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Background: We aimed to evaluate the baseline performance and improvement of ChatGPT-4 "omni" (ChatGPT-4o) and Gemini 1.5 Flash (Gemini 1.5) in answering multiple-choice questions related to pediatric nephrology after specific training. Methods: Using questions from the "Educational Review" articles published by Pediatric Nephrology between January 2014 and April 2024, the models were tested both before and after specific training with Portable Data Format (PDF) and text (TXT) file formats of the Educational Review articles removing the last page containing the correct answers using a Python script. The number of correct answers was recorded. Results: Before training, ChatGPT-4o correctly answered 75.2% of the 1395 questions, outperforming Gemini 1.5, which answered 64.9% correctly (p < 0.001). After training with PDF files, ChatGPT-4o's accuracy increased to 77.8%, while Gemini 1.5 improved significantly to 84.7% (p < 0.001). Training with TXT files showed similar results, with ChatGPT-4o maintaining 77.8% accuracy and Gemini 1.5 further improving to 87.6% (p < 0.001). Conclusions: The study highlights that while ChatGPT-4o has strong baseline performance, specific training does not significantly enhance its accuracy. Conversely, Gemini 1.5, despite its lower initial performance, shows substantial improvement with training, particularly with TXT files. These findings suggest Gemini 1.5's superior ability to store and retrieve information, making it potentially more effective in clinical applications, albeit with a dependency on additional data for optimal performance. [ABSTRACT FROM AUTHOR]

Summary: Background: The diagnosis of monogenic obesity is burdened by frequent variants of uncertain significance (VUS). We describe our real‐life approach of variant reassessment over time and we assess whether inconclusive variants are decreasing in monogenic obesity. Methods: We tested for monogenic obesity (genes: LEPR, POMC, ADCY3, PCSK1, CARTPT, SIM1, MRAP2, LEP, NTRK2, BDNF, KSR2, MAGEL2, SH2B1, MC4R, MC3R) in 101 children/adolescents (11.7 [7.3–13.7] years, 3.6 [3.3–4.0] z‐BMI) in Verona and 183 (11.3 [8.4–12.2] years, 3.2 [2.7–3.9] z‐BMI) in Naples from January 2020 to February 2023. In March–July 2024 we reassessed the baseline variants by updated software interpretation and literature renavigation. Results: We initially found 20 VUS, 4 Likely Pathogenic (LP), 5 Likely Benign (LB) and 1 benign variant in 33 individuals. At follow‐up, 6 VUS were reclassified as benign/LB, one LP as pathogenic and 3 LB as benign. Overall, 10/30 variants (6/18 in Verona, 3/11 in Naples and a variant found in both centres) were reclassified, leading to a less uncertain report for 13 of 33 variant‐carrying patients. Monogenic obesity was diagnosed in 3 probands in Verona and 4 in Naples, carrying variants at MC4R or NTRK2. Conclusion: Our variant reassessment was effective to improve classification certainty for the 39% of patients and suggested that the molecular diagnosis of monogenic obesity is becoming more accurate over time. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence and determinants of failure to thrive (FTT) among patients with vesico‐ureteral reflux (VUR) and evaluating the effects of supplementation on growth in patients with urinary solute losses. Methods: We retrospectively enrolled 1277 patients with VUR (mean age at diagnosis = 6.5 months). Patients with FTT were screened for renal tubular function impairment (TFI). If fractional excretion of sodium (FENa) >2% or blood bicarbonate <20 mmol/L, supplementation was provided. Results: Among 1277 patients, 56 (4.4%) had FTT. Of these, 42 (75%) presented extrarenal causes of FTT, 3 (5.4%) had chronic kidney disease (CKD), 9 (16.1%) had TFI, and 2 (3.5%) had CKD and TFI. FTT occurred in 8/208 patients (3.8%) with and in 48/1069 patients (4.5%) without (p = 0.68) recurrent urinary tract infections (UTIs). At multiple logistic regression, birthweight <10th percentile, preterm birth, TFI, identified or suspected syndromes and other diseases were predictors of FTT. Eleven (19.6%) patients with FTT had TFI; five with increased FENa and/or acidosis received supplementation and showed catch‐up growth. The remaining six patients exhibited spontaneous catch‐up growth. Conclusion: FTT was found in <5% of children with VUR. It was not determined by recurrent UTIs and was mainly associated with extrarenal causes. Supplementation with sodium and bicarbonates could be useful in selected cases. [ABSTRACT FROM AUTHOR]

The role of obesity as a risk factor for chronic kidney disease (CKD) in adulthood has been well established. Over the last years, kidney damage (KD) has emerged as a significant consequence of obesity since childhood. Indeed, a complex interplay of metabolic factors, including insulin resistance (IR), hypertension, oxidative stress, adipose tissue dysfunction, and systemic inflammation, might affect renal hemodynamics, contributing to CKD development over time in at-risk young patients. As the prevalence of pediatric obesity continues to rise globally, understanding the implications for kidney health in terms of early intervention is of paramount importance. Careful monitoring of kidney function within a multidisciplinary approach in children with obesity is crucial for detecting early KD, allowing for timely lifestyle modifications and treatment. In this framework, continued research is essential to further elucidate mechanisms linking obesity and KD and to explore not only effective preventive strategies but also the long-term impact of obesity on kidney health in children with obesity. Given the intimate link of KD with the metabolic milieu in children with obesity, we aimed to provide a comprehensive and insightful overview on KD and its implications in pediatric obesity by reviewing the most recent literature in the field. [ABSTRACT FROM AUTHOR]

We previously developed and retrospectively validated the estimated percentage of heart rate variation (EHRV) as a predictor of the composite outcome of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile children. The current study aimed to prospectively validate EHRV as a predictor for dehydration or AKI in a different cohort of children attending the Pediatric Emergency Department. From July 2022 to August 2023, 256 pediatric patients aged 0–18 years attending the Pediatric Emergency Department were enrolled. EHRV was calculated as follows: [(HR at admission − 50th percentile of HR for age and sex)/HR at admission] × 100. Dehydration was categorized as < 5% or ≥ 5% fluid deficit. AKI was defined according to KDIGO creatinine criteria. Statistical analyses included receiver-operating characteristic (ROC) curves and logistic regression analysis. Among enrolled patients, 52 had ≥ 5% dehydration, 50 had AKI, and 16 had both conditions. EHRV demonstrated significant predictive ability for both ≥ 5% dehydration (AUROC = 0.71; 95% confidence interval (CI), 0.63–0.78; p < 0.001) and AKI (AUROC = 0.78; 95% CI, 0.71–0.84; p < 0.001). An EHRV > 24.5% was associated with an increased odds ratio (OR), adjusted for confounders, of ≥ 5% dehydration (OR = 3.5; 95% CI, 1.6–8.0; p = 0.003) and AKI (OR = 3.4; 95% CI, 1.6–7.3; p = 0.002). The sensitivity and specificity of this cut-off were 34% and 83% for ≥ 5% dehydration and 36% and 84% for AKI, respectively. Conclusions: This study prospectively validates the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. An EHRV > 24.5% could serve as a marker for suspecting dehydration or AKI. Further validation across diverse patient populations and settings is needed. What is Known: • An increased heart rate (HR) is a readily detectable sign of dehydration in children. • In a retrospective validation cohort, an estimated HR variation (EHRV) greater than 24.5% compared to the 50th percentile of HR was predictive of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile patients. What is New: • We prospectively validated the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. • We confirmed that an EHRV greater than 24.5% is associated with increased odds of ≥ 5% dehydration and AKI. [ABSTRACT FROM AUTHOR]

Background/Objectives: The pediatric definition of severe obesity (OB) depends on the body mass index (BMI) references. We evaluated different BMI-derived metrics of the World Health Organization (WHO) system to define which cut-off is associated with the highest cardiometabolic risk (CMR); Methods: In this multicentric study, data were retrieved for 3727 youths (1937 boys; 2225 children, 1502 adolescents). OB was defined as BMI > 97th percentile (BMI97th), severe OB was defined as BMI > 99th percentile (BMI99th), BMI ≥ 120% of the 97th percentile (120% BMI97th), or BMI Z-score > 3 (WHO tables), or BMI ≥ the International Obesity Task Force (IOTF) value crossing a BMI of 35 kg/m2 at the age of 18 (IOTF35). The continuous CMR Z-score (sum of residual standardized for age and sex of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, and HDL-cholesterol x −1) and the cluster of at least two CMR factors (hypertension, high triglycerides, low HDL-cholesterol, and high waist-to-height ratio) were calculated. Results: Continuous CMR Z-score was significantly higher both in children or adolescents with severe OB defined by 120% BMI97th compared to BMI99th (p < 0.0001), while it was lower only in adolescents with severe OB defined by 120% BMI97th compared to BMI Z-score >3 (p < 0.0001). Compared to 120% BMI97th, BMI Z-score > 3 and IOTF35 had higher specificity, but lower sensitivity in identifying children and adolescents with clustered CMR factors. Conclusions: The definition of severe OB based on 120% BMI97th is superior to BMI99th but it is inferior to BMI Z score > 3 as far as the association between severe OB and CMR factors is concerned. Pediatricians should take into consideration the implication of the use of different BMI metrics in those countries that recommend the WHO system. WHO BMI Z-score > 3 and IOTF35 can be used interchangeably to predict cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Objectives: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR. Materials and methods: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria. Results: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI. Conclusion: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR. Clinical relevance statement: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention. Key Points: VCUG exposes children to radiation and is currently the gold standard for diagnosing VUR. A quarter of male children with VUR were diagnosed by IC despite normal VCUG. Recurrent fUTIs after negative VCUG may benefit from evaluation with IC. [ABSTRACT FROM AUTHOR]

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported, even in specialized centers. Mobile health technologies have been used to overcome these limits with contrasting results. This study aims at evaluating the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Seventy-five patients were randomly assigned to standard care or standard care plus mobile app (2:1) using an online randomizer system. The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: At six months of follow-up, the M-App group showed significantly lower dropout rates compared to standard care (p = 0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86, 95% C.I. 1.39–10.42, p = 0.01). After one year, we observed lower albeit non-statistically significant dropout rates in the M-App compared to the standard care group (p = 0.24). No differences were observed in z-score BMI and percentage of BMI reduction between the two groups. Conclusions: Our findings suggest that the mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction. [ABSTRACT FROM AUTHOR]

The role of obesity as risk factor for chronic kidney disease (CKD) has been well-recognized. As previously demonstrated in adults, emerging data highlighted the relevant impact of obesity on renal function since childhood. As a matter of fact, obesity also affects renal health through a complex pathogenic mechanism in which insulin resistance (IR) plays a pivotal role. Worthy of note, the vicious interplay among obesity, IR, and renal hemodynamics clinically translates into a plethora of kidney function impairments potentially leading to CKD development. Therefore, renal injury needs to be added to the well-known spectrum of cardiometabolic obesity comorbidities (e.g., type 2 diabetes, IR, metabolic syndrome, cardiovascular disease). Conclusion: Taking this into account, a careful and timely monitoring of kidney function should not be neglected in the global assessment of children with obesity. We aimed to provide a comprehensive overview on the relevance of kidney evaluation in children with obesity by shedding lights on the intriguing relationship of obesity with renal health in this at-risk population. What is Known: • Obesity has been found to be a risk factor for chronic kidney disease. • Unlike adults, pediatric data supporting the association between obesity and renal function are still limited. What is New: • As observed in adults, obesity might affect renal function since childhood. • Kidney function should be carefully evaluated in children with obesity. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) presents significant challenges in pediatric care, often remaining underrecognized. This paper provides an overview of pediatric AKI, highlighting its epidemiology, pathophysiology, diagnosis, predisposing conditions, and treatment. AKI in children stems from diverse causes, including renal tubular damage, vasoconstriction, and inflammation. Diagnosis relies on traditional markers such as serum creatinine and urine output, alongside emerging biomarkers such as Cystatin C, NGAL, KIM-1, IL-18, TIMP-2 and IGFBP7, urinary calprotectin, URBP4, L-FABP, and clusterin. Various pediatric conditions predispose to AKI, including type 1 diabetes, pneumonia, bronchiolitis, appendicitis, gastroenteritis, COVID-19, multisystem inflammatory syndrome, sickle cell disease, and malignancies. Treatment entails supportive care with fluid management and, in severe cases, renal replacement therapy. Timely recognition and management are essential to mitigating adverse outcomes. Enhanced awareness and integration of novel biomarkers could improve pediatric AKI care, warranting further research for better diagnosis and management. [ABSTRACT FROM AUTHOR]

Aim: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. Methods: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Results: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8–15.2; p = 9.4e‐09) and neutrophils levels (OR = 1.13; 95%CI: 1.08–1.2; p = 6.8e‐07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7–6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. Conclusion: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR. [ABSTRACT FROM AUTHOR]

Background: Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls. Results: Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin). Conclusions: The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life. [ABSTRACT FROM AUTHOR]

Objectives: To identify the diagnostic performance of clinical and radiological signs (on voiding cystourethrography [VCUG]) to detect posterior urethral valves (PUV) in the post-neonatal period. Materials and methods: One hundred eighteen males (median age = 0.8 years, range = 1 month–14 years, 48 toilet-trained) undergoing VCUG in a 2-year period were prospectively enrolled. Direct (dilated posterior urethra) and indirect (hypertrophied bladder neck, musculus interuretericus hypertrophy, and trabeculated appearance of the bladder wall) PUV signs on VCUG were assessed. Uroflowmetry was defined pathological by patterns suggesting infravesical obstruction. Results: Twenty-two patients with direct, 28 with indirect PUV signs on VCUG, and one with normal VCUG but persisting micturition symptoms with pathological uroflowmetry underwent urethrocystoscopy and in 43/51 a PUV diagnosis was made (n = 22, 51.2%, with direct PUV signs). In 8/28 patients with indirect signs, PUV were not confirmed. Among non-toilet-trained patients, none of the clinical signs/symptoms was associated with PUV while among toilet-trained patients only pathological uroflowmetry (odds ratio, OR = 4.0 [95% confidence interval:1.2–13.2; p = 0.02]) and pathological uroflowmetry with history of urinary tract infection (OR = infinity) were significantly associated with PUV. Significant associations with PUV of direct and indirect signs on VCUG were found both in toilet-trained and non-toilet trained patients. Direct PUV sign had 100% specificity and sensitivity while indirect PUV signs showed sensitivity = 58.1% and specificity = 89.3%. The absence of any radiological sign had a negative predictive value = 98.5%. Conclusion: Only half of patients with endoscopy-confirmed PUV presents with direct sign of PUV on VCUG. Accounting for indirect PUV signs on VCUG and pathological uroflowmetry (in toilet-trained children) could improve the PUV detection rate. Clinical relevance statement: Indirect radiological PUV signs should be valorized when interpreting VCUG to improve the PUV detection rate. The absence of any radiological PUV (direct and indirect) sign on VCUG excludes PUV with a very high negative predictive value. Key Points: • Worldwide agreement is that a non-dilated urethra on voiding cystourethrography excludes obstruction. • Half of patients with posterior urethral valves have non-dilated urethra on voiding cystourethrography. • Accounting for indirect signs of posterior urethral valves on voiding cystourethrography improves the diagnostic performance. [ABSTRACT FROM AUTHOR]

Despite the well-known role of obesity as risk factor for Juvenile Idiopathic Arthritis (JIA) severity, emerging but limited evidence suggested a similar role for underweight. We investigated the role of body mass index (BMI) across its full spectrum in a cohort of children with JIA. We retrospectively studied 113 children with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. The patients underwent a comprehensive evaluation including both clinical and biochemical assessments. According to BMI Z-score, the cohort was divided into five groups as underweight, normal weight, overweight (OW), obesity (OB), and severe OB. Disease activity was calculated by Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count and relapses were defined according to Wallace criteria. The mean age of the cohort was 7.43 ± 4.03 years. The prevalence of underweight, normal weight, OW, OB, and severe OB was 7.2%, 54.1%, 10.8%, 17.1%, and 10.8%, respectively. Significant higher ferritin levels and erythrocyte sedimentation rate values were found in patients with severe OB and underweight compared to subjects belonging to normal weight, OW, and OB groups. A greater JADAS-10 score was observed in underweight patients and in those with severe OB than other groups. The relapse rate was higher in patients with severe OB and underweight compared to other groups. Conclusions: Both underweight and OB might negatively affect JIA course. Weight control is fundamental in children with JIA to avoid a more unfavourable course of the disease. What is Known: • Obesity represents a well-known risk factor for JIA severity. • The role of underweight in children with JIA is still poorly explored. What is New: • As observed in children with obesity, underweight young patients with JIA seem to experience a more severe JIA course. • Healthy lifestyle promotion in children with JIA is a crucial step in the management of the disease. [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidney and urinary tract (CAKUT) can be associated with proteinuria, possibly leading to a decline in kidney function. The aim of this review is to evaluate evidence on the efficacy of renin-angiotensin-aldosterone system inhibitors (RAASi) in children affected by CAKUT with proteinuria or chronic kidney disease (CKD). We conducted a bibliographic search between 1 December 2022 and 20 February 2023, including randomized controlled trials, case-control studies, observational studies, meta-analyses, and systematic reviews dealing with the efficacy of RAASi in reducing proteinuria and slowing the decline of kidney function in children. RAASi are effective in reducing proteinuria and slowing CKD progression in many renal conditions; however, the efficacy of these drugs in patients affected by CAKUT with proteinuria is still unknown. While waiting for more evidence, when facing a child with CAKUT with isolated proteinuria or with proteinuria and CKD, a 6–12-month trial with RAASi with gradual increase to the maximal tolerated dose should be considered. If no improvement of proteinuria is obtained, the RAASi should be discontinued. [ABSTRACT FROM AUTHOR]

Objective: Leptin plays a key role in the regulation of body weight and other endocrine systems. Recently, impairment of leptin gene transcription due to genetic variations in a long noncoding RNA (lncOb) has been described. This retrospective study aims to characterize the clinical and metabolic phenotype of children and adolescents with obesity who were homozygous for the lncOb rs10487505 leptin lowering allele. Methods: Enrolled children underwent an anthropometrical evaluation, biochemical assessment, and genotyping for lncOb rs10487505. Plasma leptin levels were assessed in 150 participants. A total of 434 patients were included and divided into two groups according to rs10487505 recessive inheritance (CC vs. GG/GC). Results: Children who were homozygous for the C allele showed higher fasting insulin (p = 0.01), homeostasis model assessment of insulin resistance (p = 0.01), lower whole‐body insulin sensitivity index (p = 0.02), and lower disposition index (p = 0.03). Moreover, CC patients presented with a higher prevalence of prediabetes (9.3% vs. 3.4%, p = 0.04) and a 2.9‐fold (95% CI: 1.1–7.9, p = 0.04) higher risk of prediabetes compared with G‐carriers independently from confounders. Leptin plasma levels were significantly lower in the CC group (p = 0.002). Hormone levels correlated with BMI z score (r = 0.19, p = 0.04), fasting insulin (r = −0.34, p < 0.0001), homeostasis model assessment of insulin resistance (r = −0.33, p < 0.0001), and disposition index (r = 0.20, p = 0.04). Conclusions: The lncOb rs10487505 polymorphism affects leptin circulating levels, worsens insulin resistance, and heightens the risk of prediabetes in children and adolescents with obesity. [ABSTRACT FROM AUTHOR]

As the pediatric obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Pediatric NAFLD pathophysiology is tangled and still unclear, but insulin resistance (IR), genetics, epigenetics, oxidative stress, and inflammation act as key players. Due to the increased cardiometabolic risk of these patients, several biomarkers have been proposed for early NAFLD identification, but their clinical utility is poor. Recently, hepatic dysregulation of microRNAs (miRNAs) has been linked to metabolic dysfunction, which in turn implied in NAFLD development. Evidence on the intriguing role of miRNAs in NAFLD pathogenesis has emerging especially in at-risk children such as those with obesity. However, pediatric evidence supporting their potential use as early noninvasive NAFLD tools is still limited but promising. We provided an overview on the emerging role of miRNAs in pediatric NAFLD by addressing some issues regarding their pathophysiological link with the metabolic milieu and their role as reliable NAFLD markers in children with obesity. Strong evidence supports a potential role of miRNAs as early biomarkers of NAFLD in children with obesity. They might represent a valid diagnostic and targeted therapeutic tool due to its close pathogenic link with the metabolic milieu. [ABSTRACT FROM AUTHOR]

Childhood obesity and its related comorbidities have become major health issues over the last century. Among these comorbidities, cardiovascular diseases, especially hypertension, are the most significant. Recently, a polymorphism affecting the activity of lanosterol synthase has been associated with an increased risk of hypertension in adolescents. In this study, we aimed to investigate the effect of LSS rs2254524 polymorphism on blood pressure in children and adolescents with obesity. We enrolled 828 obese children aged 6–17 years. Subjects carrying the A allele showed higher rates of systolic and diastolic stage I hypertension and stage II hypertension. Carriers of the A allele showed a 2.4-fold (95% C.I. 1.5–4.7, p = 0.01) higher risk for stage II hypertension and a 1.9-fold higher risk for stage I hypertension (95% C.I. 1.4–2.6, p < 0.0001). The risk was independent of confounding factors. In conclusion, LSS rs2254524 worsens the cardiovascular health of children and adolescents with obesity, increasing their blood pressure. [ABSTRACT FROM AUTHOR]

We investigated prevalence of and factors associated with acute kidney injury (AKI) in a group of patients hospitalized with viral bronchiolitis. We retrospectively enrolled 139 children (mean age = 3.2 ± 2.1 months; males = 58.9%) hospitalized for viral bronchiolitis in a non-pediatric intensive care unit (PICU) setting. The Kidney Disease/Improving Global Outcomes creatinine criterion was used to diagnose AKI. We estimated basal serum creatinine by back-calculating it by Hoste (age) equation assuming that basal eGFR were the median age-based eGFR normative values. Univariate and multivariate logistic regression models were used to explore associations with AKI. Out of 139 patients, AKI was found in 15 (10.8%). AKI was found in 13 out of 74 (17.6%) patients with and in 2 out of 65 (3.1%) without respiratory syncytial virus (RSV) infection (p = 0.006). No patient required renal replacement therapies, while 1 out of 15 (6.7%) developed AKI stage 3, 1 (6.7%) developed AKI stage 2, and 13 (86.6%) developed AKI stage 1. Among the 15 patients with AKI, 13 (86.6%) reached the maximum AKI stage at admission, 1 (6.7%) at 48 h, and 1 (6.7%) at 96 h. At multivariate analysis, birth weight < 10th percentile (odds ratio, OR = 34.1; 95% confidence interval, CI = 3.6–329.4; p = 0.002), preterm birth (OR = 20.3; 95% CI = 3.1–129.5; p = 0.002), RSV infection (OR = 27.0; 95% CI = 2.6–279.9; p = 0.006), and hematocrit levels > 2 standard deviation score (SDS) (OR = 22.4; 95% CI = 2.8–183.6; p = 0.001) were significantly associated with AKI. Conclusion: About 11% of patients hospitalized with viral bronchiolitis in a non-PICU setting develop an AKI (frequently mild in degree). Preterm birth, birth weight < 10th percentile, hematocrit levels > 2SDS, and RSV infection are significantly associated with AKI in the setting of viral bronchiolitis. What is Known: • Viral bronchiolitis affects children in the first months of life and in 7.5% of cases it can be complicated by acute kidney injury (AKI). • No studies investigated associations with AKI in infants hospitalized for viral bronchiolitis. What is New: • About 11% of patients hospitalized with viral bronchiolitis can develop an AKI (frequently mild in degree). • Preterm birth, birth weight <10th percentile, hematocrit levels > 2 standard deviation score, and respiratory syncytial virus infection are associated with AKI development in infants with viral bronchiolitis. [ABSTRACT FROM AUTHOR]

Background: We evaluated the diagnostic performance of height-, age- and body surface area (BSA)-based kidney length (KL) percentiles in the identification of at least one small kidney (KL < 3rd) and in the prediction of reduced estimated glomerular filtration rate (eGFR) and/or elevated blood pressure (BP) in children with and without overweight (OW)/obesity(OB). Methods: In this cross-sectional study, 744 apparently healthy children (mean age 8.3 years) were recruited in a primary care setting. Clinical data were collected, and serum creatinine and KL were measured. Height-, age- and BSA-based percentiles of KL were calculated and the association of at least one small kidney per subject with reduced eGFR and/or elevated BP was explored by logistic regression. Results: Two hundred fifty-seven out of seven hundred forty-four (34.5%) subjects were OW/OB and 127 (17.1%) had reduced eGFR or elevated BP. In separate analyses in children with OW/OB, the KL percentiles calculated on the basis of BSA were lower compared with height- and age-based KL percentiles. Consequently, the prevalence of a small kidney was significantly higher when evaluating percentiles of KL based on BSA compared with other percentiles. In logistic regression analysis, a small kidney was significantly associated with reduced eGFR and/or elevated BP only when using height-based KL percentiles. The KL percentiles according to BSA for the ideal weight (iBSA) showed similar performance compared with height-based percentiles. No differences in the diagnostic performance of different percentiles were found in children with normal weight. Conclusions: BSA-based percentiles underestimate KL in children with OW/OB. In these subjects, the use of height-based or iBSA-based percentiles should be preferred. [ABSTRACT FROM AUTHOR]

Children with type 1 diabetes mellitus (T1DM) have an increased risk of developing kidney involvement. Part of the risk establishes at the beginning of T1DM. In fact, up to 65% of children during T1DM onset may experience an acute kidney injury (AKI) which predisposes to the development of a later chronic kidney disease (CKD). The other part of the risk establishes during the following course of T1DM and could be related to a poor glycemic control and the subsequent development of diabetic kidney disease. In this review, we discuss the acute and chronic effects of T1DM on the kidneys, and the implications of these events on the long-term prognosis of kidney function. [ABSTRACT FROM AUTHOR]

Lower urinary tract symptoms (LUTS) are a relevant problem in the pediatric population, having a very high prevalence. Diurnal incontinence and nocturnal enuresis are surely the most frequent symptoms, presenting, respectively, in up to 30% of school-age children and up to 10% of children between 6 and 7 years. Stypsis is the most common comorbidity, and it must be considered in the management of LUTS; indeed, the treatment of constipation is curative in most cases for both incontinence and enuresis. The presence or absence of diurnal symptoms in nocturnal enuresis and urgency in diurnal incontinence helps in the differential diagnosis. Urotherapy is always the first-line treatment, while oxybutynin and desmopressin (where appropriate) may help if the first-line treatment is unsuccessful. It is essential to identify conditions that are potentially dangerous for kidney and urinary tract well-being, for which LUTS can be the first manifestation. Starting from a series of clinical scenarios, we will underline the diagnostic clues behind LUTS in children and we will summarize clinical and surgical approaches for the proper management of these conditions. [ABSTRACT FROM AUTHOR]

Combination therapy (CT) (desmopressin plus oxybutynin) has been considered for the treatment of monosymptomatic nocturnal enuresis (MNE). We designed our study with the aim to evaluate the response rate to CT compared with desmopressin alone (primary outcome) and to identify factors associated with the response to CT (secondary outcome). We prospectively enrolled children with MNE with absent/partial response after 3 months of evening treatment with 240 mcg of desmopressin. We defined the response rate to CT compared with desmopressin alone according to the standardization of terminology document of the International Children's Continence Society: no-response, < 50% reduction; partial response, 50 to 99% reduction; and complete response, 100% reduction of wet nights. Both partial response and complete response to CT were clustered for the analyses of this manuscript. The enrolled children treated with 240 mcg/evening of desmopressin had also an additional evening administration of 0.3 mg/kg oxybutynin. A follow-up was scheduled at 3 and 6 months after the beginning of CT. At 3 months, oxybutynin dose was augmented to 0.5 mg/kg in case of absent/partial response to CT. Nocturnal diuresis was measured in 5 wet nights prior the beginning of therapy with desmopressin. Nocturnal polyuria (NP) was defined as nocturnal urine production > 130% of the expected bladder capacity. All patients with constipation were treated with macrogol. We enrolled 81 children (35.8% females) with a mean age of 8.4 ± 2.3 years. Seventy-eight patients completed the follow-up. After the CT, 59/78 (75.6%) patients showed an improvement of the response with CT compared with desmopressin alone. At multivariate analysis, both NP in more than 1 night (OR = 8.5; 95% CI, 1.4–51.6; p = 0.02) and absence of constipation (OR = 7.1; 95% CI, 1.6–31.0; p = 0.009) resulted significant after Bonferroni correction. Conclusions: CT determines an improvement of response compared to therapy with desmopressin alone in 75.6% of patients. Significant predictive factors of response to CT were presence of NP and absence of constipation. What is Known: • Combination therapy (CT) (desmopressin plus anticholinergic drug) has been described as a therapeutic option for patients with monosymptomatic nocturnal enuresis (MNE) not responding to desmopressin alone as first-line treatment. • Variable protocols and variable combination of drugs have been described with a response rate ranging from 44 to 76%. What is New: • We found that 59 patients (75.6%) treated with evening administration of 240 mcg of sublingual desmopressin plus 0.3–0.5 mg/kg of oxybutynin had an improvement of response compared to treatment with desmopressin alone. • We add evidence that presence of frequently recurring nocturnal polyuria and absence of constipation are predictors of response to CT. [ABSTRACT FROM AUTHOR]

Background: Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease (e.g., obesity, diabetes, chronic kidney disease (CKD), and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). Methods: A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. Results: At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all p < 0.05). Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. Conclusions: Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate whether serum aldosterone levels or plasmatic renin activity (PRA) measured early in life (1–3 months) could predict a future surgical intervention for obstructive congenital anomalies of kidney and urinary tract (CAKUT). Twenty babies aged 1–3 months of life with suspected obstructive CAKUT were prospectively enrolled. The patients underwent a 2-year follow-up and were classified as patients needing or not needing surgery. In all of the enrolled patients, PRA and serum aldosterone levels were measured at 1–3 months of life and were evaluated as predictors of surgery by receiver-operating characteristic (ROC) curve analysis. Patients undergoing surgery during follow-up showed significantly higher levels of aldosterone at 1–3 months of life compared to those who did not require surgery (p = 0.006). The ROC curve analysis of the aldosterone for obstructive CAKUT needing surgery showed an area under the ROC curve of 0.88 (95%CI = 0.71–0.95; p = 0.001). The aldosterone cut-off of 100 ng/dL presented 100% sensitivity and 64.3% specificity and predicted surgery in 100% of cases. The PRA at 1–3 months of life was not a predictor of surgery. In conclusion, serum aldosterone levels at 1–3 months could predict the need for surgery during obstructive CAKUT follow-up. [ABSTRACT FROM AUTHOR]

Background: There is increasing concern that infants with mild hypoxic-ischaemic encephalopathy (HIE) may develop seizures and progress to moderate HIE beyond the therapeutic window for cooling. Objective: The aim of this study was to examine the effect of therapeutic hypothermia on magnetic resonance imaging (MRI) biomarkers and neurological outcomes in infants with mild HIE and seizures within 24 h after birth. Methods: This study shows an observational cohort study on 366 (near)-term infants with mild HIE and normal amplitude-integrated electroencephalography background. Results: Forty-one infants showed progression (11.2%); 29/41 (70.7%) were cooled. Infants with progression showed cerebral metabolite perturbations and higher white matter injury scores compared to those without in both cooled and non-cooled groups (p = 0.001, p = 0.02). Abnormal outcomes were seen in 5/12 (42%) non-cooled and 7/29 (24%) cooled infants with progression (p = 0.26). Conclusions: Early biomarkers are needed to identify infants with mild HIE at risk of progression. Mild HIE infants with progression showed a higher incidence of brain injury and abnormal outcomes. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) represents the most common microvascular complication in patients with diabetes. This progressive kidney disease has been recognized as the major cause of end-stage renal disease with higher morbidity and mortality. However, its tangled pathophysiology is still not fully known. Due to the serious health burden of DN, novel potential biomarkers have been proposed to improve early identification of the disease. In this complex landscape, several lines of evidence supported a critical role of microRNAs (miRNAs) in regulating posttranscriptional levels of protein-coding genes involved in DN pathophysiology. Indeed, intriguing data showed that deregulation of certain miRNAs (e.g., miRNAs 21, -25, -92, -210, -126, -216, and -377) were pathogenically linked to the onset and the progression of DN, suggesting not only a role as early biomarkers but also as potential therapeutic targets. To date, these regulatory biomolecules represent the most promising diagnostic and therapeutic options for DN in adult patients, while similar pediatric evidence is still limited. More, findings from these elegant studies, although promising, need to be deeper investigated in larger validation studies. In an attempt to provide a comprehensive pediatric overview in the field, we aimed to summarize the most recent evidence on the emerging role of miRNAs in pediatric DN pathophysiology. [ABSTRACT FROM AUTHOR]

Hybrid closed loop systems (HCL) improve the management of type 1 diabetes (T1DM). T1DM adolescent patients represent a risk category also if they are in an automated insulin infusion delivery therapy. We describe a series of four cases in which adolescent patients have adopted incorrect behaviours in the managing of HCL systems, challenging the algorithm skills. Two patients performed fabricated sensor calibrations. The other two did not perform pre-prandial insulin boluses correctly. Despite these behaviours, the algorithm corrected the glucose values in three out of four patients. Only in one case, where fabricated calibrations were too frequent, the automatic system failed to restore the glycemic balance. Fabricated calibrations seem to be more important than uncorrected insulin boluses to challenge the HCL systems. [ABSTRACT FROM AUTHOR]

In addition to disease-specific complications, juvenile idiopathic arthritis (JIA) has been linked to metabolic impairments in adults. Recent data supported the usefulness of uric acid (UA) as risk factor for cardiometabolic derangements. Given the lack of pediatric evidence in this field, we aimed to explore this association in a cohort of children diagnosed with JIA. We retrospectively evaluated 113 children diagnosed with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. Both clinical and biochemical assessments were performed. Participants were stratified in four groups according to quartiles of serum UA. Disease activity was calculated by the Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count, and cut-offs for disease states were applied. Patients belonging to the highest UA quartile showed higher serum triglycerides, total cholesterol, creatinine, and glucose levels (p = 0.01, p = 0.025, p = 0.04, and p = 0.005, respectively) and lower HDL cholesterol values (p < 0.0001) than subjects belonging to the lowest quartiles. Ferritin, erythrocyte sedimentation rate levels, and age at disease onset did not significantly differ across UA quartiles (all p > 0.05). As activity disease index, JADAS-10 score significantly increased across UA quartiles (p = 0.009). Conclusion: Children with JIA presented with a worse cardiometabolic profile and a greater disease severity across UA quartiles. Our findings suggest that in clinical practice, UA might represent a useful marker of cardiometabolic risk and disease severity in children with JIA. What is Known: • JIA has been linked to metabolic derangements in adulthood. • UA has been recognized as a marker of cardiometabolic risk both in adults and children. What is New: • Children with JIA belonging to the highest UA quartile showed a worse cardiometabolic profile and a greater disease severity. • UA might represent a helpful marker not only of cardiometabolic risk but also of disease severity in children with JIA. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic changed adults and children's lifestyle. We focused our attention on children affected by chronic kidney disease (CKD) due to congenital abnormalities of kidney and urinary tract (CAKUT) and their behavior during the lockdown. Our aims were to evaluate the incidence of CKD progression within 6 months after the end of the first Italian lockdown and the factors associated to it. CKD progression was defined by the transition to higher CKD stage or by the drop in estimated glomerular filtration rate by a 25% or more for patients belonging to CKD stages 1 and 2. We retrospectively selected 21 children with CAKUT and CKD ≥ stage 1 observed within 3 months before and 6 months after the first Italian lockdown. We called them by phone and asked them about their lifestyle before and during lockdown focusing on physical activity, screen time, sweet/candies/sugar-sweetened beverages eaten/drunk and adherence to the Mediterranean diet (MD) (through KIDMED questionnaire). We calculated and analyzed the delta between the pre- and post- lockdown observation of all collected parameters (clinical and biochemical parameters and questionnaires scores). Analyzing the overall cohort, we found significantly increased mean BMI and mean screen time and significantly lower mean physical activity time in post- compared with pre-lockdown observations. Eleven out of twenty-one patients (52.4%) had a worsening of CKD. These patients presented higher delta of levels of uric acid and microalbuminuria and showed minor adherence to the MD and declared to have consumed more sweets or candies or sugar-sweetened beverages/week during the lockdown with a tendentially major increment of BMI compared with patients not presenting CKD progression. In conclusion, the lockdown for COVID-19 pandemic determined increase of BMI in all enrolled patients due to a "forced" negative lifestyle. About half of these patients presented CKD progression. This progression was associated to less adherence to the MD and major consumption of sweets or candies or sugar-sweetened beverages. [ABSTRACT FROM AUTHOR]

Nutcracker syndrome (NCS) is a rare pediatric disease caused by left kidney vein compression. Besides the "Triade's symptoms", including hematuria, proteinuria, and flank pain, a wide spectrum of clinical manifestations has been reported. As the significant hemodynamic changes secondary to the dilatation of the left renal vein, serious consequences such as renal vein thrombosis and severe anemia might occur in these children. NCS diagnosis includes a variety of invasive and non-invasive imaging tools, but cutoff values need to be further validated. A conservative treatment represents the most common therapeutic approach for these patients, but operative options are available in selected cases. To complicate matters, a standard diagnostic and treatment algorithm is currently lacking and scientific pediatric evidence in this field is still poor and limited. In this perspective, early recognition of NCS is crucial but challenging for pediatricians. Therefore, a better knowledge of the disease is recommended. Starting from two different clinical presentations of NCS, we aimed to provide a comprehensive overview of the disease in children. [ABSTRACT FROM AUTHOR]

Three new equations for calculating the estimated basal serum creatinine (ebSCr) in hospitalized children have been developed: the simplified acute kidney injury (AKI) baseline creatinine (ABC) equation which considered only age in the formula; the equation including age and minimum creatinine (Crmin) within the initial 72 h from hospitalization (ABC-cr); and the equation including Crmin and height, weight, and age as squared values (ABC-advanced). We aimed to test the diagnostic performance of the ABC, ABC-cr and ABC-advanced equations in diagnosing AKI in 163 prospectively enrolled children with type 1 diabetes mellitus (T1DM) onset. We considered measured basal serum creatinine (mbSCr), the creatinine measured 14 days after T1DM onset. AKI was defined by the highest/basal serum creatine (HC/BC) ratio > 1.5. On the basis of the mbSCr, the AKI was diagnosed in 66/163 (40.5%) patients. This prevalence was lower than the prevalence of AKI diagnosed on the basis of ABC ebSCr (122/163 patients; 74.8%) (p < 0.001) and similar to the prevalence of AKI diagnosed on the basis of ABC-cr ebSCr (72/163 patients; 44.2%) (p = 0.5) and to the prevalence of AKI diagnosed on the basis of ABC-advanced ebSCr (69/163; 42.3%) (p = 0.73). AKI determined using ABC ebSCr, ABC-cr ebSCr and ABC-advanced ebSCr showed, respectively, 63.5% (kappa = 0.35; p < 0.001), 87.7% (kappa = 0.75; p < 0.001), and 87.1% (kappa = 0.74; p < 0.001) agreement with AKI determined using mbSCr. Using the HC/BC ratio calculated on the basis of mbSCr as gold standard, for Bland–Altman plots the HC/BC ratio calculated on the basis of ABC formula presented higher bias and wider limits of agreement compared with the HC/BC ratio calculated on the basis of ABC-cr and ABC-advanced formulas. In the receiver–operating characteristics (ROC) curve analysis the HC/BC ratio calculated on the basis of ABC ebSCr presented lower area under the ROC curve (AUROC) (AUROC = 0.89; 95%CI: 0.85–0.95; p < 0.001) compared with HC/BC ratio calculated on the basis of ABC-cr (AUROC = 0.94; 95%CI: 0.91–0.98; p < 0.001) or ABC-advanced ebSCr (AUROC = 0.914; 95%CI: 0.91–0.97; p < 0.001). In both Bland–Altman plots and ROC curve analysis, the ABC-cr and ABC-advanced formulas performed similarly. In conclusion, the ABC-cr and ABC-advanced formulas present very good diagnostic performance toward AKI identification in a population of children with T1DM onset. [ABSTRACT FROM AUTHOR]

Aims: To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). Materials and Methods: Cross‐sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5–17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high‐density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. Results: The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06–1.68) for MetS (p = 0.02), 3.19 (2.51–4.05) for HUA (p < 0.0001) and 3.72 (2.65–5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. Conclusions: HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study. [ABSTRACT FROM AUTHOR]

Pediatric obesity is associated with an increased risk of morbidity during childhood. Alongside the well-known metabolic syndrome, during the last decades scientific research has deeply investigated the risk of sleep breathing disorders. Among them, obstructive sleep apnea (OSA) commonly affects children with obesity. The presence of OSA heightens the risk of metabolic impairment and weight gain. Therefore, it deserves specific treatment. However, polysomnography (PSG) is not always available in clinical settings, and alternative diagnostic tools are needed. This study aimed to investigate the predictivity of the pediatric sleep questionnaire (PSQ) for moderate-to-severe OSA diagnosis. Children and adolescents with obesity and suspected OSA with available full-night cardiorespiratory PSG were retrospectively enrolled. Receiver operating curve analysis was performed to test the ability of PSQ in predicting moderate-to-severe OSA (AHI > 5 episode/h). The final sample included 60 children and adolescents. The PSQ showed a good area under the curve (AUC) of 0.88 (95% CI 0.78–0.98, p < 0.0001). Moreover, a value above or equal to 0.65 showed an 80% sensitivity and 100% specificity for moderate and severe OSA. These findings suggest that PSQ might be used in clinical settings with limited access to PSG for stratifying disease severity and for selecting children with urgent need of sleep study. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a huge impact on children's lifestyle and eating behaviour, resulting in an increase of obesity prevalence. The CEBQ (Children's Eating Behaviour Questionnaire) is a validate questionnaire that investigates children's eating behaviour. Knowing the psychological consequences of daily routine disruption during lockdown, we evaluated the changes in eating behaviours in a paediatric cohort before and during the lockdown period through the evaluation of the Italian version of the CEBQ. We prospectively enrolled children attending the pediatric clinic of the University of Campania 'Luigi Vanvitelli'. All parents answered the parent-report version of the CEBQ before lockdown containment. During lockdown, the second survey was carried out by telephone call. The study sample included 69 children. Food responsiveness and emotional overeating subscales showed higher scores during lockdown compared to data before lockdown (p = 0.009 and p = 0.001, respectively). Conversely, desire to drink and satiety responsiveness showed lower scores at follow-up (p = 0.04 and p = 0.0001, respectively). No differences were observed for slowness in eating and enjoyment of food. Delta changes were higher in normal-weight children compared to children with obesity (p = 0.02). Our results confirm that containment measures during the COVID-19 pandemic have acted as triggers on certain eating behaviors that mostly predispose to an obesogenic manner. [ABSTRACT FROM AUTHOR]

At type 1 diabetes mellitus (T1DM) onset, acute kidney injury (AKI) is very common. To diagnose AKI, the availability of a baseline serum creatinine (bSCr) is pivotal. However, in most hospitalized children the bSCr is unknown. We aimed to test whether the bSCr estimated on the basis of height (ebSCr) could be a reliable surrogate for AKI diagnosis compared with the measured bSCr (mbSCr). As the mbSCr, we considered the creatinine measured 14 days after T1DM onset while ebSCr (mg/dL) = (k × height [cm])/120 mL/min/1.73 m2, where k = 0.55 for children and adolescent girls and k = 0.7 for adolescent boys. AKI was defined as serum creatinine values >1.5 times the baseline creatinine. Kappa statistics and the percentage of agreement in AKI classification by ebSCr–AKI versus mbSCr–AKI definition methods were calculated. Bland–Altman plots were used to show the agreement between the creatinine ratio (highest/baseline creatinine; HC/BC) calculated with mbSCr and ebSCr. The number of 163 patients with T1DM onset were included. On the basis of mbSCr, 66/163 (40.5%) presented AKI while, on the basis of ebSCr, 50/163 (30.7%) accomplished AKI definition. ebSCr showed good correlation with mbSCr using both the Spearman test (rho = 0.67; p < 0.001) and regression analysis (r = 0.68; p < 0.001). Moreover, at the Bland–Altman plots, the bias of the highest/baseline creatinine ratio calculated on the basis of the mbSCr compared to ebSCr was minimal (bias = −0.08 mg/dL; 95% limits of agreement = −0.23/0.39). AKI determined using ebSCr showed 90% agreement with AKI determined using mbSCr (kappa = 0.66; p < 0.001). Finally, we compared the area under a receiver–operating characteristic curve (AUROC) of HC/BC ratio calculated on the basis of ebSCr with AUROC of the gold standard HC/BC ratio calculated on the basis of mbSCr. As expected, the gold standard had an AUROC = 1.00 with a 95% confidence interval (CI) between 0.98 and 1.00, p < 0.001. The HC/BC ratio calculated on the basis of ebSCr also had significant AUROC (AUROC = 0.94; 95% CI: 0.90–0.97; p < 0.001). The comparison of the two ROC curves showed a p < 0.001. In conclusion, when mbSCr is unknown in patients with T1DM onset, the ebSCr calculated on the basis of height could be an alternative to orientate clinicians toward AKI diagnosis. [ABSTRACT FROM AUTHOR]

We hypothesized that the heart rate (HR) variation in an acute setting compared with HR in wellbeing status could be a good marker of both dehydration and acute kidney injury (AKI). Since HR in wellbeing status is unknown in most cases, we assumed as reliable surrogate the 50th percentile of HR according to age and gender. We evaluated if the estimated percentage of heart rate variation in acute setting compared with 50th percentile of HR (EHRV) could be marker of dehydration and AKI in children. Two independent cohorts, one prospective comprehending 185 children at type 1 diabetes mellitus onset (derivation) and one retrospective comprehending 151 children with acute gastroenteritis and pneumonia (validation), were used to develop and externally validate EHRV as predictor of the ≥ 5% dehydration and/or AKI composite outcome. Febrile patients were excluded. EHRV was calculated as ((HR at admission–50th percentile of HR)/HR at admission) × 100. The prevalences of ≥ 5% dehydration and AKI were 61.1% and 43.8% in the derivation and 34.4% and 24.5% in the validation cohort. For the ≥ 5% dehydration and/or AKI composite outcome, the area under receiver-operating characteristic curve of the EHRV in the derivation cohort was 0.69 (95%CI, 0.62–0.77; p < 0.001) and the best EHRV cut-off was > 24.5%. In the validation cohort, EHRV > 24.5% showed specificity = 100% (95%CI, 96.2–100.0), positive predictive value = 100%, and negative predictive value = 67.1% (95%CI, 64.7–69.5). The positive likelihood ratio was infinity, and odds ratio was not calculable because all the patients with EHRV > 24.5% showed ≥ 5% dehydration and/or AKI. Conclusions: EHRV appears a rather reliable marker of dehydration and AKI. Further validations could allow implementing EHRV in the clinical practice. What is Known: • Increased heart rate (HR) is an easily and quickly detectable sign of dehydration in childhood, but its cut-off to suspect dehydration or acute kidney injury (AKI) is not defined. What is New: • We found that a percentage of estimated HR variation in acute setting in comparison with 50th percentile of HR (EHRV)>24.5% predicted ≥5% dehydration and/or AKI in non-febrile patients. • We provide a one-page tool to suspect ≥5% dehydration and/or AKI on the basis of the HR. If furtherly validated, this tool could be implemented in the daily clinical practice. [ABSTRACT FROM AUTHOR]

We hypothesized that—as in other common pediatric conditions—acute appendicitis (AA) could be complicated by acute kidney injury (AKI). We aimed to investigate the prevalence of, and the factors associated with AKI in a cohort of patients with AA. We retrospectively collected data of 122 children (63.9% of male gender; mean age 8.6 ± 2.9 years; range: 2.2–13.9 years) hospitalized for AA. AKI was defined according to the Kidney Disease/Improving Global Outcomes creatinine criteria. We considered a basal serum creatinine value as the value of creatinine estimated with the Hoste (age) equation, assuming that the basal estimated glomerular filtration rate (eGFR) was 120 mL/min/1.73 m2. Explorative univariate logistic regression analysis was used to explore the associations with AKI. Out of 122 patients, nine (7.4%) presented with AKI. One patient had stage two AKI and the remaining had stage one AKI. The maximum AKI stage was found at admission. The patients with AKI showed a higher prevalence of fever ≥ 38.5 °C (p = 0.02), vomiting (p = 0.03), ≥5% dehydration (p = 0.03), and higher levels of both C-reactive protein (CRP) (p = 0.002) and neutrophils (p = 0.03) compared with patients without AKI. Because all patients with AKI also presented with vomiting, an Odds Ratio (OR) for the vomiting was not calculable. The exploratory univariate logistic regression analysis confirmed that fever ≥ 38.5 °C (OR = 5.0; 95% CI: 1.2/21.5; p = 0.03), ≥5% dehydration (OR = 8.4; 95% CI: 1.1/69.6; p = 0.04), CRP (OR = 1.1; 95% CI: 1.05/1.2; p = 0.01), and neutrophil levels (OR = 1.1; 95% CI: 1.01/1.3; p = 0.04) were all predictive factors of AKI. AKI can occur in 7.4% of patients with AA. Particular attention should be paid to the kidney health of patients with AA especially in the presence of vomiting, ≥5% dehydration, fever ≥ 38.5 °C, and high CRP and neutrophils levels. [ABSTRACT FROM AUTHOR]

Background: Increased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in CPP rates and in sleep patterns in CPP and healthy controls. Methods: CPP were retrospectively evaluated from April 2020 to April 2021. Parents of girls diagnosed with CPP during lockdown and of matched healthy controls filled out a questionnaire about sleep disturbances (SDSC questionnaire) and sleep schedules. Results: Thirty-five CPP and 37 controls completed the survey. Incidence of new CPP cases significantly increased in 2020–2021 compared to 2017–2020 (5:100 vs 2:100, p = 0.02). Sleep disturbance rates did not differ between CPP and healthy controls before lockdown. During lockdown, CPP reported higher rates of sleep disturbs for total score (p = 0.005), excessive somnolence (p = 0.049), sleep breathing disorders (p = 0.049), and sleep–wake transition disorders (p = 0.005). Moreover, CPP group more frequently shifted toward later bedtime (p = 0.03) during lockdown compared to controls. Hours of sleep and smartphone exposure around bedtime did not differ between groups. Conclusions: Our study confirms the observation of increased incidence of CPP after lockdown measures. Additionally, CPP showed higher rates of sleep disturbances and later bedtime compared to controls. The causality link between sleep disturbances and CPP should be further investigated to gain knowledge in this association. [ABSTRACT FROM AUTHOR]

Abbreviations JADAS-10 Juvenile Arthritis Disease Activity Score JIA juvenile idiopathic arthritis NSAIDs non-steroidal anti-inflammatory drugs Patients with autoimmune diseases have a higher risk of COVID-19, hospitalisation and death than the general population and are a priority for vaccination.1 Two messenger ribonucleic acid vaccines from Pfizer and Moderna have been approved for patients with rheumatic disease.1 It is not completely clear whether these vaccines could make underlying rheumatic disease flare up, as a result of immune activation, but adult studies have reported that they are safe and effective.1 Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease.2 The Pfizer vaccine has been shown to be safe and effective in adolescents with JIA.3 In spring 2021, the Pfizer vaccine was approved for children aged 12 years and above with rheumatic disease,4 but data about the Pfizer vaccine for children with JIA have been lacking. Preliminary observations on the immunogenicity and safety of vaccines to prevent COVID-19 in patients with juvenile idiopathic arthritis The vaccine coverage and vaccine immunity status and risk factors of non-protective levels of antibodies against vaccines in children with juvenile idiopathic arthritis: cross-sectional Russian tertiary Centre study. [Extracted from the article]

Scurvy is generated by lack of vitamin C; although it is considered a rare and past disease, scurvy continues to be detected in children with neurodevelopmental disorders and with selective diet habits. Identifying scurvy can be demanding due to the perceived rarity of the condition, and it can become a tricky diagnostic question given to the variety of nonspecific symptoms, including gingival manifestations. This study aims to identify most common clinical features in order to provide a complete picture of the signs and symptoms, and to offer clinicians the diagnostic tools for identifying patients suffering from scurvy. We present a case report of a child affected by scurvy; it has also been performed as a systematic review about scurvy in pediatric population. A search yielded 107 relevant studies since 1990. Most of the identified cases have shown oral, musculoskeletal and cutaneous manifestation that improved within a few days of starting vitamin C therapy. Identifying scurvy's characteristic clinical features allows a timely diagnosis, thus avoiding invasive investigations. Pediatric dentists should possess adequate knowledge and experience to identify the main characteristics of scurvy. This can help facilitate a prompt diagnosis in order to provide timely intervention to the patient that is relatively ease and safe. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) enhances the risk of later chronic kidney disease. Significant prevalence of AKI is reported in adults with community acquired pneumonia (CAP). We investigated prevalence of and prognostic factors for AKI in children hospitalized for CAP. Methods: We retrospectively collected clinical and biochemical data of 186 children (48.4% male; mean age 2.6±2.4 years) hospitalized for X-ray-confirmed CAP. AKI was defined according to Kidney Disease/Improving Global Outcomes creatinine criteria. We considered as basal serum creatinine the value estimated with Hoste (age) equation assuming basal eGFR were median age-based eGFR normative values for children ≤ 2 years of age and eGFR= 120 mL/min/1.73m2 for children > 2 years. Univariate and multivariate logistic regression models were used to explore associations with AKI. Results: AKI was found in 38/186 (20.4%) patients. No patient required hemodialysis nor reached AKI stage 3, 5 (2.7%) reached AKI stage 2, and 33 (17.7%) AKI stage 1. Mean length of stay was 6.0±1.7, 6.9±2.3, and 12.2±1.5 days, for patients without AKI, stage 1 AKI, and stage 2 AKI (p < 0.001), respectively. Duration of symptoms before hospitalization (OR 1.2; 95%CI 1.09–1.43; p = 0.001), severe pneumonia (OR 11.9; 95%CI 4.3–33.3; p < 0.001), and serum C-reactive protein levels (OR 1.1; 95%CI 1.04–1.23; p = 0.004) were independent AKI predictors. Conclusions: About 1/5 of children hospitalized for CAP present a generally mild AKI with a longer stay for those with more severe AKI. Attention should be paid to kidney health of children with CAP especially in presence of higher duration of symptoms before hospitalization, severe pneumonia and higher serum CRP levels. [ABSTRACT FROM AUTHOR]

Introduction: Over the past decades, a large amount of both adult and pediatric data has shown relationship between Nonalcoholic Fatty Liver Disease (NAFLD) and chronic kidney disease (CKD), resulting in an overall increased cardiometabolic burden. In view of the remarkable role of the genetic background in the NAFLD pathophysiology, a potential influence of the major NAFLD polymorphisms (e.g. the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene, the E167K allele of the Transmembrane 6 superfamily member 2 (TM6SF2), the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), and the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) genes) on renal function has been supposed. A shared metabolic and proinflammatory pathogenesis has been hypothesized, but the exact mechanism is still unknown. Areas covered: We provide a comprehensive review of the potential genetic link between NAFLD and CKD in children. Convincing both adult and pediatric evidence supports this association, but there is some dispute especially in childhood. Expert opinion: Evidence supporting a potential genetic link between NAFLD and CKD represents an intriguing aspect with a major clinical implication because of its putative role in improving strategy programs to counteract the higher cardiometabolic risk of these patients. [ABSTRACT FROM AUTHOR]

Context: Acute kidney injury (AKI) and renal tubular damage (RTD), especially if complicated by acute tubular necrosis (ATN), could increase the risk of later chronic kidney disease. No prospective studies on AKI and RTD in children with type1diabetes mellitus (T1DM) onset are available.Objectives: To evaluate the AKI and RTD prevalence and their rate and timing of recovery in children with T1DM onset.Design: Prospective study.Settings and Patients: 185 children were followed up after 14 days from T1DM onset. The patients who did not recover from AKI/RTD were followed-up 30 and 60 days later.Main Outcome Measures: AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin and/or tubular reabsorption of phosphate < 85% and/or fractional excretion of Na (FENa) > 2%. ATN was defined by RTD+AKI, prerenal (P)-AKI by AKI+FENa < 1%, and acute tubular damage (ATD) by RTD without AKI.Results: Prevalence of diabetic ketoacidosis (DKA) and AKI were 51.4% and 43.8%, respectively. Prevalence of AKI in T1DM patients with and without DKA was 65.2% and 21.1%, respectively; 33.3% reached AKI stage 2, and 66.7% of patients reached AKI stage 1. RTD was evident in 136/185 (73.5%) patients (32.4% showed ATN; 11.4%, P-AKI; 29.7%, ATD). All patients with DKA or AKI presented with RTD. The physiological and biochemical parameters of AKI and RTD were normal again in all patients. The former within 14 days and the latter within 2months.Conclusions: Most patients with T1DM onset may develop AKI and/or RTD, especially if presenting with DKA. Over time the physiological and biochemical parameters of AKI/RTD normalize in all patients. [ABSTRACT FROM AUTHOR]

Background: Vesicoureteral reflux (VUR) may be associated with renal dysplasia and reduced renal length (RL). The diagnosis of VUR in children with congenital solitary functioning kidney (CSFK) identifies patients at risk of kidney injury but exposes to invasive procedures. Objective: We aimed to test the hypothesis that an RL >2 standard deviation score (SDS) in the first months of life – reflecting renal hyperplasia – could identify CSFK patients with lower probability of presenting VUR. Method: We retrospectively selected 207 CSFK patients with prenatal diagnosis of CSFK and having undergone renal ultrasound (RUS) both at 0–3 and 10–13 months of life, renal scintigraphy, and cystourethrography/cysto-scintigraphy. We compared the cumulative proportion of an RL >2 SDS by Kaplan-Meier analysis and evaluated the odds to present VUR of patients with an RL >2 SDS both at the first and second RUS. Results: Overall, 3.3% of patients with VUR and 22.0% of patients without VUR presented an RL >2 SDS at the first RUS (p = 0.02). At the second RUS, 53.3% of patients with VUR and 52.5% of patients without VUR presented an RL >2 SDS (p = 0.93). Patients without VUR presented higher cumulative proportion of an RL >2 SDS at 3 months of life than those with VUR (p = 0.02). This difference however disappeared at 11 and 13 months of age (p = 0.17 and p = 0.54, respectively). An RL >2 SDS within 3 months of life presented an OR for VUR of 0.12 (95% CI: 0.02–0.92; p = 0.005), while an RL >2 SDS at 12 months of life presented an OR for VUR of 0.96 (95% CI: 0.45–2.1; p = 0.93). Conclusion: Only an RUS made in the first months of life could identify CSFK patients at lower risk of presenting an associated VUR. [ABSTRACT FROM AUTHOR]