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.
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.
AimTo systematically assess the impact of commercially available hybrid closed loop (HCL) systems on psychological outcomes in youths with type 1 diabetes and their parents.MethodsWe 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.ResultsA 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.ConclusionsEvidence 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.
BackgroundEvidence-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.MethodsWe 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.ResultsSeven 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.DiscussionNeonatal 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.ConclusionsKetamine 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.
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 β-cell differentiation during embryogenesis. Moreover, both KMT2D gene and KDM6A gene are implicated in promoting the transcription of essential pancreatic β-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 β-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.
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