[Retrospective analysis of clinical outcomes of patients with COVID-19 depending on receiving antihypertensive, lipid-lowering and antihypertensive therapy].

BACKGROUND: The main factors that increase the risk of cardiovascular accidents and mortality among patients with COVID-19 include hyperglycemia, arterial hypertension and dyslipidemia. Therefore, all patients with COVID-19 and metabolic syndrome should receive antihypertensive (AHT), hypolipidemic (GLT) and hypoglycemic therapy (GGT). Currently, there is a limited number of studies regarding the effectiveness and safety of this therapy in patients with COVID-19. AIM: Evaluate the clinical outcomes of patients with COVID-19, depending on the recipient of AHT, GLT and GGT. MATERIALS AND METHODS: A retrospective analysis of the clinical outcomes "discharged/died" of 1753 patients with COVID-19 was carried out depending on the received AHT, GLT and GGT. RESULTS: A significant reduction in the risk of mortality among patients with COVID-19 was observed during therapy with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers ACE inhibitors/ARBs (OR 0.39, 95% CI 0.210.72; p0.05) and b-adrenergic blockers b-AB (OR 0.53, 95% CI 0.281; p0.05). At the same time, against the background of therapy with ACE inhibitors/ARBs and b-ABs, the chance of mortality decreased more significantly among patients with type 2 diabetes mellitus (T2DM) compared with patients without T2DM. Diuretic therapy was associated with a 3-fold increase in the chances of death: OR 3.33, 95% CI 1.884.79; p0.05. Statin therapy did not affect clinical outcomes in COVID-19 patients. On the background of therapy with oral hypoglycemic drugs, the risk of mortality decreased 5-fold (OR 0.19, 95% CI 0.070.54; p0.05). Against the background of insulin therapy, there was an increase in mortality risk by 2.8 times (OR 2.81, 95% CI 1.55.29; p0.05). CONCLUSION: A significant reduction in mortality among patients with COVID-19 was observed during therapy with ACEI/ARB, b-AB, and oral hypoglycemic therapy. Increased risk of death was associated with insulin therapy and diuretic therapy.

[Empagliflozin and heart failure: position paper of the experts on the results of the online meeting and discussion of the EMPEROR-Preserved Trial].

At an international online expert meeting held on September 16, 2021, the results of the empagliflozin research program EMPA-REG Outcome, EMPEROR-Reduced and EMPEROR-Preserved were reviewed. We analyzed cardiovascular and renal outcomes during the treatment with empagliflozin in patients with chronic heart failure, regardless of the presence of type 2 diabetes mellitus. The positive results of the EMPEROR-Preserved study are updated and their significance for clinical practice is discussed. Several proposals have been adopted that will accelerate the introduction of empagliflozin therapy into practice in patients with heart failure and overcome clinical inertia.

[MULTIDISCIPLINARY TEAM APPROACH FOR DIABETIC FOOT PATIENTS IN AN OUT-PATIENT CLINIC].

AIM: To assess the effectiveness of multidisciplinary team approach in daily practice of diabetic foot. MATERIALS AND METHODS: 376 diabetic patients (446 ulcers) treated in a diabetic foot department in 2014 were examined. All patients were screened for diabetic peripheral polyneuropathy and blood insufficiency of lower extremities in order to diagnose the type of diabetic foot ulcer: neuropathic or neuroischemic. Patients were treated by a multidisciplinary team. The number of healed ulcers, minor and major amputations was analyzed. RESULTS: 80% of diabetic foot ulcers were neuropathic with normal blood supply, 20% had signs of ischemia. 77.8% of the ulcers healed in the general group during the study period. 13 amputations (2.9%) were done in the study group: 7 minor amputations (1.6%), 2 below the knee (0.4%), and 4 above knee (0.9%). Two patients died from cardiovascular events (0.4%). The comparative analysis of outcomes of neuropathic and neuroischemic ulcers showed that 84% of neuropathic ulcers healed. Minor amputations were done in 1% of the cases, no major amputations were performed. In patients with neuroischemic ulcers, 60% of them healed, minor amputations were made in 3.4% of cases (2.3% below knee, 4.6% above knee). CONCLUSION: The majority of diabetic ulcers in the study group were neuropathic with normal blood supply. The main risk factor of major amputations is ischemia of the affected limb. The multidisciplinary team approach in daily practice of the diabetic foot department of an out-patient clinic is instrumental in healing ulcers and minimizing the risk of major amputations.

[Unification of pathomorphological examination of patients with neuroendocrine tumors of the pituitary gland. Controversial issues of the new classification].

The progressive improvement of the classification using modern analytical methods is an essential tool for the development of precise and personalized approaches to the treatment of pituitary adenomas. In recent years, endocrinologists have witnessed evolutionary changes that have occurred in the histopathological identification of pituitary neoplasms, revealing new possibilities for studying tumorigenesis and predicting biological behavior.The paper considers the historical aspects of the gradual improvement of the classification of pituitary adenomas, as well as the new international 2022 WHO classification, according to which pituitary adenomas are included in the list of neuroendocrine tumors (PitNETs) to reflect the biological aggressiveness of some non-metastatic pituitary adenomas. The characteristics of pituitary adenoma are presented, as well as a list of histological subtypes of aggressive neuroendocrine tumors of the pituitary gland, marked by the main potentials for invasive growth, an increased risk of recurrence and a negative clinical prognosis.The expediency of changing the definition of «pituitary adenoma¼ to «neuroendocrine tumor¼ is discussed. It is emphasized that the introduction of a unified clinical, laboratory and morphological protocol into national clinical practice will help provide comparable comparative studies on the prognosis of the disease and the effectiveness of secondary therapy and also contribute to adequate management of potentially aggressive PitNETs.

[The clinical laboratory evaluation of accuracy of portable glucometers "Satellite Express" and "Satellite Express mini"].

The portable glucometers "Satellite Express" and "Satellite Express mini" were applied during 35 days to analyze 200 blood samples of patients with diabetes mellitus type I and II and of healthy people. The results were compared with the data of reference analyzer The results of clinical laboratory trials revealed that these glucometers have enough degree of accuracy detection of glucose in capillary blood - 100% of results are within the permissible limits as directed by ISO 15197:2003. Furthermore, 98.3% of results are within the limits of +/- 15% from reference analyzer results. Thereby, the glucometers "Satellite Express" and "Satellite Express mini" can be recommended to detect the glucose concentration in capillary blood for the purpose of glycaemia level self-control by patients with diabetes mellitus. The devices can also be used by medical personnel for express diagnostics in case of emergency care.

[Selective screening of patients with associated somatic diseases as a method of early detection of acromegaly].

Backgraund: Acromegaly is a multi-organ disabling disease, the effectiveness of treatment of which directly depends on timely diagnosis. Latent course and delayed diagnosis increase the exposure of pathological hypersecretion of growth hormone and insulin-like growth factor-1, contributing to the development of irreversible systemic and metabolic changes in the body that negatively affect survival. AIMS: The aim of the study was to clinically test a comprehensive diagnostic approach using selective screening to detect cases of acromegaly in patients with combined somatic diseases. MATERIALS AND METHODS: The diagnostic search algorithm included a 2-stage questionnaire, expert assessment of the clinical status, laboratory and instrumental examination. The inpatient examination included the use of additional laboratory and instrumental methods and expert evaluation of the results obtained by filling out a doctor's questionnaire. When the score was higher than 18 points, a more specific examination was performed: double determination of the insulin-like growth factor-1 level, oral glucose tolerance test with determination of the nadir of growth hormone value, and MRI of the brain with contrast enhancement. The diagnosis of acromegaly was made on the basis of personal data, expert assessment of the clinical status, results of laboratory and instrumental examinations. RESULTS: A survey of 1249 patients with combined systemic and metabolic disorders conducted using the point system allowed us to suspect acromegaly in 367 patients (29.4%), who were offered further examination. The majority of patients were previously seen by specialists for diabetes mellitus (79.3%) or thyroid pathology (10%). In the result of inpatient -examination of 329 patients, 35 (10.6%) patients showed an increase in the blood level of IGF-I. In 19 patients, a persistent increase in the level of IGF-I was combined with the absence of GH suppression of less than 0.4 ng/ml against the background of glucose load. During MRI in 9 patients, pituitary adenoma was detected (in 2 - microadenoma and 7 - -macroadenoma). CONCLUSIONS: As a result of the study, among the group of 1249 patients (mean age 58±13 years) with the presence of concomitant diseases, 9 newly identified patients with acromegaly were found who were prescribed adequate treatment. The introduction of selective screening technology into the practice of an endocrinologist will improve the effectiveness of diagnostic search for patients with acromegaly, more accurately assess the prevalence of the disease in Russia and the need for specialized medical care.

[Cytokines and their role in pathogenesis of diabetic retinopathy].

The role of cytokines is estimated in development of diabetic retinopathy. Titer of cytokines is compared in healthy subjects and patients with impaired glucose metabolism. Fundus examination and specific cytokines level assessment allowed us to conclude that cytokines directly take part in pathogenesis of retinopathy before clinical manifestation. It provides rational to use cytokine level as a predictor of early manifestation of diabetic retinopathy, its timely treatment and prevention of progressing till end stages.

[Resolution on the results of the first working meeting of the Scientific Advisory Board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy¼].

June 19, 2018 the meeting of the Scientific Advisory Board took place in Moscow, chaired by Professor G.R. Galstyan, (co-chair - A.V. Zilov) devoted to the discussion of the possibilities of improving the results of treatment of diabetes mellitus (DM) by consideration of «variability of glycemia¼ (VG) as an additional criterion of the glycemic control effectiveness (especially of insulin therapy) as well as one of the goals of treatment in patients with unstable glycemia. The purpose of the working meeting was to develop a strategy for the introduction of VG as a predictor and an additional criterion in assessing the effectiveness and safety of hypoglycemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality. Aims: - to conduct a comprehensive data analysis of the relationship between VG and adverse DM outcomes, such as hypoglycemia, micro-and macrovascular complications, cardiovascular and total mortality; - to accumulate and analyze published data and the experience of decrease of VG and improving outcomes of diabetes on the background of different versions of insulin therapy; - to compare existing methods of glycaemia monitoring and VG assessment, their validity and availability in real practice in the context of limited budget; - to analyze the informativeness, clinical and prognostic significance of various parameters of VG assessment and determine their reasonable «minimum¼ for a comprehensive assessment of VG as a criterion for evaluating the effectiveness of treatment of DM and predictors of negative diabetes outcomes. The following reports were heard during the discussion: Glycemic variability: clinical and prognostic value. Types of glycemic variability. (Alexey V. Zilov, MD, PhD in Medicine, Assistant Professor). Methods of assessment of variability of glycemia in clinical trials and routine practice (Tatiana N. Markova, MD, PhD in Medicine, Professor). Current international and national recommendations on glycemic monitoring (Gagik R. Galstyan, MD, PhD in Medicine, Professor). Peculiarities of glycemic variability and its evaluation among children and adolescents (Alisa V. Vitebskaya, MD, PhD in Medicine).

[Primary hyperparathyroidism in Russia according to the registry].

BACKGROUND: There are no large-scale epidemiological studies on primary hyperparathyroidism (PHPT) in Russia. The high prevalence of the disease, the high risk of disability and death in this cohort of patients requires the study of the epidemiological and clinical structure of PHPT to determine the extent of medical care. AIM: Evaluate the frequency of PHPT detection and characterize its clinical forms in Russia using an online registry. METHODS: The object of the study is the database of the State Register of Patients with PHPT 1914 patients from 71 regions of the Russian Federation. New cases of the disease, as well as dynamic indicators are recorded when patients visit outpatient clinics or medical institutions. The analysis of data made at the end of December 2017 was carried out. The following parameters were evaluated: demographic and clinical indicators; indicators of phosphorus-calcium metabolism, the main forms of PHPT and its course, the primary characteristic of PHPT in hereditary syndromes and parathyroid carcinoma. Results are presented as mean and standard deviations, or medians and quartiles; descriptive statistics of qualitative attributes absolute and relative frequencies. RESULTS: the total number of patients with PHPT in the registry on 31 of December 2017 was 1914 cases (0.001% of the population of the Russian Federation). Identification of PHPT was 1.3 cases per 100 thousand of the population in Russia, 7.6 cases in Moscow, 6.1 cases per 100 thousand in the Moscow region. The average age of patients at the time of diagnosis was 55.6 10 years. The active phase of the disease was registered in 84.6% of patients (1620/1914), most of whom had a symptomatic PHPT 67.1% (1087/1620), and 32.9% a asymptomatic disease (533/1620). Symptomatic disease with visceral complications was detected in 15.8% cases (172/1087), with bone complications in 48.4% (526/1087). The mixed form of the disease was detected in 35.8% of patients with manifest form (389/1087). Normocalcemic variant PHPT (nPHPT) was registered in 14.5% cases (234/1620). Sporadic PHPT occurs in 83% of cases (1592/1914). 326 patients (17%) had a suspicion for hereditary form of the disease: average age was 31.2 12.3 years. A genetic analysis was conducted in 61 patients (3.2%): showed the mutation in the MEN1 gene in 2.9% of cases (55/1914) and the mutation in the CDC73 gene in 0.3% of cases (6/1914) (HPT-JT syndrome). Parathyroid carcinoma was confirmed in 1.8% of all patients (35/1914). Surgical treatment was performed in 64.5% of patients (1234/1914). Remission was achieved in 94% of cases (1160/1234), in 6% of cases relapse after surgical treatment or persistence of PHPT was recorded. CONCLUSION: detection of PHPT in the Russian Federation raised in comparison to 2016, which is associated with an active start of registration of patients in the regions. At this stage, it is necessary to modify the principles of registration and control, to make a platform for gathering information and calculating the necessary volumes of medical care for PHPT patients.

A 10-year (1996-2005) prospective study of the incidence of Type 1 diabetes in Moscow in the age group 0-14 years.

AIMS: To provide data on the incidence of Type 1 diabetes (T1D) in Moscow, determined prospectively from 1996 to 2005 for a total of > 10 million subjects aged < 15 years. METHODS: Data on T1D incidence in patients with newly discovered T1D resident in Moscow diagnosed between 1 January 1996 and 31 December 2005 were analysed. Primary ascertainment was based in endocrinology departments of children's hospitals in Moscow. A secondary source were the archives of Moscow Region where patients are registered to obtain exemption from paying for medication. RESULTS: We identified 2031 new cases of T1D patients with a degree of ascertainment through primary and secondary sources of 94%. Overall the incidence rate of the disease was 12.9 per 100,000 per year (95% confidence interval 12.3- 13.4). The cumulative risk of the disease was 0.28 per 1000 in the age group 0-4 years, 0.84 in the age group 5-9 years and 1.8 in the age group 10-14 years. The incidence rate in girls increased by a mean of 6% per year in all age groups (P < 0.05 for all comparisons), whereas in boys it increased by a mean of 7% in the age group 10-14 years. Thirty percent of cases presented with diabetic ketoacidosis and coma at diagnosis, whereas hyperglycaemia without ketonuria was present in 20% of patients. CONCLUSIONS: This is the first study to report on validated incidence data for T1D in Moscow. We conclude that the incidence of T1D in Moscow is comparable to that of those European countries having intermediate incidence rates, and that the incidence is increasing.

[Role of vascular endothelial growth factor in the development of diabetic retinopathy in patients with type 1 diabetes mellitus].

The influence of vascular endothelial growth factor (VEGF) on the course of diabetic retinopathy (DR) was studied in 35 patients, including 11 males and 24 females, aged 21 to 56 years (mean 37 +/- 2.6 years) who had type 1 diabetes mellitus (DM) whose history was 14 to 40 years (mean 21.4 +/- 2.7 years). Tear and serum VEGF was examined by solid-phase enzyme-linked immunosorbent assay (ELISA), by using diagnostic Bender MedSystems (Austria) on a Stat Fax-2100 (USA). In the active phase of proliferative DR, the patients with type 1 DM were found to have the highest level of tear VEGF; when the process changed to a inactive phase, the content of this factor significantly reduced. There was a relationship between the tear level of VEGF and the degree of various manifestations of DR. There is an agreement of the tear and serum levels of VEGF in patients with different stages and manifestations of DR, which may be evidence for the single mechanism responsible for vascular endothelial damage in DM. There is a relationship between the presence of VEGF, the proliferative stage of DR, and diabetic nephropathy.

Effect of raising injection-site skin temperature on isophane (NPH) insulin crystal dissociation.

In eight healthy subjects, skin temperature at the injection site was raised from mean +/- SD 31.7 +/- 0.5 to 40.8 +/- 0.9 degrees C 180 min after injection of 0.25 U/kg isophane (NPH; Human Insulatard) insulin and maintained for 180 min. On the control day, skin temperature was kept constant. On warming of the injection site, serum insulin concentration rose from mean +/- SE 14.4 +/- 2.5 to 17.7 +/- 3.1 mU/L after 40 min (P less than .01) but did not change on the control day over the same period. The change in insulin concentration from the prewarming hour was higher on the warming day than control day in the 1st h (123 +/- 8 vs. 93 +/- 7%, P less than .01), 2nd h (115 +/- 14 vs. 83 +/- 9%, P less than .05), and 3rd h (113 +/- 17 vs. 80 +/- 10%, P less than .05) of warming, providing evidence for both early increased absorption of the free-insulin pool surrounding the protamine-insulin complexes and continuing increased dissociation of the complexes.

The effects of subcutaneous human proinsulin on the production of 64/65 split proinsulin, glucose turnover and intermediary metabolism in non-insulin-dependent diabetic man.

We have compared the effects of subcutaneously injected human proinsulin, insulin zinc suspension and inactive diluent (control) on glucose turnover, intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetic man. Six weight-matched (24.8 +/- 1.6 kg M-2) non-insulin-dependent diabetic subjects underwent 3 separate, randomized, 10 h isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6'6'2H2] glucose. Each subject received 0.35 U/kg of hormone or control made up to isovolumetric amounts. The mean blood glucose level of 7.3 +/- 0.8 mmol/l was similar at the start of each isoglycemic clamp. Incremental area under the curve proinsulin levels (1195 +/- 146 nmol/l) were about 21-fold higher, on a molar basis, than insulin (62.4 +/- 10 nmol/l). Des 64/65 split proinsulin increased in a parallel manner to intact proinsulin (r = 0.99, P < 0.0001) and comprised approximately 13% of the intact proinsulin concentration. Hepatic glucose production was suppressed similarly following proinsulin and insulin zinc injection. However, both proinsulin and insulin zinc had a significantly greater effect on suppression of hepatic glucose production compared to control (P = 0.01, P = 0.009, respectively). Metabolic clearance rate of glucose fell significantly during the control studies compared to insulin zinc or proinsulin injections (P < 0.05). Blood lactate, pyruvate and alanine concentrations were similar following control or hormone injections. However blood glycerol, 3-hydroxybutyrate and plasma-non-esterified fatty acids were suppressed significantly by proinsulin and insulin zinc compared to control injections. The conclusions were: (1) In overnight fasted hyperglycemic non-insulin-dependent subjects s.c. injections of proinsulin and insulin zinc can produce similar effects on glucose turnover, intermediary lipid and carbohydrate metabolism. (2) Similar carbohydrate intermediary metabolism profiles can be obtained following insulin zinc, proinsulin or control injections. (3) However lipolysis and ketogenesis were significantly suppressed by both hormones compared to control. (4) Subcutaneous proinsulin injection resulted in approximately 13% conversion to des 64/65 split proinsulin.

Association of blindness to intensification of glycemic control in insulin-dependent diabetes mellitus.

Intensive glycemic control (IGC) in previously hyperglycemic insulin-dependent diabetes mellitus (IDDM) patients is associated with a decreased long-term risk of progression of diabetic retinopathy (DR); up to 12 months after institution of IGC, however, the risk of progression of DR transiently increases. In an observational study, a cohort of 122 patients with IDDM was followed prospectively for changes in glycosylated hemoglobin (HbA1, normal < 8%) and in DR 0-12 months after institution of IGC. In six of these patients (women, mean age 24 years, duration of diabetes 14.3 years, with incipient nephropathy and retinopathy) a total of seven eyes went blind after 6-12 months of IGC, despite laser coagulation treatment. From the whole sample, a control groups of eight patients (six women) was set up, matched for age, duration of IDDM, degree of retinopathy, visual acuity, blood pressure, and microalbuminuria, with preserved vision after 12 months of IGC. In the case patients, the mean (95% confidence interval) initial HbA1 was 14.9% (13.8%-16.1%), versus 13.4% (12.4%-14.4%) in the control patients (p < 0.05). The mean HbA1 decrements after 4 months of IGC, were 3.0% (1.9%-4.1%) in the cases, and 2.1% (1.2%-3.0%) in the controls (NS); and after 12 months, the respective decrements were 4.9% (2.4%-7.4%) in the cases versus 2.0% (0.5%-3.5%) in the controls (p = 0.04). In conclusion, IGC with a decrement of > 2% per year is associated with a high risk of progression of antecedent diabetic retinopathy to blindness in IDDM patients with an extremely high initial HbA1.(ABSTRACT TRUNCATED AT 250 WORDS)

[Determination of natural foci of tularemia in the Tuva ASSR]. / Ustanovlenie prirodnoi ochagovosti tularemii v Tuvinskoi ASSR

Eleven strains of tularemia causative agents were isolated in 1974 in bacteriological study of ixodes ticks Dermacentor nuttalli (13088 in all) by biotests on albino mice. Tularemia was confirmed retrospectively in two humans who contracted the disease from ondatra cadavers. Skin allergic test with tularin was used to examine 1733 residents of seven populated localities; a positive result was obtained in 2 persons. Finally, in examination of 240 sera of cattle agglutination reaction proved to be positive in 6 cases in titres of from 1:20 to 1:80. Thus, natural nidality of tularemia in Tuva was established for the first time.

[Ectoparasites of small mammals, their nests and of the nests of birds in the floodplain of the Kamchatka River]. / Ektoparazity melkikh mlekopitaiushchikh, ikh gnezd i gnezd ptits v poime reki Kamchatki.

The paper presents data on the specific composition and abundance of bloodsucking arthropods parasitic on small mammals and birds in the valley of the Kamchatka river. One species of ixodids, I. lividus, 9 species of gamasids, P. crassipes, E. kraepelini, G. bispinosus, V. bujakova, H. casalis, H. mandschuricus, M. decoloratus, P. bujakovae, Macroheles sp., and one species of fleas, C. riparius, were first recorded from Kamchatka. 723 rodents were bacteriologically examined for tularemia with negative results.

[The biochemical markers of bone metabolism in differential diagnosis of hematogenic osteomyelitis of foot bones and acute stage of diabetic osteoarthropathy]. / Biokhimicheskie markery kostnogo metabolizma v differentsial'noi diagnostike gematogennogo osteomielita kostei stopy i ostroi stadii diabeticheskoi osteoartropatii.

The determination of the level of leukocytes and ESR in 25 patients was shown to be of low informative value in differential diagnostics of destructive injuries of feet in patients with diabetes mellitus. An analysis of the biochemical markers of the bone remodeling has demonstrated high informative value of this method in differential diagnostics of acute stage of diabetic osteoarthropathy and osteomyelitis that allows to use it in complex examinations of osteomyelitis suspects.

[Initiation of insulin therapy for type 2 diabetes mellitus].

This program is designed to identify patients in whom diabetes mellitus resists therapy with oral hypoglycemic agents (OHA) and basal insulin administration is needed to maintain the HbA1c at the desired level below 7. Data from 2895 patients (2034 women and 851 men) were available for analysis. Only 2.6% of the patients had the glycated hemoglobin (HbA1c) level within the normal values prior to the onset of therapy. The remaining ones had decompensated diabetes mellitus that required supplementation of regular OHA therapy with Lantus insulin. Characteristics of carbohydrate metabolism significantly improved and decreased to the desired values within 12 weeks after the initiation of the combined treatment without enhancement of the risk of hypoglycemia. Results of the study demonstrate beneficial effect of the early prescription of basal insulin. Administration of glargine insulin permits to rapidly and safely reach optimal parameters of carbohydrate metabolism in the majority of the patients.

[A system for preventing lower limb amputations in patients with diabetes and prospects for its introduction in Moscow].

We initiated the implementation of a program for the prevention of lower limb amputations in patients with diabetes in Moscow. The long-term goal of this project is to carry out specialized treatment and preventive measures based on diabetic foot cabinets, aimed at reducing the number of lower limb amputations in patients with diabetes mellitus, who are at risk of developing diabetic foot syndrome.