifestyle intervention. In this narrative review, we revised the most up-to-date evidence on medical treatment of weight loss in children and adolescents with obesity, including FDA- or EMA-approved and -experimented, not approved, drugs for pediatric population. Multidisciplinary treatment of childhood obesity, regulation of appetite control, energy balance and body weight were also discussed, in order to clarify the indications and mechanism action of drugs. Despite a substantial number of medications used for the treatment of obesity in adults, a limited number of drugs are approved by the drug regulatory agencies for pediatric population. Further research is needed to evaluate the efficacy and safety of novel pharmacological approaches for treatment of pediatric obesity in order to optimize weight management for children and adolescents and limit the development obesity-related comorbidities.

Fibroblast growth factor 23: translating analytical improvement into clinical effectiveness for tertiary prevention in chronic kidney disease.

OBJECTIVES: Fibroblast growth factor 23 (FGF23) plays a key role in the pathophysiology of chronic kidney disease (CKD) and of the associated cardiovascular diseases, ranking on the crossroads of several evolving areas with a relevant impact on the health-care system (ageing, treatment of CKD and prevention from cardiovascular and renal events). In this review, we will critically appraise the overall issues concerning the clinical usefulness of FGF23 determination in CKD, focusing on the analytical performances of the methods, aiming to assess whether and how the clinical introduction of FGF23 may promote cost-effective health care policies in these patients. CONTENT: Our comprehensive critical appraisal of the literature revealed that we are currently unable to establish the clinical usefulness of FGF23 measured by ELISA in CKD, as stability issues and suboptimal analytical performances are the major responsible for the release of misleading results. The meta-analytical approach has failed to report unambiguous evidence in face of the wide heterogeneity of the results from single studies. SUMMARY AND OUTLOOK: Our review has largely demonstrated that the clinical usefulness depends on a thorough analytical validation of the assay. The recent introduction of chemiluminescent intact-FGF23 (iFGF23) assays licensed for clinical use, after passing a robust analytical validation, has allowed the actual assessment of preliminary risk thresholds for cardiovascular and renal events and is promising to capture the iFGF23 clinically relevant changes as a result of a therapeutic modulation. In this perspective, the analytical optimization of FGF23 determination may allow a marriage between physiology and epidemiology and a merging towards clinical outcomes.

A new formula to improve the screening of impaired glucose tolerance in youths with overweight or obesity.

AIM: To assess a new formula to improve the screening of isolated impaired glucose tolerance (IGT) in youth with overweight/obesity (OW/OB). METHODS AND RESULTS: A cross-sectional study was performed in 1189 Caucasian youths with OW/OB aged 5-17 years, in whom impaired fasting glucose and high glycosylated hemoglobin were excluded. The sample was divided into training set (TS) (n = 883) and validation set (VS) (n = 306). Fasting (FG) and post-load plasma glucose, alanine aminotransferase (ALT), lipids and familial history for type 2 diabetes (FD) were available in all individuals. In the TS youths with IGT (n = 58, 7.0%) showed higher prevalence of female sex (FS), FD, and higher levels of FG, post-load glucose, ALT and lower levels of HDL-cholesterol vs individuals without IGT. The linear formula was obtained by logistic regression analysis in the TS: 0.05∗ALT + 0.07∗FG + 0.87∗FD + (0.06∗HDL∗ - 1) + 1∗FS. The best cut-off was 5.84. The performance of the formula vs IGT was: sensitivity: 0.74 and specificity: 0.71. Similar results were obtained in the VS. CONCLUSIONS: Using metabolic and anamnestic data we obtained a simple formula with a good performance for screening isolated IGT. This formula may support pediatricians to identify youths with OW/OB in whom the OGTT may be useful for detecting IGT.

Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model.

PURPOSE: We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. METHODS: We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. RESULTS: We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than -2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R2 87.2%). CONCLUSION: This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies.

Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of Ca2+ and Voltage-Activated K+ Channel Activity in Human Insulin Secretion.

Liang-Wang syndrome (LIWAS) is a polymalformative syndrome first described in 2019 caused by heterozygous mutation of the KCNMA1 gene encoding the Ca2+ and voltage-activated K+ channel (BKC). The KCNMA1 variant p.(Gly356Arg) abolishes the function of BKC and blocks the generation of K+ current. The phenotype of this variant includes developmental delay, and visceral and connective tissue malformations. So far, only three cases of LWAS have been described, one of which also had neonatal diabetes (ND). We present the case of a newborn affected by LIWAS carrying the p.(Gly375Arg) variant who manifested diabetes in the first week of life. The description of our case strongly increases the frequency of ND in LIWAS patients and suggests a role of BK inactivation in human insulin secretion. The knowledge on the role of BKC in insulin secretion is very poor. Analyzing the possible mechanisms that could explain the association of LIWAS with ND, we speculate that BK inactivation might impair insulin secretion through the alteration of ion-dependent membrane activities and mitochondrial functions in ß-cells, as well as the impaired intra-islet vessel reactivity.

Predictive Fat Mass Equations for Children With Inflammatory Bowel Disease.

OBJECTIVE: Evaluate accuracy of skinfold thicknesses and body mass index (BMI) for the prediction of fat mass percentage (FM%) in paediatric inflammatory bowel disease (IBD) and to develop population-specific formulae based on anthropometry for estimation of FM%. METHODS: IBD children (n = 30) and healthy controls (HCs, n = 144) underwent anthropometric evaluation and dual-energy X-ray absorptiometry (DEXA) scan, as the clinical reference for measurement of body composition. Body FM% estimated with skinfolds thickness was compared with FM% measured with DEXA. By means of 4 prediction models, population specific formulae for estimation of FM% were developed. RESULTS: No significant difference in terms of FM% measured by DEXA was found between IBD population and HCs (FM% 29.6% vs 32.2%, P = 0.108). Triceps skinfold thickness (TSF, Model 2) was better than BMI (Model 1) at predicting FM% (82% vs 68% of variance). The sum of 2 skinfolds (biceps + triceps; SF2, Model 3) showed an improvement in the prediction of FM% as compared with TSF, Model 2 (86% vs 82% of variance). The sum of 4 skinfolds (biceps + triceps + suprailiac + subscapular; Model 4) showed further improvement in the prediction of FM% as compared with SF2 (88% vs 86% of variance). CONCLUSIONS: The sum of 4 skinfolds is the most accurate in predicting FM% in paediatric IBD. The sum of 2 skinfolds is less accurate but more feasible and less prone to error. The newly developed population-specific formulae could be a valid tool for estimation of body composition in IBD population and an alternative to DEXA measurement.

Insulin resistance and potential modulators of ovarian reserve in young reproductive-aged women with obesity and type 1 diabetes.

INTRODUCTION: Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmed trait d'union. We evaluated the relationship between IR and an established ovarian reserve biomarker such as anti-mullerian hormone (AMH) together with other potential modulators of ovarian physiology (adiponectin and kisspeptin) in young reproductive-aged group women with obesity and type 1 diabetes (T1D). PATIENTS AND METHODS: We recruited 32 female youths: 14 of them presented with T1D (14.6 ± 2.6 years) and 18 with obesity (15.1 ± 2.6 years). The control group included 20 age-matched normal weight females. Each patient underwent physical examination and hormonal assessment. AMH, kisspeptin and adiponectin levels were also measured. IR was calculated as the homeostasis model assessment for insulin resistance (HOMA-IR) and the glucose disposal rate (eGDR) in patients with obesity and with T1D, respectively. RESULTS: adiponectin and kisspeptin levels were significantly different into groups (p ≤ .001), whereas AMH levels were not. Adiponectin values were higher in controls compared to patients with obesity (p < .001) and T1D (p = .02). Kisspeptin levels were lower in controls compared to patients with obesity (p = .001), without reaching statistical significance when compared to T1D (p = .06). IR was associated with lower adiponectin and higher kisspeptin levels (p < .001 and p = .02, respectively), but not with AMH. CONCLUSIONS: IR displays a relationship with adiponectin and kisspeptin in young reproductive-aged women with obesity and T1D. Interventions to correct IR in adolescents could be part of an early approach to prevent reproductive disorders and to promote factors associated with longevity in adult women.