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Background: Type 1 diabetes is a serious, chronic disorder with an increasing incidence among children and adolescents. Glycemic control in individuals with type 1 diabetes is better managed through a basal-bolus regimen with either regular human or rapid-acting insulin analogues administered as a bolus at mealtimes. Rapid-acting insulin analogues have been hypothesized to cause optimal glycemic control and less risk of hypoglycemic episodes compared to regular human insulins. However, this has never been systematically assessed in children and adolescents with type 1 diabetes. Therefore, this systematic review aims to assess the beneficial and harmful effects of regular human insulins versus rapid-acting insulin analogues in children and adolescents., Methods: This is a protocol for a systematic review. A search in major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries will be performed by a search specialist. We will include published and unpublished randomized clinical trials comparing regular human insulins versus rapid-acting insulin analogues (lispro, aspart, or glulisine). Two review authors will independently extract data and conduct risk of bias assessments. Primary outcomes will be severe hypoglycemia, ketoacidosis, and serious adverse events. Secondary outcomes will be quality of life, HbA1c, and non-serious adverse events. Data will be analyzed using fixed-effect meta-analyses, random-effects meta-analyses, and Trial Sequential Analysis. Several subgroup analyses are planned. Risk of bias will be assessed with the Cochrane Risk of Bias tool-version 2, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE)., Discussion: The beneficial and adverse effects of regular human insulins versus rapid-acting insulin analogues have not been systematically assessed in children and adolescents. There is a need for a comprehensive systematic review of the current evidence., Systematic Review Registration: PROSPERO: CRD42024508625., Competing Interests: Ethics approval and consent to participate: Not applicable. Consent for publication: All authors approve publication of the protocol. Competing interests: CDBS’s husband is employed at Novo Nordisk, Kalundborg, Denmark, as “facility manager” since September 1, 2024., (© 2025. The Author(s).)

Introduction: Celiac disease (CD) is among the diseases most commonly associated with type 1 diabetes (T1D). This study aimed to evaluate the worldwide practices and attitudes of physicians involved in pediatric diabetes care regarding diagnosing and managing CD in children with T1D., Methods: The 30-item survey was conducted between July and December 2023 aimed at targeting pediatricians with special interest in T1D and CD. It was shared by the JENIOUS - young investigators group of the International Society of Pediatric and Adolescent Diabetes (ISPAD) - and the YES - early career group of the European Society for Pediatric Endocrinology (ESPE)., Results: Overall, 180 physicians (67.8% female) from 25 countries responded. Among respondents, 62.2% expected sustaining optimal glycemic control in children with T1D and CD (T1D + CD) to be more difficult than in children with T1D alone. Majority (81.1%) agreed that more specific guidelines are needed. The follow-up routine for patients with T1D + CD differed, and one-quarter of physicians scheduled more frequent follow-up checkups for these patients. Seventy percent agreed multidisciplinary outpatient clinics for their follow-up is needed. In the multivariate ordinal logistic regression model, a statistically significant predictor of a higher degree of practice according to ISPAD 2022 guidelines was a higher level of country income (OR = 3.34; p < 0.001)., Conclusions: These results showed variations in physicians' practices regarding managing CD in children with T1D, emphasizing the need for more specific guidelines and intensive education of physicians in managing this population, especially in lower-income countries. Our data also suggest the implementation of multidisciplinary outpatient clinics for their follow-up., (© 2024 S. Karger AG, Basel.)

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1-3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively.

Background: Advances in diabetes technological devices led to optimization of diabetes care; however, long-lasting skin exposure to devices may be accompanied by an increasing occurrence of cutaneous reactions., Methods: We used an open-link web-based survey to evaluate diabetes-care providers' viewpoint on prevalence, management practices, and knowledge related to skin reactions with the use of diabetes technological devices. A post hoc analysis was applied to investigate differences in the level of awareness on this topic in relation to the experience in diabetes technology., Results: One hundred twenty-five responses from 39 different countries were collected. Most respondents (69%) routinely examine patients' skin at each visit. All the preventive measures are not clear and, mainly, homogenously put into clinical practice. Contact dermatitis was the most frequently reported cutaneous complication due to diabetes devices, and its most common provocative causes are not yet fully known by diabetes-care providers. Almost half of the respondents (42%) had discussed the presence of harmful allergens contained in adhesives with device manufacturers. There is general agreement on the need to strengthen knowledge on dermatological complications., Conclusions: Although diabetes-care providers are quite aware of the chance to develop skin reactions in people with diabetes using technological devices, there are still some unmet needs. Large follow-up studies and further dissemination tools are awaited to address the gaps revealed by our survey., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Anna Korsgaard Berg has received project grants from Medtronic and received speaking honoraria from Rubin Medical and Convatec. Laurel Messer has received speaking/consulting honoraria from Tandem Diabetes, Dexcom, Inc., Capillary Biomedical, and Lilly. Her institution receives research/project grants from Medtronic, Tandem Diabetes, Beta Bionics, Dexcom, Abbott, and Insulet Corp. As of 2023, Laurel Messer is also an employee of Tandem Diabetes Care. No conflict of interest exists for the other authors.

Staphylococcus lugdunensis produces lugdulysin, a metalloprotease that may contribute to its virulence. This study aimed to evaluate the biochemical aspects of lugdulysin and investigate its effect on Staphylococcus aureus biofilms. The protease was isolated and characterized for its optimal pH and temperature, hydrolysis kinetics, and influence of metal cofactor supplementation. The protein structure was determined via homology modeling. The effect on S. aureus biofilms was assessed by the micromethod technique. The protease optimal pH and temperature were 7.0 and 37 °C, respectively. EDTA inhibited protease activity, confirming it as a metalloprotease. Lugdulysin activity was not recovered by divalent ion supplementation post-inhibition, and supplementation with divalent ions did not change enzymatic activity. The isolated enzyme was stable for up to 3 h. Lugdulysin significantly inhibited the formation and disrupted preestablished protein-matrix MRSA biofilm. This preliminary study indicates that lugdulysin has a potential role as a competition mechanism and/or modulation of staphylococcal biofilm., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Objective: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success., Methods: All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities., Results: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004-2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014-2019), participants indicated that the program was valuable/useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards., Conclusions: From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Telemedicine for routine care of people with diabetes (PwD) during the COVID-19 pandemic rapidly increased in many countries, helping to address the several barriers usually seen., Objective: This study aimed to describe healthcare professionals' (HCPs) experience on telemedicine use in diabetes care and investigate the changes and challenges associated with its implementation., Methods: A cross-sectional electronic survey was distributed through the global network of JENIOUS members of ISPAD. Respondents' professional and practice profiles, clinic sizes, their country of practice, and data regarding local telemedicine practices during COVID-19 pandemic were investigated., Results: Answers from 209 HCPs from 33 countries were analyzed. During the pandemic, the proportion of PwD receiving telemedicine visits increased from <10% (65.1% of responders) to >50% (66.5%). There was an increase in specific privacy requirements for remote visits (37.3% to 75.6%), data protection policies (42.6% to 74.2%) and reimbursement for remote care (from 41.1% to 76.6%). Overall, 83.3% HCPs reported to be satisfied with the use of telemedicine. Some concerns (17.5%) about the complexity and heterogeneity of the digital platforms to be managed in everyday practice remain, feeding the need for unifying and making interoperable the tools for remote care. Also, 45.5% of professionals reported to feel stressed by the need for extra-time for telemedicine consultations., Conclusions: Telemedicine was rapidly and broadly adopted during the pandemic globally. Some issues related to its use were promptly addressed by local institutions. Challenges with the use of different platforms and for the need of extra-time still remain to be solved., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Frequency, dimensions, management, and outcomes of the COVID-19 pandemic in children with endocrine disorders and diabetes were assessed., Methods: A cross-sectional electronic survey was distributed to the global network of endocrine societies. Respondents' professional and practice profiles, clinic sizes, their country of practice, and the impact of COVID-19 on endocrine diseases were investigated., Results: Respondents from 131 pediatric endocrine centers in 51 countries across all continents completed the survey. Routine check-ups and education were altered in most pediatric endocrine clinics. Over 20% of clinics experienced a shortage of critical medications or essential supplies. ICU treatment was required for patients with diabetes and COVID-19 in 21.2% of centers. In diabetes, 44% of respondents reported increased diabetic ketoacidosis episodes in newly diagnosed cases and 30% in established cases. Biopsychosocial and behavioral changes were explicitly reported to be occurring among pediatric patients with endocrine disorders., Conclusions: This large global survey conducted during the COVID-19 pandemic highlights that diabetes is more challenging to manage than any other pediatric endocrine disorder, with an increased risk of morbidity. Psychological distress due to COVID-19 needs to be recognized and addressed. The importance of close contact with healthcare professionals should be emphasized, and medical supplies should be readily available to all patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elbarbary, dos Santos, de Beaufort, Wiltshire, Pulungan and Scaramuzza.)

Introduction: To study healthcare professionals' (HCP) perceptions on decision making to start insulin pumps and continuous glucose monitoring (CGM) systems in pediatric type 1 diabetes., Research Design and Methods: An electronic survey supported by the International Society for Pediatric and Adolescent Diabetes (ISPAD) was disseminated through a weblink structured as follows: (1) HCP's sociodemographic and work profile; (2) perceptions about indications and contraindications for insulin pumps and (3) for CGM systems; and (4) decision making on six case scenarios., Results: 247 responses from 49 countries were analyzed. Seventy per cent of respondents were members of ISPAD. Most of participants were women over 40 years old, who practice as pediatric endocrinologists for more than 10 years at university/academic centers and follow more than 500 people with type 1 diabetes. Although insulin pumps and CGMs are widely available and highly recommended among respondents, their uptake is influenced by access to healthcare coverage/insurance. Personal preference and cost of therapy were identified as the main reasons for turning down diabetes technologies. Parental educational level, language comprehension and income were the most relevant socioeconomic factors that would influence HCPs to recommend diabetes technologies, while gender, religious affiliation and race/ethnicity or citizenship were the least relevant., Conclusions: Responders seem to be markedly supportive of starting people on diabetes technologies. However, coverage/insurance for devices holds the biggest impact on the extent of their recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) and non-randomized studies (NRS) to assess the effectiveness and equity of continuous subcutaneous insulin infusions (CSII) versus multiple-daily injections (MDI) on glycemic outcomes., Methods: Searches were conducted between 2000 and 2019 in MEDLINE, CENTRAL, EMBASE and HTA. Included studies compared the CSII vs MDI in children and young people (CYP) ≤ 20 years with type 1 diabetes. Two independent reviewers screened the articles, extracted the data, assessed the risk of bias, evaluated the quality of evidence, and identified equity data. Results were pooled with a random-effects model., Results: Of the 578 articles screened, 16 RCT (545 CYP on CSII) and 70 NRS (73253 on CSII) were included in the meta-analysis. There was moderate-level evidence that the CSII lower HbA 1c in RCT (pooled mean difference [MD]: -0.22%; 95% confidence interval [CI]: -0.33, -0.11%; I 2 :34%) and insufficient in NRS (pooled MD: -0.45%; 95%CI: -0.52, -0.38%; I 2 :99%). The pooled incidence rate ratio of severe hypoglycemia on CSII vs MDI in RCT was 0.87 (95%CI: 0.55, 1.37; I 2 :0%; low-level evidence), and 0.71 (95%CI: 0.63, 0.81; I 2 :57%, insufficient evidence) in NRS. Health-related quality of life presented insufficient evidence. Equity data were scarcely reported., Conclusions: CSII modestly lower HbA 1c when compared with MDI. Current literature does not provide adequate data on other glycemic outcomes. Future assessment on diabetes technology should include individual and area-level socioeconomic data. The study protocol was pre-registered in PROSPERO (CRD42018116474)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose of Review: This review aims to address the actual state of the most advanced diabetes devices, as follows: continuous subcutaneous insulin infusions (CSII), continuous glucose monitoring systems (CGM), hybrid-closed loop (HCL) systems, and "Do-it-yourself" Artificial Pancreas Systems (DIYAPS) in children, adolescents, and young adults. This review has also the objective to assess the use of telemedicine for diabetes care across three different areas: education, social media, and daily care., Recent Findings: Recent advances in diabetes technology after integration of CSII with CGM have increased the popularity of this treatment modality in pediatric age and shifted the standard diabetes management in many countries. We found an impressive transition from the use of CSII and/or CGM only to integrative devices with automated delivery systems. Although much has changed over the past 5 years, including a pandemic period that precipitated a broader use of telemedicine in diabetes care, some advances in technology may still be an additional burden of care for providers, patients, and caregivers. The extent of a higher rate of "auto-mode" use in diabetes devices while using the HCL/DIYAPS is essential to reduce the burden of diabetes treatment., Summary: More studies including higher-risk populations are needed, and efforts should be taken to ensure proper access to cost-effective advanced technology on diabetes care., Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-021-00248-7., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Background: Coronavirus diasease (COVID-19) is an infectious disease that started in Wuhan, China in late 2019 and later spread around the world. Diabetes has been recognized as a possible risk factor for COVID-19 complications., Objective: International Society for Pediatric and Adolescent Diabetes (ISPAD) investigated perceptions, challenges and experience of health care professionals (HCP) taking care of children and young people with diabetes worldwide during COVID-19 pandemic., Methods: From 21st April to 17th May 2020, during COVID-19 pandemic, a web-based survey was sent to ISPAD members and former participants of ISPAD conferences by email., Results: Responders from 215 diabetes centers from 75 countries completed the survey. Majority were from UK (35; 16.3%), USA (20; 9.3%), and India (15; 7%). HCP were mostly pediatric endocrinologists (64%). During COVID-19 pandemic, 16.5% of responders continued face-to-face consultation while most changed to telephone (32%) or video (18%) consultations. 19% reported a shortage of medical supplies. 22% reported a delay in diagnosis of patients with new-onset diabetes, while 15% reported a higher incidence of DKA. 12% reported having one or more patients with COVID-19. Most of the 86 children and adolescents with diabetes and COVID-19 had only mild/moderate symptoms, while 5 required admission to an intensive care unit. No deaths were reported., Conclusions: This large global survey during COVID-19 pandemic showed that many HCP adapted to the pandemic by resorting to telemedicine. One fourth of HCP reported delays in diagnosis and an increased rate of DKA. The emergence of COVID-19 pandemic had an important impact on family's behavior that might have led to increase in diabetic ketoacidosis presentation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Children with "metabolically healthy obesity" (MHO) are a distinct subgroup of youth with obesity, who are less prone to the clustering of cardiometabolic risk factors. Although this phenotype, frequently defined by the absence of metabolic syndrome components or insulin resistance, was first described during the early 1980s, a consensus-based definition of pediatric MHO was introduced only recently, in 2018. The purpose of this review was to concisely summarize current knowledge regarding the MHO phenomenon in youth. The prevalence of MHO in children varies from 3 to 87%, depending on the definition used and the parameters evaluated, as well as the ethnicity and the pubertal status of the sample. The most consistent predictors of MHO in youth include younger age, lower body mass index, lower waist circumference, and lower body fat measurements. Various hypotheses have been proposed to elucidate the underlying factors maintaining the favorable MHO phenotype. While preserved insulin sensitivity and lack of inflammation were previously considered to be the main etiological factors, the most recent findings have implicated adipokine levels, the number of inflammatory immune cells in the adipose tissue, and the reduction of visceral adiposity due to adipose tissue expandability. Physical activity and genetic factors also contribute to the MHO phenotype. Obesity constitutes a continuum-increased risk for cardiometabolic complications, which is less evident in children with MHO. However, some findings have highlighted the emergence of hepatic steatosis, increased carotid intima-media thickness and inflammatory biomarkers in the MHO group compared to peers without obesity. Screening should be directed at those more likely to develop clustering of cardiometabolic risk factors. Lifestyle modifications should include behavioral changes focusing on sleep duration, screen time, diet, physical activity, and tobacco smoke exposure. Weight loss has also been associated with the improvement of insulin sensitivity and inflammation. Further investigative efforts are needed in order to elucidate the mechanisms which protect against the clustering of cardiometabolic risk factors in pediatric obesity, to provide more efficient, targeted treatment approaches for children with obesity, and to identify the protective factors preserving the MHO profile, avoiding the crossover of MHO to the phenotype with metabolically unhealthy obesity., (Copyright © 2019 Vukovic, Dos Santos, Ybarra and Atar.)

Background: Optimal type 1 diabetes mellitus (T1D) care requires lifelong appropriate insulin treatment, which can be provided either by multiple daily injections (MDI) of insulin or by continuous subcutaneous insulin infusion (CSII). An increasing number of trials and previous systematic reviews and meta-analyses (SRMA) have compared both CSII and MDI but have provided limited information on equity and fairness regarding access to, and the effect of, those insulin devices. This study protocol proposes a clear and transparent methodology for conducting a SRMA of the literature (1) to assess the effect of CSII versus MDI on glycemic and patient-reported outcomes (PROs) among young patients with T1D and (2) to identify health inequalities in the use of CSII., Methods: This protocol was developed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P), the PRISMA-E (PRISMA-Equity 2012 Guidelines), and the Cochrane Collaboration Handbook. We will include randomized clinical trials and non-randomized studies published between January 2000 and June 2019 to assess the effectiveness of CSII versus MDI on glycemic and PROs in young patients with T1D. To assess health inequality among those who received CSII, we will use the PROGRESS framework. To gather relevant studies, a search will be conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews, and the Health Technology Assessment (HTA) database. We will select studies that compared glycemic outcomes (the glycosylated hemoglobin values, severe hypoglycemia episodes, diabetic ketoacidosis events, and/or time spent in range or in hyper-hypoglycemia), and health-related quality of life, as a PRO, between therapies. Screening and selection of studies will be conducted independently by two researchers. Subgroup analyses will be performed according to age group, length of follow-up, and the use of adjunctive technological therapies that might influence glycemic outcomes., Discussion: Studies of the average effects of CSII versus MDI may have not assessed their impact on health equity, as some intended populations have been excluded. Therefore, this study will address health equity issues when assessing effects of CSII. The results will be published in a peer-review journal. Ethics approval will not be needed., Systematic Review Registration: PROSPERO CRD42018116474.

Background Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycemia (HH) not addressed as a potential differential diagnosis in current pediatric guidelines. We present a case of IAS in a child with no previous history of autoimmune disease, no previous intake of triggering medications and absence of genetic predisposition. Case presentation A 6-year-old boy presented with recurrent HH (blood glucose of 26 mg/dL [1.4 mmol/L] and insulin of 686 μU/mL). Abdominal imaging was normal. After multiple therapeutic failures, we hypothesized misuse of exogenous insulin and factitious hypoglycemia. Council of Guardianship had the child separated from his mother, but insulin levels remained high. A chromatography test was then performed which showed high titers of endogenous insulin autoantibody (IAA) with early dissociation from the insulin molecule. The human leukocyte antigen (HLA) test showed a DRB1 *13:01/*08:02 genotype. The patient was advised to control food intake and physical activity routines. During a 5-year follow-up, hypoglycemic episodes were sparse, despite high insulin levels. Conclusions Misdiagnosis of IAS with factitious hypoglycemia may happen if IAS is not considered as a differential diagnosis, leading to potential traumatic consequences. Further efforts should be made to increase awareness of IAS as a differential diagnosis of hypoglycemia and to include it in pediatric guidelines.

Transient hypothyroidism can present itself as clinically asymptomatic or with few symptoms. Early treatment with levothyroxine (L-T4) prevents complications related to this disorder. We report a case of a male infant with concomitant short bowel syndrome and transient hypothyroidism treated with rectal L-T4. A 4-month-and-10-day-old boy with previous gastroschisis underwent multiple surgical approaches for small bowel resection and developed short bowel syndrome. We suspected hypothyroidism because of jaundice (direct bilirubin up to 59 mg/dL), the absence of evacuation, oral diet intolerance, and intestinal dysmotility. Because of a thyrotropin level of 34.45 μIU/mL and a free thyroxine level of 0.64 ng/dL, the diagnosis was confirmed. Because fasting was demanding, we started the patient on rectal diluted L-T4. After 4 weeks, the patient had spontaneous peristalsis, improvement of jaundice (direct bilirubin: 4.6 mg/dL), and normalized free thyroxine and thyrotropin values. In the present case, the patient was diagnosed with hypothyroidism and was on absolute fasting. An alternative route of drug administration was warranted. We empirically prescribed rectal diluted L-T4 when intravenous and suppository L-T4 were not available. This method was proven to be safe and effective in improving the patient's clinical and biochemical status. Rectal L-T4 is a possible alternative route of administration to treat hypothyroidism in patients who are unable to take the medication orally., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background The approach to the clinical management of Graves' disease (GD) is debatable. This study aimed to identify predictors of remission in pediatric GD. Methods A longitudinal study of 36 children and adolescents with GD followed from 1997 to 2017 at a single tertiary hospital was performed. Clinical and biochemical parameters, including comorbidities, treatment with anti-thyroid drugs (ATD) or definitive therapy (radioiodine [RIT] and thyroidectomy), and remission as the main outcome were collected. We performed a multivariable logistic regression analysis to identify likely predictors of remission. Results Among patients, most were female, in late puberty, with exuberant symptoms at onset. Eleven also suffered from Down syndrome (DS). Thirty-four patients (94%) started on methimazole from disease onset, and 25 (69%) received it as the only therapy, with a mean duration of 2.7±1.8 years. Six changed to RIT and three underwent thyroidectomy; no DS patient received definitive therapy. Remission was higher in DS patients (45% vs. 25%, p=0.24), but afterwards (3.9±2.5 vs. 2.3±1.4 years, p<0.05); there was no significance in relapsing (20% vs. 15%). Females were less likely to reach remission (p<0.05); serum free thyroxine at onset was higher (p<0.05) in patients who required definitive therapy. Thyroid-stimulating immunoglobulin (TSI) values normalized in exclusively ATD therapy, especially from 2 years on (p<0.05). Conclusions Males were more likely to achieve remission. TSI values may normalize in GD, notably from the second year of treatment. DS children may benefit with conservative management in GD.

Objective: To assess the effects of physical activity interventions in preventing cardiovascular risk factors in childhood through a systematic review and meta-analysis of randomized clinical trials (RCTs)., Methods: A search of online databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted from inception until June 2013. RCTs enrolling children 6-12years old conducted physical activity interventions longer than 6months, assessing their effect on body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC) and triglycerides (TG) were included. Data analysis was performed using a random-effects model., Results: Of 23.091 articles retrieved, 11 RCTs (10.748 subjects) were included. Physical activity interventions were not associated with reductions of BMI [-0.03kg/m(2) (95%CI -0.16, 0.13) I(2) 0%]. However, there was an association between the interventions and reduction of SBP [-1.25mmHg (95%CI -2.47, -0.02) I(2) 0%], DBP [-1.34mmHg (95%CI -2.57, -0.11) I(2) 43%] and TG [-0.09mmol/L (95%CI -0.14, -0.04) I(2) 0%], and increase of TC [0.14mmol/L (95%CI 0.01, 0.27) I(2) 0%]., Conclusion: As physical activity intervention programs lasting longer than 6months are associated with reductions in blood pressure levels and triglycerides, they should be considered to be included in prevention programs for cardiovascular diseases in schoolchildren., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Few studies have investigated the prevalence of 22q11.2 deletion syndrome (22q11.2DS) among patients with isolated heart defects or nonconotruncal heart defects. Polymerase chain reaction (PCR) followed by length polymorphism restriction fragment analysis (RFLP) is useful for low-cost molecular diagnosis and screening. This cross-sectional study included 392 patients with congenital heart disease, described clinical features, and performed PCR-RFLP for analysis of polymorphism in three loci with a high heterozygosity rate located in the typically deleted region of 1.5 megabases. Heterozygosity excluded 22q11.2DS. Patients with homozygosity for the three markers underwent multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) for the final diagnosis, estimating the prevalence of 22q11.2DS. The use of PCR-RFLP excluded 22q11.2DS in 81.6 % (n = 320) of 392 patients. Of the remaining 72 patients, 65 underwent MLPA, showing 22q11.2DS in five cases (prevalence, 1.27 %). Four of these five patients underwent FISH, confirming the MLPA results. All five patients with the deletion had heart diseases commonly found with 22q11.2DS (interrupted aortic arch, persistent truncus arteriosus, tetralogy of Fallot, and ventricular septal defect plus atrial septal defect). Two patients had congenital extracardiac anomaly (one with arched palate and micrognathia and one with hypertelorism). Three patients reported recurrent respiratory infections, and one patient reported hypocalcemia. All were underweight or short in stature for their age. This study contributed to showing the prevalence of 22q11.2DS in patients with any congenital heart disease, with or without other features of the syndrome. Patients with 22q11.2DS may not have all the major features of the syndrome, and those that are found may be due to the heart defect.

Lifestyle changes have an impact on lipid metabolism. The overload of circulating lipids may lead to endothelial dysfunction, oxidative stress and exaggerated inflammatory response, which may be further aggravated in the presence of overweight. This study aims to describe the postprandial metabolism and inflammatory response in overweight and normal-weight adolescents. Sixty-two adolescents aged 11-18 years were divided into two groups: overweight (OW; n=38) and normal weight (NW; n=24). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and leukocytes were collected for fasting and 4 and 6 h after a oral fat tolerance test (OFTT) consisting of a high-fat meal with 1.000 Kcal, 27.4% carbohydrates, 14.7% protein and 57.8% lipids (30.4% saturated, 32.7% monounsaturated, 26.5% polyunsaturated fatty acids and 288 mg TC). Data were analyzed with repeated measures ANOVA, multiple linear regression, and Pearson, Spearman and partial correlations. OW adolescents showed significantly higher fasting values of TC (P=0.036), LDL-C (P=0.010), fibrinogen (P=0.036) and hs-CRP (P=0.004). All variables, except for glucose, increased in response to OFTT, but there were no interactions between group and time. body mass index z-score was positively correlated to LDL-C, TG, fibrinogen and hs-CRP, and inversely correlated to HDL-C. In conclusion, adolescents with OW showed higher TC, LDL-C and inflammatory markers levels than NW adolescents. These findings have clinical implications for prevention of chronic diseases, as we spend most of our days in a postprandial state.

Health professionals (HP) are frequently exposed to accidents with materials contaminated with blood and/or body fluids, thus representing a population at risk for the acquisition of human immunodeficiency virus (HIV) and hepatitis B virus (HBV). PURPOSE--To determine the prevalence of HIV and HBV infection among HP admitted to the University Hospital, Faculty of Medicine, University of São Paulo (UH-FMUSP), and to identify the possible sources of contamination. METHODS--A total of 345 HP who sequentially passed the hiring examination at UH-FMUSP from March 1 to June 23 1993 were evaluated and compared to 2521 blood donors using serologic tests for the detection of AgHBs and total anti-HBc of HBV. The ELISA method was also used for HIV-1, with subsequent confirmation by Western blot. Questionnaires were distributed to the HP for the identification of possible sources of contamination. RESULTS--Positivity to HIV-1 was 0.48% for HP and 0.23% for blood donors, and positivity to HBV was 8.89% and 6.17%, respectively. CONCLUSION--There was no statistically significant difference in the results of the serologic tests for HIV and HBV detection between the two groups, even taking into consideration the different professions of those who work in the health area and their potential exposure to blood and secretion.