Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

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.

Recovery of the Decreased Phagocytic Function of Peripheral Monocytes and Neutrophil Granulocytes following Cytoreductive Surgery in Advanced Stage Epithelial Ovarian Cancer.

(1) Monocytes and neutrophil granulocytes are the phagocytic cells of the innate immune system, playing a crucial role in recognizing and eliminating tumor-transformed cells. Our objective was to assess the impact of advanced-stage epithelial ovarian cancer (EOC) and cytoreductive surgery on the phagocytic function of peripheral monocytes and neutrophil granulocytes. We aimed to compare the pre- and postoperative phagocytic function of these immune cells in EOC patients with healthy control women. Additionally, we aimed to examine the influence of surgery on phagocytic function by comparing pre- and postoperative samples from patients with benign gynecological tumors. (2) We examined peripheral blood samples from 20 patients with FIGO IIIC stage high-grade serous EOC and 16 patients with benign gynecological tumors as surgical controls, collected before and seven days after tumor removal surgery, and from 14 healthy women. After separation, the cells were incubated with Zymosan-A particles, and the phagocytic index (PI) was assessed using immunofluorescence microscopy. One-way ANOVA, the Kruskal-Wallis H-test, and the paired samples t-test were used for the statistical analysis of the data. A significance level of p < 0.05 was applied. (3) Peripheral monocytes and neutrophils from EOC patients exhibited significantly lower preoperative PI values compared to healthy controls (p < 0.001; p < 0.001, respectively). Following cytoreductive surgery, the PI values of immune cells in EOC patients significantly increased by the 7th postoperative day (p < 0.001; p < 0.001), reaching levels comparable to those of healthy controls (p = 0.700 and p = 0.991). In contrast, there was no significant disparity in the PI values of cells obtained from pre- and postoperative blood samples of surgical controls when compared to healthy women (monocytes: p = 0.361 and p = 0.303; neutrophils: p = 0.150 and p = 0.235). (4) EOC and/or its microenvironment may produce factors that reduce the phagocytic function of monocytes and neutrophils, and the production of these factors may be reduced or eliminated after tumor removal.

Evaluating the Phagocytic Index of Peripheral Leukocytes in Endometriosis by Plasma Experiments.

Background and Objectives: Endometriosis is a benign, chronic disease, that negatively influences the quality of life of affected women and is responsible for a remarkable amount of infertility. The pathophysiology of the disease is still not clarified, but the insufficient immune surveillance plays a significant role in it. The phagocyte function of innate immune cells may play a role in the elimination of ectopic endometrium. The purpose of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes, incubated in heat-inactivated and not-inactivated plasma samples from healthy women and from women with endometriosis before and after the surgical treatment. Materials and Methods: Blood samples were collected from eight preoperative and eight postoperative patients with endometriosis before and after the surgical treatment, and from 16 healthy patients as controls. Neutrophil granulocytes, monocytes and blood plasma samples were isolated. Cells were incubated in different plasma samples, and the phagocytic index was determined with a fluorescence microscope. Results: The phagocytic index of granulocytes and monocytes isolated from patients with endometriosis was significantly decreased compared to healthy women after the cells were incubated in their own plasma. Preoperatively isolated cells from patients with endometriosis demonstrated an improved phagocyte function after incubating them in plasma samples from healthy controls. In contrast, the phagocytic activity of cells from healthy women significantly reduced after being incubated in the plasma of preoperative endometriosis patients. The heat-inactivation of plasma samples did not affect the results. Conclusions: Active endometriosis lesions may produce heat-stable systemic immunomodulatory factors, which reduced the phagocyte function of peripheral monocytes and neutrophil granulocytes. The phagocyte function of these cells can be normalized after the complete surgical removal of endometriosis, which then demonstrates similar values as in healthy women.

Hystero-salpingo scintigraphy for fallopian tubal patency assessment: results from a prospective study.

OBJECTIVE: To evaluate the diagnostic accuracy of a bygone method, hystero-salpingo-scintigraphy (HSSG), for tubal patency assessment of infertile women. MATERIAL AND METHODS: Prospective cohort study involving women in the infertility workup at the University of Debrecen, Hungary. Seventy infertile patients were scheduled to either basic dynamic HSSG, post-purge dynamic HSSG, or post-purge dynamic HSSG followed by SPECT/CT for reducing tracer contamination. The primary endpoint was the evaluation of the diagnostic accuracy of HSSG for the three methods. RESULTS: During the basic dynamic group, the examination yielded a sensitivity of 87.5%, with a specificity of 71.7%, while positive and negative predictive values were 31.8%, and 97.4% respectively. Using post purge dynamic HSSG, it resulted in a sensitivity of 87.5%, a specificity of 88.7%, a positive predictive value of 53.8%, and a negative predictive value of 97.9%. Adding SPECT/CT to post-purge dynamic HSSG increased diagnostic accuracy with 100% sensitivity and 88.7% specificity, while positive and negative predictive values were 57.1% and 100%, respectively. CONCLUSION: HSSG is a non-invasive and well-tolerated technique for tubal patency. It could be used initially to predict tubal patency in case of infertility. Its diagnostic accuracy is higher when it is carried out by adding SPECT/CT to the post-purge dynamic method.

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.

The Effect of Vaginal Microablative Fractional CO2 Laser Treatment on Vaginal Cytology.

BACKGROUND AND OBJECTIVES: Most recently vaginal laser treatment was introduced as a new option for women with genitourinary syndrome of menopause, vaginal dryness. Our objective was to assess the effects of intravaginal CO2 laser treatment on vaginal cytology. STUDY DESIGN/MATERIALS AND METHODS: Fifty-two women with symptoms of vaginal dryness were enrolled and underwent vaginal laser treatment using a fractional CO2 laser. Patients received three vaginal laser treatments 4 weeks apart. Vaginal cytology was obtained before the first treatment and 4 weeks after each additional treatment. Vaginal dryness was assessed by using a Visual Analog Scale (VAS). RESULTS: Out of the 52 women enrolled, 34 were in menopause. Postmenopausal women had significantly lower vaginal maturation values (VMV) compared with premenopausal women at the baseline visit (mean ± standard deviation [SD], 42 ± 23 vs. 68 ± 13, P < 0.01). The vaginal dryness VAS was higher (worse) in postmenopausal women compared with premenopausal cases (mean ± SD, 5.7 ± 4 vs. 2.4 ± 3, P < 0.01). The VMV did not change significantly over time after vaginal laser treatment. However vaginal dryness VAS improved significantly after each treatment. Both in the premenopausal and postmenopausal groups, vaginal dryness scores improved significantly from baseline after the three treatments (postmenopausal 5.7 ± 4 vs. 1.6 ± 2.5, P < 0.01 and premenopausal 2.4 ± 3 vs. 0.2 ± 0.5, P < 0.01). Those patients who had improvement in VMV had significantly better (lower) dryness VAS compared with those women without an improvement in VMV after the three treatments (mean ± SD, 0.3 ± 0.8 vs. 1.6 ± 2.6, P = 0.04). CONCLUSIONS: Vaginal dryness VAS improved significantly in a cohort of premenopausal and postmenopausal women undergoing vaginal CO2 laser treatment despite no significant change in vaginal cytology. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Suprapubic pressure facilitates the procedure of office hysteroscopy: A randomized controlled trial.

AIM: To minimize the experienced pain during office hysteroscopy, a number of technical approaches and maneuvers are used. The aim of the study was to assess the effect of suprapubic pressure (SuPuP) applied during hysteroscopy. The impact of this maneuver on experienced pain (assessed by visual analog scale [VAS]) and duration of passage through the cervical canal was measured and compared to a reference group with no SuPuP. METHODS: Hysteroscopy was performed in study subjects as part of their infertility work-up. Patients were randomized into two groups as part of a controlled trial. In group 1, SuPuP was applied while inserting the scope; in group 2, SuPuP was not applied. Pain experienced during the procedure was measured on a 0-10 VAS. Duration of passage through the cervical canal was measured by analyzing the video of the procedure. The effect of SuPuP was estimated by testing for between-groups differences in these outcomes. RESULTS: The number of patients included the study was 60. Mean (SD) VAS score was 3.40 (1.276) in group 1 compared to 3.33 (0.802) in group 2 (P = 0.809). Mean (SD) time of passage through the cervical canal in group 1 was 30.5 (18.37) seconds compared to 43.0 (24.51) seconds in group 2 (P = 0.029). CONCLUSION: Applying suprapubic pressure could facilitate the procedure by significantly shortening the duration of the passage through the cervical canal, but significantly not reduces the pain experienced during hysteroscopy. Further studies are to be undertaken to investigate the advantages of suprapubic pressure during office hysteroscopy.

[Phagocytic function of monocytes and neutrophil granulocytes in ovarian cancer]. / Monocyták és neutrophil granulocyták fagocitafunkciója ovariumcarcinomában.

INTRODUCTION: Recently, tumor-infiltrating immune cells have been studied in various cancers. However, fewer studies address the role of peripheral immune cells in the pathogenesis of cancer. AIM: Our aim was to investigate whether the phagocytic activity of peripheral monocytes and neutrophil granulocytes is affected by the removal of tumor in advanced ovarian cancer. METHOD: We investigated peripheral blood samples from 12 patients with advanced stage of serous epithelial ovarian cancer - which were collected before the optimal tumor reduction surgery and on the 7th postoperative day - and from 8 healthy women. After separation of monocytes and neutrophils, the cells were incubated with opsonized fluorescein isothiocyanate-labeled zymosan A particles as the target of phagocytosis. By using fluorescence microscope we counted the number of particles phagocytized by the cells and calculated the phagocytic index. Statistical analysis of the data was performed using analysis of variances method. RESULTS: Preoperative phagocytic indexes of monocytes and neutrophils from patients were significantly lower than phagocytic indexes of the corresponding cells from healthy women. The phagocytic function of monocytes and granulocytes isolated from postoperative samples of patients significantly increased compared to preoperative values and reached the phagocytic indexes of monocytes and neutrophils from healthy controls. CONCLUSION: Based on our results we assume that the tumor and/or its microenvironment in ovarian cancer may produce factors that can depress the phagocytic function of monocytes and granulocytes. Since the phagocytic indexes increased following the cytoreductive surgery, it can be assumed that after the removal of the tumor, the production of these factors is reduced or eliminated. Orv Hetil. 2018; 159(33): 1353-1359.

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.

[Comparison of laparoscopic and open radical hysterectomies in the surgical treatment of cervical cancer]. / A laparoszkópos és nyitott radikális hysterectomia összehasonlítása a méhnyakrák mutéti ellátásában.

INTRODUCTION: Cervical cancer is one of the most common causes of death among women with malignant tumours. The two most common ways of surgical technique of early stage cervical cancer is the laparoscopy and the laparotomy. AIM: Our aim was to compare the intra- and postoperative results of total laparoscopic radical hysterectomy and abdominal radical hysterectomy. METHOD: Ten nerve sparing laparoscopic and 11 abdominal radical hysterectomies were performed from June 2016 until June 2017 because of early stage cervical cancer. Results were analysed retrospectively. RESULTS: There was no significant difference between the two groups in the length of the operation, in blood loss and in intra- and postoperative complications. Significantly more lymph nodes were harvested by abdominal surgery and the length of hospitalisation was significantly shorter in the laparoscopy group. CONCLUSION: Results of total laparoscopic radical hysterectomy are comparable and not worse than abdominal radical hysterectomy. Laparoscopic way may have a priority because of the general advantages of laparoscopic surgery in the surgical treatment of early stage cervical cancer. Orv Hetil. 2017; 158(36): 1403-1409.

[Total laparoscopic hysterectomy with the coagulation of the uterine arteries at their origin]. / Totális laparoszkópos hysterectomia az arteria uterinák eredésüknél történo ellátásával.

INTRODUCTION: Hysterectomy is one of the most frequently performed gynecological operations worldwide. Due to patient perceived advantages of technical development laparoscopic hysterectomy has become a widely used method. The attitude of patients, surgeons and service providers to laparoscopic procedures is not uniform, but total laparoscopic hysterectomy has prevailed due to its advantages from other types of laparoscopic hysterectomies. Coagulation of the uterine arteries at their origin during the standardized method of total laparoscopic hysterectomy provides further benefits for this procedure. AIM: Our aim was the presentation of our experience together with a review of the relevant literature. METHOD: Operations were performed with the coagulation of the uterine arteries at their origin right at the beginning of the procedure. Inclusion criteria were the use of the standardized method, video documentation of the surgery, and pre- and postoperative haemostatus results. RESULTS: Our results confirm that the procedure involves an acceptable operating time that is comparable to that of open abdominal and vaginal hysterectomies, minimal blood loss that is far less than that in open procedures, a much shorter duration of hospitalization and a low complication rate. CONCLUSION: In skilled hands with proper knowledge of the anatomy the standardized method of total laparoscopic hysterectomy with the coagulation of the uterine arteries at their origin is a safe and reproducible technique which suitably utilizes the advantages of minimally invasive surgery. Orv. Hetil., 2017, 158(8), 298-303.

Prognostic Significance of Preoperative NLR, MLR, and PLR Values in Predicting the Outcome of Primary Cytoreductive Surgery in Serous Epithelial Ovarian Cancer.

(1) The degree of cytoreduction achieved during primary debulking surgery (PDS) is an important prognostic factor for the survival of patients with epithelial ovarian cancer (EOC). Our aim was to investigate the prognostic value of preoperative laboratory parameters for the outcome of PDS. (2) We analyzed the preoperative laboratory parameters of 150 serous EOC patients who underwent PDS between 2006 and 2013. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the variables for predicting the PDS outcome. We used binary logistic regression to examine the independent predictive value of the factors for incomplete cytoreduction. (3) Among the parameters, we established optimal cut-off values for cancer antigen (Ca)-125, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) to predict the outcome of PDS. The results of binary logistic regression showed that stage (FIGO III-IV), MLR (>0.305), and Ca-125 (>169.15 kU/L) were independent significant predictors of the degree of tumor reduction achieved during PDS. (4) In the future, MLR, especially in combination with other parameters, may be useful in determining prognosis and selecting the best treatment option (PDS or neoadjuvant chemotherapy + interval debulking surgery) for ovarian cancer patients.

The sexual abuse of female children in Hungary: 20 years' experience.

INTRODUCTION: The purpose of this study is to describe the characteristics of female children who experience sexual abuse and explore common features that may assist in developing prevention strategies. MATERIALS AND METHODS: Between 1990 and 2010, 266 girls under the age of 18 years, suspected of being sexually abused, visited the Department of Adolescent Gynecology. We retrospectively collected data illustrating the features of all cases. Seventy-eight percent of the victims were primary school students, and 45% of them were between 11 and 14 years of age. RESULTS: The perpetrator knew the victim in 67% of the cases and was a stranger in 33%. Seventy-five (28%) perpetrators were members of the victims' families. In 14% of cases, the perpetrator was the victim's father and in 9% her stepfather. The abuse had occurred on multiple occasions in 29% of the cases. The occurrence rate of abuse was highest in the summer season (54%). As much as 63% of children experienced vaginal penetration, while 37% experienced a variety of sexual contact that did not involve penetration. Eighty-five victims were physically injured, and in 40 cases the presence of sperm was confirmed in vulvo-vaginal smears. A high proportion of female child sexual abuse takes place within the family and is revealed only after multiple episodes. The true prevalence of sexual abuse is being appreciated now that Hungarian law and society have recognized this societal problem. CONCLUSION: Prevention requires a systematic and lifelong approach to educating children about personal space and privacy and is the responsibility of parents and professionals.

[Superoxide-anion production by neutrophil granulocytes in healthy and preeclamptic pregnant women]. / A neutrophil granulocyták szuperoxid-anion termelése egészséges és praeeclampsiás terhességben.

Data on respiratory burst activity of granulocytes from healthy and preeclamptic pregnant women are contradictory. To further investigate a possible role of reactive oxygen species in the etiology of preeclampsia, the induced superoxide-anion generation by granulocytes from non-pregnant, healthy pregnant and preeclamptic pregnant women were measured. The reciprocal effects of heat-inactivated and non-inactivated plasma on superoxide production by neutrophils from non-pregnant, healthy pregnant and preeclamptic pregnant subjects were also examined. Superoxide generation was measured by ferricytochrome c reduction. Both phorbol-12.13-dibutirate- and N-formyl-methionyl-leucyl-phenylalanine-induced superoxide production was significantly decreased in normal pregnancy compared to results obtained in non-pregnant and preeclamptic pregnant women. Phorbol-12.13-dibutirate-induced superoxide generation by non-pregnant and preeclamptic neutrophils was significantly inhibited by heat-inactivated and non-inactivated healthy pregnant plasma. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide production by non-pregnant and preeclamptic granulocytes was suppressed only by non-inactivated healthy pregnant plasma. Phorbol-12.13-dibutirate-induced superoxide generation of healthy pregnant neutrophils was significantly increased by inactivated and non-inactivated non-pregnant and preeclamptic plasma. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide production by healthy pregnant granulocytes was significantly enhanced following treatment of the cells with non-inactivated non-pregnant and preeclamptic pregnant plasma. Deficient superoxide generation in normal pregnancy may be caused by maternal immunosuppressive factors. The failure of reduction in superoxide production in preeclampsia may be partly responsible for endothelial dysfunction. Apart from oxidative stress, a possible role of inefficient maternal immunosuppression should also be considered in the pathogenesis of preeclampsia.

A Comprehensive Investigation into the Distribution of Circulating B Cell Subsets in the Third Trimester of Pregnancy.

Maternal B cells play a crucial role in the development and maintenance of pregnancy, due to their humoral activities and regulatory functions. In the study, we investigated the alterations in the distributions of naïve and memory B cell subsets, as well as regulatory B (Breg) cells, in the third trimester of pregnancy. Peripheral blood from 14 healthy pregnant women in the third trimester and 7 healthy non-pregnant women was collected and examined for the frequencies of B cell subsets, including IgD+CD27- naïve, IgD+CD27+ un-switched memory, IgD-CD27+ switched memory, CD38intCD24int mature-naïve, CD38-CD24hi primarily memory and CD38hiCD24hi transitional B cells by flow cytometry. Breg cell subsets were also characterized based on the expression of CD5, CD1d and IL-10. In pregnant women, the proportions of un-switched memory and transitional B cells were significantly decreased. Additionally, the frequencies of both CD5+CD1d+ Breg and IL-10-producing B10 cells were decreased in pregnancy. Changes in the distribution of transitional B cells as well as Breg cells may be crucial contributors for the development of altered maternal immune responses and tolerance needed for the maintenance of normal pregnancy in the third trimester.

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.

Application of ultrasound elastography in obstetrics and gynecology / Ultrahang-elasztográfia alkalmazásának lehetoségei a szülészet-nogyógyászatban.

Összefoglaló. Az ultrahang-elasztográfia az elmúlt évek során egyre növekvo figyelmet kapott a lágyszövetek elaszticitásának vizsgálatában. A módszer használatát az teszi szükségessé, hogy egyes, a mechanikai tulajdonságaikban különbözo szövetek hasonló echogenitásúak lehetnek, valamint hogy egy adott szövet megváltozott struktúrája vagy mechanikai tulajdonsága nem minden esetben jár együtt a szövet hagyományos ultrahangképének megváltozásával. Az elmúlt évtizedben a deformációs és a nyírási ultrahang-elasztográfia vált széles körben elérhetové. Ezen új képalkotási technika egyre nagyobb szerepet tölt be a szülészeti-nogyógyászati ultrahang-diagnosztikában is. A nogyógyászatban szerephez juthat az endometriosis és az adenomyosis kimutatásában, valamint a benignus és a malignus cervicalis és ovarialis képletek elkülönítésében. A nogyógyászathoz hasonlóan a szülészetben is jelentos változást hozhat az ultrahang-elasztográfia: alkalmas lehet a szülésindukció sikerességének, a koraszülés bekövetkezésének és a praeeclampsia kialakulásának elorejelzésére. Orv Hetil. 2021; 162(18): 690-695. Summary. Ultrasound elastography has received significant attention for the assessment and measurement of soft tissue elastic properties in recent years. The advantage of ultrasound elastography lies in the fact that two different tissues can share similar echogenicities but may have other mechanical properties or, on the contrary, mechanical abnormalities of a designated tissue do not necessarily go hand in hand with an altered appearance on a conventional ultrasound image. In the last decade, strain and shear-wave elasticity imaging methods have become the most widely available among commercial ultrasound equipments. The importance of this new method expands rapidly also in the field of obstetrics and gynecology. Ultrasound elastography has a promising role in the diagnosis of endometriosis and adenomyosis and helps to differentiate benign and malignant cervical and ovarian lesions. The use in the prediction of the outcome of labor induction and preterm birth, and in the evaluation of preeclampsia are emerging. Orv Hetil. 2021; 162(18): 690-695.

Zinc Transporter 9 (SLC30A9) Expression Is Decreased in the Vaginal Tissues of Menopausal Women.

Our aim was to compare zinc transporter (ZnT/SLC30A, and ZIP/SLC39A) expression between pre- and postmenopausal women in human vaginal tissues. Zinc transporter families are responsible for the maintenance of intracellular zinc concentrations. Zinc has significant effects on the extracellular matrix composition. Vaginal wall biopsies were obtained from seven premenopausal and seven postmenopausal women. mRNA expression of twenty-four zinc transporters was determined by quantitative real-time PCR. Zinc transporter expression at the protein level was assessed by immunohistochemistry. Student's t test and Mann-Whitney U test were used to compare data. ZnT4 and ZnT9 mRNA expression were significantly lower in postmenopausal women compared with premenopausal women (mean ± SD mRNA expression in relative units, 96.43 ± 140.61 vs. 410.59 ± 304.34, p = 0.03 and 0.62 ± 0.39 vs. 1.13 ± 0.31, p = 0.02). In addition, ZIP2, ZIP3, and ZIP6 mRNA expressions were significantly lower in postmenopausal women compared with premenopausal women (mean ± SD mRNA expression in relative units, 1.11 ± 0.61 vs. 2.29 ± 1.20, p = 0.04; 2.32 ± 1.90 vs. 15.82 ± 12.97, p = 0.02 and 1.10 ± 0.80 vs. 5.73 ± 4.72, p = 0.03). ZnT9 protein expression in the stratum spinosum was significantly lower in postmenopausal women (p = 0.012). Zinc transporters were expressed differentially in the vaginal tissues. ZnT9 expression was significantly lower in postmenopausal women compared with premenopausal women.

Phagocyte function of peripheral neutrophil granulocytes and monocytes in endometriosis before and after surgery.

INTRODUCTION: Endometriosis is a chronic systemic disease, which influence negatively the quality of life of affected women and responsible for infertility and chronic pelvic pain. Pathophysiology of the disease is still enigmatic, but insufficient immune surveillance may play a role in it. Peripheral natural immune cell function is rarely examined. The aim of the study was to examine phagocyte function of peripheral neutrophil granulocytes and monocytes, whether this phagocytic activity is affected by the presence or removal of endometriotic lesions in women with endometriosis. MATERIAL AND METHODS: Twenty-six preoperative, 13 postoperative samples from women with endometriosis, 23 samples from healthy women, 14 pre- and postoperative samples from the surgical control group were enrolled. Cells were isolated from peripheral blood samples, marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosane molecules. RESULTS: Phagocyte function of monocytes and neutrophil granulocytes decreased significantly women with endometriosis before surgery compared to healthy controls. However, 7 days after surgery the postoperative values showed significant improvement compared to the preoperative results of women with endometriosis. This increment reached the values of the healthy women. In the surgical control group no difference was detected between the pre- and postoperative outcomes. DISCUSSION: Decreased phagocyte function of the examined cells, which can be the result of the circulating immunosuppressive factors, may play a role in the deficient clearance of ectopic endometrial tissue. Based on the postoperative results, these immunosuppressive factors may be reduced or eliminated 7 days after surgery in women with endometriosis.