Biomechanical Integrity Score of the Female Pelvic Floor for Stress Urinary Incontinence.

INTRODUCTION AND HYPOTHESIS: This study is aimed at developing and validating a new integral parameter, the Biomechanical Integrity score (BI-score) of the female pelvic floor for stress urinary incontinence conditions. METHODS: A total of 130 subjects were included in the observational cohort study; 70 subjects had normal pelvic floor conditions, and 60 subjects had stress urinary incontinence (SUI). A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t test, correlation) to identify the VTI parameters sensitive to the pelvic SUI conditions. RESULTS: Twenty-seven parameters were identified as statistically sensitive to SUI development. They were subdivided into five groups to characterize tissue elasticity (group 1), pelvic support (group 2), pelvic muscle contraction (group 3), involuntary muscle relaxation (group 4), and pelvic muscle mobility (group 5). Every parameter was transformed to its standard deviation units using the dataset for normal pelvic conditions, similar to the T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups 1-5 and to the BI-score in standard deviation units. The p value for the BI-score has p = 4.0 × 10-28 for SUI versus normal conditions. CONCLUSIONS: Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the SUI BI-score in future research and clinical applications.

Activity of Potassium Channels in CD8+ T Lymphocytes: Diagnostic and Prognostic Biomarker in Ovarian Cancer?

CD8+ T cells play a role in the suppression of tumor growth and immunotherapy. Ion channels control the Ca2+-dependent function of CD8+ lymphocytes such as cytokine/granzyme production and tumor killing. Kv1.3 and KCa3.1 K+ channels stabilize the negative membrane potential of T cells to maintain Ca2+ influx through CRAC channels. We assessed the expression of Kv1.3, KCa3.1 and CRAC in CD8+ cells from ovarian cancer (OC) patients (n = 7). We found that the expression level of Kv1.3 was higher in patients with malignant tumors than in control or benign tumor groups while the KCa3.1 activity was lower in the malignant tumor group as compared to the others. We demonstrated that the Ca2+ response in malignant tumor patients is higher compared to control groups. We propose that altered Kv1.3 and KCa3.1 expression in CD8+ cells in OC could be a reporter and may serve as a biomarker in diagnostics and that increased Ca2+ response through CRAC may contribute to the impaired CD8+ function.

A randomized controlled pilot trial to assess the effectiveness of a specially formulated food supplement and pelvic floor muscle training in women with stress-predominant urinary incontinence.

BACKGROUND: Pelvic floor muscle training (PFMT) is the first-line treatment approach for stress urinary incontinence. Creatine and leucine have been shown to improve muscle function. Our aim was to assess the effectiveness of a food supplement and PFMT in women with stress-predominant urinary incontinence. METHODS: Women with stress-predominant urinary incontinence were randomized in 1:1 ratio to receive daily oral supplementation for six weeks with either a food supplement (treatment group) or placebo (control group). Both groups were instructed to perform standardized daily PFMT. The primary outcome was the Urogenital Distress Inventory Short Form (UDI-6) score. Secondary outcomes were the Incontinence Impact Questionnaire (IIQ-7) score, Patient's Global Impression of Severity (PGI-S), and Biomechanical Integrity score (BI-score) measured by Vaginal Tactile Imager. To have a power of 80% and a significance level of 5% to detect a decrease of 16 points in the UDI-6 score, a sample size of 32 was needed, with 16 patients in each arm of our trial. RESULTS: Sixteen women in the control group and sixteen in the treatment group completed the trial. Between-group analysis revealed no significant differences between the control and treatment group except for mean change (delta) in vaginal squeeze pressure [(cmH2O, mean ± SD), 5 ± 12 vs. 15 ± 15, P = 0.04] and mean change (delta) in PGI-S score [(mean ± SD), -0.2 ± 0.9 vs. -0.8 ± 0.8, P = 0.04]. Within-group analysis showed that UDI-6 and IIQ-7 scores improved significantly from baseline to six weeks in the treatment group but not in the control group [UDI-6 score (mean ± SD) 45 ± 21 vs. 29 ± 21, P = 0.02; 43 ± 18 vs. 33 ± 26, P = 0.22] [IIQ-7 score (mean ± SD) 50 ± 30 vs. 30 ± 21, P = 0.01; 48 ± 23 vs.40 ± 28, P = 0.36]. PGI-S scores only improved in the treatment group from baseline to six weeks after treatment [PGI-S score (mean ± SD) 3.1 ± 0.8 vs. 2.3 ± 0.8, P = 0.0001]. BI-score, on average, improved significantly in the treatment and control group as well [SD unit, mean, from - 1.06 to -0.58, P = 0.001; from - 0.66 to -0.42, P = 0.04]. CONCLUSIONS: Women with stress-predominant urinary incontinence receiving a specially formulated supplement in addition to daily PFMT for six weeks had significantly improved urinary symptoms (decrease in UDI-6 score and IIQ-7) and BI-score compared to their baseline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05358769. 27/04/2022.

Correlation between the female pelvic floor biomechanical parameters and the severity of stress urinary incontinence.

BACKGROUND: Stress urinary incontinence (SUI) is a common condition that requires proper evaluation to select a personalized therapy. Vaginal Tactile Imaging (VTI) is a novel method to assess the biomechanical parameters of the pelvic floor. METHODS: Women with SUI were enrolled in this cross-sectional study. Participants completed the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire and the Patient Global Impression of Severity Question (PGI-S) and underwent a VTI examination. Based on the MESA and PGI-S questionnaires, participants were divided into mild, moderate, and severe SUI groups. Fifty-two biomechanical parameters of the pelvic floor were measured by VTI and compared between the groups (mild vs. moderate and severe). SUI Score and Index were calculated from the MESA questionnaire. Pearson correlation was used to determine the strength of association between selected VTI parameters and the MESA SUI Index and MESA SUI Score. RESULTS: Thirty-one women were enrolled into the study. Significant differences were observed in the VTI parameters 16, 22-24, 38, 39 when the difference between mild and severe subgroups of SUI based on the PGI-S score was examined. Parameter 16 refers to the maximum gradient at the perineal body, parameter 22-24 refers to the pressure response of the tissues behind the vaginal walls, and parameter 38, 39 refers the maximum pressure change and value on the right side at voluntary muscle contraction. VTI parameter 49, describing the displacement of the maximum pressure peak in the anterior compartment, showed a significant difference between the mild SUI and the moderate-severe SUI according to the MESA SUI score (mean ± SD 14.06 ± 5.16 vs. 7.54 ± 7.46, P = 0.04). The MESA SUI Index and SUI Score displayed a positive correlation concerning VTI parameters 4 (the maximum value of the posterior gradient) and 27 (the displacement of the maximum pressure peak in the anterior compartment) (VTI4 vs. MESA SUI Index r = 0.373, P = 0.039; VTI4 vs. MESA SUI Score r = 0.376, P = 0.037; VTI27 vs. MESA SUI Index r = 0.366, P = 0.043; VTI27 vs. MESA SUI Score r = 0.363, P = 0.044). CONCLUSIONS: Female pelvic floor biomechanical parameters, as measured by VTI, correlate significantly with the severity of SUI and may help guide therapeutic decisions.

The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling.

Ovarian cancer is characterized by dysbiosis, referred to as oncobiosis in neoplastic diseases. In ovarian cancer, oncobiosis was identified in numerous compartments, including the tumor tissue itself, the upper and lower female genital tract, serum, peritoneum, and the intestines. Colonization was linked to Gram-negative bacteria with high inflammatory potential. Local inflammation probably participates in the initiation and continuation of carcinogenesis. Furthermore, local bacterial colonies in the peritoneum may facilitate metastasis formation in ovarian cancer. Vaginal infections (e.g. Neisseria gonorrhoeae or Chlamydia trachomatis) increase the risk of developing ovarian cancer. Bacterial metabolites, produced by the healthy eubiome or the oncobiome, may exert autocrine, paracrine, and hormone-like effects, as was evidenced in breast cancer or pancreas adenocarcinoma. We discuss the possible involvement of lipopolysaccharides, lysophosphatides and tryptophan metabolites, as well as, short-chain fatty acids, secondary bile acids and polyamines in the carcinogenesis of ovarian cancer. We discuss the applicability of nutrients, antibiotics, and probiotics to harness the microbiome and support ovarian cancer therapy. The oncobiome and the most likely bacterial metabolites play vital roles in mediating the effectiveness of chemotherapy. Finally, we discuss the potential of oncobiotic changes as biomarkers for the diagnosis of ovarian cancer and microbial metabolites as possible adjuvant agents in therapy.

COVID 19 pandemic and minimally invasive gynecology: consequences and future perspectives.

The extent of the 2020 pandemic not only extends to the infected patients but also to patients who have been waiting for medical procedures. Reevaluation of the healthcare system is important in order to help assist the needs of intensive care units. The urgency of the gynaecological cases should be aligned based on surgical interventions and minimally invasive methods should be preferred. This will not endanger professional and other resource demands of ICUs. In acute cases, laparoscopy or hysteroscopy (preferring office hysteroscopy) should be chosen, that require no or only short period of hospitalization. Postponing non-acute surgeries is recommended to the post-pandemic period. Abbreviations: ICU: intensive care unit; COVID-19: coronavirus disease; SARS-CoV-2: severe acute respiratory syndrome Coronaviruses; IgM-IgG: immunoglobulin M; GAGP: aerosol generating procedures; PPE: personal protective equipment; ERAS: early recovery after surgery; mESAS: modified elective surgery acuity scale; RPOC: retained product of concept; PMB: postmenopausal bleeding.

Intention-to-Treat Analysis of Radical Trachelectomy for Early-Stage Cervical Cancer With Special Reference to Oncologic Failures: Single-Institutional Experience in Hungary.

OBJECTIVE: The aim of our study was to evaluate clinical and pathological data in order to draw eligibility criteria for oncologically sufficient radical trachelectomy (RT) in early-stage cervical cancer. Reviewing all cases of attempted RT performed at our unit, we focused attention on prognostic indicators of the need for additional oncologic treatment following RT. The analysis was extended by extensive literature review to include previously published cases of oncologic failures. METHODS: The authors retrospectively analyzed data of patients who underwent RT at the Department of Obstetrics and Gynecology, University of Debrecen. Electronic records and case notes of RT cases were reviewed to determine the incidence of abdominal and vaginal route, distribution of clinicopathologic data, and follow-up results of individual cases. Individual procedures were categorized as oncologically insufficient if additional oncologic treatment was necessary following RT. Theoretical eligibility criteria for RT in early-stage cervical cancer were determined retrospectively by selecting prognostic features that were associated with oncologic insufficiency from clinicopathologic indicators of the complete series. RESULTS: Twenty-four cases of RT were performed by the authors, 15 vaginal RTs with laparoscopic pelvic lymphadenectomy and 9 abdominal RTs with open pelvic lymphadenectomy. Fifteen of 24 cases proved oncologically sufficient. Three cases required immediate conversion to radical hysterectomy because of positive sentinel nodes and/or positive isthmic disc on frozen section. In further 5 cases, final pathology results indicated additional oncologic treatment, that is, radical hysterectomy (n = 2), chemoradiotherapy (n = 2), or chemotherapy (n = 1). One patient among immediately converted cases and another 3 among those who required additional oncologic treatment died of their disease later. There were no other cases of recurrences over a median follow-up of 34 months (range, 12-188 months). Factors that may predict oncologic insufficiency of RT were stage IB1 or greater, tumor size of greater than 2 cm in 1 dimension or greater than 15 mm in 3 dimensions, G3, nonsquamous/adeno histological type, stromal invasion of greater than 9 mm, and lymphovascular space involvement in the primary tumor. CONCLUSIONS: Most cases of oncologically insufficient RTs have significant risk features that can be identified preoperatively. There is a need for more clinicopathologic data on oncologic failure of RT cases in order to improve patient selection.

Seminal vesicle secretion 2 acts as a protectant of sperm sterols and prevents ectopic sperm capacitation in mice.

Seminal vesicle secretion 2 (SVS2) is a protein secreted by the mouse seminal vesicle. We previously demonstrated that SVS2 regulates fertilization in mice; SVS2 is attached to a ganglioside GM1 on the plasma membrane of the sperm head and inhibits sperm capacitation in in vitro fertilization as a decapacitation factor. Furthermore, male mice lacking SVS2 display prominently reduced fertility in vivo, which indicates that SVS2 protects spermatozoa from some spermicidal attack in the uterus. In this study, we tried to investigate the mechanisms by which SVS2 controls in vivo sperm capacitation. SVS2-deficient males that mated with wild-type partners resulted in decreased cholesterol levels on ejaculated sperm in the uterine cavity. SVS2 prevented cholesterol efflux from the sperm plasma membrane and incorporated liberated cholesterol in the sperm plasma membrane, thereby reversibly preventing the induction of sperm capacitation by bovine serum albumin and methyl-beta-cyclodextrin in vitro. SVS2 enters the uterus and the uterotubal junction, arresting sperm capacitation in this area. Therefore, our results show that SVS2 keeps sterols on the sperm plasma membrane and plays a key role in unlocking sperm capacitation in vivo.

Predicting Complete Cytoreduction with Preoperative [18F]FDG PET/CT in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis.

The cornerstone of ovarian cancer treatment is complete surgical cytoreduction. The gold-standard option in the absence of extra-abdominal metastases and intra-abdominal inoperable circumstances is primary cytoreductive surgery (CRS). However, achieving complete cytoreduction is challenging, and only possible in a selected patient population. Preoperative imaging modalities such as [18F]FDG PET/CT could be useful in patient selection for cytoreductive surgery. In our systematic review and meta-analysis, we aimed to evaluate the role of preoperative [18F]FDG PET/CT in predicting complete cytoreduction in primary and secondary debulking surgeries. Publications were pooled from two databases (PubMed, Mendeley) with predefined keywords "(ovarian cancer) AND (FDG OR PET) AND (cytoreductive surgery)". The quality of the included studies was assessed with the Prediction model Risk Of Bias Assessment Tool (PROBAST). During statistical analysis, MetaDiSc 1.4 software and the DerSimonian-Laird method (random effects models) were used. Primary and secondary cytoreductive surgeries were evaluated. Pooled sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated and statistically analyzed. Results were presented in forest plot diagrams and summary receiver operating characteristic (SROC) curves. Overall, eight publications were included in our meta-analysis. Four publications presented results of primary, three presented results of secondary cytoreductions, and two presented data related to both primary and secondary surgery. Pooled sensitivities, specificities, and positive and negative predictive values were the following: in the case of primary surgeries: 0.65 (95% CI 0.60-0.71), 0.73 (95% CI 0.66-0.80), 0.82 (95% CI 0.77-0.87), 0.52 (95% CI 0.46-0.59); and in the case of secondary surgeries: 0.91 (95% CI 0.84-0.95), 0.48 (95% CI 0.30-0.67), 0.88 (95% CI 0.81-0.93), 0.56 (95% CI 0.35-0.75), respectively. The PPVs of [18F]FDG PET/CT proved to be higher in cases of secondary debulking surgeries; therefore, it can be a valuable predictor of complete successful secondary cytoreduction.

The impact of short-term pelvic floor muscle training on the biomechanical parameters of the pelvic floor among patients with stress urinary incontinence: A pilot study.

OBJECTIVE: Our study aimed to improve the understanding of the biomechanical changes occurring in the pelvic floor due to pelvic floor muscle training (PFMT), which is responsible for improving stress urinary incontinence (SUI) symptoms. STUDY DESIGN: In this prospective cohort study, we examined the impact of a six-week PFMT program in women with stress or stress-predominant urinary incontinence on the biomechanical parameters of the pelvic floor. Fifty-two biomechanical parameters were measured by Vaginal Tactile Imager (VTI) at baseline and at a six-week follow-up. In addition, we have assessed the Urinary Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), and Patient's Global Impression of Severity (PGI-S) scores at enrolment and at six-week follow-up. We have divided our cohort into two groups, Improved Group (IG) and Not-improved Group (NIG), based on the change in UDI-6 score after six weeks and compared the biomechanical changes within and between the two groups. RESULTS: The overall cohort included twenty women with stress or stress-predominant SUI based on MESA questionnaire [MESA SUI index (mean ± SD) 63.3 % ± 24.0 %, MESA UUI index (mean ± SD) 13.3 % ± 15.3 %, p < 0.01]. Nine of the 52 VTI parameters have changed significantly after six weeks of PFMT in the entire cohort. Eleven women (IG) achieved the minimum 11-point change in the UDI-6 scaled score. In IG, we found that three VTI parameters differed significantly: Parameter 1: the maximum value of force measured during the VTI probe insertion [(N, mean ± SD) 0.55 ± 0.18 vs. 0.78 ± 0.31, p < 0.049], parameter 18: the maximum gradient at the upper third of the vagina (posterior) [(kPa/mm, mean ± SD) 0.16 ± 0.05 vs. 0.36 ± 0.28, p < 0.048], and parameter 47: integral force change in the anterior compartment at reflex pelvic muscle contraction (cough) [(N, mean ± SD) 1.61 ± 0.85 vs. 1.97 ± 0.71, p < 0.045]. CONCLUSION: Our study revealed a significant association between the improvement of strength in targeted muscle groups and a reduction in urinary incontinence symptoms. Identifying specific muscles changing PFMT provides valuable insights for specific interventions. Our findings may help to create personalized and targeted interventions to improve the quality of life of women affected by SUI.

Endocrine Characteristics and Obstetric Outcomes of PCOS Patients with Successful IVF and Non-IVF Pregnancies.

Background/Objective: Infertility affects an estimated 40-50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11-1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 µmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66-1.01, p = 0.06), and 1 µg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33-1.02, p = 0.056). DHEAS levels <6.5 µmol/L had an OR 3.86 (95% CI 1.10-13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18-10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75-11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89-10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40-7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02-6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too.

Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFß-ERK signaling.

Ascites plays a key role in supporting the metastatic potential of ovarian cancer cells. Shear stress and carry-over of cancer cells by ascites flow support carcinogenesis and metastasis formation. In addition, soluble factors may participate in the procarcinogenic effects of ascites in ovarian cancer. This study aimed to determine the biological effects of cell-free ascites on carcinogenesis in ovarian cancer cells. Cell-free ascites from ovarian cancer patients (ASC) non-selectively induced cell proliferation in multiple models of ovarian cancer and untransformed primary human dermal fibroblasts. Furthermore, ASC induced a Warburg-type rearrangement of cellular metabolism in A2780 ovarian cancer cells characterized by increases in cellular oxygen consumption and glycolytic flux; increases in glycolytic flux were dominant. ASC induced mitochondrial uncoupling and fundamentally reduced fatty acid oxidation. Ascites-elicited effects were uniform among ascites specimens. ASC-elicited transcriptomic changes in A2780 ovarian cancer cells included induction of the TGFß-ERK/MEK pathway, which plays a key role in inducing cell proliferation and oncometabolism. ASC-induced gene expression changes, as well as the overexpression of members of the TGFß signaling system, were associated with poor survival in ovarian cancer patients. We provided evidence that the activation of the autocrine/paracrine of TGFß signaling system may be present in bladder urothelial carcinoma and stomach adenocarcinoma. Database analysis suggests that the TGFß system may feed forward bladder urothelial carcinoma and stomach adenocarcinoma. Soluble components of ASC support the progression of ovarian cancer. These results suggest that reducing ascites production may play an essential role in the treatment of ovarian cancer by inhibiting the progression and reducing the severity of the disease.

The indirect costs of human papillomavirus-related cancer in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Human papilloma virus (HPV) is a common cause of several types of cancer, including head and neck (oral cavity, pharynx, oropharynx, hypopharynx, nasopharynx, and larynx), cervical, vulval, vaginal, anal, and penile cancers. As HPV vaccines are available, there is potential to prevent HPV-related disease burden and related costs. METHOD: A model was developed for nine Central Eastern European (CEE) countries (Bulgaria, Croatia, Czechia, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia). This model considered cancer patients who died from 11 HPV-related cancers (oropharynx, oral cavity, nasopharynx, hypopharynx, pharynx, anal, larynx, vulval, vaginal, cervical, and penile) in 2019. Due to data limitations, Bulgaria only included four cancer types. The model estimated the number of HPV-related deaths and years of life lost (YLL) based on published HPV-attributable fractions. YLL was adjusted with labor force participation, retirement age and then multiplied by mean annual earnings, discounted at a 3% annual rate to calculate the present value of future lost productivity (PVFLP). RESULTS: In 2019, there were 6,832 deaths attributable to HPV cancers resulting in 107,846 YLL in the nine CEE countries. PVFLP related to HPV cancers was estimated to be €46 M in Romania, €37 M in Poland, €19 M in Hungary, €15 M in Czechia, €12 M in Croatia, €10 M in Serbia, €9 M in Slovakia, €7 M in Bulgaria and €4 M in Slovenia. CONCLUSIONS: There is a high disease burden of HPV-related cancer-related deaths in the CEE region, with a large economic impact to society due to substantial productivity losses. It is critical to implement and reinforce public health measures with the aim to reduce the incidence of HPV-related diseases, and the subsequent premature cancer deaths. Improving HPV screening and increasing vaccination programs, in both male and female populations, could help reduce this burden.

Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss.

Background: SARS-CoV-2 infection during pregnancy increases the risk of severe obstetrical complications. Detailed evaluation of COVID-19-associated coagulopathy in a pregnancy with stillbirth hasn't been described so far. Besides knowledge gaps in the pathomechanism leading to stillbirth in COVID-19 pregnancies, currently, no prognostic biomarker is available to identify pregnant patients who are at imminent risk of COVID-19-associated maternal and fetal complications, requiring immediate medical attention. Case: Here we report the case of a 28-year-old SARS-CoV-2 infected pregnant patient, admitted to our hospital at 28 weeks of gestation with intrauterine fetal loss. The presence of SARS-CoV-2 placentitis was confirmed by immunohistological evaluation of the placenta. She had only mild upper respiratory symptoms and her vital signs were within reference throughout labor and postpartum. The stillborn infant was delivered per vias naturales. Fibrinogen concentrate was administered before and after labor due to markedly decreased fibrinogen levels (1.49 g/l) at admission and excessive bleeding during and after delivery. Although coagulation screening tests were not alarming at admission, the balance of hemostasis was strikingly distorted in the patient. As compared to healthy age- and gestational age-matched pregnant controls, increased D-dimer, low FVIII activity, low FXIII level, marked hypocoagulability as demonstrated by the thrombin generation assay, together with shortened clot lysis and decreased levels of fibrinolytic proteins were observed. These alterations most likely have contributed to the increased bleeding observed during labor and in the early postpartum period. Interestingly, at the same time, only moderately altered inflammatory cytokine levels were found at admission. Serum ACE2 activity did not differ in the patient from that of age- and gestational age-matched healthy controls, suggesting that despite previous speculations in the literature, ACE2 may not be used as a potential biomarker for the prediction of COVID-19 placentitis and threatening fetal loss in SARS-CoV-2-infected pregnancies. Conclusions: Although based on this case report no prognostic biomarker could be identified for use in pregnant patients with imminent risk of fetal loss associated with COVID-19 placentitis, the above-described hemostasis alterations warrant awareness of postpartum hemorrhagic complications and could be helpful to identify patients requiring intensified medical attention.

In Vivo Preclinical Assessment of the VEGF Targeting Potential of the Newly Synthesized [52Mn]Mn-DOTAGA-Bevacizumab Using Experimental Cervix Carcinoma Mouse Model.

Among humanized monoclonal antibodies, bevacizumab specifically binds to vascular endothelial growth factor A (VEGF-A). VEGF-A is an overexpressed biomarker in cervix carcinoma and is involved in the development and maintenance of tumor-associated neo-angiogenesis. The non-invasive positron emission tomography using radiolabeled target-specific antibodies (immuno-PET) provides the longitudinal and quantitative assessment of tumor target expression. Due to antibodies having a long-circulating time, radioactive metal ions (e.g., 52Mn) with longer half-lives are the best candidates for isotope conjugation. The aim of our preclinical study was to assess the biodistribution and tumor-targeting potential of 52Mn-labeled DOTAGA-bevacizumab. The VEGF-A targeting potential of the new immuno-PET ligand was assessed by using the VEGF-A expressing KB-3-1 (human cervix carcinoma) tumor-bearing CB17 SCID mouse model and in vivo PET/MRI imaging. Due to the high and specific accumulation found in the subcutaneously located experimental cervix carcinoma tumors, [52Mn]Mn-DOTAGA-bevacizumab is a promising PET probe for the detection of VEGF-A positive gynecological tumors, for patient selection, and monitoring the efficacy of therapies targeting angiogenesis.

[Epidemiology of cervical cancer in Hungary and the world]. / A méhnyakrák epidemiológiája Magyarországon és a világban.

Cervical cancer is one of the most common cancers among women and one of those completely preventable according to the current state of medical science. The pathogenesis of the disease is known, the human papillomavirus plays an essential role in the development in 99.9% of cases. With the available vaccines against the virus and the use of effective screening methods, the complete elimination of the disease can be achieved within a few decades, according to WHO estimates. Despite all these facts, the current state of the fight against the disease is still very controversial, which can be characterized by the epidemiological indicators of the disease. We would like to present these data in our publication, highlighting the challenges that not only developing but also developed countries face every day in relation to the prevention of cervical cancer.

[The treatment of ovarian cancer. Recommendation of the Hungarian Society of Gynaecologic Oncologists]. / A petefészekrák kezelése. A Magyar Nogyógyász Onkológusok Társaságának (MNOT) ajánlása.

In Hungary, there is no actual ovarian cancer guideline, despite this disease being the most lethal gynaecologic cancer. An expert panel was created by the Hungarian Society of Gynaecologic Oncologists to prepare a recommendation for the reatment of ovarian cancer patients. This multidisciplinary expert group worked together during the first trimester of 2022 using the guidelines and recommendations of the European Society of Gynaecologic Oncologists (ESGO) and the European Society for Medical Oncology (ESMO) and created the updated recommendations. This paper presents the recommended surgical and medical treatment of early, advanced stage and recurrent ovarian cancer.

The role of bile acid measurement in the management of intrahepatic cholestasis of pregnancy / Az epesavmérés szerepe a súlyos terhességi cholestasis szülészeti ellátásában

Introduction: Intrahepatic cholestasis of pregnancy complicates 1% of pregnancies. It increases the risk of severe fetal complications significantly, including preterm delivery and stillbirth. Objective: To summarize our experience with serum total bile acid level measurement that has recently become available for clinical routine in Hungary, and to present the way of gestational cholestasis care at our university. Patients and method: In a retrospective case series, we analyse the data of 12 patients suffering from severe cholestasis of pregnancy treated between September 2020 and September 2021 at the Department of Obstetrics and Gynecology, University of Debrecen. We also determine the statistical correlation between bile acid, transaminase and bilirubin levels in severe cholestasis. Results: 1258 serum samples of 758 patients were measured. 5 of them (0.7% of all cases, 6.4% of cholestasis cases) had severe (total bile acid 40-99 mu mol/L), 7 (0.9% of all cases and 9.0% of cholestasis cases) had very severe (total bile acid >= 100 mu mol/L) disease. The average age of the 12 cases was 30.6 (21-43) years, 7 of them were primigravid. 5 of the patients had a predisposing disease in their history. 6/12 patients received ursodeoxycholic acid treatment, resulting in significant decrease in the bile acid concentrations. Bile acid and GOT (R-2 = 0,14) and bile acid and GPT (R-2 = 0,17) correlations were found to be week in severe cholestasis (n = 45). Postpartum bile acid levels showed rapid improvement. So far, 11 of the patients have delivered and 13 neonates were born, 2/12 were multiple pregnancies. Average gestational age at delivery was 37 (33-40) weeks. 3/11 (27%) were preterm deliveries. 7/8 (88%) of term deliveries were induced. Elective cesarean delivery was not indicated in any of the cases, and in only 2/11 (18%) of the cases did emergency cesarean sections become necessary during labour. No stillbirth occurred. Conclusion: Serum total bile acid measurement is an effective tool in the diagnosis and follow-up of intrahepatic cholestasis of pregnancy, and is inevitable for the protocoll-based obstetrical management of patients. We also present the local protocol of our Department for the management of obstetrical cholestasis.

Multimodal hyperspectroscopy ­ the use of digital technology in cervical cancer screening / Multimodális hiperspektroszkópia - elorelépés a digitális technológia felé a méhnyakszurésben.

Összefoglaló. Bevezetés: Bevezetés: A citológiai alapú méhnyakrákszurés átmeneti kategóriáinak optimális menedzselése a humán papillomavírus (HPV) szurése és tipizálása ellenére jelenleg is kihívás. Vizsgálatunk célja a modern cervixspektroszkópiának (multimodális hiperspektroszkópia - MHS), egy azonnali eredményt nyújtó, digitális technológiára épülo módszernek a vizsgálata volt a citológiai alapú méhnyakszurés találati biztonságának javítására. Betegek és módszer: Vizsgálatainkat 208, 18 és 75 év közötti nobeteg bevonásával végeztük, akiknél már indikálásra került valamely, a méhnyakon végzendo mutét, citológiai eredményük rendelkezésre állt (a HPV-tesztet, amennyiben nem történt meg, elvégeztük), valamint valamennyi betegnél elvégeztük a mutét elott az MHS-vizsgálatot. A szövettani mintavétel 166 betegnél történt meg. Eredmények: A citológiai vizsgálatot (az összes betegre tekintve) magas álpozitív arány jellemezte (69,28%), amely megfigyelések mindenképpen utalnak az újabb komponens alkalmazásának igényére a triázsban. Az összes citológiai kategóriára nézve az MHS-eredmények közül kiemelendo az álnegatív leletek rendkívül alacsony aránya (3/166 = 1,8%), mely a HPV-teszt esetén ennél magasabb volt (11/165 = 6,66%). A spektroszkópiás vizsgálat álpozitív aránya ugyanakkor kedvezotlenebbnek bizonyult (91/166 = 54,81%) a HPV-vizsgálat álpozitív arányánál (40/165 = 24,24%). Az atípusos laphámsejt (ASC-US/ASC-H) citológiai kategória esetén a spektroszkópia álnegatív eredményeinek aránya (3/126 = 2,38%) szintén kedvezobb volt, mint a HPV-vizsgálaté (9/126 = 7,14%). A cervicalis intraepithelialis neoplasia-2 vagy súlyosabb fokozatú hámelváltozások azonosításában a spektroszkópia szenzitivitása 94% (95% CI = 0,84-0,99), specificitása 22% (95% CI = 0,15-0,31), negatív prediktív értéke 90% (95% CI = 0,73-0,98), pozitív prediktív értéke 34% (95% CI = 0,26-0,43) volt (p = 0,00130). Következtetés: Az MHS fejlett innovatív technológián alapuló, azonnali eredményt adó vizsgálóeljárás, amely kiemelkedoen alacsony álnegatív eredménye miatt nagy segítséget nyújt a citológiai eltéréssel rendelkezo betegek további vizsgálatában. Orv Hetil. 2021; 162(20): 790-799. INTRODUCTION: Despite the use of human papillomavirus (HPV) testing, the management of the transitional categories of cytology-based screening still remains a challenge. The modern multimodal hyperspectroscopy (MHS) of the cervix is a novel digital technology based on artificial intelligence, providing an instant result in the assessment of cytology-based screening abnormalities. PATIENTS AND METHODS: 208 women (age 18-75) were enrolled. The patients already had cytology results and an operation on the cervix indicated at the time of inclusion. HPV and the hyperspectroscopy examination was performed pre-operatively. The pre-indicated operation was performed on 166 patients. RESULTS: Cytology-based screening alone (in the category of all patients) resulted in a high false-positive rate (69.28%). In this category, the MHS had an outstanding false-negative rate (3/166 = 1.80%) compared to the HPV (11/165 = 6.66%). The false-positive rate of the spectroscopy examination (91/166 = 54.81%) was higher than that of the HPV testing (40/165 = 24.24%). In the atypical squamous cell (ASC-US/ASC-H) category, the false-negative rate of the spectroscopy (3/126 = 2.38%) was also lower than that of the HPV test (9/126 = 7.14%). In the detection of high-grade abnormalities (cervical intraepithelial neoplasia 2 and worse), the spectroscopy had a 94% sensitivity (95% CI = 0.84-0.99), with a 22% specificity (95% CI = 0.15-0.31), an 90% negative predictive value (95% CI = 0.73-0.98), and a 34% positive predictive value (95% CI = 0.26-0.43) (p = 0.00130). CONCLUSION: In the case of cytological abnormality, the MHS provides an immediate result based on advanced digital technology, and because of its outstanding false negative rate it is a great aid and should be considered in the triage of such patients. Orv Hetil. 2021; 162(20): 790-799.

Functional implications of membrane modification with semenogelins for inhibition of sperm motility in humans.

Semenogelin I and II (Sgs) are the major component of human semen coagulum. The protein is rapidly cleaved after ejaculation by a prostate-specific antigen, resulting in liquefaction of the semen coagulum and the progressive release of motile spermatozoa. Sgs inhibit human sperm motility; however, there is currently no information on its effect on the sperm membrane. This study investigated the role of Sgs on human sperm motility through regulation of membrane potential and membrane permeability. Fresh semen samples were obtained from normozoospermic volunteers, and studies were conducted using motile cells selected using the swim-up method. Sgs changed the characteristics of sperm motion from circular to straightforward as evaluated by a computer-assisted motility analyzer, and all parameters were decreased more than 2.5 mg/mL. The results demonstrate that Sgs treatment immediately hyperpolarized the membrane potential of swim-up-selected sperm, changed the membrane structure, and time-dependently increased membrane permeability, as determined through flow cytometric analysis. The biphasic effects of Sgs were time- and dose-dependent and partially reversible. In addition, a monoclonal antibody against Sgs showed positive binding to cell membrane proteins in fixed cells, observed with confocal fluorescence microscopy. These results demonstrate that Sgs modifies the membrane structure, indirectly inhibiting motility, and provides suggestions for a therapy for male infertility through selection of a functional sperm population using Sgs.