High Tg/HDL-Cholesterol Ratio Highlights a Higher Risk of Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Few data are currently available on the reliability of the different anthropometric, instrumental and biochemical indexes in recognizing the presence of metabolic syndrome (MetS) in children and adolescents with severe obesity. Therefore, the objective of our study was to find out the simplest and most accurate predictive index of MetS in this population at-risk. In 1065 children and adolescents (563 f, 502 m), aged 14.6 ± 2.1 years (range 10-17), with severe obesity [BMI-SDS 3.50 ± 0.36 (range 3.00-5.17)], the following indexes were evaluated: BMI, BMI-SDS, Tri-Ponderal Mass Index, Waist-to-Height ratio, TG/HDL-Cholesterol ratio, Cardiometabolic Index (CMI), and Visceral Adiposity Index (VAI). For each subject, all the components of MetS, defined according to the IDF criteria, were determined. Overall, the presence of MetS was found in 324 patients (30.4%), 167 males (33.3%) and 157 females (27.9%). According to the ROC analysis, three indexes (VAI, CMI and TG/HDL-Cholesterol ratio), performed significantly better than the other ones in identifying MetS, with no difference among them. In conclusion, the TG/HDL ratio, which just needs the evaluation of two simple biochemical parameters, offers the same accuracy as other more sophisticated indexes in recognizing MetS in children and adolescents with severe obesity, thus making it the best predictor to be easily used.

Seronegative phenotype in a pediatric population with Hashimoto's thyroiditis.

PURPOSE: The aim was to verify in a pediatric population with Hashimoto's thyroiditis whether there is a relationship between antithyroid antibodies and inflammatory status on thyroid ultrasound and thyroid function. SUBJECTS AND METHODS: A total of 154 children and adolescents, aged 4 to 18 years, diagnosed with Hashimoto's thyroiditis with normal body weight were followed up for 1 year. RESULTS: Patients with only antiperoxidase antibodies presented with higher TSH levels than subjects with only antithyroglobulin antibodies (p 0.027) but with similar FT4 levels and thyroid score. Prevalence of seronegative Hashimoto's thyroiditis in this cohort was 12.3% (19/154). At diagnosis, the seronegative group presented with lower prevalence of overt hypothyroidism, symptoms of hypothyroidism, and thyroid score, meaning less severe thyroid involvement. In contrast, similar TSH and FT4 values were found at diagnosis and during follow-up in both the seronegative and seropositive groups. A comparison between patients with seronegative Hashimoto's thyroiditis and an overweight/obese antibody-negative population, who presented superimposable altered parenchymal pattern on thyroid ultrasound without circulating antithyroid antibodies, presented similar clinical data. CONCLUSION: We report for the first time in the literature that seronegative Hashimoto's thyroiditis in the pediatric age group has a less severe pattern. The seronegative group presents similar characteristics to those of overweight/obese children and adolescents with ultrasound changes, but, according to the established knowledge, the latter condition is reversible and does not need follow-up examinations.

Impact of personal protective equipment on neonatal resuscitation procedures: a randomised, cross-over, simulation study.

BACKGROUND AND OBJECTIVE: Healthcare providers should use personal protective equipment (PPE) when performing aerosol-generating medical procedures during highly infectious respiratory pandemics. We aimed to compare the timing of neonatal resuscitation procedures in a manikin model with or without PPE for prevention of SARS-COVID-19 transmission. METHODS: A randomised controlled cross-over (AB/BA) trial of resuscitation with or without PPE in a neonatal resuscitation scenario. Forty-eight participants were divided in 12 consultant-nurse teams and 12 resident-nurse teams. The primary outcome measure was the time of positive pressure ventilation (PPV) initiation. The secondary outcome measures were duration of tracheal intubation procedure, time of initiation of chest compressions, correct use of PPE and discomfort/limitations using PPE. RESULTS: There were significant differences in timing of PPV initiation (consultant-nurse teams: mean difference (MD) 6.0 s, 95% CI 1.1 to 10.9 s; resident-nurse teams: MD 11.0 s, 95% CI 1.9 to 20.0 s), duration of tracheal intubation (consultant-nurse teams: MD 22.0 s, 95% CI 7.0 to 36.9 s; resident-nurse teams: MD 9.1 s, 95% CI 0.1 to 18.1 s) and chest compressions (consultant-nurse teams: MD 32.3 s, 95% CI 14.4 to 50.1 s; resident-nurse teams: MD 9.1 s, 95% CI 0.1 to 18.1 s). Twelve participants completed the dressing after entering the delivery room. PPE was associated with visual limitations (43/48 participants), discomfort in movements (42/48), limitations in communication (32/48) and thermal discomfort (29/48). CONCLUSIONS: In a manikin model, using PPE delayed neonatal resuscitation procedures with potential clinical impact. Healthcare workers reported limitations and discomfort when wearing PPE. TRIAL REGISTRATION NUMBER: NCT04666233.

Parameters of Glucose Homeostasis in the Recognition of the Metabolic Syndrome in Young Adults with Prader-Willi Syndrome.

To verify the accuracy of different indices of glucose homeostasis in recognizing the metabolic syndrome in a group of adult patients with Prader-Willi syndrome (PWS), 102 PWS patients (53 females/49 males), age ±SD 26.9 ± 7.6 yrs, Body Mass Index (BMI) 35.7 ± 10.7, were studied. The following indices were assessed in each subject during an oral glucose tolerance test (OGTT): 1 h (>155 mg/dL) and 2 h (140-199 mg/dL) glucose levels, the oral disposition index (ODI), the insulinogenic index (IGI), the insulin resistance (HOMA-IR) were evaluated at baseline, 1 h and 2 h. Although minor differences among indices were found, according to the ROC analysis, no index performed better in recognizing MetS. Furthermore, the diagnostic threshold levels changed over the years and therefore the age-related thresholds were calculated. The easily calculated HOMA-IR at baseline may be used to accurately diagnose MetS, thus avoiding more complicated procedures.

Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature.

Intracranial penetration during attempted nasotracheal intubation is a potentially devastating complication, which should be carefully evaluated and the risk should be addressed in neonatal resuscitation trainings.

The Role of Different Indexes of Adiposity and Body Composition for the Identification of Metabolic Syndrome in Women with Obesity.

The aim of this study was to compare the accuracy of different indexes of adiposity and/or body composition in identifying the metabolic syndrome (MetS) in a group of 1528 Caucasian women with obesity: (age ± standard deviation (SD): 50.8 ± 14 years (range 18-83); body mass index (BMI) 43.3 ± 5.9 kg/m2 (30.7-72.9 kg/m2)). The following indexes were assessed in each subject: BMI, fat-free mass index (FFMI), fat mass index (FMI), tri-ponderal mass index (TMI), waist-to-height ratio (WtHR), and the body mass fat index (BMFI). Thereafter, a threshold value adjusted for age, which could identify MetS, was calculated for each index. A significant correlation was found among all indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, WtHR performed significantly better in the whole group and in the different age groups, apart from a lack of statistical difference between WtHR and BMFI in the 45-55 years age group. In conclusion, WtHR seems to be a fair index useful for identifying MetS in women with obesity. The use of thresholds appropriate for age can help further improve its accuracy, thus reinforcing the clinical evaluation for MetS screening.

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy.

Introduction: Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients. Methods: We analyzed data of patients identified by the Regional Centre for Newborn Screening of Verona and followed by the Inherited Metabolic Disease Unit of Verona and Neonatal Intensive Care Unit of Bolzano, Italy, from 2014 to 2020. Results: Thirty-seven patients were diagnosed by NBS (five profound and 32 partial BD), with a total incidence of 1:5,996. All were started on biotin at diagnosis and presented no symptoms at follow-up. Analysis of parents and siblings led to identification of five asymptomatic patients with partial BD: one asymptomatic parent and four young siblings. Genetic analysis of the BTD gene identified 17 different genotypes and one mutation not previously known. Discussion: Our data confirm that NBS introduction had a dramatic impact on BD diagnosis, and the incidence has increased significantly compared to other areas. Partial defects are more common than profound and have a distinctive genotype. Partial BD treatment is still controversial even at what dose of biotin and for how long. At the end, BD treatment is very easy and inexpensive and prevents severe neurological damage. Sharing experiences is essential to achieving guidelines for treatment and follow-up and a better genotype-phenotype correlation.

Accuracy of Different Indexes of Body Composition and Adiposity in Identifying Metabolic Syndrome in Adult Subjects with Prader-Willi Syndrome.

(1) Objective: To compare the accuracy of different indexes of adiposity and/or body composition in identifying metabolic syndrome (MetS) in adult patients suffering from Prader‒Willi syndrome (PWS). (2) Study Design: One hundred and twenty PWS patients (69 females and 51 males), aged 29.1 ± 9.4 years, body mass index (BMI) 36.7 ± 9.9, were evaluated. The following indexes were assessed in each subject: body mass index (BMI), fat-free mass index (FFMI), fat mass index (FMI), tri-ponderal mass index (TMI), waist-to-height ratio (WtHR) and the body mass fat index (BMFI), which adjusts the BMI for the percentage of body fat and waist circumference. Thereafter, a threshold value adjusted for age and sex, which could identify MetS, was calculated for each index. (3) Results: A significant correlation was found among all indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, BMFI performed better than FMI (p < 0.05) and BMI better than TMI (p < 0.05), but only in females. (4) Conclusions: Besides small differences, all the indexes taken into consideration seem to have the same ability to identify MetS in adults with PWS. Consequently, the most easily calculated index, i.e., BMI, should be considered as the best choice. The use of thresholds appropriate for sex and age can further improve its accuracy.

Indexes of adiposity and body composition in the prediction of metabolic syndrome in obese children and adolescents: Which is the best?

BACKGROUND AND AIM: There is no agreement about which index of adiposity and/or body composition is the most accurate in identifying the metabolic syndrome (METS). The aim of our study was to compare the accuracy of the different indexes in order to recognize the most reliable. METHODS AND RESULTS: We evaluated 1332 obese children and adolescents (778 females and 554 males), aged 14.4 ± 1.8 yrs, Body Mass Index (BMI) standard deviation scores (SDS) 2.99 ± 0.55, followed at the Istituto Auxologico Italiano, a tertiary center for childhood obesity. For each subject the following indexes were assessed: BMI, BMI SDS, Fat-Free Mass Index (FFMI), Fat Mass Index (FMI), Tri-Ponderal Mass Index (TMI), Waist-to-Height ratio (WtHR) and a new one, the Body Mass Fat Index (BMFI), which normalizes the BMI for percentage of body fat and the waist circumference. Thereafter we calculated for each index a threshold value for age and sex, in order to compare their accuracy, sensitivity and specificity in identifying the METS. There was a good correlation among indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, some of them, in particular the BMFI and the BMI, performed better than the other ones, although the differences were small. CONCLUSIONS: BMI, which neither considers body composition nor fat distribution, performs as good as other indexes, and should therefore be the preferred one, also because of the easiness of its calculation.

Bone Geometry, Quality, and Bone Markers in Children with Type 1 Diabetes Mellitus.

Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA). Bone strength was evaluated as Bending Breaking Resistance Index (BBRI) from the geometric data. Bone turnover markers (PINP, CTX-I, and BAP), sclerostin, Dkk-1, PTH, and 25OH-Vitamin D were also assessed. A group of healthy 40 subjects of normal body weight and height served as controls for the bone markers. D (- 0.99 ± 0.98), d (- 0.41 ± 0.88), CA (- 0.85 ± 0.78), and MA (- 0.46 ± 0.78) were all significantly smaller than in controls (p < 0.01). BBRI was significantly lower (- 2.61 ± 2.18; p < 0.0001). PTH, PINP, and BAP were higher in the diabetic children. Multiple regression analysis showed that CA and D were influenced by insulin/Kg/day and by BMI, while d was influenced by PINP only. Type 1 diabetic children show smaller and weaker bones. The increased bone turnover could play a key role since it might amplify the deficit in bone strength associated with the inadequate osteoblastic activity caused by the disease itself.

Serum α-klotho levels are not informative for the evaluation of growth hormone secretion in short children.

BACKGROUND: α-Klotho is a transmembrane protein that can be cleaved and act as a circulating hormone (s-klotho). s-Klotho serum levels seem to reflect growth hormone (GH) secretory status. We investigated the role of s-klotho as a reliable marker of GH secretion in short children and the factors influencing its secretion. METHODS: We enrolled 40 short Egyptian children (20 GH deficiency [GHD] and 20 idiopathic short stature [ISS]). They underwent a pegvisomant-primed insulin tolerance test (ITT) and were accordingly reclassified as 16 GHD and 24 ISS. The samples obtained before and 3 days after pegvisomant administration, prior to the ITT, were used for assaying insulin-like growth factor (IGF)-I and s-klotho. RESULTS: IGF-I and s-klotho serum levels were not significantly different (p=0.059 and p=0.212, respectively) between GHD and ISS. After pegvisomant, a significant reduction in IGF-I and s-klotho levels was found in both groups. s-Klotho significantly correlated only with IGF-I levels in both groups. CONCLUSIONS: s-Klotho mainly reflects the IGF-I status and cannot be considered a reliable biomarker for GH secretion in children.

Thyroid function in children and adolescents with Hashimoto's thyroiditis after l-thyroxine discontinuation.

OBJECTIVE: Thyroid function may recover in patients with Hashimoto's thyroiditis (HT). DESIGN: To investigate thyroid function and the need to resume l-thyroxine treatment after its discontinuation. SETTING: Nine Italian pediatric endocrinology centers. PATIENTS: 148 children and adolescents (25 m and 123 f) with HT on treatment with l-thyroxine for at least one year. INTERVENTION AND MAIN OUTCOME MEASURE: Treatment was discontinued in all patients, and serum TSH and fT4 concentrations were measured at the time of treatment discontinuation and then after 2, 6, 12 and 24 months. Therapy with l-thyroxine was re-instituted when TSH rose >10 U/L and/or fT4 was below the normal range. The patients were followed up when TSH concentrations were between 5 and 10 U/L and fT4 was in the normal range. RESULTS: At baseline, TSH was in the normal range in 139 patients, and was between 5 and 10 U/L in 9 patients. Treatment was re-instituted after 2 months in 37 (25.5%) patients, after 6 months in 13 patients (6.99%), after 12 months in 12 patients (8.6%), and after 24 months in an additional 3 patients (3.1%). At 24 months, 34 patients (34.3%) still required no treatment. TSH concentration >10 U/L at the time of diagnosis was the only predictive factor for the deterioration of thyroid function after l-thyroxine discontinuation. CONCLUSIONS: This study confirms that not all children with HT need life-long therapy with l-thyroxine, and the discontinuation of treatment in patients with a TSH level <10 U/L at the time of diagnosis should be considered.

The Influence of GH Treatment on Glucose Homeostasis in Girls With Turner Syndrome: A 7-Year Study.

CONTEXT: Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity. OBJECTIVE: To longitudinally study insulin sensitivity [via homeostasis model assessment of insulin sensitivity (HOMA-S)], insulin secretion [insulinogenic index (IGI)], and capacity of ß cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in girls with Turner syndrome (TS) undergoing GH treatment. DESIGN AND SETTING: Longitudinal, retrospective, 7-year study conducted in a tertiary pediatric endocrine unit and university pediatric clinic. PATIENTS AND METHODS: We studied 104 patients with TS (mean age ± standard deviation, 9.1 ± 3.4 years) for a median of 7.2 years. INTERVENTION: Every year, the children underwent an oral glucose tolerance test, which was used to calculate HOMA-S, IGI, and ODI. RESULTS: HOMA-S, IGI, and ODI did not significantly change. CONCLUSION: The results are reassuring, showing no negative influence of GH treatment on insulin sensitivity and on ß-cell secretory capacity in girls with TS.

A thicker intima-media carotid wall was found in a cohort of children with recent onset migraine.

AIM: Migraine affects approximately 10-20% of the general population, including children and adolescents, and an association between migraine and increased risks for cardiovascular disease and stroke have been reported in adult patients. This study aimed to address the lack of data on children with migraine. METHODS: This study comprised 30 children and adolescents (16 male) with migraine. We evaluated their biochemical profile, glucose homeostasis, vascular function by flow-mediated dilatation and arterial structure by carotid intima-media thickness (cIMT). A group of 32 age, sex and auxologically matched children (17 male) served as controls. RESULTS: The group of children with migraine had a normal biochemical profile and glucose homeostasis, but presented with significantly thicker cIMT than the control group (0.48 ± 0.07 mm versus 0.45 ± 0.04, p < 0.05). CONCLUSION: We observed a significantly thicker cIMT in children with migraine compared with the controls. The brief time interval between the onset of the disease and the time of the study makes it unlikely that repetitive migraine attacks could be responsible for the thickening of the cIMT. Thus, it may be speculated that primitive vascular function abnormalities were wholly or partly responsible for the development of migraine in this paediatric cohort.

The Influence of Growth Hormone Treatment on Glucose Homeostasis in GrowthHormone-Deficient Children: A Six-Year Follow-Up Study.

BACKGROUND: Growth hormone (GH) influences glucose homeostasis by negatively affecting insulin sensitivity, leading to a compensatory increase in insulin secretion. It has recently been reported, in animals and humans, that GH might also stimulate insulin secretion by directly affecting the growth and function of pancreatic ß-cells. The aim of this work was to longitudinally study the insulin sensitivity (HOMA-S), insulin secretion [insulinogenic index (IGI)] and capacity of ß-cells to adapt to changes in insulin sensitivity [oral disposition index (ODI)] in GH-deficient (GHD) children under GH treatment. METHODS: We studied 99 GHD (62 male, 37 female; age 8.9 ± 3.5 years) children for a median period of 6 years (range 1.5-16.2). Every year, our patients underwent an oral glucose tolerance test, which was used to calculate the HOMA-S, IGI and ODI. RESULTS: Although HOMA-S remained unchanged, an increase in IGI and ODI was observed, becoming significant after 6 years of treatment (1.25 ± 1.28 vs. 2.35 ± 2.38, p < 0.05 and 0.57 ± 0.68 vs. 1.50 ± 1.92, p < 0.01, respectively). CONCLUSION: Our results suggest a positive influence of GH treatment on the ß-cell secretory capacity in children with GH deficiency. © 2016 S. Karger AG, Basel.

The effect of two different GH dosages on final height and bone geometry.

BACKGROUND: Growth hormone (GH) has a strong positive influence on bone, stimulating both bone elongation and increase in size. The aim of the study was to compare the effect of two different GH dosages on final height and bone geometry in two groups of GH-deficient children. METHODS: We evaluated 121 children (86 m, 35f). Group 1 (77 patients) treated with GH at a mean dose of 0.16 mg/kg/week and group 2 (44 patients) at 0.3 mg/kg/week. Bone geometry was evaluated at final height from a digitalized X-ray of the left hand considering the following parameters: metacarpal index (MI), cross-sectional area (CSA), cortical area (CA) and medullary area (MA). RESULTS: At baseline, group 2 was shorter than group 1 (-1.54 vs -1.01 SDS; p < 0.005), while at final height there was no difference. Height gain was significantly greater in group 2 than in group 1 (1.62 vs 1.13 SDS; p < 0.001). Bone geometry: MI was significantly greater in group 2 (0.62 vs 0.55; p < 0.001) as well as CA (46.87 vs 42.69 cm(2); p < 0.005), while MA was significantly lower in group 2 (8.48 vs 11.65 cm(2); p < 0.002). CONCLUSION: Higher GH doses elicit a significantly greater statural gain and a greater bone cortical area.