Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

Функциональное состояние эндокринной системы и минеральная плотность костной ткани в отдаленном периоде после комбинированного лечения злокачественных опухолей головного мозга в детском и молодом возрасте

Aim. To study the traditional risk factors for cardiovascular disease (CVD), indicators of endothelial function and exercise tolerance in patients received complex treatment for cranial and craniospinal tumors in childhood, including radiation therapy.Material and methods. We compared examination data of 48 patients who underwent treatment for brain tumors using cranial and craniospinal irradiation in childhood (mean age, 21,7±4,3 years, mean period after the end of treatment, 6,9±5,4 years), and 20 healthy volunteers. Examination methods included assessment of lipid profile, vascular stiffness and endothelial function using the Photoplethysmography and occlusion test, cardiopulmonary test, and in patients who underwent craniospinal irradiation, also echocardiography and duplex ultrasound of extracranial arteries.Results. Compared to healthy individuals, patients after a brain tumor were found to have lower blood pressure, higher heart rate (HR), significantly lower exercise performance (peak oxygen consumption, 19,8±6,4 ml×min-1×kg vs 30,3±5,8 ml×min-1×kg, p<0,0001) and a higher prevalence of dyslipidemia (56% vs 5%, p<0,0001), as well as an increase in the augmentation index, indicating higher stiffness of large vessels (-7,3±16,3 vs -20,3±7,9, p=0,001), and a trend towards a decrease in the occlusion index (p=0,051). Echocardiography and duplex ultrasound revealed no radiation-associated abnormalities.Conclusion. Determining the mechanisms and prognostic significance of the identified risk factors for CVD (dyslipidemia, decreased exercise tolerance, increased heart rate and vascular stiffness) in this category of patients requires further research. Regular monitoring of risk factors, primarily the lipid profile, and the use of preventive measures for individuals with an increased risk of CVD should be recommended.

BACKGROUND: The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI). AIM: To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI. METHODS: A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 57 days. The cortisol, ACTH, and glucose levels were measured. RESULTS: Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT 499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise 340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was 500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l). CONCLUSION: GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.

Diabetes self-management education (DSME) is an essential part of effective and safe treatment of chronic conditions such as diabetes mellitus (DM). Though the data on DSME effectiveness in elderly are limited, all patients should be educated regardless of age. The form of learning and education program may vary depending on the clinical situation and the patient’s characteristics. Age-related problems, so-called geriatric syndromes, determinant heterogeneity of elderly diabetic population. Geriatric syndromes should be taken into account to choose proper treatment goals and optimal education programs. Functional dependency, cognitive decline, depression, sarcopenia, malnutrition and polypharmacy seems to be most important in the education context. The development of geriatric education program with a broad focus on solving both diabetic and age-related problems and its implementation on a wider range of institutions may be useful to improve diabetes self-management education of elderly in clinical practice. It is also necessary to initiate clinical studies to evaluate DSME effectiveness in elderly not only from the generally accepted diabetological criteria, but also considering its impact on age-related problems.

Kearns-Sayre Syndrome (KSS) is a variant of mitochondrial disorder caused by a Mitochondrial Deoxyribonucleic Acid (mtDNA) deletion. Clinical manifestations of KSS can include different organ and system involvement. Different organ malfunctions, more often cardiac dysfunction, can lead to death. No effective treatment of this condition exists to date. Here, we report two patients with KSS. Female patient with a large-scale deletion of 7,020 base pairs (bp) suffered from hypogonadism, diabetes mellitus with fluctuating glucose levels, and had poor general health. A male patient with a common 4,977 bp deletion did not have diabetes mellitus but had impaired glucose tolerance. He also had a higher level of general health than our female patient. Both patients had reduced Bone Mineral Density (BMD). In female patients, calcium and vitamin D supplementation combined with metabolic therapy and nutritional drink supplements helped increase BMD (up to 32% in L1-L4). Comparing these two patients suggests that the larger the mtDNA deletion is, the more severe the course of the disease is. Not only does the size of the mtDNA deletion probably determine the severity of the disease, but also such factors as mtDNA heteroplasmy level, presence of mtDNA duplications, and pleioplasmy. Moreover, continuous nonconsecutive metabolic therapy and nutritional supplements are helpful in the prevention of deterioration of symptoms and general health.