Pharmateca

The review presents a comprehensive analysis of the use of bacterial lysate Uro-Vaxom^® in the prevention of recurrent lower urinary tract infections. The molecular mechanisms of action of the drug based on the activation of both innate and adaptive immunity through interaction with Toll-like receptors are considered. The data of clinical studies confirming the efficacy and safety of the drug are systematized, which is reflected in Russian clinical guidelines [1] and patient management protocols approved by the Ministry of Health of the Russian Federation and the Russian Society of Urologists. Particular attention is paid to other promising areas of drug use in patients with neurogenic bladder dysfunction and chronic prostatitis. The results of new experimental studies demonstrating the absence of cytotoxicity and a standardized composition of the drug are presented. The uniqueness of the review lies in the integration of the latest data from fundamental and clinical studies, including ongoing phase 4 trials, which allows for a comprehensive assessment of the drug’s potential as an alternative to long-term antibiotic prophylaxis in the context of growing antibiotic resistance. The analysis also noted the important role of immunoprophylaxis in pregravid preparation and during pregnancy. The safety and efficacy of E. coli bacterial lysate in reducing urinary tract infection recurrence were assessed.

Background: According to the recommendations of the International Society for the Study of Vulvar and Vaginal Diseases (ISSVD), bacterial vaginosis is considered a condition associated with an imbalance in the vaginal microflora, in which there is a decrease in the number of lactobacilli and the predominance of anaerobic microorganisms. ISSVD specialists emphasize the importance of an approach that combines pathogen eradication and restoration of normal vaginal microbiota. This approach is especially relevant for patients who have undergone chemo- or radiation therapy for cervical and uterine cancer, due to changes in the hormonal profile, vaginal microflora and local immunity, which significantly increases the risk of BV recurrence.

Objective: Analysis of current literature data on the effectiveness of BV treatment with dequalinium chloride (LS Septofemin^®) in patients with oncological processes of the cervix and uterine body.

Material and methods: A review of articles available in search databases published over the past decade was performed. Current scientific results on the efficacy of dequalinium chloride (LS Septofemin^®) in patients with a history of cervical and uterine cancer are outlined.

Results: This review showed the importance of determining the vaginal microbiota in BV for the selection of effective therapy. Dequalinium chloride (LS Septofemin^®) has confirmed its clinical efficacy and drug safety in patients with a history of cancer.

Conclusion: Dequalinium chloride (LS Septofemin^®) can be recommended as a therapy for BV, as well as mixed vaginitis in women who have received antitumor treatment and are faced with the problem of vaginal dysbiotic disorders after chemo- or radiation therapy for cervical and uterine cancer.

Background: More than 50% of breast cancer (BC) cases are currently defined with lower levels of HER2 protein expression (HER2-low): HER2–1+ or 2+ with negative ISH. Most of the available retrospective analyses have not found that low HER2 expression has significant prognostic value.

Objective: Comparative analysis of long-term treatment outcomes in patients with early BC depending on the HER2 expression level and HR status, analysis of survival rates in groups of patients with different HER2 expression levels, depending on menopausal status.

Materials and methods: The study included 265 patients with BC (stage II) who received treatment at the N.N. Petrov National Medical Research Center of Oncology from 2011 to 2019. The patients were divided into groups depending on the HER2 expression level and HR status. Then, all patients were divided into 2 groups depending on menopausal status, then into subgroups depending on the HER2 expression level and HR status.

Results: The data of 265 patients with BC were analyzed, including 97 (36.6%) cases with HER2-low, of which 71 were HR+ (73.2%) and 26 (26.8%) patients were HR-. No statistically significant differences were observed in the survival analysis, but the worst 5-year relapse-free survival (RFS) was 73.1% in patients with HR-/HER2-low versus 76% with HR-/HER2-0. Overall survival (OS) rates were 88.5% with HR-/HER2-low and 98%, respectively. Also, in the HR-/HER2+ subgroup, RFS rates were low – 71.4%, OS – 94.3%. In premenopausal patients, 5-year RFS was 74.3% in the HR+/HER2-low subgroup versus HR+/HER2+ – 93.9% (p=0.010). In postmenopausal patients, there were no statistically significant differences in the RFS and OS analysis.

Conclusion: The lowest RFS and OS rates were observed in patients with HR-/HER2-low BC. Premenopausal patients had lower RFS rates with HR+/HER2-low versus HR+/HER2+ (74.3% versus 93.9%). Further studies to assess the relationship between hormone receptors, their levels, and the magnitude of HER2 expression are required.

Objective: Identification of the most significant predictors of infection with antibiotic-resistant pathogens in puerperas with endometritis after abdominal delivery.

Materials and methods: Retrospective analysis of 648 cases of cesarean section (406 – endometritis after cesarean section, 242 – uncomplicated postoperative period) and the results of microbiological examination of lochia (identification of microorganisms and determination of antibiogram). The number of concomitant extragenital diseases was calculated according to the cumulative illness rating scale (CIRS).

Results: 106 (26.1%) drug-resistant isolates were verified in post-caesarean section endometritis (p<0.001). MDR strains of the rESKAPE group were isolated from every sixth postpartum woman (16.8%) with endometritis.

The lowest (25%) and highest (97%) prevalence of susceptibility were observed with clindamycin and vancomycin, respectively. The main drug-resistant pathogens include gram-negative ESBL producers of the order Enterobacterales.

The vast majority of the main predictors of endometritis development after abdominal delivery were also associated with an aggravated somatic background: emergency CS during labor with a long anhydrous interval of ≥12 hours, a sum of 4 points or more according to the CIRS system, anemia of inflammation/chronic disease, extragenital infections during this pregnancy, the presence of a cervical cerclage/pessary, a body mass index of ≥30.00 kg/m2, asymptomatic bacteriuria and a fasting venous plasma glucose level during pregnancy of >5.1 mmol/l. Conclusion: Comorbidity (4 points or more according to the CIRS) was the most reliable predictor of colonization with multidrug-resistant pathogens and a risk factor for the development of endometritis after CS. An important predictor of MDR pathogen isolation was emergency CS in combination with a long (≥12 h) anhydrous interval and long (≥10 h) labor before surgery. The risk of carriage of drug-resistant strains was influenced by «antibacterial history» and hospitalizations/invasive procedures or surgeries in the second half of pregnancy.

Background: The relevance of the study is attributable to the importance of intimate hygiene as an essential component of the prevention of various skin and venereal diseases. Despite medical awareness, modern studies demonstrate an insufficient level of knowledge about the rules of intimate hygiene, both among the population and among healthcare professionals. The presented study is aimed at a comparative analysis of awareness of intimate hygiene issues among three key groups: students as representatives of the younger generation, patients, and healthcare professionals (obstetricians-gynecologists) as experts in this field.

Objective: Comparative analysis of awareness in the field of intimate hygiene among patients, students, and healthcare professionals (obstetricians-gynecologists).

Material and methods: From September to December 2024, two interconnected sociological studies were conducted using the anonymous remote survey method by the Yandex Forms platform. All respondents were city residents of Novosibirsk, St. Petersburg and Moscow. The first study covered 564 students of NSMU (Novosibirsk), the second – 605 respondents, of which 242 were obstetricians-gynecologists and 363 were patients (Novosibirsk, St. Petersburg and Moscow). Both studies used a questionnaire specially developed by the staff of the Department of Dermatovenereology of NSMU, consisting of 40 questions adapted for each group of respondents. Statistical analysis was carried out using Microsoft Excel and SPSS using the χ² criterion and Student’s t-test at a significance level of p<0.05. Results and discussion: The results obtained demonstrate an alarming trend of insufficient awareness of young people in matters of intimate hygiene. Of particular concern is the fact that even among healthcare workers, only 47% comply with the recommended frequency of hygiene procedures. The differences in the use of special products (antibacterial gels) between the groups require further study.

Conclusion: The study confirmed the presence of significant gaps in knowledge and practical skills of intimate hygiene among all the study groups. The most pronounced deficiencies were identified among the student population. The data obtained indicate the need to develop educational programs for young people and conduct regular training events for healthcare workers.

Background: Obesity, which prevalence in Russia ranges from 24 to 36%, leads to negative consequences for reproductive health - menstrual cycle disorders (MCD) and infertility. The results of the study of the mechanisms of the obesity influence on the menstrual cycle, folliculogenesis and ovulation are still controversial.

Objective: Assessment of the metabolic, hormonal, immune, vitamin and mineral status in patients with obesity and determination of the most significant risk factors for menstrual and reproductive dysfunction.

Materials and methods: Design: a simple observational study. 70 patients were included: Group I (n=40) – with obesity and oligo-/amenorrhea-type MCD, and Group II (n=30, control) – healthy. Clinical and laboratory research methods, pelvic ultrasound and folliculometry were used.

Results: The age of the participants ranged from 20 to 37 years (mean – 27.9 (SD 3.8), p=0.99). The body mass index (BMI) in patients with obesity corresponded to stage I (32.1 kg/m²), oligomenorrhea occurred in 90% of them, amenorrhea – in 10%, heavy menstrual bleeding (HMB) in 85%, ovulation was recorded 2.5 times less frequently than in group II (35 versus 86.7%, respectively, OR 0.40, 95% CI: 0.23–0.26), and the risk of anovulation was 5 times higher, respectively (OR 4.88, 95% CI: 1.90–12.48). The profile of obese patients showed the following: insulin resistance (HOMA index – 3.1 c.u.), significant increase in the insulin (by 3 times), homocysteine ( by 2.4 times), CRP (by 6 times), leptin (by 6 times), free testosterone (by 3 times), DHEA-S (by 1.4 times), cytokines (by 6 times on average) levels, decreased levels of HDL and LH (both – by 1.5 times), folic acid (by 3 times), manganese and 25-hydroxycalciferol (by 2 times) compared to the control group. Based on the analysis of the principal components, it was established that the factor loadings of the key markers reflected a greater contribution of the metabolic factor and, to a lesser extent, the hormonal factor in the formation of anovulation in obese patients. The most significant risk factors for anovulation were insulin resistance and leptin, insulin, triglycerides, LDL levels above the reference values and HDL level below the reference values. Among the hormonal profile parameters, the key marker of anovulation was a decrease in LH levels in combination with low serum folate concentrations. The inflammatory status typical for obese patients was associated with MCD but did not affect ovulatory function.

Conclusion: In patients with stage I obesity, metabolic disorders play a leading role in the pathogenesis of MCD and anovulation, and hormonal disorders play a lesser role.

Background: In modern obstetrics, induced labor is one of the generally recognized methods of terminating pregnancy. Most publications note that the main indications for labor induction are a pregnancy period of more than 287 days, premature rupture of membranes, and extragenital pathology. However, data on the results of induction are contradictory. Along with studies indicating improved pregnancy and labor outcomes with the use of induction, opposite data have been published on an increase in the frequency of cesarean sections and instrumental assistance during childbirth. A favorable outcome of spontaneous and induced labor depends on the readiness of the pregnant woman’s body for childbirth. In human reproduction, the leading role of the immune system in carrying a pregnancy and initiating labor has been determined. Markers of these complex immunological events are the body’s reactions that occur as a local and systemic inflammatory response. The preliminary inflammatory process, developing in the cervix, leads to its remodeling before labor. The activity of this process can be used to judge the readiness of the pregnant woman’s body for labor. Determination of total glycosaminoglycans (GAGs) in cervical mucus, the level of which reflects the activity of preliminary inflammation in the cervix, is a non-invasive method for diagnosing readiness for labor and, accordingly, an effective response to labor induction. The level of total glycosaminoglycans in cervical mucus before labor induction allows predicting an unfavorable outcome of labor - an emergency cesarean section.

Objective: Determination of total GAG level in cervical mucus that predict the outcome of induced labor.

Materials and methods: An open prospective study was conducted involving 118 women with full-term pregnancy who delivered in the healthcare institution «Clinical Maternity Hospital of Minsk Region». Using the spectrophotometric method and calculation formulas the concentration of total glycosaminoglycans (GAGs) in the cervical mucus of pregnant women was determined before and after pre-induction of labor with drugs or mechanical means, as well as in pregnant women with term labor before the spontaneous onset of labor. The total GAGs levels in the cervical mucus were used to assess the outcomes of labor – completion through the natural birth canal or emergency cesarean section.

Results: The concentration of total glycosaminoglycans in the cervical mucus of pregnant women at the time of spontaneous onset of physiological labor has an average value of 2.7 g/l in the interval of 7 days before the onset of labor. Low levels of total GAGs in the cervical mucus of pregnant women before preinduction of labor, regardless of the chosen method, predict the risk of labor ending in cesarean section due to complications for the mother and/or fetus. In induced labor ending in cesarean section, the concentration of total GAGs in the cervical mucus before preinduction was 2 times lower than in the case of labor ending in vaginal delivery (p=0.039). In the case of cervical preparation by mechanical means, the risk of cesarean section before preinduction (1–24 hours) was demonstrated by the level of total GAGs in the cervical mucus of 2.0 g/L or less when using laminaria, and 0.2 g/L or less when using a Foley catheter. When pre-induction of labor was performed with a drug (dinoprostone gel for vaginal administration), the completion of induced labor by cesarean section was associated with the level of total GAGs in cervical mucus of 1.4 g/l or less, determined 4–6 hours after the introduction of the inducer.

Conclusion: Low levels of total GAGs before and after pre-induction of labor with drugs or mechanical means indicate the likelihood of complications in induced labor and their completion by surgery. Caesarean section in this situation is an emergency.

Background: Cervical cancer (CC) remains one of the most pressing problems in oncology, especially in developing countries. Despite advances in treatment, survival rates for metastatic and recurrent forms of the disease remain unsatisfactory. The introduction of immunotherapy, in particular pembrolizumab, has opened up new opportunities, but the effectiveness of therapy varies among patients. In this regard, it is important to study biomarkers such as the neutrophil-lymphocyte index (NLI) to predict the response to treatment.

Objective: Evaluation of the prognostic role of the NLI in patients with metastatic cervical cancer treated with pembrolizumab and determination of its threshold value for patient stratification and optimization of treatment tactics.

Materials and methods: A retrospective study involving 80 patients with metastatic or recurrent cervical cancer and positive PD-L1 expression (CPS ≥1) was conducted. The NLI was calculated based on clinical blood test data before the start of therapy. Statistical methods were used, including the χ² criterion for qualitative variables and the Kaplan-Meier method for survival analysis.

Results: The results showed that in 57.5% of patients, the NLI exceeded 4.0, indicating the presence of systemic inflammation. A significant relationship was established between the NLI value and treatment efficacy: with NLI ≥4, the risk of progression was 80.4% versus 50% in the group with NLI <2 (p=0.038). The median progression-free survival in patients with NLI <4 was significantly higher (12.1 months versus 6.8 months with NLI ≥4; p=0.003).

Conclusion: NLI is a simple and accessible prognostic marker of response to immunotherapy in metastatic cervical cancer. The threshold NLI value (4.0) can be used to stratify patients and select the optimal treatment strategy. It is recommended to include NLI determination in the standard examination before prescribing immunotherapy and consider a more aggressive approach in patients with an increased NLI.

Background: Dysbiotic disorders of the vaginal microflora remain one of the most pressing problems in obstetrics and gynecology today. According to the Ministry of Health of the Russian Federation, this condition accounts for about 40% of all gynecological pathology cases in the general population. Bacterial vaginosis (BV), in case of untimely diagnosis and treatment, poses a threat to the development of inflammatory diseases of the small pelvis, premature birth, genitourinary menopausal syndrome.

Objective: Clinical evaluation of the effectiveness of including сomplex biologically active supplement with probiotic action in the scheme for correcting vaginal biotope disorders in women during perimenopause.

Materials and methods: An observational case-control study was conducted at the Department of Obstetrics and Gynecology No. 2 of the Voronezh State Medical University named after N.N. Burdenko in the period from 2024 to 2025. The study involved 50 women during the perimenopausal transition (STRAW+10). 3 comparison groups were formed: Group 1 (n=20) – perimenopausal patients receiving the classical regimen for the correction of dysbiotic disorders (metronidazole 500 mg + chloramphenicol 200 mg + natamycin 150 mg + hydrocortisone acetate 15 mg for 10 days, then Maxilac^© for 10 days); Group 2 (n=20) – perimenopausal patients receiving a combined experimental regimen for the correction of dysbiotic disorders (metronidazole 500 mg + chloramphenicol 200 mg + natamycin 150 mg + hydrocortisone acetate for 10 days, then lactobacilli preparation for 10 days); Group 3 – control (n=10) – perimenopausal patients without vaginal biotope disorders. Women included in the experiment underwent a full range of laboratory and instrumental studies in accordance with the clinical recommendations of the Russian Ministry of Health “Bacterial vaginosis” and “Menopause and climacteric state in women”. Statistical processing was performed in Statistica 10.0 (StatSoft), differences were considered statistically significant at p<0.05.

Results: For patients of Group 2 receiving the classical BV therapy regimen, in comparison with the Group 2 receiving the experimental regimen (taking the synbiotic Maxilac^©), a relatively low rate of pathogen elimination was characteristic, as well as a low rate of colonization of the vaginal biotope with acidophilic lactobacilli. In the Group 2 of the experimental BV therapy regimen, early elimination of pathogenic and opportunistic microflora, early colonization with normoflora were established.

Conclusion: Inclusion of synbiotic Maxilac^© in the treatment regimen for BV in perimenopausal women improves the clinical effects of therapy due to the relatively rapid elimination of opportunistic and pathogenic pathogens, as well as due to the early restoration of the vaginal biocenosis.