B Cell Lymphocytes as a Potential Source of Breast Carcinoma Marker Candidates.

Despite advances in the genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein-level information. Nowadays breast cancer clinical treatment selection is based on the immunohistochemical (IHC) determination of four protein biomarkers: Estrogen Receptor 1 (ESR1), Progesterone Receptor (PGR), Human Epidermal Growth Factor Receptor 2 (HER2), and proliferation marker Ki-67. The prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, but tumor-infiltrating B cells have not received so much attention. We aimed to find a correlation between immunohistochemical results and a proteomic approach in measuring the expression of proteins isolated from B-cell lymphocytes in peripheral blood samples. Shotgun proteomic analysis was chosen for its key advantage over other proteomic methods, which is its comprehensive and untargeted approach to analyzing proteins. This approach facilitates better characterization of disease-associated changes at the protein level. We identified 18 proteins in B cell lymphocytes with a significant fold change of more than 2, which have promising potential to serve as breast cancer biomarkers in the future.

Peripheral Blood CD8+ T-Lymphocyte Immune Response in Benign and Subpopulations of Breast Cancer Patients.

Peripheral blood CD8+ T lymphocytes play a crucial role in cell-mediated immunity and tumor-related immune responses in breast cancer. In this study, label-free quantification analysis and gene set enrichment analysis (GSEA) of CD8+ T lymphocytes in the peripheral blood of benign patients and patients with different breast cancer (BC) subtypes, i.e., luminal A, luminal B, and triple-negative breast cancer (TNBC), were performed using nano-UHPLC and Orbitrap mass spectrometry. Differential protein expression in CD8+ T lymphocytes revealed significant downregulation (log2 FC ≥ 0.38 or ≤-0.38, adj. p < 0.05), particularly in proteins involved in cytotoxicity, cytolysis, and proteolysis, such as granzymes (GZMs) and perforin 1 (PRF1). This downregulation was observed in the benign group (GZMH, GZMM, and PRF1) and luminal B (GZMA, GZMH) subtypes, whereas granzyme K (GZMK) was upregulated in TNBC in comparison to healthy controls. The RNA degradation pathway was significantly downregulated (p < 0.05, normalized enrichment score (NES) from -1.47 to -1.80) across all BC subtypes, suggesting a potential mechanism for regulating gene expression during T cell activation. Also, the Sm-like proteins (LSM2, LSM3, and LSM5) were significantly downregulated in the RNA degradation pathway. Proteomic analysis of CD8+ T lymphocytes in peripheral blood across different breast cancer subtypes provides a comprehensive view of the molecular mechanisms of the systemic immune response that can significantly contribute to advancements in the diagnosis, treatment, and prognosis of this disease.

Prevalence of diastasis m. rectus abdominis and pelvic floor muscle dysfunction in postpartum women.

OBJECTIVE: The aim of this study was to determine the prevalence of Diastasis of the rectus abdominis muscles (DRAM) and pelvic floor muscle dysfunction (PFMD) in postpartum women. Design: The observational prospective study. MATERIAL: 150 of 180 women (83.3 %) from 6 weeks to 6 months postpartum, with a mean age of 33.1 years. METHODS: For diastasis examination, inter recti distance (IRD) was measured by a linear 2D ultrasound probe, 4.5 cm above the navel, in its area and 4.5 cm below the navel when lying on the back at rest and under a load test. The degree of DRAM was classified into four grades. Urinary leakage symptoms were assessed by the International Incontinence Consultation Questionnaire (ICIQ - UI SF). RESULTS: The first degree of diastasis during the load test was 38.1 % above the navel, 36.4 % in the navel area, and 23.7 % below the navel. The second degree of diastasis with load was 28.8 % above the navel, 21.2 % in the navel area, and 10.2 % below the navel. PFMD showed 31.3 % of women with mild symptoms of SUI, 32.2 % of women with grade 1 cystocele. CONCLUSION: The average IRD distance at rest and during the load test confirmed the first grade of DRAM out of four degrees of severity. Moderate and medium DRAM occurred according to location in an average of one-third of the cases. The highest percentage of DRAM was above the navel, and the lowest percentage below the navel. PFMD was detected in an average of one-third of cases. It is important to monitor these parameters with a view to improving the quality of life index in the future (Tab. 5, Ref. 22).

The Importance of Natural Antioxidants in Female Reproduction.

Oxidative stress (OS) has an important role in female reproduction, whether it is ovulation, endometrium decidualization, menstruation, oocyte fertilization, or development andimplantation of an embryo in the uterus. The menstrual cycle is regulated by the physiological concentration of reactive forms of oxygen and nitrogen as redox signal molecules, which trigger and regulate the length of individual phases of the menstrual cycle. It has been suggested that the decline in female fertility is modulated by pathological OS. The pathological excess of OS compared to antioxidants triggers many disorders of female reproduction which could lead to gynecological diseases and to infertility. Therefore, antioxidants are crucial for proper female reproductive function. They play a part in the metabolism of oocytes; in endometrium maturation via the activation of antioxidant signaling pathways Nrf2 and NF-κB; and in the hormonal regulation of vascular action. Antioxidants can directly scavenge radicals and act as a cofactor of highly valuable enzymes of cell differentiation and development, or enhance the activity of antioxidant enzymes. Compensation for low levels of antioxidants through their supplementation can improve fertility. This review considers the role of selected vitamins, flavonoids, peptides, and trace elements with antioxidant effects in female reproduction mechanisms.

Adolescent Pregnancy Outcomes and Risk Factors.

One of the major social and public health problems in the world is adolescent pregnancy. Adolescent pregnancy is strongly associated to less favorable results for both the mother and the newborn. We conducted this research to ascertain the impact of teenage age on neonatal outcomes and also observed the lifestyles of pregnant teenage girls. We conducted a study of 2434 mothers aged ≤19 years (n = 294) or 20-34 years (n = 2140) who gave birth in 2019-2020 at the Department of Gynaecology and Obstetrics of Louis Pasteur University Hospital in Kosice. The data on mothers and newborn infants have been reported from the reports on mothers at childbirth. Women between the ages of 20 and 34 served as the reference group. The teenage mothers were more likely to become pregnant if they were unmarried (OR = 14.2; 95% CI = 9.3-21.6; p < 0.001) and had a basic education or lack of education (OR = 16.8; 95% CI = 11.5-24.6; p < 0.001). Additionally, they were more likely to smoke when pregnant (OR = 5.0; 95% CI = 3.8-6.6; p < 0.001). Low birth weight was more common in newborns born to adolescent mothers than in those born to adult mothers (p < 0.001). Our findings showed that infants of teenage mothers often had lower birth weights (-332.6 g, p < 0.001). Adolescent mothers were associated with lower Apgar scores at the first minute (p = 0.003). As compared with the control group, pregnant teenage girls had a greater prevalence of preterm deliveries in our research (p = 0.004). This study finds significant age-related disparities in neonatal outcomes between mothers. These results might be used to identify vulnerable groups who need special assistance and actions to reduce the probability of negative outcomes for such groups.

A randomised interventional parallel study to evaluate the effect of different frequencies of pelvic floor muscle exercises with core stabilisation using three-dimensional ultrasound: the PELSTAB study.

INTRODUCTION AND HYPOTHESIS: The primary objective was to compare high- and low-frequency pelvic floor muscle training (PFMT) with the impact on urinary incontinence episode frequency over 1 week (IEF/week). The secondary objective was to compare the two groups with regard to pelvic floor muscle function, morphometry, incontinence quality of life, and patient global impression. METHODS: This was a randomised parallel controlled study. The setting was regional gynaecological and urological outpatient clinics. The subjects consisted of a sample of 86 women with stress urinary incontinence (SUI). Group A underwent high-frequency PFMT and group B underwent low-frequency PFMT for 12 weeks. We recorded the IEF/week. The International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF) was used. Pelvic floor muscle function was evaluated using a perineometer. Pelvic floor muscle morphometry was evaluated with 3D/4D ultrasound. The Urinary Incontinence Quality of Life Scale (I-QoL) was used. RESULTS: Significant differences between group A and B after treatment (p<0.001) were noted in favour of group A in IEF/week (group A 10.2±7.0/2.3±3.0 vs group B 9.3±4.7/6.3±4.9), in the ICIQ-UI SF (group A 9.7±3.0/3.7 ± 3.6 vs group B 9.9±3.2/9.4±3.4). Significant differences between groups A and B after treatment were noted in favour of group A for pelvic floor muscle function in terms of maximal voluntary contraction and its duration, and also for pelvic floor muscle morphometry in terms of a reduction of the hiatal area during rest, contraction, and the Valsalva manoeuvre. CONCLUSIONS: High-frequency PFMT for 12 weeks significantly decreased IEF/week in comparison with low-frequency PFMT. In the high-frequency exercise group, women had significantly better pelvic floor muscle function, morphometry and quality of life than the low-frequency exercise group.

Differential Urinary Proteomic Analysis of High-Risk Cervical Intraepithelial Neoplasia.

Human papillomavirus (HPV)-associated lesions and malignancies exhibit alterations in the composition and functionality of the extracellular matrix (ECM) that represent the complex molecular pathways present between infection and disease. A total of 20 urine samples were used, including from 10 patients with cervical intraepithelial neoplasia grade 3 (CIN3) and 10 healthy controls to perform the label-free quantitative analysis using the nano-HPLC and ESI-MS ion trap mass analyzer and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) fast screening. Among 476 identified/quantified proteins, 48 were significantly changed (log2-fold change ≥1.0 or ≤-1.0, -log10 (bbinominal, p-value ≥ 1.3), of which were 40 proteins (down-regulated) and 8 proteins (up-regulated) in CIN3, in comparison to healthy controls. The biological function and key pathway enrichment of the gene set using gen set enrichment analysis (GSEA) were analyzed. The ECM-receptor interaction pathway (NES = -1.64, p = 0.026) was down-regulated by 13 proteins (HSPG2, COL6A1, COL6A3, SPP1, THBS1, TNC, DAG1, FN1, COMP, GP6, VTN, SDC1, and CD44; log2 FC range from -0.03 to -1.48) for the CIN3 group in the KEGG database. The MALDI-TOF/MS screening showed the difference of protein profiles between the control and CIN3 groups, i.e., using the scatter plot with a well-separated shape, as well as effectively distinguishing both groups (control and CIN3) using genetic algorithms (GA) with cross-validation (51.56%) and recognition capability (95.0%). Decreased levels of ECM-receptor interaction proteins may cause disturbances in the interactions of cells with the ECM and play an important role in the development and progression of cervical cancer.

Influence of uterine manipulator use on the incidence of lymphovascular propagation in the treatment of endometrial cancer.

BACKGROUND: Endometrial cancers are among the epithelial malignancies of the lining of the uterine cavity. The invasion of carcinoma into the lymphovascular space (LVSI) is considered a risk factor for the course of the disease. MATERIAL AND METHODS: We evaluated 170 female patients. Our primary objective was to find any difference in the incidence of LVSI in female patients treated with and without an intrauterine manipulator. In addition, we analyzed the effect of the type of intrauterine manipulator used on the incidence of LVSI, tumor grading, myometrial invasion, and the method of obtaining primary histology with regard to the incidence of LVSI. RESULTS: Using a manipulator during surgery was not associated with LVSI (with a manipulator vs. without, 11.5 vs. 21.7%; OR 1.8; 95% CI 0.73-4.39; p = 0.199). However, the method used to obtain the primary histology had a statistically significant effect on the incidence of LVSI in our set (p-value = 0.011). CONCLUSIONS: In our study, we did not confirm the effect of a uterine manipulator on the possible increase of LVSI positive cases. The secondary analysis indicated a higher incidence of LVSI in the female patients diagnosed with curettage than in those who underwent hysteroscopy. Trail registration: Trail is registered in ClicincalTrails.gov with identifier: NCT05261165.

Predictive Value of Pelvic Floor Muscle Morphometry Using 3D/4D Ultrasound in Relation to the Success of Pelvic Floor Muscle Training in Women with Stress Urinary Incontinence.

The aim of our study was to establish the predictive value of pelvic floor muscle morphometry using 3D/4D ultrasound in relation to the success of pelvic floor muscle training (PFMT) for 12 weeks in women with stress urinary incontinence (SUI). A total of 86 women with SUI from regional gynaecological and urological outpatient clinics were enrolled on this cross-sectional study. SUI symptoms were assessed by the International Consultation on Incontinence Questionnaire (ICIQ-UI SF). Pelvic floor muscle function was evaluated using a perineometer. Pelvic floor muscle morphometry (PFMM) was evaluated by the size of the urogenital hiatus (HA in cm2) at rest (R), at contraction (C) and during the Valsalva manoeuvre, i.e., a strong push (V), by 3D/4D USG. The intervention was PFMT for 12 weeks. After PFMT, we noted significant improvement in SUI symptoms, pelvic floor muscle function and morphometry. Moderately significant (0.001) negative correlations were confirmed between the total ICIQ-UI SF score and strength (-0.236 **) and endurance (-0.326 **) of the maximal voluntary contraction (MvC), the number of MvC lasting 3 s (-0.406 **) and 1 s (-0.338 **). Moderately significant (0.001) positive correlations were confirmed between the total ICIQ-UI SF score and R (r = 0.453 **), C (r = 0.533 **) and V (r = 0.442 **). The predictive value of PFMM reached a positive prediction of a decrease with an ICIQ-UI SF score below 8. HA during V was most strongly associated with SUI reduction, with an area under the curve (AUC) of 0.87 (p ≤ 0.001), a positive predictive value of 83.3%, a negative predictive value of 75.0%, sensitivity of 78.9% and specificity of 80.0%. The predictive values of pelvic floor muscle morphometry using 3D/4D USG confirmed the success of PFMT in women with SUI.

Small Non-Coding RNAs as New Biomarkers to Evaluate the Quality of the Embryo in the IVF Process.

The increased interest in assisted reproduction through in vitro fertilization (IVF) leads to an urgent need to identify biomarkers that reliably highly predict the success of pregnancy. Despite advances in diagnostics, treatment, and IVF approaches, the 30% success rate of IVF seems insurmountable. Idiopathic infertility does not have any explanation for IVF failure especially when a patient is treated with a healthy competitive embryo capable of implantation and development. Since appropriate intercellular communication is essential after embryo implantation, the emergence of the investigation of embryonic secretome including short non-coding RNA (sncRNA) molecules is crucial. That's why biomarker identification, sncRNAs secreted during the IVF process into the blastocyst's cultivation medium, by the implementation of artificial intelligence opens the door to a better understanding of the bidirectional communication between embryonic cells and the endometrium and so the success of the IVF. This study presents a set of promising new sncRNAs which are revealed to predictively distinguish a high-quality embryo, suitable for an embryo transfer in the IVF process, from a low-quality embryo with 86% accuracy. The identified exact combination of miRNAs/piRNAs as a non-invasively obtained biomarker for quality embryo determination, increasing the likelihood of implantation and the success of pregnancy after an embryo transfer.

Influence of maternal smoking during pregnancy on birth outcomes.

OBJECTIVES: Smoking during pregnancy is causally associated with reduced birth weight and is strongly related to preterm birth. This study analyses the differences in birth outcomes between non-smokers and women who continued to smoke during pregnancy. METHODS: We conducted a study of 1,359 mothers who gave birth in 2017-2019 at the Department of Gynaecology and Obstetrics of Louis Pasteur University Hospital in Kosice. Data on mothers and newborn infants have been reported from the birth book and from the reports on mothers at childbirth. For low birth weight we considered the weight of a newborn being less than 2,500 g and as for premature birth we referred to childbirth before pregnancy week 37. Two groups of mothers were classified according to the smoking habit during pregnancy and statistically processed in IBM SPSS Statistics 23.0. RESULTS: Infants born by women who smoked during pregnancy had the lower birth weight (2,769.0 grams on average) compared to non-smokers (3,224.1 grams) (p < 0.001). The differences in prevalence of premature birth have not been confirmed as statistically significant. Women who continued smoking during pregnancy were significantly more likely to be very young (OR = 5.9; 95% CI: 3.9-8.9; p < 0.001), unmarried (OR = 9.3; 95% CI: 6.1-14.0; p < 0.001), of lower level of education (OR = 39.6; 95% CI: 22.6-69.5; p < 0.001), and more likely to consume alcohol (OR = 6.6; 95% CI: 5.8-7.5; p < 0.01), and drugs (OR = 6.6; 95% CI: 5.8-7.5; p < 0.01) during pregnancy. When pregnant, they were most likely to see a doctor for the first time after the first trimester (OR = 0.1; 95% CI: 0.1-0.2; p < 0.001) and were more likely to see a doctor less than 8 times (OR = 6.1; 95% CI: 4.2-8.8; p < 0.001) during pregnancy. CONCLUSION: Tobacco prevention and cessation campaigns should focus on improving pregnancy outcomes in the future.

Risk factors associated with low birth weight.

OBJECTIVES: Low birth weight (LBW) is one of the major factors affecting child morbidity and mortality worldwide. Every day, approximately 800 women die from causes related to pregnancy and childbirth worldwide. Maternal ill health increases the risk of LBW. This study seeks to investigate determinants and incidence of LBW. METHODS: This study was conducted based on the medical records of mothers and their 1,946 infants born in 2016-2019 at the Department of Gynaecology and Obstetrics of Louis Pasteur University Hospital in Kosice. Data on mothers and newborn infants were obtained from the Reports on mothers at childbirth. The inclusion criteria were singleton births and birth weight > 500 g. The exclusion criteria were twins or multiple births, congenital anomalies and stillbirths, birth weight ≥ 4,000 g or ≤ 500 g, and Roma ethnicity. Roma children are more likely to be born prematurely, with low birth weight. Roma mothers have different lifestyle. Univariate analysis was employed to evaluate the association between the independent variables and LBW. Variables that were found to be statistically significant were then further analysed using multivariable logistic analysis for each dependent variable. The implementation of the research was approved by the Ethics Committee. RESULTS: Of 1,946 newborns, 271 (13.90%) have low birth weight. The mean of birth weight at delivery was 3,068.62 (SD 671.16) grams. Factors that were associated with LBW were primary maternal education (OR = 2.98, 95% CI: 1.08-8.21, p = 0.034), marital status single (OR = 2.88, 95% CI: 1.68-4.94, p < 0.001), number of prenatal care visits less than 8 (OR = 1.62, 95% CI: 1.01-2.61, p = 0.047), and preterm birth (OR = 74.94, 95% CI: 45.44-123.61, p < 0.001). CONCLUSION: The reducing of LBW requires strategies to improve maternal lifestyle, maternal care before, during and after birth and to strengthen social support.

Potential differences in occurrence of preterm births according to quality of relationship between mothers and fathers of the children.

OBJECTIVES: Premature birth is a serious pregnancy complication that is affected by many biological as well as psychosocial factors. Several studies have shown that a mother's positive relationship with her child's father reduces the mother's stress, anxiety and depression during pregnancy, promotes a healthier mother's lifestyle and thus has a positive effect on pregnancy as such. This research was therefore aimed at identifying possible differences in the incidence of premature births in mothers depending on the quality of the relationship with the father of their child. METHODS: The research involved 210 mothers after childbirth in the period from October 2020 to September 2021. A questionnaire aimed at obtaining descriptive data about the mother and her child and a questionnaire aimed at determining the quality of the relationship - Quality of Relationship Inventory (QRI) were distributed. Mann-Whitney U tests were used to determine differences between groups. RESULTS: Of 210 children, 44 (21%) were born prematurely, 154 (73.3%) mothers were married and 176 (83.8%) lived with the father of their child in the same household. The results showed that the degree of quality of the mother's relationship with the child's father is approximately the same for mothers who gave birth prematurely and for those who gave birth at term, so there were no differences in this factor between the two groups of mothers. CONCLUSION: The results of other researchers have shown the positive impact of partners on pregnancy and the overall well-being of the mothers. However, our research has not confirmed the positive effect of the quality of the relationship between mother and father of her child on reducing the incidence of premature births. Further research is needed to clarify how specifically and whether the quality of the relationship between parents can affect the incidence of premature births at all.

Lower-limb progressive paraparesis management and diagnosis overview in a pregnant woman with vertebral haemangioma.

Vertebral haemangioma is a benign vascular tumour mostly seen in the thoracic region of the spine. Spinal haemangiomas are usually asymptomatic and are discovered incidentally. In a few patients, however, aggressive vertebral haemangiomas can cause local pain, radicular pain or neurologic deficits, which result from neural compression. The aetiology of the origin is unclear and is probably multifactorial. Hormonal and biological changes in pregnant women can lead to accelerated vascular growth of haemangioma. In our report, we present the case of a pregnant patient who was diagnosed with an aggressive vertebral haemangioma that further led to progressive paraparesis. We had to take the fact that she was pregnant into account in the diagnostic procedure, in the choice of examination method and also in the method of therapy. The goal of this case report is threefold: (1) provide an overview of the possible methods of management, specifically imaging, which will aid in diagnosis and based on that, (2) determining the appropriate therapy and (3) review the risks and benefits of each will be presented when choosing individual approaches.

Zinc(II) niflumato complex effects on MMP activity and gene expression in human endometrial cell lines.

Endometriosis is a chronic inflammatory disease which increasingly affects young women under 35 years of age and leads to subfertility even infertility. Analysis of the cytotoxic effect of zinc(II) niflumato complex with neocuproine ([Zn(neo)(nif)2] or Zn-Nif) on immortalized human endometriotic cell line (12Z) and on control immortalized human endometrial stromal cell line (hTERT) was performed using xCELLigence technology for approximately 72 h following the treatment with Zn-Nif as well as cell viability Trypan Blue Assay. 12Z cell line proliferated more slowly compared to unaffected cells, whereas hTERT cells did not show similar behavior after treatment. The complex probably reduces the effect of pro-inflammatory pathways due to the effect of NSAID, while presence of zinc might reduce the level of ROS and regulate ER2 levels and MMP activity. The observed effects and high selectivity for rapidly proliferating cells with increased inflammatory activity suggest a good prognosis of successful decrease of endometriosis stage with this complex.

Roma Ethnicity and Sex-Specific Associations of Serum Uric Acid with Cardiometabolic and Hepatorenal Health Factors in Eastern Slovakian Population: The HepaMeta Study.

Background: Health characteristics associated with uric acid (UA) in the Roma minority remain less well known. The study sought to determine the ethnicity- and sex-specific associations of serum UA with health factors in Eastern Slovakian Roma and non-Roma populations. Methods: Data from the comparative cross-sectional HepaMeta study conducted in Slovakia in 2011 were used. The study enrolled 452 Roma subjects (35.2% men) and 403 non-Roma individuals (45.9% men) aged 18-55 years. Results: All study parameters differed between the sexes in both the Roma and non-Roma participants (p < 0.05). UA was related to sex with odds ratio for female sex 0.873, 95% CI 0.853-0.893 (p < 0.0001) per 10-unit increase of UA. Average level of UA ± standard deviation was lower in Roma than in non-Roma (226.54 ± 79.8 vs. 259.11 ± 84.53 umol/L; p < 0.0001). The Roma population presented with greater levels of high-sensitivity C-reactive protein (hsCRP) (3.07 ± 4 mg/L vs. 1.98 ± 2.83 mg/L; p < 0.0001) and ferritin in Roma males (403.78 ± 391.84 vs. 302.67 ± 236.26 mg/L; p < 0.0001). Conclusions: Serum UA is sex- and ethnicity specific. Elevated levels of hsCRP and ferritin particularly in Roma males can reflect low-grade systemic inflammation and thus serve as a marker of an increased cardiovascular risk.

Pelvic organ prolapse and uterine preservation: a survey of female gynecologists (POP-UP survey).

BACKGROUND: The aim of this study was to explore the personal views of female gynecologists regarding the management of POP with a particular focus on the issue of uterine sparing surgery. METHODS: A questionnaire based survey of practicing female gynecologists in the Czech Republic, Slovenia and Slovakia. RESULTS: A total of 140 female gynecologists from 81 units responded to our questionnaire. The majority of respondents stated they would rely on a urogynecologist to aid them with their choice of POP management options. The most preferred options for POP management were sacrocolpopexy and physiotherapy. Almost 2/3 of respondents opted for a hysterectomy together with POP surgery, if they were menopausal, even if the anatomical outcome was similar to uterine sparing POP surgery. Moreover, 81.4% of respondents, who initially opted for a uterine sparing procedure, changed their mind if the anatomical success of POP surgery with concomitant hysterectomy was superior. Discussing uterine cancer risk in relation to other organs had a less significant impact on their choices. CONCLUSIONS: The majority of female gynecologists in our study opted for hysterectomy if they were postmenopausal at the time of POP surgery. However, variation in information provision had an impact on their choice.

A randomized interventional parallel study to evaluate the effect of pelvic floor muscle training with stabilization exercises of high and low intensity in women with stress urinary incontinence: The PELSTAB study.

INTRODUCTION: The effect of different intensities of pelvic floor muscle training (PFMT) assessed by 2D/3D ultrasound (USG) have not been sufficiently monitored in the literature. The objective of the study will be to evaluate the effect of this intervention by assessing the change in incontinence episode frequency, hiatal area (HA) and hiatal diameter by 2D/3D USG and quality of life over 12 weeks of treatment. METHODS: Using a randomized interventional parallel study, patients will be assigned to groups A and B using simple software randomization according to odd and even patient sequence numbers. The following methods will be used for evaluation: change in incontinence episode frequency, power and endurance of pelvic floor muscles assessed by perineometer (in cmH2O), HA (in cm) during contraction, Valsalva manoeuvre assessed by 3D USG, hiatal diameter assessed by 2D USG, the Incontinence Quality of Life scale (I-QoL) and the Patient Global Impression of Improvement score (PGI-I). INTERVENTIONS: Group A, high-intensity PFMT 5 times a week for 30 minutes per day. Group B, low-intensity PFMT twice a week for 15 minutes per day. The duration of the intervention will be 12 weeks. DISCUSSION: The study protocol presents the starting points, design, and methods of the PELSTAB Study. We expect that, after 12 weeks of high-intensity PFMT, women with stress urinary incontinence will have significantly less incontinence episode frequency, better reduction of HA during contraction and Valsalva manoeuvre, higher power and endurance of pelvic floor muscles and better quality of life compared to the group with low-intensity PFMT. REGISTRATION: This study was registered in the ClinicalTrials.govNCT04340323.

Systemic treatment of the metastatic renal cell carcinoma: usefulness of the apparent diffusion coefficient of diffusion-weighted MRI in prediction of early therapeutic response.

Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration-7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05-11.61), 7.40 ± 2.50 months (95% CI = 5.61-9.19) and 4.20 ± 1.99 months (95% CI = 2.78-5.62) accordingly (p < 0.05). There was no difference in change of main lesions' longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35-25.87) and by 7.66 ± 6.72% (95% CI = 2.86-12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.

MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma.

None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan-Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E - 03 ± 3.11E - 03 RU (p < 0.001). Overexpression of miR-15a was strongly associated with poor histologic prognostic features of ccRCC. Poorly differentiated tumors tend to have more pronounced upregulation of miR-15a compared to highly differentiated lesions: Mean expression values were 4.57 ± 3.19 RU for Fuhrman grade 4 versus 0.02 ± 0.01 RU for Fuhrman grade 1 (p < 0.001). The metastatic involvement of the regional lymphatic nodules (N +) was associated with significantly upregulated miRNA-15a in comparison with N - cases: Mean expression values were 4.92 ± 2.80 RU versus 1.10 ± 2.29 RU, respectively (p < 0.001). In patients with miR-15a expression in RCC tissues ≤ 0.10 RU, mean 5-year CSS was significantly longer compared to patients with expression levels above this threshold: 92.31% (mean duration of survival-59.88 ± 0.12 months) versus 54.8% (mean duration of survival-49.74 ± 2.16 months), respectively (p < 0.001). The tissue expression of miR-15a could be used as a potential prognostic molecular biomarker for conventional RCC.