Terapevticheskii Arkhiv最新文献

The parathyroid glands (PG) and diseases associated with changes in their functional activity have been studied since the 19th century. In the last few decades, the basic principles of calcium-phosphorus metabolism, diagnostic methods, and treatment options for mineral disorders has changed significantly. The knowledge and experience of previous investigators in the anatomical, physiological, morphological, molecular, and genetic aspects of normal and abnormal PG, along with the introduction of innovative laboratory and instrumental methods, has been instrumental in the development of the field. Recent advances have opened new possibilities for personalized patient care. In our historical review, we describe the approaches to mineral and bone pathology, starting with the discovery of the PG and ending with modern achievements using the single endocrinology center as an example.

The rates of increase in the incidence of type 2 diabetes mellitus (T2DM) and obesity in the world are steadily increasing and exceed even the wildest forecasts, which forces specialists to seek, develop and implement more effective therapeutic methods for these two interrelated non-communicable pandemics. This article discusses promising areas in the pharmacotherapy of obesity and T2DM with an emphasis on the development of a class of incretin hormone receptor agonists. Monoagonists (liraglutide, dulaglutide, semaglutide) and dual incretin receptor agonists (tirzepatide), as well as triple- and tetra-agonists of gastrointestinal hormones currently under development, which are expected to be even more effective in the complex treatment of both type T2DM and obesity, are being discussed.

Background: It is assumed that chronic immune-inflammatory rheumatic disease may be a factor increasing the likelihood of developing hypogonadism syndrome, and vice versa - the presence of uncompensated testosterone deficiency may predispose to a higher risk of developing or a more severe course of immune-inflammatory rheumatic disease.

Aim: To study the frequency of hypogonadism in men with systemic sclerosis (SSc) and idiopathic inflammatory myopathy (IIM) and its associations with clinical manifestations of SSc and IIM.

Materials and methods: A total of 65 patients were included in the one-stage continuous study, including 39 with SSc and 26 with IIM, who were undergoing inpatient treatment at Nasonova Research Institute of Rheumatology. The patients underwent determination of the level of total testosterone with subsequent division into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was performed using the main indicators used in clinical rheumatology practice to assess the clinical and demographic characteristics of SSc and IIM. A correlation analysis was performed between the level of total testosterone and some clinical and laboratory indicators.

Results: The frequency of detected testosterone deficiency in SSc was 23.1%, and in IIM - also 23.1%. Patients with hypogonadism and SSc, compared with the group with normal testosterone levels, were characterized by a higher body mass index - BMI (27.0 [25.8; 29.8] kg/m² vs 23.5 [22.0; 26.1] kg/m²; p=0.033), were more often obese (77.8% vs 33.3%; p=0.022) and had a higher mean fasting glucose level (5.62 [5.27; 5.69] mmol/l vs 5.03 [4.82; 5.33] mmol/l; p=0.037). In addition, patients with hypogonadism were more often positive for anti-Scl70 (100.0% vs 40.7%; p=0.003) and had a trend towards higher titers of antinuclear factor (p=0.063). Significant inverse correlations were found between total testosterone levels and BMI, as well as antinuclear factor titer. Patients with IIМ and hypogonadism were characterized by a higher frequency of interstitial lung disease (66.7% vs 15.0%; p=0.012). Significant negative correlations were found between total testosterone levels and age, BMI and erythrocyte sedimentation rate.

Conclusion: A high frequency of hypogonadism was shown in men with SSc and IIМ. Reduced testosterone levels were accompanied by some metabolic disorders, as well as a high frequency of antibodies and clinical features characteristic of a more unfavorable course of the disease.

Background: Obesity is associated with some types of cancer including breast cancer (BC). But still there are not so much studies on the relationship between the adipose tissue distribution, visceral obesity (VO), and insulin resistance with the development of BC. This study is devoted to the effect of VO and insulin resistance on the development of BC.

Aim: To assess the frequency of VO and insulin resistance in patients with newly diagnosed BC in an outpatient setting.

Materials and methods: An observational retrospective study was conducted, including 160 electronic medical records of women with suspected cancer. The control group (n=103) consisted of women with negative histological results. The study group consisted of patients in whom BC was confirmed histologically. Anthropometric data, glycemia, and lipid profile were studied. Statistical processing of the results was performed using the method of descriptive statistics and calculation of the Spearman correlation coefficient with reliability assessment by the Student's t-test.

Results: The maximum frequency of BC is observed in women over 60 years old (80%). The average age in the group of participants with confirmed BC was 64.51±10.30, in the control group 55.81±12.20 (p<0.0004%). The average Body Mass Index in patients in the group with BC was 30.50±4.98, in the control group - 25.76±5.70 (p<0.05). The average Body Mass Index in the BC group was 30.50, in the control group - 25.76 (p<0.05). A high level of VO was found in 82% of patients with BC. We have found that in the group of patients with BC the frequency of occurrence of high Total Cholesterol values is 72%, Triglycerides - 61%, Low-Density Lipoprotein - 68%, while in the group of patients with unconfirmed BC 10, 33, 24% respectively. When assessing indirect signs of insulin resistance in patients with BC high values of the indicators were recorded, which indicates the presence of insulin resistance. In the control group, Visceral Adiposity Index was detected in 22% of cases above normal values, the Triglycerides to High-Density Lipoprotein Cholesterol index was detected above normal values in 12% of cases, Metabolic Index - 1%, Lipid Accumulation Product - 14%.

Conclusion: The results of the study emphasize the importance of VO and insulin resistance in the pathogenesis of breast cancer, which is important for early diagnosis and prevention of the disease.

The article presents a description of a clinical case of an ectopic focus of adrenocorticotropic hormone (ACTH) hypersecretion located in the adrenal medulla in a 64-year-old obese woman without other characteristic clinical signs of hypercorticism, with complaints of rapidly progressing lower limb edema, severe muscle weakness, loss of appetite, weight loss by 4 kg, as well as stage 2 arterial hypertension and type 2 diabetes mellitus. The patient's blood biochemistry showed severe hypokalemia, up to 2.2 mmol/l, despite infusion and oral therapy with potassium preparations. Taking into account the clinical picture and ECG and Echo-CG results, coronary heart disease, functional class II angina, and stage II A chronic heart failure, functional class II according to the New York Heart Association scale were diagnosed. During the laboratory and instrumental examination, endogenous hypercorticism was confirmed, high ACTH values were revealed, there were no visualized pituitary formations - ACTH ectopic syndrome was diagnosed. The patient's severe condition (severe hypokalemia, myopathy, progressive edema of the lower extremities) against the background of the added SARS-CoV-2 infection did not allow for a full topical diagnosis, and therefore the patient underwent a life-saving operation in the amount of bilateral adrenalectomy. In the postoperative period, a significant decrease in the ACTH level was noted, which became the basis for searching for the primary focus of ACTH ectopia in the removed adrenal tissue. According to the results of the immunohistochemical study, ACTH -secreting cells were detected in the medulla of both adrenal glands. This clinical case demonstrates the need for clinical alertness regarding endogenous hypercorticism and demonstrates the uniqueness of the localization of the primary focus of ACTH ectopia.

Aim: To investigate the presence of statistically significant correlations between clinical and laboratory characteristics and features of contrast-enhanced computed tomography (CT) images, as well as to assess the possibility of predicting group classification according to the PASS scale based on clinical, laboratory, and contrast-enhanced CT imaging data.

Materials and methods: A retrospective analysis was performed on preoperative four-phase contrast-enhanced CT images of 230 patients with a pathomorphologically verified diagnosis of pheochromocytoma/paraganglioma. Clinical manifestations such as the presence and duration of arterial hypertension, carbohydrate metabolism disorders, and dyslipidemia were assessed. In the first stage, comparative and correlation analyses were conducted between hormonal parameters and contrast-enhanced CT data. In the second stage, based on morphological characteristics, patients were divided into two groups: with PASS scores <4 (n=155) and PASS scores ≥4 (n=56). Logistic regression analysis was conducted to evaluate the possibility of predicting group classification based on clinical, laboratory, and contrast-enhanced CT imaging data.

Results: Pheochromocytomas/paragangliomas with isolated normetanephrine secretion type accumulate significantly more contrast agent in the arterial and venous phases of the study (p<0.001) compared to other secretion types. Correlation analysis revealed statistically significant moderate positive correlations between blood normetanephrine levels and the volume of functioning tumor tissue without necrotic areas, as well as a moderate negative correlation between blood metanephrine levels and the maximum density in the venous phase, the percentage of venous contrast enhancement, and the 90th percentile of X-ray density of the functioning tumor tissue in the venous CT phase. A statistically significant association was also found between the presence/absence of necrosis and tumor size (p<0.001), as well as between structure and tumor size (p=0.004). No statistically significant correlations were identified between laboratory parameters, imaging data, and clinical manifestations (arterial hypertension, carbohydrate metabolism disorders, dyslipidemia, and carotid artery atherosclerosis). CT image characteristics allow for prediction of group classification according to the PASS scale with an AUC of 0.647 (95% confidence interval 0.471-0.797), sensitivity of 0.923 (0.727-1.000), specificity of 0.400 (0.250-0.548), PPV of 0.333 (0.176-0.500), and NPV of 0.941 (0.800-1.000).

Conclusion: Pheochromocytomas/paragangliomas are heterogeneous pathologies with diverse clinical, hormonal, and radiological characteristics that are associated with pathomorphological findings (PASS scale).

Ultra-fast acting insulin analogs were created to achieve a physiological profile of action with more rapid and pronounced initial insulin peak. The accelerated absorption of ultra-fast-acting insulin analogues results in a more rapid onset of action, with insulin concentrations reaching their peak in the bloodstream earlier compared to rapid-acting insulin analogues. This rapid peak of insulin action better matches the postprandial glucose absorption profile, resulting in improved glycemic control and a reduced risk of postprandial hyperglycemia. Thus, the rapid onset and offset of action of ultra-rapid-acting insulin analogues provides greater flexibility in adjusting insulin doses based on the carbohydrate content of meals and physical activity levels. A shorter duration of action allows for a reduction in the frequency of hypoglycemic events, which may improve overall quality of life and reduce the fear of hypoglycemia, which is a serious problem for many patients with diabetes. The use of ultra-fast-acting insulin analogues has shown its effectiveness in compensating postprandial hyperglycemia and reducing glucose variability in various patient groups, including patients with type 1 and type 2 diabetes, children and pregnant women, in addition, their use in closed-loop systems has promising results in improving glycemic outcomes.

Immunoinflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis and systemic lupus erythematosus, are characterized by common mechanisms of development and similar comorbid pathology, including diabetes mellitus (DM) type 2. Patients with IIRD with concomitant DM represent one of the most difficult groups to manage due to serious complications and forced polypharmacy. The article considers risk factors for carbohydrate metabolism disorders, both traditional and directly associated with rheumatoid arthritis and systemic lupus erythematosus, including the effect of anti-inflammatory therapy on insulin resistance, the risk of DM type 2 and glycemic control, as well as positive pleiotropic properties of some hypoglycemic drugs for the treatment of IIRD, and shows the prospects for further clinical research in this area.

Aim: The aim of this study was to identify the prevalence of steatosis degrees and stages of liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) in connection with the presence of carbohydrate metabolism disorders, such as prediabetes and type 2 diabetes mellitus (DM).

Materials and methods: Retrospective database search (4101 records) was performed. Vibration-controlled transient liver elastography with controlled attenuation parameter module was used for the assessment of liver steatosis and fibrosis. Based on the presence of carbohydrate metabolism disorders, subjects with MASLD were allocated to one of the following groups: MASLD without prediabetes or DM (group 1), MASLD with prediabetes (group 2) and MASLD with DM (group 3).

Results: Proportion of patients with severe liver steatosis (S3) was lowest in the group 1 (61.9%), while no difference was found between groups 2 and 3 (74.3% vs 76.7%; p = 0.5). Moderate-to-severe liver fibrosis (stages F2-F4) was less widespread in the group 1 (24.1%); significant difference by this parameter was also revealed between groups 2 and 3 (34.0% vs 45.4%; p = 0.004). Proportion of patients with metabolic dysfunction-associated steatohepatitis was similar in groups 2 and 3 (33.9% vs 35.4%; p = 0.7), but was lower in the group 1 (26.7% vs 33.9% and 35.4%; p = 0.02 and p < 0.001, respectively).

Conclusion: Carbohydrate metabolism disorders are closely associated with progressive steatosis and liver fibrosis in patients with MASLD. No differences in the severity of liver steatosis was found between groups with prediabetes and T2DM, however, in T2DM, the prevalence of advanced/severe liver fibrosis was highest among all studied groups.

Aim: To evaluate the possibility of using serum markers of atrophy (pepsinogens - PG I and II) to form high-risk groups for gastric cancer (Operative Link for Gastritis Assessment - OLGA stage III-IV) depending on the etiology of gastritis.

Materials and methods: A total of 237 (56 men and 181 women) patients were examined. All patients underwent a ¹³C-urea breath test, a blood test for GastroPanel (PG I, PG II, gastrin-17, antibodies to Helicobacter pylori immunoglobulin G), a blood test for antibodies to gastric parietal cells. All patients underwent esophagogastroduodenoscopy with a biopsy of the gastric mucosa from 5 standard points according to the Sydney system and a histomorphological study according to the OLGA system, as well as a biopsy to detect H. pylori infection using the polymerase chain reaction. The patients were divided into 3 groups depending on the etiology of gastritis: Group 1 included 55 patients with chronic gastritis, autoimmune gastritis and associated with H. pylori gastritis (AIG+HP+); Group 2 - 47 patients with AIG and negative tests for H. pylori infection (AIG+HP-); Group 3 - 135 patients with chronic gastritis associated with H. pylori and negative markers of AIG (AIG-HP+).

Results: The analysis showed that in patients with AIG (group 2), the most reliable serological markers of atrophy predicted severe atrophy (OLGA stage III-IV): when the ratio PG I/PG II was ≤ 3, it was detected in 70.21% of cases, and when PG I decreased to ≤ 30 μg/L, it was found in 68.08%. In group 1, stages III-IV according to OLGA were diagnosed in 20% of cases with PG I/PG II indicators ≤ 3; and in 18.18% with a decrease in PG I ≤ 30 μg/L. When analyzing the diagnostic accuracy of GastroPanel biomarkers in identifying severe atrophy (OLGA stages III-IV) in the total sample of patients (all 3 groups), it was possible to achieve cut-off indicators as close as possible to the reference values while maintaining a relatively high sensitivity and specificity - 75.81% and 81.50% for PG I ≤ 30 μg/L and 85.48% and 64.50% for PG I/PG II ≤ 3, respectively. The optimal cut-off in the study population for the PG I indicator was < 22.5 μg/L (sensitivity - 72.58%, specificity - 88.00%), and for the PG I/PG II ratio ≤ 2 (sensitivity - 80.65%, specificity - 78.50%).

Conclusion: Serum pepsinogens can be used in the Moscow population as a non-invasive marker of gastric mucosa atrophy for the formation of high-risk patient groups for gastric cancer requiring endoscopic examination.