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Hyponatraemia is frequently encountered in adults with coronavirus disease 2019 (COVID-19) and is associated with poor prognosis. This review aims to describe for the first time the prevalence, aetiology, prognostic value, pathophysiology, and management of hyponatraemia in children and adolescents with COVID-19, taking into account all relevant studies published in PubMed and Cochrane Library studies until 26th September 2021. Literature search did not detect any studies evaluating the prevalence and prognostic value of sodium disorders in paediatric patients with COVID-19. A broader literature review showed a high prevalence of hyponatraemia in children with bacterial pneumonia, while some studies have reported that hyponatraemia is relatively common in Multisystem Inflammatory Syndrome in Children (MIS-C). In adults with COVID-19, an inverse association between sodium and interleukin-6 levels has been found, indicating that hyponatraemia could be used as a surrogate marker for the risk of cytokine storm and may facilitate the identification of patients who could benefit from immunomodulatory agents. Studies are urgently needed to evaluate the frequency and prognostic impact of electrolyte abnormalities in children with COVID-19. In the meantime, clinicians are urged to consider hyponatraemia in children with COVID-19 as a potential red flag, investigate the cause and administer fluids and other therapies accordingly. (www.actabiomedica.it)

Objective: Subjects with normal glucose tolerance (NGT) but 1-hour post-load plasma glucose (1-h OGTT) ≥ 155 mg/dl (8.6 mmol/L; H-NGT) have an increased risk for developing Type 2 diabetes mellitus (T2DM), determining a new risk factor category with deeper metabolic impairment. The aim of this study was to evaluate the H-NGT as a diagnostic predictor of future dysglycemia in β-transfusion dependent thalassemia (β-TDT). Indices of insulin secretion and insulin sensitivity derived at baseline from OGTTs, were also reviewed. Study design and methods: OGTT and indices of insulin secretion and insulin sensitivity, derived at baseline during OGTT, in 17 β-TDT with H-NGT and 29 β-TDT with normal OGTT (NGT) and without H-NGT followed for 12 years were studied. Results: H-NGT was associated with decreased insulin sensitivity and progressive deterioration of glucose tolerance. At baseline, serum ferritin and serum alanine aminotransferase (ALT) levels were higher in patients with H-NGT compared to patients with NGT. A strong correlation was observed between ALT and 1-hour plasma glucose value during OGTT in the total group of 36 patients . Compliance to iron chelation therapy was poor in β-TDT patients with H-NGT. An inverse correlation was found between 1-hour plasma glucose value during OGTT and insulin secretion-sensitivity index-2 (ISSI-2) (r: -0.3298; p: 0.025), between ISSI-2 and ALT (r: -0.3262; p: 0.027), and between 1-hour plasma glucose value and ISSI-2 (r: -0.537; p: 0.005) in the whole group of β-TDT patients enrolled in our study. Conclusions: It is of paramount importance to screen early β-TDT patients at increased risk for glucose dysregulation. This retrospective study displayed that finding an isolated high 1-hour post-load glucose level (≥155 mg/dL; H-NGT) during the OGTT may serve as a simple biomarker to detect high-risk patients, with chronic liver disease and/or iron overload, who need periodic glycemic surveillance. Measuring the ISSI 2 represented another valuable predictive marker in the assessment of glycemia in these patients.

BACKGROUND: The natural history of the glycometabolic state in transfusion-dependent β-thalassemia (TDT) patients is characterized by a deterioration of glucose tolerance over time. AIMS: This review depicts our current knowledges on the complex and multifacet pathophysiologic mechanisms implicated in the development of alteration of glucose homeostasis in patients with TDT. SEARCH STRATEGY: A systematic search was done on December 2020 including Web of Science (ISI), Scopus, PubMed, Embase, and Scholar for papers published in the last 20 years. Moreover, we checked the reference lists of the relevant articles and previously performed reviews for additional pertinent studies. The personal experience on the care of patients with thalassemias is also reported. CONCLUSION: A regular packed red blood cells (PRBCs) transfusion program, optimization of chelation therapy, and prevention and treatment of liver infections are critical to achieve adequate glucometabolic control in TDT patients. Many exciting opportunities remain for further research and therapeutic development.

This review examines the prevalence, aetiology, pathophysiology, prognostic value, and investigation of dysnatraemia in hospitalised COVID-19 patients, taking into account all relevant studies published in PubMed and Cochrane Library studies until March 2021. Hyponatraemia is commonly observed in patients with bacterial pneumonia and is an independent predictor for excess mortality and morbidity. However, it remains unknown whether this association applies to coronavirus disease-2019 (COVID-19). Several studies reported a 20-35% prevalence for hyponatraemia and 2-5% for hypernatraemia in patients admitted with COVID-19. In addition, hyponatraemia on admission was a risk factor for progression to severe disease, being associated with an increased likelihood for the need for invasive mechanical ventilation, with an odds ratio (OR) of 1.83-3.30. Hyponatraemia seems to be an independent risk factor for mortality, with an OR of 1.40-1.50 compared to normonatraemia, while hypernatraemia is related to even worse outcomes than hyponatraemia. Furthermore, preliminary data show an inverse association between serum sodium and interleukin-6 levels, suggesting that hyponatraemia might be used as a surrogate marker for the risk of a cytokine storm and the need for treatment with interleukin antagonists. In conclusion, dysnatraemia is common and carries a poor prognosis in COVID-19 patients, indicating that it may play a future role in risk stratification and individualising therapy.

Background: Glucose dysregulation (GD), including prediabetes and diabetes mellitus (DM), is a common complication of transfusion-dependent beta-thalassemia (TDT) patients. The prevalence increases with age and magnitude of iron overload, affecting a significant proportion of patients. According to the international guidelines, the development of GD is frequently asymptomatic. Therefore, an early diagnosis requires an annual oral glucose tolerance test (OGTT) in all TDT patients aged ten years or older. Purpose: This retrospective study aims to evaluate the prevalence of GD in a homogenous population of prepubertal TDT patients and to enhance understanding of the pathogenesis and progression of glucose homeostasis in this group of patients. Methods: A selected group of 28 TDT patients was followed for at least 10.3 years (range: 10.3 - 28.10 years) from prepubertal age (mean 11.0 +/- standard deviation 1.1 years) to adulthood (28.7 +/- 3.7 years). Glucose tolerance and insulin response to OGTT were assessed, and indices of beta-cell function, insulin sensitivity, and insulin secretion were calculated. Results: At baseline, 18 TDT patients had normal glucose tolerance (NGT) and 10 had isolated impaired fasting glycemia (IFG), according to the American Diabetes Association (ADA) criteria. Compared to 18 healthy prepubertal controls (mean +/- SD age: 10.9 +/- 1.1 years), the fasting plasma glucose (FPG), basal insulin level, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were significantly higher in the group of TDT patients (p= 0.001, 0.01 and 0.012, respectively). At the last observation, 7/18 patients (38.8%) with NGT and 9/10 (90%) with IFG at baseline deteriorated; 3 female patients developed type 2 DM (1 from the NGT group and 2 from the IFG group). Compared to adult controls, TDT patients with NGT had a reduced oral disposition index (DI) (p= 0.006) but no significant difference in HOMA-IR and Matsuda index. Conversely, all insulin indices (HOMA-IR, nil, and DI) but one [insulinogenic index (IGI)] were statistically different in TDT patients with GD compared to controls. Conclusion: This study underlines the concept that the spectrum of glucose tolerance in TDT patients represents a continuum of glucose homeostasis disturbances and that prepubertal patients with IFG are at higher risk of developing a further deterioration of glucose metabolism with time. Moreover, it appears that one-third of adult TDT patients with normal fasting glucose may develop GD in the second-third decade of life. Thus, early intervention could help to prevent an expected further decline of glucose tolerance.

Objective To study the endocrine pancreas’ function in transfusion-dependent β-thalassemia (β-TDT) patients with a normal glucose tolerance test (NGT) and hypoinsulinemia. In addition, the prospective long–term follow-up using an annual oral glucose tolerance test (OGTT) to detect any abnormality of glucose metabolism. Patients and methods Seven β-TDT patients (mean age 22.4 ± 4.2 years) with NGT and inadequate insulin response (hypoinsulinemia) to OGTT were referred for a second opinion to an Italian Centre. Results The first-phase insulin response (FPIR), expressed as the sum of 1 and 3 minutes insulin, to intravenous glucose tolerance test (IVGTT), was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in five. The results were not associated with β-cell autoimmunity. After 43 ± 26 months (range 11 – 80 months) of follow-up, two patients developed impaired glucose tolerance (IGT), three both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline, the lowest value of the insulinogenic index (IGI: 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at the diagnosis of IFG, IGT, and DM. There was a significant inverse correlation between ISSI-2 and area under the curve plasma glucose (AUC-PG). Conclusions These data demonstrated, for the first time, progressive deterioration in glucose homeostasis in β-TDT subjects with NGT and hypoinsulinemia and that the ISSI-2 index may be a valuable parameter to identify patients at high risk for developing glucose dysregulation.