Short-Term Weight Gain after Tonsillectomy Does Not Lead to Overweight: A Systematic Review.

Different studies and systematic reviews have reported weight increase after tonsillectomy. However, the odds of a child being overweight or obese after tonsillectomy were no different than before surgery, according to a few studies. This systematic review aims to analyze the impact of adenotonsillectomy (TA) on weight gain and identify subgroups of children and adolescents at risk of experiencing weight gain. A systematic search included studies published in the last ten years. The PICO framework was used in the selection process, and evidence was assessed using the GRADE system. A total of 26 studies were included, and moderate-high level quality ones showed that children who underwent TA could present an increase in BMI z-score. However, this weight gain was significant in individuals younger than six years old and was considered catch-up growth in underweight subjects at baseline. In contrast, for normal-weight or overweight individuals, TA did not lead to overweight per se. At the same time, diet changes and overfeeding did not have a leading role in weight gain. In conclusion, TA may not be an independent risk factor for unfavorable weight gain in children; however, individuals who were underweight pre-operatively or younger than six years reported more weight gain after TA than expected.

Drug-Induced Hypoglycemia in Neonates Born to Nondiabetic Women Treated with Medications during the Pregnancy or the Labor: A Systematic Review of the Literature.

The prompt identification of at-risk newborns for drug-induced hypoglycemia can minimize the risk for adverse side effects, inappropriate investigations, and considerable unnecessary costs. Existing literature discusses drug-induced hypoglycemia, but a systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing. We reviewed the association between neonatal hypoglycemia and maternal medications. We systematically searched the literature according to the PICOS model on drug-induced hypoglycemia in neonates born to nondiabetic women treated with medications during the pregnancy or the labor. The main outcomes of the review were: (1) prevalence of hypoglycemia, (2) risk factors and potential confounders, (3) time at onset and severity of hypoglycemia, (4) dose-response gradient, (5) metabolic features of hypoglycemia, (6) modalities to treat hypoglycemia, and (7) quality of the studies. We included 69 studies in this review and we identified 11 groups of maternal drugs related to neonatal hypoglycemia. Results were classified for each outcome. Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia and in the differential diagnosis of neonatal hypoglycemia. Further studies are necessary to assess the risk of neonatal hypoglycemia associated with common maternal medications. KEY POINTS: · A systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing.. · In our review we identified 11 groups of maternal drugs related to neonatal hypoglycemia.. · Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia..

Drug-induced hyperinsulinemic hypoglycemia: An update on pathophysiology and treatment.

The initial step for the differential diagnosis of hypoglycemia is to determine whether it is hyperinsulinemic or non hyperinsulinemic. Existing literature discusses drug-related hypoglycemia, but it misses a focus on drug-induced hyperinsulinemic hypoglycemia (DHH). Here we reviewed the association existing between drugs and hyperinsulinemic hypoglycemia. We primarily selected on the main electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) the reviews on drug-induced hypoglycemia. Among the drugs listed in the reviews, we selected the ones linked to an increase in insulin secretion. For the drugs missing a clear association with insulin secretion, we investigated the putative mechanism underlying hypoglycemia referring to the original papers. Our review provides a list of the most common agents associated with hyperinsulinemic hypoglycemia (HH), in order to facilitate both the recognition and the prevention of DHH. We also collected data about the responsiveness of DHH to diazoxide or octreotide.

A narrative review on pathogenetic mechanisms of hyperinsulinemic hypoglycemia in Kabuki syndrome.

Objective. Kabuki syndrome (KS) is associated with hyperinsulinemic hypoglycemia (HH) in 0.3-4% of patients, thus exceeding the prevalence in the general population. HH association is stronger for KS type 2 (KDM6A-KS, OMIM #300867) than KS type 1 (KMT2D-KS, OMIM #147920). Both the disease-associated genes, KMD6A and KMT2D, modulate the chromatin dynamic. As such, KS is considered to be the best characterized pediatric chromatinopathy. However, the exact pathogenetic mechanisms leading to HH in this syndrome remain still unclear. Methods. We selected on the electronic database PubMed all articles describing or hypothesizing the mechanisms underlying the dysregulated insulin secretion in KS. Results. The impact on the gene expression due to the KDM6A or KMT2D function loss may lead to a deregulated pancreatic ß-cell differentiation during embryogenesis. Moreover, both KMT2D gene and KDM6A gene are implicated in promoting the transcription of essential pancreatic ß-cell genes and in regulating the metabolic pathways instrumental for insulin release. Somatic KMT2D or KDM6A mutations have also been described in several tumor types, including insulinoma, and have been associated with metabolic pathways promoting pancreatic cell proliferation. Conclusions. The impact of pathogenic variants in KDM6A and KDM2D genes on ß-cell insulin release remains to be fully clarified. Understanding this phenomenon may provide valuable insight into the physiological mechanisms of insulin release and into the pathological cascade causing hyperinsulinism in KS. The identification of these molecular targets may open new therapeutic opportunities based on epigenetic modifiers.

Efficacy and safety of ketamine for neonatal refractory status epilepticus: case report and systematic review.

Background: Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE. Methods: We described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science. Results: Seven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1-17 months of life. Discussion: Neonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting. Conclusions: Ketamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed.

Deep Medullary Vein Thrombosis in Newborns: A Systematic Literature Review.

BACKGROUND: Deep medullary vein (DMV) thrombosis is a rare cause of brain damage in both preterm and full-term neonates. In this study, we aimed to collect data on clinical and radiological presentation, treatment, and outcome of neonatal DMV thrombosis. METHODS: Systematic literature review on neonatal DMV thrombosis was carried out in PubMed, ClinicalTrial.gov, Scopus, and Web of Science up to December 2022. RESULTS: Seventy-five published cases of DMV thrombosis were identified and analysed (preterm newborns were 46%). Neonatal distress, respiratory resuscitation, or need for inotropes were present in 34/75 (45%) of patients. Signs and symptoms at presentation included seizures (38/75, 48%), apnoea (27/75, 36%), lethargy or irritability (26/75, 35%). At magnetic resonance imaging (MRI), fan-shaped linear T2 hypointense lesions were documented in all cases. All had ischaemic injuries, most often involving the frontal (62/74, 84%) and parietal lobes (56/74, 76%). Signs of haemorrhagic infarction were present in 53/54 (98%). Antithrombotic treatment was not mentioned in any of the studies included. Although mortality was low (2/75, 2.6%), a large proportion of patients developed neurological sequelae (intellectual disability in 19/51 [37%] and epilepsy in 9/51 [18%] cases). CONCLUSIONS: DMV thrombosis is rarely identified in the literature, even if it is possibly under-recognized or under-reported. Presentation in neonatal age is with seizures and non-specific systemic signs/symptoms that often cause diagnostic delay, despite the pathognomonic MRI picture. The high rate of morbidity, which determines significant social and health costs, requires further in-depth studies aimed at earlier diagnosis and evidence-based prevention and therapeutic strategies.

A systematic review on the impact of commercially available hybrid closed loop systems on psychological outcomes in youths with type 1 diabetes and their parents.

AIM: To systematically assess the impact of commercially available hybrid closed loop (HCL) systems on psychological outcomes in youths with type 1 diabetes and their parents. METHODS: We performed a systematic review including studies published in the last 10 years. PICOS framework was used in the selection process, and evidence was assessed using the GRADE system. RESULTS: A total of 215 studies were identified after duplicate removal, and 31 studies were included in this systematic review: 20 on first-generation HCL and 11 on second-generation HCL systems. According to studies with moderate- to high-level quality of evidence, HCL systems led to better, or in some studies, unchanged psychological outcomes such as distress and burden related to diabetes management, fear of hypoglycemia, quality of life, satisfaction; instead, quality of sleep was perceived as improved, although results were not confirmed in studies using actigraphy. From semi-structured interviews, answers were more homogeneous, and participants reported a positive experience and attitude towards HCL technology, which was felt to be easy to use and apt to achieve glycemic targets. CONCLUSIONS: Evidence confirms the importance of evaluating the psychosocial needs of youths with diabetes and their families when starting HCL systems and during follow-up, and to set realistic expectations of what can be achieved along with awareness of the limitations of the systems, and educate and motivate families to overcome barriers.

Optimal Prandial Timing of Insulin Bolus in Youths with Type 1 Diabetes: A Systematic Review.

The aim of this systematic review was to report the evidence on optimal prandial timing of insulin bolus in youths with type 1 diabetes. A systematic search was performed including studies published in the last 20 years (2002-2022). A PICOS framework was used in the selection process and evidence was assessed using the GRADE system. Up to one third of children and adolescents with type 1 diabetes injected rapid-acting insulin analogues after a meal. Moderate-high level quality studies showed that a pre-meal bolus compared with a bolus given at the start or after the meal was associated with a lower peak blood glucose after one to two hours, particularly after breakfast, as well as with reduced HbA1c, without any difference in the frequency of hypoglycemia. There were no differences related to the timing of bolus in total daily insulin and BMI, although these results were based on a single study. Data on individuals' treatment satisfaction were limited but did not show any effect of timing of bolus on quality of life. In addition, post-prandial administration of fast-acting analogues was superior to rapid-acting analogues on post-prandial glycemia. There was no evidence for any difference in outcomes related to the timing of insulin bolus across age groups in the two studies. In conclusion, prandial insulin injected before a meal, particularly at breakfast, provides better post-prandial glycemia and HbA1c without increasing the risk of hypoglycemia, and without affecting total daily insulin dose and BMI. For young children who often have variable eating behaviors, fast-acting analogues administered at mealtime or post-meal could provide an additional advantage.

The impact of gluten-free diet on growth, metabolic control and quality of life in youth with type 1 diabetes and celiac disease: A systematic review.

AIMS: To evaluate the impact of gluten free diet (GFD) on growth, metabolic control and quality of life in children and adolescents with type 1 diabetes (T1D) and celiac disease (CD). METHODS: A systematic search was performed including studies published in the last 15 years. PICOS framework was used in the selection process and evidence was assessed using the GRADE system. RESULTS: Overall, studies comparing youth with T1D + CD on GFD to those with T1D only, showed no significant differences in growth parameters, HbA1c, number of episodes of hypoglycemia, total daily insulin doses. Studies assessing the effect of GFD introduction showed stable BMI and HbA1c. Only two studies assessed QoL of life, which was not different between T1D + CD vs T1D only youth, as well as pre- and post-CD diagnosis and introduction of GFD. CONCLUSION: This systematic review, including only studies of moderate-high evidence quality level and reporting data on objectively assessed adherence to GFD, highlights that adherence to GFD in youth with T1D + CD leads to regular growth, stable BMI, without any negative effect on HbA1c and insulin requirements. Although assessed in few studies, lipid profile and QoL improved with the introduction of GFD.

Esophageal Dysphagia in Children: State of the Art and Proposal for a Symptom-Based Diagnostic Approach.

Pediatric esophageal dysphagia (PED) is an infrequent condition that can be determined by a large number of disorders. The etiologic diagnosis is challenging due to overlapping clinical phenotypes and to the absence of pediatric diagnostic guidelines. This review aims to summarize the most relevant causes of ED during childhood, highlight the clinical scenarios of PED presentation and discuss the indications of available diagnostic tools. Available information supports that PED should always be investigated as it can underlie life-threatening conditions (e.g., foreign body ingestion, mediastinal tumors), represent the complication of benign disorders (e.g., peptic stenosis) or constitute the manifestation of organic diseases (e.g., eosinophilic esophagitis, achalasia). Therefore, the diagnosis of functional PED should be made only after excluding mucosal, structural, or motility esophageal abnormalities. Several clinical features may contribute to the diagnosis of PED. Among the latter, we identified several clinical key elements, relevant complementary-symptoms and predisposing factors, and organized them in a multi-level, hierarchical, circle diagram able to guide the clinician through the diagnostic work-up of PED. The most appropriate investigational method(s) should be chosen based on the diagnostic hypothesis: esophagogastroduodenoscopy has highest diagnostic yield for mucosal disorders, barium swallow has greater sensitivity in detecting achalasia and structural abnormalities, chest CT/MR inform on the mediastinum, manometry is most sensitive in detecting motility disorders, while pH-MII measures gastroesophageal reflux. Further studies are needed to define the epidemiology of PED, determine the prevalence of individual underlying etiologies, and assess the diagnostic value of investigational methods as to develop a reliable diagnostic algorithm.

Impact of intermittently scanned continuous glucose monitoring with alarms on sleep and metabolic outcomes in children and adolescents with type 1 diabetes.

AIMS: Data about sleep quality and quantity are not available in patients with type 1 diabetes (T1D) using intermittently scanned continuous glucose monitoring (isCGM). We questioned whether the isCGM with alarms could fragment sleep in patients and parents, compared to isCGM without alarms. METHODS: A prospective, observational study including 47 child-adolescents with T1D who had experience with isCGM without alarms (Freestyle Libre 1-FSL1). They were asked to wear the isCGM with alarms (Freestyle Libre 2-FSL2) for 14 days. Patients enrolled and their caregiver (s), during a 14 day period with FSL1 and the following 14 days with FSL2, completed psychosocial and sleep-related questionnaires. Furthermore they wore an actigraph that was downloaded to a web platform and processed by the validated and certified algorithm "Dormi®." RESULTS: By the switch to the alarmed FSL2 we found about a 5% increase in Time In Range (from 62.5 to 67.8%), a reduction in time spent in hypoglycemia, number of weekly hypoglycemic events, and coefficient of variation. We did not find significant differences in sleep parameters in patients and their parents; therefore, alarms did not worsen the duration and quality of sleep. A significant improvement in the Quality of Life was perceived by parents using FSL2. CONCLUSIONS: Introduction of alarms in isCGM systems gives, in the short term, an improvement in metabolic control in terms of time in range and reduction in hypoglycemia, without worsening duration and quality of sleep, measured by actigraphy, in children-adolescent and their parents.

A systematic review of the prevalence, risk factors and screening tools for autonomic and diabetic peripheral neuropathy in children, adolescents and young adults with type 1 diabetes.

AIMS: We aimed to estimate the prevalence of Diabetic peripheral neuropathy (DPN) and Cardiac autonomic neuropathy (CAN) in youth with type 1 diabetes; identify key risk factors; identify the most useful tests for the diagnostic evaluation of DPN and CAN; identify key treatment options for DPN and CAN. METHODS: A systematic search was performed including studies published in the last 15 years. PICO framework was used in the selection process and evidence was assessed using the GRADE system. RESULTS: A total of 758 studies were identified and a final number of 49 studies were included in this systematic review. According to moderate-high level quality studies, the prevalence of probable DPN, ranged between 13.5 and 62%; subclinical DPN between 22 and 88%; confirmed DPN between 2.6 and 11%. The Michigan Neuropathy Screening Instrument was the tool with higher sensitivity and specificity for detecting DPN, which needs to be confirmed by nerve conduction velocity. The prevalence of CAN was 4-39%. Specific treatment options for DPN or CAN in patients younger than 25 years are not available. Key risk factors for DPN and CAN are hyperglycemia/HbA1c, age, diabetes duration, the presence of other microvascular complications, waist/height ratio, lipid profile and blood pressure. For CAN, additional risk factors were cigarette smoking, BMI and total daily insulin. CONCLUSIONS: Prevalence of neuropathy in youth with type 1 diabetes varies depending on different screening methods and characteristics of the study populations. However, the assessed studies confirmed a relatively high prevalence of subclinical neuropathy, reiterating the importance of early identification of risk factors to prevent this complication.

Determinants of severe bradycardia in adolescents hospitalized for anorexia nervosa.

BACKGROUND: Severe bradycardia is an indication supporting hospitalization in adolescents with eating disorders. Some adolescents with anorexia nervosa (AN) and significant weight loss present with a normal pulse rate at admission, whereas others have severe bradycardia, suggesting that total weight loss is not the most important determinant of bradycardia. The aims of this study were to define the prevalence of severe bradycardia as the cause for hospital admission in adolescents with AN, to evaluate correlations between known determinants of severe bradycardia and pulse rate at admission, and to evaluate the average time required to recover from severe bradycardia after re-feeding. METHODS: Ninety-nine hospitalized patients with AN were enrolled. Weight loss history, anthropometric, laboratory, and electrocardiogram data were collected at admission to and at discharge from hospital. Multivariate analysis was performed to detect the most important determinants of severe bradycardia. RESULTS: Forty-eight percent of the AN patient admissions were due to severe bradycardia (AN-B+ group). Patients in this group had a higher maximum lifetime weight (P = 0.0045), greater premorbid weight loss (P = 0.0011), and more rapid weight loss (P = 0.0001). Multivariate analysis showed that recent weight loss is an independent predictor of bradycardia at hospital admission (R2 : 0.35, P = 0.0001). Severe bradycardia normalized after minimal weight gain of 0.25 ± 0.18 kg/day for 3-10 days. CONCLUSIONS: This study confirms that recent weight loss is probably the most important determinant of severe bradycardia in adolescents with AN.