Burosumab Efficacy and Safety in Patients with X-Linked Hypophosphatemia: Systematic Review and Meta-analysis of Real-World Data.

To assess the efficacy and safety of burosumab in children and adults with X-linked hypophosphatemia based on real-world evidence. MEDLINE (via PubMed) and Cochrane Library were searched until 18 October 2023 for single-arm (before-after) studies. Registries including Clinicaltrials.gov, EU Clinical Trials, WHO International Clinical Trials Registry Platform, and conference abstracts. The outcomes were a change in serum phosphorus concentrations and change in RSS, a change in serum ALP, bone-specific ALP, a change in the ratio of Tubular maximum reabsorption of Phosphate to Glomerular Filtrate rate, a change in serum 1,25(OH)2D and 25(OH)2D concentrations, change in height Z-score, McMaster Universities Osteoarthritis Index (WOMAC) and safety outcomes. An inverse variance random-effects meta-analysis was applied for data synthesis. Fifteen studies (289 participants) were included. Burosumab treatment improved serum phosphate concentrations [mean difference 0.88 mg/dl, 95% confidence interval 0.70 to 1.07, I2 = 92%), Rickets Severity score (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I2 = 71%), serum alkaline phosphate concentrations (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I2 = 71%), serum 1,25(OH)2D concentrations (mean difference 18.91 pg/ml, 95% confidence interval 6.39 to 31.43, I2 = 96%) and renal phosphate reabsorption (mean difference 1.22 mg/dl, 95% confidence interval 0.70 to 1.74, I2 93%). Burosumab treatment improved overall clinical and laboratory findings in patients with X-linked hypophosphatemia.

Fibroblast growth-factor 23 and vitamin D are associated with iron deficiency and anemia in children with chronic kidney disease.

BACKGROUND: This cross-sectional study investigates the association of fibroblast growth-factor 23 (FGF23) and other bone mineral parameters with iron status and anemia in pediatric chronic kidney disease (CKD). METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), intact parathormone, c-terminal FGF23, a-Klotho, iron (Fe), ferritin, unsaturated iron-binding capacity, and hemoglobin (Hb) were measured in 53 patients from 5 to 19 years old with GFR < 60 mL/min/1.73 m2. Transferrin saturation (TSAT) was calculated. RESULTS: Absolute (ferritin ≤ 100 ng/mL, TSAT ≤ 20%) and functional iron deficiency (ferritin > 100 ng/mL, TSAT ≤ 20%) were observed in 32% and 7.5% of patients, respectively. In CKD stages 3-4 (36 patients), lnFGF23 and 25(OH)D were correlated with Fe (rs = - 0.418, p = 0.012 and rs = 0.467, p = 0.005) and TSAT (rs = - 0.357, p = 0.035 and rs = 0.487, p = 0.003) but not to ferritin. In this patient group, lnFGF23 and 25(OH)D were correlated with Hb z-score (rs = - 0.649, p < 0.001 and rs = 0.358, p = 0.035). No correlation was detected between lnKlotho and iron parameters. In CKD stages 3-4, in multivariate backward logistic regression analysis, including bone mineral parameters, CKD stage, patient age, and daily alphacalcidol dose as covariates, lnFGF23 and 25(OH)D were associated with low TSΑΤ (15 patients) (OR 6.348, 95% CI 1.106-36.419, and OR 0.619, 95% CI 0.429-0.894, respectively); lnFGF23 was associated with low Hb (10 patients) (OR 5.747, 95% CI 1.270-26.005); while the association between 25(OH)D and low Hb did not reach statistical significance (OR 0.818, 95% CI 0.637-1.050). CONCLUSIONS: In pediatric CKD stages 3-4, iron deficiency and anemia are associated with increased FGF23, independently of Klotho. Vitamin D deficiency might contribute to iron deficiency in this population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Association Between Adipokine Profile, Systemic Inflammation, Muscle and Protein Energy Wasting in Children With Chronic Kidney Disease.

OBJECTIVES: This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD). METHODS: We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL. RESULTS: PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 µg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance. CONCLUSIONS: In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

Arterial stiffness indices in children and adolescents with type 1 diabetes mellitus: A meta-analysis.

AIMS: Cardiovascular disease (CVD) represents the most frequent cause of morbidity and mortality among patients with type 1 diabetes mellitus (T1DM). Our aim was to review the evidence and conduct a meta-analysis assessing measures of arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx) in children and adolescents with T1DM compared to healthy controls. METHODS: PubMed and the Cochrane Library were searched for relevant studies published up to 10 May 2021. RESULTS: Twenty-one studies were finally included in the meta-analysis. The T1DM group had significantly higher carotid to femoral PWV levels than that of the control group (mean difference [d]: 0.53 CI: 0.35-0.71, P < 0.00001) but with a fair heterogeneity (I 2:73%). By omitting one study with marked heterogeneity, mean difference in cfPWV remained significantly increased in the T1DM group compared to the control group (mean difference [d]: 0.37 CI: 0.27-0.48, P < 0.00001) but with improved heterogeneity (I2 = 26%). Regarding Aix, the T1DM group had a significantly higher AI@75 index than that of the control group (mean difference [d]: 0.28 CI: 0.17-0.39, P < 0.00001) and with no heterogeneity (I 2 = 8%). CONCLUSIONS: Youths with T1DM show increased arterial stiffness, either as increased carotid-femoral pulse wave velocity or increased augmentation index, early in their course of life compared to healthy controls. PROSPERO REGISTRATION NUMBER: CRD42021253236.

Circulating serum and plasma levels of micro-RNA in type-1 diabetes in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a complex metabolic disorder characterized by hyperglycaemia, with constantly increasing incidence in paediatric population. The discovery of new molecules, such as microRNAs, and their possible interactions with T1DM create novel aspects in the diagnosis of the disease. METHODS: This systematic review and meta-analysis adhered to PRISMA guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and Clinicaltrials.gov. were searched up to 20 April 2020. Inclusion criteria for individual studies were quantification of microRNAs in serum/plasma samples and study groups consisting of children and adolescents with T1DM and healthy controls. Primary outcome of the study was the qualitative expression of microRNAs between the two groups. Statistical analysis was performed with Comprehensive Meta-Analysis Software v3.0. Methodological quality of included studies was assessed using Newcastle-Ottawa scale. RESULTS: A total of 484 studies were retrieved from the initial search of the databases. These were subsequently limited to seven included studies. Seven microRNAs demonstrated contrasting expression between the two groups, with two of them showing significant overexpression in T1DM group (miR-181:95% CI: 0.429 to 1.341 P < .001, miR-210:95% CI: 0.381 to 0.852, P < .001) and one micro-RNA being significantly overexpressed in control group (miR-375:95% CI: 0.293 to 1.459, P = .003). CONCLUSION: A total of three micro-RNA molecules appeared to have a significantly different expression in T1DM patients, serving as a possible diagnostic panel of biomarkers. These findings may contribute as reference for future research to further support the use of microRNAs as a novel diagnostic tool in T1DM.

Muscle-bone axis in children with chronic kidney disease: current knowledge and future perspectives.

Bone and muscle tissue are developed hand-in-hand during childhood and adolescence and interact through mechanical loads and biochemical pathways forming the musculoskeletal system. Chronic kidney disease (CKD) is widely considered as both a bone and muscle-weakening disease, eventually leading to frailty phenotype, with detrimental effects on overall morbidity. CKD also interferes in the biomechanical communication between two tissues. Pathogenetic mechanisms including systemic inflammation, anorexia, physical inactivity, vitamin D deficiency and secondary hyperparathyroidism, metabolic acidosis, impaired growth hormone/insulin growth factor 1 axis, insulin resistance, and activation of renin-angiotensin system are incriminated for longitudinal uncoordinated loss of bone mineral content, bone strength, muscle mass, and muscle strength, leading to mechanical impairment of the functional muscle-bone unit. At the same time, CKD may also interfere in the biochemical crosstalk between the two organs, through inhibiting or stimulating the expression of certain osteokines and myokines. This review focuses on presenting current knowledge, according to in vitro, in vivo, and clinical studies, concerning the pathogenetic pathways involved in the muscle-bone axis, and suggests approaches aimed at preventing bone loss and muscle wasting in the pediatric population. Novel therapeutic targets for preserving musculoskeletal health in the context of CKD are also discussed.

Association between insulin growth factor-1, bone mineral density, and frailty phenotype in children with chronic kidney disease.

BACKGROUND: This cohort study investigates the association between insulin growth factor-1 (IGF-1), bone mineral density, and frailty phenotype in children with chronic kidney disease (CKD). METHODS: Forty-six patients (median age 14.5 years) were prospectively enrolled. Frailty phenotype was defined as the presence ≥ 3 of the following indicators: suboptimal growth/weight gain (body mass index height age < 5th percentile or height < 3rd percentile or loss of ≥ 10 percentiles/year in at least one parameter), low muscle mass (lean tissue mass height age < 5th percentile or loss of ≥ 10 percentiles/year), general fatigue reported by parent or child, and C-reactive protein > 3 mg/l. Lumbar bone mineral apparent density (LBMAD) was measured by dual-energy X-ray absorptiometry, body composition by bioimpedance spectroscopy, and IGF-1 by enzyme-labeled chemiluminescent immunometric assay. RESULTS: Frailty phenotype (seven patients) was more frequent in advanced CKD (estimated glomerular filtration rate < 30 ml/min/1.73m2) (p = 0.014). IGF-1 and LBMAD z-scores were lower in patients with suboptimal growth/weight gain (14 patients) (p = 0.013, p = 0.012), low muscle mass (nine patients) (p = 0.001, p = 0.009), and general fatigue (eight patients) (p < 0.001, p = 0.004). IFG-1 and LBMAD z-scores were associated with frailty phenotype (OR 0.109, 95% CI 0.015-0.798 and OR 0.277, 95% CI 0.085-0.903) after adjustment for CKD stage. IGF-1 z-score was associated with LBMAD < 5th percentile (six patients) (OR 0.020, 95% CI 0.001-0.450) after adjustment for CKD stage. The association between LBMAD and frailty phenotype lost significance after adjustment for IGF-1. CONCLUSION: Frailty phenotype is more frequent in advanced pediatric CKD. IGF-1 is negatively associated with frailty phenotype and interferes in the association between frailty and LBMAD.

Association between relative fat mass, uric acid, and insulin resistance in children with chronic kidney disease.

INTRODUCTION: This cross-sectional study investigates the association between insulin resistance (IR) and serum uric acid (sUA) and relative fat (RFM) and lean mass (RLM) profiles in children with chronic kidney disease (CKD). MATERIAL AND METHODS: RLM and RFM were assessed by bioimpedance spectroscopy in 41 children and adolescents. Normal weight obesity (NWO) was defined as normal height-age body mass index and RFM >85th percentile, according to age and sex. Homeostatic model assessment of insulin resistance (HOMA-IR) level >95th percentile, according to sex and pubertal stage, and sUA >7 mg/dl were used to define IR and hyperuricemia, respectively. RESULTS: High RFM (15 patients) and NWO (7 patients) were associated with higher HOMA-IR in total (p < 0.001) and normal-weight patients (p = 0.004), respectively. RFM was positively and RLM negatively correlated to HOMA-IR (rs = 0.500, p = 0.001 and rs = -0.539, p < 0.001, respectively) and sUA (rs = 0.370, p = 0.017 and rs = -0.325, p = 0.038, respectively), while sUA was positively correlated to HOMA-IR (rs = 0.337, p = 0.031). Hyperuricemia (16 patients) was positively associated with higher RFM and HOMA-IR (p = 0.001 and p = 0.010, respectively). The correlation between sUA and HOMA-IR lost significance after adjustment for RFM. In logistic regression analysis, a 5% increase in RFM was associated with IR (11 patients) independently of the age, sex, sUA, and CKD stage in both total (OR 2.174, 95% CI 1.115-4.225) and normal-weight (OR 3.504, 95% CI 1.110-11.123) patients. CONCLUSION: Children with high RFM, including those presenting NWO, are at risk for IR regardless of CKD stage. RFM is probably the mediator of the link between sUA and IR.

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature.

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to ß-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

Evaluation of continuous flash glucose monitoring in a pediatric ICU setting.

Glucose monitoring is of great importance among patients in intensive care units (ICU). The purpose of this study is to assess the performance of a new flash glucose monitoring (FGM) system in a pediatric ICU setting. Sixteen consecutive patients admitted in pediatric ICU aged > 4 years, expected length stay > 2 days and with no medication or existing diagnosis affecting glucose metabolism were enrolled. FreeStyle Libre sensor was applied to the upper arm of the patients (8 boys). FGM measurements were compared to 3 "references": arterial blood gas analysis, capillary blood analysis and biochemical serum analysis. Mean age of patients was 8.03 ± 2.91 years. Sensors remained in situ for a median of 9.71 ± 5.35 days. Removal of the sensor was mainly attributed to the completion of the predefine life-span of the sensor or discharge of the patient from the ICU. We compared 711 pairs of measurements between the sensor and other glucose measurement methods. Glucose values from the sensor were consistently lower with mean absolute relative difference (MARD) being 28.34%, 25.11% and 18.99% compared to the blood gas analyzer, capillary blood glucose meter, and biochemical serum analysis, respectively, but a wide interindividual variability. Significant linear correlations between age and MARD values were observed. Surveillance error grid (SEG) analysis showed 92.04%, 94.67% and 95.52% of the readings in the none or slight risk zone respectively. FreeStyle Libre is well tolerated although not adequately accurate with a tendency to underestimate glucose levels in critically ill pediatric patients.

Cortisol Levels in Glucagon Stimulation Test in Children Assessed for Short Stature: Clinical and Laboratorial Correlations.

To assess total cortisol levels in children being evaluating for short stature with normal cortisol reserve and to correlate this response to clinical and laboratory data. Children assessed with glucagon test in our department were recruited in this study retrospectively. Inclusion criteria were: i) age>1 year, ii) absence of chronic illness or medication interfering with ACTH-cortisol axis, iii) GH stimulation levels>3ng/mL at least in one provocation test (glucagon or clonidine), iv) absence of multiple pituitary growth hormone deficiencies, v) normal short Synacthen test in cases of low cortisol response in glucagon test.Two hundred and thirty-seven subjects (160 males, 67.5%) with a mean age of 9.02±3.19 years, were finally included in the analysis. Cortisol peak levels but not cortisol AUC were significantly increased in females compared to males (26.83±7.31 µg/dl vs. 24.04±7.20 µg/dl). When linear correlations were studied, both cortisol peak levels and cortisol AUC were linearly but inversely correlated to age (r=-0.234, p<0.001 and r=-0.315, p<0.001, respectively). Finally, cortisol AUC was inversely correlated to weight Z-scores (r=-0.160, p=0.014). When our analysis was limited only to subjects with intact GH response (GH peak> 7 ng/mL), age was still inversely correlated to cortisol AUC (r=-0.312, p<0.001), and cortisol AUC was linearly correlated to GH AUC assessed with clonidine test (r=0.223, p=0.013). Girls, younger and thinner children exhibit higher cortisol response to glucagon test.

Subclinical arterial damage in children and adolescents with type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Type 1 diabetes is an important risk factor for the development of cardiovascular disease. Pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) measurements are well recognized as independent predictors for future cardiovascular disease. The aim of the present study was to systematically review the literature and conduct a meta-analysis assessing measures of subclinical arterial damage in children and adolescents with type 1 diabetes in comparison to healthy controls. METHODS: PubMed and Cochrane Library were searched to identify studies comparing cIMT and carotid-femoral PWV levels between children with type 1 diabetes and healthy controls. Meta-analysis was performed to compare the difference of overall mean cIMT and carotid-femoral PWV levels between the two groups. New Castle Ottawa quality assessment scale for case-control studies was used to assess study quality. RESULTS: Twenty-three studies were finally included in the meta-analysis (20 studies for cIMT and 4 studies for carotid-femoral PWV). Youth with type 1 diabetes had significantly higher cIMT levels than controls (mean difference [d] = 0.03, 95% confidence interval [CI] = 0.02-0.04), as well as higher carotid-femoral PWV levels (d = 0.26, 95% CI = 0.18-0.34). Heterogeneity was present only in the cIMT analysis (I2 > 90%). CONCLUSIONS: Youth with type 1 diabetes showed signs of subclinical arterial damage, as suggested by higher levels of cIMT and carotid-femoral PWV compared to healthy controls at childhood and adolescence. Preventive and therapeutic interventions early in course of disease may be further studied to decrease morbidity in this high-risk young patient group. PROSPERO registration number: 2018 CRD42018094354.

TIMING OF GH PEAK IN BOTH GLUCAGON AND CLONIDINE TESTS IS OF MAJOR CLINICAL IMPORTANCE.

Objective: To detect a possible correlation between timing of the peak value of growth hormone (GH) during stimulatory tests (STs) and the effectiveness of treatment with recombinant human growth hormone (rhGH) in children with idiopathic GH deficiency (iGHD). Methods: We retrospectively studied 92 patients with iGHD (57 boys; mean age at diagnosis: 9.93 years). Diagnosis was confirmed by 2 different STs, glucagon stimulation test (GST), and clonidine stimulation test (CST). Auxologic parameters were recorded, while observed and predicted (according to KIGS Prediction Model) height velocity during the first year of treatment and the index of responsiveness (IoR) were calculated for the prepubertal children (n = 65). Results: Atypical GST was defined as that with peak GH value at time 0 minutes, 30 minutes, 60 minutes, or 180 minutes, whereas atypical CST was defined as that with peak timing at 0 minutes, 30 minutes, or 120 minutes. Atypical GST was detected in 18 patients (19.57%). IoR was lower in the prepubertal children with atypical GST (-1.81 ± 0.67 versus -1.34 ± 0.85; P = .051). In the CST, the 18 children who had atypical timing, had significantly lower IoR (-1.86 ± 0.66 versus -1.35 ± 0.84; P = .047). When the patients were categorized according to the number of atypical tests, significant differences in the IoR were detected (-2.09 ± 0.68 with 2 atypical STs [n = 6], -1.64 ± 0.61 with 1 atypical ST [n = 16], and -1.29 ± 0.87 with no atypical ST [n = 43], P = .045). Conclusion: The presence of atypical peak GH timing during ST may be a factor that predicts lower growth hormone velocity during the first year of rhGH treatment in prepubertal children with iGHD. Abbreviations: CST = clonidine stimulation test; GH = growth hormone; GHD = growth hormone deficiency; GST = glucagon stimulation test; iGHD = idiopathic growth hormone deficiency; IoR = index of responsiveness; rhGH = recombinant human growth hormone; SDS = standard deviation scores; ST = stimulatory test.

Glucose Levels Before the Onset of Asparaginase Predicts Transient Hyperglycemia in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Transient hyperglycemia (TH) represents an acknowledged adverse event that occurs during treatment in children with acute lymphoblastic leukemia (ALL) and has recently been associated with an increased risk for developing metabolic disturbances in future life. Our aim was to estimate the incidence of TH and to identify risk factors, thus serving as markers for identifying candidates for prevention interventions. PROCEDURE: All patients treated with induction treatment for ALL in our department from January 2004 to April 2015 had their data retrieved from medical files and retrospectively analyzed. RESULTS: One hundred and two children with ALL treated at our department were identified (49 females and 53 males) with a mean age of 6.03 ± 3.78 years at the time of diagnosis. Sixteen patients developed TH (15.68%). Age at diagnosis >10 years is associated with an 11-fold increase in the risk of developing TH. Additionally, fasting glucose on the eighth day of treatment is an important prognostic factor as fasting glucose >100 mg/dl at that time point is associated with a threefold increase in developing TH during residual treatment period. CONCLUSIONS: Fasting glucose levels >110 mg/dl on the eighth day of treatment could serve as a trigger for intervention strategies that will prevent the development of TH in pediatric patients treated for ALL. Additional studies are needed to confirm and further extend this preliminary observation.

Longitudinal assessment of bone quality in pediatric patients with chronic kidney disease in relation to treatment modality.

Children with chronic kidney disease (CKD) are at high risk of developing impaired bone quality. Our aim was to investigate changes of bone quality in children with CKD in relation to their treatmant using two imaging techniques-dual energy X-ray absorptiometry and quantitative ultraSonography (QUS). Thirty-three patients with CKD (18 boys and 15 girls, mean age 10.37 ± 3.37 years) were evaluated with bone mineral density (BMD) measured by DXA at the lumbar spine and hip and with speed of sound (SOS) measured by QUS at the radius and tibia at the beginning and at the end of the study. The patient cohort consisted of 14 patients with CKD stage 3-4 not treated with dialysis (CKD group), 5 patients on peritoneal dialysis treatment (PD group) and 14 patients after kidney transplantation (RTx group). BMD measurements did not show any significant changes in CKD and PD patients during the study. There was a reduction in BMD measured at the lumbar spine, femoral neck and total hip in RTx patients that was approaching significance. During the 2-year follow-up, SOS measurements at the radius decreased significantly in PD patients, whereas SOS measurements at the tibia significantly improved in RTx patients. No significant changes in QUS parameters were recorded for patients in the CKD group. In conclusion, our study shows that QUS parameters seem to better reflect the state of hyperparathyroidism of renal osteodystrophy as they deteriorate significantly in patients on dialysis and improve after renal transplantation.

Assessment of arterial stiffness in paediatric patients with type 1 diabetes mellitus.

AIMS: To investigate early indicators of cardiovascular disease (CVD) in children and adolescents with type 1 diabetes mellitus (T1DM), focusing on pulse wave velocity (PWV) and its associations with various anthropometric and glycemic parameters. PATIENTS AND METHODS: A total of 124 children and adolescents with T1D (mean age 10.75 ± 3.57 years) were included in this cross-sectional study. Anthropometric data, including height, weight, body mass index (BMI), glycemic parameters, such as HbA1c and time in range (TIR) were assessed. PWV was assessed by oscillometric method using the Mobil-O-Graph PWA device. Univariate and multivariate linear regression were used to explore the association of PWV z-score with anthropometric, demographic, and glycaemic variables. RESULTS: Significant negative association between PWV and age and height (ß = -0.336, 95 % CI -0.44 to -0.25, p < 0.001 and ß = -0.491, 95 % CI -0.62 to -0.36, p < 0.001, respectively), while gender showed a significant positive association with PWV, with females displaying higher PWV values compared to males (ß = 0.366, 95 % CI 0.17 to 0.56, p < 0.001). TIR was positively associated with PWV (ß = 0.092, 95 % CI 0.01 to 0.16, p = 0.017 only for patients having TIR ≤ 50 %. Finally, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively associated with PWV (ß = 0.086, 95 % CI 0.02 to 0.14, p = 0.007 and ß = 0.152, 95 % CI 0.07 to 0.23, p < 0.001, respectively). CONCLUSION: Youth with T1DM who spend <50 % of time in range exhibit uniquely increased signs of arterial stiffness, indicating that poor glycemic control may contribute to early vascular damage. Differences related to age, gender and height should be considered.

Earlier Menarche in Greek Girls Born by Caesarean Section: A Case-Control Study.

Objectives: The purpose of this study was to report on the menarcheal age in girls of Greek origin and assess its potential associations with their demographic and perinatal data, as well as their maternal menarcheal age. Methods: In this case-control study, adolescent girls were recruited between September 2021 and September 2022 from two Pediatric Endocrinology Units, Aristotle University of Thessaloniki, Greece. Eligible participants included Greek girls up to the age of 18 years, with menarche and the absence of chronic disease or chronic medication use. Participants were divided into two groups, the early menarche group and the control group (menarche before or after 11 years of age, respectively). Data included participants' maternal menarcheal age, their chronological age, place of residence, anthropometric data (at recruitment) and perinatal data (birth order, gestational age, type of delivery, birth weight/length). Results: A total of 100 girls aged 7-17 years (mean age ± SD 12.51 ± 2.59 years) were included in this study. The mean ± SD menarcheal age of the total sample was 11.47 ± 1.55 years (median 11.20 years; range 7.50-16.25 years); 43% had early menarche (median menarcheal age 10.50 years; range 7.50-10.91 years), and 57% had menarche after age 11 (median menarcheal age 12.08 years; range 11.00-16.25 years). The caesarean section rate was significantly (p < 0.001) higher in girls with early menarche (83.7%) than controls, whereas other variables did not differ significantly between groups. Conclusions: This Greek sample demonstrated a relatively young age at menarche with a significant proportion of girls with early menarche; in the latter group, the rate of caesarian sections was significantly higher than controls.

A two-yr prospective study of bone health in children after renal transplantation employing two imaging techniques.

The aim of this study was to prospectively and longitudinally evaluate bone properties with the use of two bone imaging techniques (dual energy X-ray absorptiometry [DXA], and quantitative ultraSonography [QUS]) in pediatric renal transplant recipients. Fourteen patients (eight boys and six girls) with a mean age of 12.25 ± 3.11 yr (range: 8-17.5 yr) completed a two-yr follow-up. Measurements of bone mineral density (BMD) by DXA at lumbar spine and hip and speed of sound (SOS) by QUS at radius and tibia were performed at the beginning and at the end of the study. A significant improvement in mean Z-score of SOS values measured at tibia (1.01 ± 1.31 vs. -0.46 ± 1.14, p = 0.005) was observed. On the contrary, mean Z-score of BMD values measured at femoral neck was significantly reduced (-1.95 ± 2.15 vs. -0.33 ± 1.13, p = 0.041). Finally, multivariate stepwise regression analyses showed that glomerular filtration rate at the beginning of the study was the best predictor of the difference in BMD Z-scores measured at lumbar spine. Additionally, values of intact parathormone (iPTH) at the beginning of the study and the change in iPTH throughout the study predicted the 72.3% of the difference in Z-score of SOS measured at radius with an inverse relationship.