Vol 53, No 3 (2025)

Background: Ovarian cancer is one of the most aggressive gynecological malignancies with a high mortality rate related to delayed diagnosis and high rates of resistance to conventional therapies. Results of clinical trials indicate that soluble galectin-3 could be considered as a potentially significant biomarker for malignant neoplasms of various locations. Its increased serum levels are frequently associated with aggressive tumors, risk of metastasis, resistance to therapy, and poor prognosis. However, data on its role and diagnostic value in ovarian cancer remains limited and contradictory.

Aim: To analyze the diagnostic and prognostic value of the soluble galectin-3 in patients with various ovarian neoplasms.

Methods: This retrospective study included 176 patients with ovarian tumors and 20 healthy donors who were examined and treated from January 2017 to December 2024 at the N. N. Blokhin National Medical Research Center of Oncology and Khabarovsk Territory Regional Clinical Center of Oncology. In all patients, the diagnosis was confirmed by morphological examination of the tumor according to the 2020 World Health Organization (WHO) Classification of Female Genital Tumors. Serum levels of soluble galectin-3 were measured in samples obtained before the initiation of specific treatment with the Human Galectin-3 Quantikine ELISA enzyme immunoassay kit (R&D Systems, USA) in accordance with the manufacturer's instructions. Measurements were performed on a BEP 2000 Advance automated enzyme immunoassay analyzer (Siemens Healthcare Diagnostics, Germany) according to the manufacturer’s specifications.

Results: One hundred and sixteen patients (116/176) had epithelial ovarian cancer (EOC), 6/176 had non-epithelial ovarian cancer (NEOC), 32/176 were diagnosed with benign ovarian tumors (BOT), and 22/176 with borderline ovarian tumors (BLOT). In the healthy controls, the median galectin-3 level was 8.02 ng/mL being significantly lower than that in the patients with EOC (10.35 ng/mL) (p = 0.0219). In the BOT group, the median galectin-3 level was 7.43 ng/mL, in the BLOT group 7.22 ng/mL, and in the NEOC group 5.49 ng/mL (p > 0,999 for all comparisons to the control group). The ROC analysis demonstrated a moderate diagnostic significance of galectin-3 for EOC, with the area under the curve (AUC) of 0.702 and 95% confidence interval (CI) of 0.585 to 0.818 (p = 0.004). With a threshold value of galectin-3 concentration of 8.84 ng/mL, the test sensitivity was 62.93% and specificity 65%. If the median value were used as a cutoff, the sensitivity decreased to 50%, while the specificity increased to 75%. In the EOC group the galectin-3 levels were significantly associated with the patients age, in those above 57 of age its median value was 11.69 ng/mL, being significantly higher compared to the patients ≤ 57 years of age (9.03 ng/mL, p = 0.009). No associations were found between galectin-3 levels and other clinical and morphological characteristics, such as tumor size, disease stage, cancer spreading / metastasis). Depending on the histological type of epithelial tumors, median galectin-3 levels ranged from 9.64 ng/mL (serous type) to 13.18 ng/ml (clear cell type), but the differences were not significant (p = 0.358). In the univariate and multivariate analysis, elevated galectin-3 levels were significant predictors of unfavorable outcome (hazard ratio [HR]: 2.246, p = 0.046 and HR: 1.137, p = 0.017, respectively).

Conclusion: Elevated soluble galectin-3 levels is a predictor of unfavorable prognosis in EOC. High serum concentration of this protein may be a promising additional diagnostic marker for EOC.

Background: Current rates of cardiovascular morbidity among professional athletes depend not only on the sport type, but also on gender, age, ethnicity, screening strategies, and level of physical activity, its frequency, duration and intensity. Biochemical, immunological, hormonal, and psychological parameters are used as overtraining markers; however, they are not accurate enough for prediction of overtraining. In this regard, leukocyte indices calculated from a routine hematology test seem promising.

Aim: To screen for cardiovascular disorders in a group of professional athletes with standard cardiological assessment methods, to evaluate the prognostic significance of leukocyte indices in the diagnosis of endogenous inflammation and overtraining, and to compare the values of leukocyte indices with the competitive results of the athletes.

Methods: This was an observational cross-sectional, single stage, uncontrolled study in a random subject sample. From September 2021 to August 2022, we examined 180 highly qualified professional athletes on an outpatient basis. The athletes were practicing highly dynamic sport types (contact sport types such as combat sports, ice hockey, and football were excluded). All athletes had a routine hematology test (blood samples were taken 2 to 3 days before competitions) followed by calculation of hematological leukocyte indices: systemic inflammation response index (SIRI), systemic inflammation index (SII), aggregate index of systemic inflammation (AISI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), leukocyte intoxication index (LII), lymphocyte index (LI), and lymphocyte-to-monocyte ratio index (LMRI). The instrumental cardiovascular assessments included electrocardiography (ECG), 24-hour ECG monitoring, 24-hour blood pressure monitoring, cycling exercise functional test, and echocardiography (EchoCG). The study endpoints were adverse events occurring during the competition: 1) sports injuries during competition evaluated by a staff doctor of the national team; 2) deterioration of athletic performance compared to that shown by the athlete during training sessions (evaluated by a group of trainers).

Results: The cohort consisted of 180 highly qualified professional athletes (orienteering, alpine skiing, biathlon, athletics, and swimming), with a mean age of 20.55 ± 2.69 years, including 42.2% (n = 76) women and 57.8% (n = 104) men. A high percentage of individuals with varying degrees of arterial hypertension (AH) were identified based on 24-hour blood pressure monitoring: mild AH, mostly at night, was found in 18.3% (n = 33) of the cases, while severe night AH in 7.2% (n = 13) of the cases. 24-hour ECG monitoring showed the following heart rhythm and conduction disorders: incomplete right bundle branch block in 15% (n = 27), sinus arrhythmia in 48.3% (n = 87), and atrial rhythm in 7.8% (n = 14). At EchoCG, the most common change was an apical or median chord of the left ventricle (44.4%, n = 80). In 13 (7.2%) of the patients, the cycling exercise test was discontinued due to an inadequate increase in diastolic blood pressure. Among the 90 athletes who had a valid assessment of their sports injury history, 26 (28.9%) had a sports injury. Deterioration in athletic performance was recorded in 39 cases (48.1%) of the 81 checkup lists available for the analysis. SIRI, SII, AISI, NLR, PLR, and MLR were significant predictors of deterioration in athletic performance. The deterioration of the competitive sports results was associated with SIRI ≥ 2.097 (sensitivity 53.85%, specificity 85.71%; AUC = 0.713, p < 0.001), SII ≥ 616.95 (sensitivity 56.41%, specificity 76.19%; AUC = 0.705, p < 0.001), AISI ≥ 180.15 (sensitivity 97.44%, specificity 45.24%; AUC = 0.733, p < 0.001). LMRI ≥ 4.44 had 100.00% sensitivity and 60.94% specificity in the prediction of sports injuries (AUC = 0.870, p < 0.001).

Conclusion: A preliminary screening for cardiovascular disorders aimed primarily at identifying those associated with a sudden cardiac death, is necessary when conducting an in-depth medical examination of athletes. LMRI (threshold value ≥ 4.44), which reflects the relationship between the affecter and effector components of the immune process, can be considered a promising marker of the risk of sports-related injuries.

A combination of vulgar pemphigus and toxic epidermal necrolysis is an extremely rare and clinically complex comorbidity characterized by divergent immune mechanisms of skin damage. We present a case report of a 33-year old patient with rapidly progressive bullous and erosive skin lesions. Immunofluorescence studies showed IgG and the C3 complement component deposits in the intercellular epidermal contacts; the diagnosis of vulgar pemphigus was confirmed. The Pemphigus Disease Area Index (PDAI) at the moment of maximal clinical symptoms was 78. Just before the hospitalization, the patient had been treated with antibiotics. Pathomorphological examination showed virtually total intra-epidermal detachment of the epidermis, in addition to IgG and C3 complement component deposits found by direct immunofluorescence. These findings, combined with clinical manifestations characteristic of toxic epidermal necrolysis, allowed to suspect two diseases. For 9 weeks, the patient was treated with high dose systemic glucocorticosteroids and plasmapheresis, which led to stabilization of the disease. At week 9 from the day of hospitalization, there was a dramatic deterioration in the patient’s condition. At week 10 of the hospitalization, rituximab was added to high dose systemic glucocorticosteroids resulting in clinical improvement at week 13. By week 24 after the treatment initiation, a significant clinical result was achieved, seen as complete epithelialization of the erosions and stable remission of the skin disease.

The treatment strategy chosen has led to simultaneous exhaustion of B cell pool responsible for production of pathogenic auto-antibodies in pemphigus and to significant suppression of cell immunity, which plays a key role in toxic epidermal necrolysis. Toxic epidermal necrolysis should be excluded in patients with pemphigus, especially with atypical rapidly progressive course and medication-associated. Immunofluorescence methods play a decisive role in the diagnosis of these comorbid disorders. Combination therapy with rituximab and corticosteroids can be considered as a strategy targeting the pathogenic pathways of both diseases. This case report highlights the need for a thorough diagnostic analysis and the development of clear management algorithms for such complex cases.