Vol 53, No 6 (2025)

Background: The prevalence of obesity among working-age men with high occupational stress reaches 41%, significantly exceeding the average population level (28.6%). In this cohort, obesity is recognized as one of the leading risk factors for the early development of cardiovascular and cerebrovascular diseases. Experimental evidence indicates the influence of obesity and intermittent hypoxia on the disruption of the blood-brain barrier (BBB). As a biological marker reflecting BBB dysfunction, claudin-5 is of interest, with increased serum concentrations observed in neurodegenerative, psychiatric, autoimmune diseases, and in the acute stage of ischemic stroke.

Aim: To determine the association of abdominal obesity and intermittent hypoxia with serum claudin-5 levels and the severity of cerebral microangiopathy in working-age men with high occupational stress.

Methods: A single-center continuous cross-sectional study was conducted with sequential enrollment of 100 men from the personnel of the Russian Ministry of Emergency Situations (EMERCOM), aged 20 to 60 years, with cardiovascular risk factors, who underwent examination and treatment at the clinic of the Nikiforov Russian Center for Emergency and Radiation Medicine, EMERCOM of Russia, from February 1, 2024, to March 1, 2025. Stress levels were assessed using the Psychological Stress Measure (PSM-25). All patients underwent ultrasound scanning of the brachiocephalic arteries with measurement of intima-media thickness (IMT) and the percentage of stenosis in the presence of atherosclerotic plaques. The severity of cerebral vascular lesions was evaluated by the number of gliosis foci and the Fazekas scale based on brain magnetic resonance imaging (MRI). Laboratory tests included determination of total cholesterol and its fractions, triglycerides, glucose, high-sensitivity C-reactive protein (hs-CRP), glycated hemoglobin (HbA1c), fibrinogen, and claudin-5. For screening for obstructive sleep apnea syndrome, overnight 8-hour pulse oximetry was performed with calculation of the desaturation index (DI).

Results: Abdominal obesity was detected in 76 of the 100 examined individuals. Overnight pulse oximetry was not performed in 13 patients for technical reasons. The final analysis included data from 87 patients, who were divided into 3 groups based on the presence of obesity and intermittent hypoxia: Group 1, 20 patients without abdominal obesity and significant intermittent hypoxia (waist circumference (WC) ≤ 94 cm, DI < 15); Group 2, 46 patients with isolated abdominal obesity (WC > 94 cm, DI < 15); Group 3, 21 patients with abdominal obesity and moderate-to-severe intermittent hypoxia (WC > 94 cm, DI ≥ 15). A progressive increase in the severity of hyperglycemia was observed with rising HbA1c levels (5.0 [4.8; 5.4], 5.4 [5.0; 5.7], 5.7 [5.4; 6.2] %; p = 0.0002, p_1–2 = 0.072, p_1–3 = 0.0001, p_2–3 = 0.036) and an increase in serum claudin-5 (1.9 [1.1; 3.1], 2.9 [1.4; 7.7], 5.3 [2.0; 7.9] ng/mL; p = 0.040, p_1–2 = 0.163, p_1–3 = 0.041, p_2–3 = 1.0) across the three groups, respectively. A significant increase in the severity of cerebral vascular lesions on MRI was noted only in the group with combined obesity and intermittent hypoxia. The prevalence of periventricular changes on the Fazekas scale in Group 1was 0 (0%), in Group 2, 2 (4%), and in Group 3, 4 (23.5%) (p = 0.015, p_1–2 = 0.77, p_1–3 = 0.0225, p_2–3 = 0.027).

Conclusion: Abdominal obesity, and especially its combination with intermittent hypoxia, is associated with increased HbA1c levels and serum claudin-5 concentrations, as well as with the development of cerebral vascular lesions diagnosed by MRI. It is hypothesized that intermittent hypoxia contributes additionally to the alteration of vascular wall proteins, leading to BBB disruption, which promotes the development of cerebrovascular diseases. Measurement of claudin-5 holds promise as a marker of BBB damage.

Background: 5-Aminosalicylates (5-ASA) are first-line therapy for patients with ulcerative colitis (UC). Although the 2022 ECCO Consensus considers 5-ASA to be low-risk, data on their use during pregnancy remain conflicting.

Aim: To investigate the course and outcomes of pregnancy in women with UC, as well as the disease activity during gestation, according to adherence to prescribed 5-ASA therapy.

Methods: Data from the registries of seven inflammatory bowel disease centers in Russia were analyzed. The analysis included women with UC (International Classification of Diseases, 10^th edition code K51) who received 5-ASA therapy alone and for whom medical records contained information on pregnancy course and outcome. Disease and pregnancy courses were compared between two groups: those adherent and those non adherent to prescribed 5-ASA therapy. Adherence was defined as starting 5-ASA at least 3 months before conception and continuing a stable dose admission throughout pregnancy; non adherence was defined as self-discontinuation of therapy upon becoming pregnant.

Results: The study included 73 women with UC (48 aged < 30 years, 25 aged 30–40 years). Of these, 58.9% received oral 5-ASA only (41 women mesalamine, 2 sulfasalazine), and 41.1% (n = 30) received combination therapy with rectal 5-ASA. In 8.2% (n = 6) of cases, patients switched from oral to combination therapy during pregnancy. The majority (82.2%, n = 60) continued prescribed 5-ASA therapy throughout pregnancy, while 17.8% (n = 13) discontinued it on their own upon becoming pregnant. The overall rate of UC relapse during pregnancy was 39.7% (29/73). UC recurrence was more frequent in the discontinuation group than in the fully adherent group: 92.3% (12/13) and 28.3% (17/60) respectively (p < 0.001). Threatened miscarriage was also higher in the discontinuation group: 38.5% (5/13) and 13.3% (8/60) (p = 0.047) respectively. The composite rate of pregnancy complications (threatened miscarriage, preterm birth, early pregnancy termination) was 76.9% (10/13; 95% confidence interval [CI] 49.7–91.8) in non adherent patients vs. 21.7% (13/60; 95% CI 13.1–33.6) in adherent patients (p < 0.001). Newborns in the maintenance 5-ASA therapy group more frequently had normal birth weight and Apgar scores (90.5%, n = 48) compared to those born to mothers who discontinued 5-ASA (42.8%, n = 3) (p = 0.007). No adverse events in women or congenital malformations in newborns were registered during 5-ASA treatment before conception and throughout pregnancy.

Conclusion: Adherence to maintenance 5-ASA therapy in women with UC is associated with a more favorable pregnancy course and outcomes compared to discontinuation of therapy upon conception.

Background: Non-muscle-invasive bladder cancer (NMIBC) is characterized by high prevalence and a high recurrence rate. Data on the association of type 2 diabetes mellitus (T2DM) with the risk and prognosis of bladder cancer are conflicting. Understanding the effect of comorbid T2DM on the insulin signaling system in NMIBC patients may improve the diagnostic work-up and optimize antitumor treatment.

Aim: To identify differences in the levels of insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) in blood, urine and tumor tissue between patients with NMIBC and T2DM, patients with NMIBC without T2DM, patients with T2DM without cancer, and healthy controls (donors).

Methods: This pilot single-center cross-sectional comparative study included 20 newly diagnosed NMIBC patients with comorbid T2DM (middle-aged and elderly) hospitalized from September 2022 to May 2024. IGF-1 and IGF-2 levels were measured by enzyme-linked immunosorbent assay in serum and urine samples collected before surgery, and in tumor tissue homogenates. The results were compared with those from 20 NMIBC patients without T2DM, 12 outpatients with T2DM without cancer, and 10 healthy donors examined during the same period. Blood glucose and glycated hemoglobin (HbA1c) levels were determined in all subjects.

Results: In NMIBC patients with T2DM, the blood IGF-1 level did not exceed the median value of the donor group (589 ng/mL) in 18 out of 20 cases and was on average two-fold lower than in T2DM patients without cancer (p < 0.001). In 25% (5/20) of NMIBC patients and 50% (6/12) of T2DM patients, the blood IGF-1 level exceeded the maximum donor value (998 ng/mL). Blood IGF-2 levels were higher in T2DM patients than in all other groups (p < 0.001), whereas the other groups did not differ from each other. The NMIBC group showed the highest variability in circulating IGF-2 (coefficient of variation 273%) and included isolated cases with levels close to those observed in T2DM patients. Urinary IGF-1 excretion in NMIBC patients with T2DM did not differ from that in donors and was on average four-fold lower than in NMIBC patients without diabetes (p = 0.003). Tumor tissue IGF levels did not differ between patients with and without diabetes.

In NMIBC patients with T2DM receiving metformin, a positive correlation was found between blood IGF-1 and glucose levels (Spearman’s rank correlation coefficient +0.803, p = 0.034), and their blood IGF-1 level was on average 1.7-fold lower than in other patients of this group (p = 0.047). In normoglycemic cases on metformin, the blood IGF-1 level was the lowest, on average 3.8-fold below donor values (p = 0.007).

Conclusion: In middle-aged and elderly patients of both sexes with NMIBC and comorbid T2DM, in contrast to T2DM patients without cancer and NMIBC patients without T2DM, relatively low blood and urine IGF-1 and IGF-2 levels were observed, close to those in donors, and tumor IGFs levels did not differ from control values. In NMIBC patients with T2DM receiving metformin, unlike other patients and donors, a strong positive correlation between blood IGF-1 and glucose levels was found. In normoglycemic patients on metformin, the blood IGF-1 level was the lowest among all patients and donors. This may indicate a possible mechanism of the antitumor effect of metformin, but this observation requires confirmation in larger clinical studies.