Performance of Tandem Control IQ During Outdoor Physical Activity in Children and Adolescents with Type 1 Diabetes.

Background: Few data are available in children with type 1 diabetes using automated insulin delivery systems during physical activity (PA). We evaluated the time in range (TIR) during 2-h of outdoor PA in children using t:slim X2 with Control-IQ® technology. Materials and Methods: Caucasian children and adolescents, aged 9-18 years using t:slim X2 with Control-IQ technology were recruited during a local sporting event. Participants were divided into two groups: Group A practiced endurance activities for 60 min (1000-meter run, a jump circuit) and then power activities for 60 min (80-meter run, long jump); Group B practiced power activities for 60 min and then followed by endurance activities for 60 min. Ninety minutes before the PA, participants had lunch and self-administered a low-dose insulin, reduced by 50% compared to their regularly calculated meal dose per pump calculator. DexcomG6® data were downloaded. Results: Twenty-six children were recruited, 2 refused PA. Participants were divided as follows: 13 in Group A (7 males, median age 14.6 years) and 11 in Group B (8 males, median age 13.5 year). The mean glucose level when PA started was similar between groups (P = 0.06). Subjects in Group B showed a higher TIR than those in Group A ([50.4%, 95% confidence interval, CI: 33.8-75] vs. 39.6% [95% CI: 26.9-58.3], respectively [P = 0.39]). A significantly better TIR in Group B (53.8%, 95% CI: 30.2-96.1) compared to Group A (17.4%, 95% CI: 7.3-41.7, P = 0.02) was recorded during the first session. During the second session, TIR increased in both groups. There were no episodes of serious or severe hypoglycemia. Conclusions: No serious or severe hypoglycemic episodes were recorded during PA performed 90 min after lunch. Future studies using t:slim X2 with Control-IQ technology are necessary.

Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty.

BACKGROUND: Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation. METHODS: The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up). RESULTS: Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23-0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 - 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control. CONCLUSIONS: uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.

Pediatric obesity: a mini-review for pediatrician.

Obesity is a multifactorial disease, and its prevalence in children has been increased over the last 30 years in Italy and many other European Countries. Obesity significantly impacts the quality of life of affected patients and health care systems. Obesity is related to several clinical comorbidities, especially metabolic syndrome and diabetes. The standard of care in this patient is still considered lifestyle changes and a healthy diet with regular physical activity to prevent associated metabolic complications (impaired glucose tolerance and type 2 diabetes) and reduce cardiovascular risk.Therefore, pediatricians should recognize potential risk factors (sedentary lifestyle, sugar, and fats-rich diet, genetic syndromes) and early signs of overweight and obesity to promptly address the child to a pediatric endocrinologist and a specialized reference Center.

Recurrent reactive non-sexually related acute genital ulcers: a risk factor for Behcet's disease?

BACKGROUND AND AIM: Lipschutz ulcers (LU) are idiopathic genital lesions characterized by the sudden appearance of painful, usually symmetric vulvar ulcers, typically occurring in sexually inactive adolescents. LU is a diagnosis of exclusion. As these lesions heal spontaneously, in the absence of tissue scarring, the therapy is mainly symptomatic and focuses on pain relief. Recurrence of LU associated with oral ulcers describes the clinical picture of complex aphthosis, which belongs to Behçet's disease (BD) pathological spectrum. Our work aims to analyze the correct diagnostic approach to recurrent aphthous, focusing on the importance of a multidisciplinary assessment and immunogenetic investigation to identify the subjects at risk of progression towards BD.   Methods: We present the case of a 12-year-old non sexually active Italian girl who was diagnosed with LU. After 15 months, she presented recurrent reactive non sexually related acute genital ulcer associated with a history of oral aphthous. According to clinical features and anamnesis, complex aphthosis was diagnosed. For diagnostic purposes, she underwent an immunogenetic analysis that showed HLA-B51 positivity. RESULTS: In the absence of clinical and laboratory criteria to define the risk of progression of complex aphtosis towards BD, we think that besides a strict follow-up, in pediatric patients with a suggestive clinical history, it is crucial to adopt a multidisciplinary approach, comprehensive of HLA investigation, in order to guarantee an early diagnosis and a prompt therapeutic intervention. CONCLUSIONS: In children and adolescents with genital ulcers, it is essential to consider all the possible differential diagnoses to undertake a timely and correct course of treatment.

Pseudohypoparathyroidism: a diagnosis to consider once a PTH elevation is detected.

BACKGROUND AND AIM: Pseudohypoparathyroidism (PHP) is a rare disease, which can occur in the youth, characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH) in target organs. This condition encompasses different conditions which differ between one another by different clinical, biochemically, and genetic features. METHODS: Herein we report the clinical history of a boy with PHP1B with an interesting clinical presentation. He came in fact to the attention of the Emergency Department because of a spontaneously resolving epileptic attack, lasting about 15 minutes, characterized by loss of consciousness, fall to the ground, tonic-clonic shocks, and sphincter release. Moreover, the personal history was characterized by congenital long QT syndrome (LQTS), with a documented mutation of the KCNQ1 gene, treated with beta-blockers (nadolol). RESULTS: The simultaneous presence of symptomatic acute hypocalcemia and long QT syndrome undoubtedly required particular attention both in the management of the onset and in the more in-depth subsequent diagnostics. In this regard, laboratory tests and molecular analyzes have proved to be crucial in the diagnostic process. Conclusions: this case underlines the diagnostic path complexity in patients with PTH elevation and the importance of considering all the possible differential diagnoses in order to undertake a timely and correct course of treatment.

Obesity and COVID-19 in children and adolescents: a double pandemic.

BACKGROUND AND AIM OF THE STUDY: The high prevalence of obesity and obesity-related comorbidities has reached pandemic proportions, particularly in Western countries. It has been recently recognized as a significant risk factor in severe cases of COVID-19 in children and adolescents. Here, we summarize the existing knowledge regarding the pathophysiology of COVID-19 and consider how its various components may be exacerbated by the presence of obesity to investigate the impact of obesity on disease severity among patients with COVID-19 and collaborate for better clinical care of these patients. METHODS: The literature search was conducted from March 2020 to January 2022. A review of articles was performed via the online database PubMed, combining the terms "obesity," "weight gain," "COVID-19", "children." RESULTS: Excessive adipose tissue, insulin resistance, dyslipidemia, hypertension, high levels of proinflammatory cytokines are factors that compromise the functioning of organs and systems in obese patients. In obese patients with COVID-19 these changes can increase the risk of death, need for ventilatory assistance, risk of thromboembolism, and perpetuation of inflammatory response. CONCLUSIONS: Obesity increases the risk for hospitalization, intensive care admission, mechanic ventilation requirement, and death among children and adolescents with COVID-19. These findings emphasize the need for effective actions by health professionals to increase awareness of the risks resulting from obesity and how these are heightened in the current global pandemic.

46, XY Disorders of Sexual Development: a case report and theoretical framework.

BACKGROUND AND AIM: Disorders of sexual differentiation (DSD) with karyotype 46,XY include gonadal developmental differences such as complete gonadal dysgenesis, partial gonadal dysgenesis, testicular regression and ovotesticular sexual differentiation disorder, differences in androgen synthesis or action, such as androgen synthesis deficiency, androgen action deficits, LH receptor deficiency, AMH synthesis or action deficits, and other conditions such as severe hypospadias, cloaca estrophy, etc. Methods: A 17 years-old girl came to our attention for hirsutism, clitoral hypertrophy, primary amenorrhea, and bilateral mammary hypoplasia. According to clinical features and anamnesis, the diagnosis of 46, XY DSD was made. For diagnostic purposes, she underwent an extensive genetic analysis, hormone dosage and instrumental examinations. After a clitoridoplasty and hormone replacement treatment, the patient performs appropriate multidisciplinary follow-up and regular psychotherapy. RESULTS: The clinical case reported falls, according to the recent classification developed by the Chicago Consensus, within the scope of DSD with karyotype 46, XY. About 160 cases of patients with 17ß-HSD3 deficiency, diagnosed at a mean age of 12 years, are described in the literature, most of them coming from Western Asia and Europe and only three cases from Eastern Asia. Clinically, about 30% of patients showed virilization, 20% clitoromegaly, ambiguous genitalia, inguinal/labial mass, 16% primary amenorrhea, and 5% absence of mammary development, features that are partly traced in the case described here. CONCLUSIONS: This case underscores the complexity of managing individuals with DSD. Having acquired the concept that irreversible surgery should be avoided, except in cases where failure to do so would determine health risks, the primary objective of the medical decision lies in meeting conditions aimed at harmonious sexual identification, especially regarding sexual activity and fertility, involving a team of experienced professionals (psychologists, pediatricians, surgeons, endocrinologists, radiologists), capable of promptly identifying suggestive clinical signs.

Type 1 diabetes onset in Lombardy region, Italy, during the COVID-19 pandemic: The double-wave occurrence.

BACKGROUND: The Italian Lombardy region has been the epicenter of COVID-19 since February 2020. This study analyses the epidemiology of pediatric type 1 diabetes (T1D) onset during the first two pandemic waves and three previous years. METHODS: All the 13 pediatric diabetes centers in Lombardy prospectively evaluated charts of children at T1D onset (0-17 years), during year 2020. After calculating the annual incidence, the data were compared with those of the 3 previous years, using generalized linear models, adjusted for age and sex. Monthly T1D new onsets and diabetic ketoacidosis (DKA) were investigated yearly from 2017 to 2020. Data were extracted from outpatients charts of the pediatric diabetes centers and from the database of the national institute of statistics. FINDINGS: The estimated incidence proportion of T1D was 16/100·000 in 2020, compared to 14, 11 and 12 in 2019, 2018 and 2017, respectively. When adjusting for age and gender, the incidence was significantly lower in 2018 and 2017 compared to 2020 (adjusted incidence ratio: 0.73 and 0.77 respectively, with 95% CI: 0.63 to 0.84, and 0.67 to 0.83; p = 0·002 and p = 0·01), but no difference was found between the years 2020 and 2019. A reduction trend in the percentage of T1D diagnosis during the first wave (March-April) over the total year diagnoses was observed compared to previous years (11·7% in 2020, 17·7% in 2019, 14·1% in 2018 and 14·4% 2017). No difference was observed during the second wave (October-December) (32·8% in 2020, 33·8% in 2019, 34% in 2018, 30·7% in 2017). The proportion of DKA over the total T1D diagnoses during the second wave had higher trend than the first one (41·7% vs 33·3%), while severe DKA over the total DKA appeared higher during the first wave (60% vs 37·1%). INTERPRETATION: The study suggests an increase in the incidence of pediatric T1D in Lombardy throughout the past five years. Pandemic waves may have affected the clinical presentation at onset. FUNDING: None.

Comparison of triptorelin acetate vs triptorelin pamoate in the treatment of Central precocious puberty (CPP): a retrospective study.

The aim of this study is to compare the clinical and biochemical outcomes of triptorelin acetate (TPA) versus triptorelin pamoate (TPP) treatment in girls with central precocious puberty. A total of 60 patients with idiopathic CPP were retrospectively recruited. Thirty girls were treated with triptorelin acetate 3.75 mg/month (TPA group) and thirty girls in a second group received triptorelin pamoate 3.75 mg/4 weeks (TPP group). Patient follow-up at 12 and 24 months included GnRH Test at 12 months and baseline LH at 24 months. Patients were monitored with pelvic ultrasound, X-Ray of the hand and wrist and anthropometric evaluations. A total of 60/60 girls showed a good response to both formulations. Significant reductions in basal and LH peaks, estradiol values, breast pubertal stage, progression of bone age and growth velocity rate after 12 months treatment were obtained in both groups, demonstrating the equivalence of the two formulations in regulating the hypothalamic-pituitary-gonadal (HPG) axis. Triptorelin pamoate provided a more effective and significant reduction in LH peak after 12 months in comparison with triptorelin acetate more effective in reducing ovarian volume and endometrial thickness. Both formulations were equivalent, even though the LH peak was significantly lower in girls treated with triptorelin pamoate.

Pediatric Obesity and the Immune System.

Obesity has reached pandemic proportion and represents a major risk for several comorbidities. In addition to metabolic and cardiovascular obesity-related diseases, recent evidence suggested that obesity might affect immune system function. Adipose tissue is considered an endocrine organ that actively secretes cytokines also referred to as "adipokines." Adipokines play an important role in the control of human metabolism. The dysfunctional adipose tissue in obese individuals is characterized by an altered cytokine secretion pattern that promotes chronic low-grade inflammation. Epidemiological evidence highlights the association between obesity and allergic and immune-mediated diseases, such as asthma, allergic rhinitis, rheumatic arthritis, and psoriasis. Less is known about underlying pathogenic mechanisms. However, several recent in vivo and in vitro studies have reported that adipokines are involved in inflammatory and autoimmune disorders by influencing both innate and acquired immune responses. In addition, obesity has been associated with reduced immune surveillance and increased risk of cancer. This paper reviews the evidence regarding the role of adipokines in immune system regulation, with particular emphasis on autoimmune, allergic, and inflammatory disorders. Understanding how obesity affects immune system functions may enable researchers to find new potential therapeutic targets in the management of allergic and autoimmune diseases.