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.

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.

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.

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.

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.

How the cesarean delivery rate decreased at the Department of Obstetrics and Gynecology, University of Debrecen during the COVID-19 pandemic / Hogyan csökkent a császármetszések aránya a debreceni Szülészeti Klinikán a koronavírus-pandémia alatt?

Összefoglaló. Bevezetés: Az új koronavírus (SARS-CoV-2) okozta pandémia számos változást eredményezett életünk minden területén, így a debreceni Szülészeti és Nogyógyászati Klinikán is. Célkituzések: A koronavírus-járvány többek között a terminus körüli elektív szülésindukciók gyakorlatának megváltoztatását igényelte. A bevezetett új szakmai eljárásrendeknek, járványügyi intézkedéseknek, a megyei kórházi funkciót ellátó debreceni Kenézy Kórház Szülészeti Osztálya és a Szülészeti Klinika összevonásának, illetve a megváltozott jogi környezetnek a szülészeti ellátásra kifejtett együttes hatásait elemezzük. Módszerek: Helyi protokollokat és részletes eljárásrendeket készítettünk és vezettünk be. 1. Szülésindukció. 2. Szülésindukció cervixérlelést igénylo esetekben. 3. A szülés módjának megválasztása elozményi császármetszés után. 4. A császármetszés utáni hüvelyi szülést támogató, terminus körüli gondozási protokoll. A protokollok bevezetését követo elso 9 hónap szülészeti mutatóit (szülésszám, császármetszések aránya, perinatalis kimenetel, szülésindukciók aránya és sikeressége) vizsgáltuk és hasonlítottuk össze a megelozo idoszak debreceni adataival, illetve az országos szülészeti mutatókkal. Eredmények: Klinikánkon a császármetszés aránya 2020-ban 33,5%-ra csökkent, a protokollok bevezetése óta pedig 30,7%, miközben a 2020. évi magyarországi arány 40,3%. Az összes szülés 20%-a volt 2020-ban szülésindukció, melyek közül 74% végzodött hüvelyi szüléssel, míg ugyanez 2019-ben 11% indukcióból 47%-nak adódott. A havi szülésszám 2020. január és 2021. január között folyamatosan emelkedett (250-rol 450-re), a havi császármetszési arány pedig 41%-ról 25%-ra csökkent. Mindezen változások mellett 2019-rol 2020-ra csökkent mind a perinatalis mortalitás (6,3‰-rol 4,2‰-re), mind a szülés után a Neonatalis Intenzív Centrumba történo felvételek aránya (14,8%-ról 13,5%-ra). Következtetések: A bemutatott tényezok együttes hatásaként - elsodlegesen a megfelelo és következetesen betartott protokolloknak köszönhetoen - a szülésindukciók aránya és sikeressége jelentosen növekedett, a császármetszések aránya szignifikánsan csökkent, javuló perinatalis morbiditási és mortalitási mutatók mellett. Orv Hetil. 2021; 162(21): 811-823. INTRODUCTION: The pandemic caused by the new coronavirus (SARS-CoV-2) has catalized several changes in many fields of our lives, and also at the Department of Obstetrics and Gynecology of the University of Debrecen, Hungary. OBJECTIVES: We wanted to analyse the compound effect of our new local protocols regarding elective labour inductions at term, the coronavirus pandemic and the resulting infection control measures, the merging of the Obstetrics and Gynecology Ward of the Kenézy County Hospital of Debrecen and the University Department of Obstetrics and Gynecology, and also the change of the legal environment. METHODS: Local protocols were introduced: 1. Labour induction. 2. Cervical ripening in labour induction. 3. Choosing the route of delivery after cesarean. 4. Management of pregnancy around term in the case of planned trial of labour after cesarean. We compared the obstetrical data (number of deliveries, cesarean section rate, perinatal outcome and the rate and success rate of labour inductions) before and after the implementation of the protocols. The results were also compared to the Hungarian national database. RESULTS: The annual cesarean rate at our department dropped to 33.5% in 2020. In the first 9-month period, after the introduction of the new reforms, the cesarean rate decreased to 30.7%, whereas the Hungarian national rate was 40.3% in 2020. At our department, 20% of all the deliveries were induced and 74% of them led to vaginal deliveries in 2020, while in 2019 only 11% of deliveries were labour inductions, and 47% of these cases were vaginal deliveries. The monthly number of deliveries was rising constantly between January 2020 (250 deliveries) and January 2021 (450 deliveries), and the monthly cesarean rate decreased from 41% to 25%. Comparing the data of 2019 and 2020, the annual perinatal mortality rate dropped from 6.3‰ in 2019 to 4.2‰ in 2020. Neonatal morbidity, as measured by admissions to the neonatal intensive care unit, also decreased (14.8% in 2019 and 13.5% in 2020). CONCLUSIONS: As a compound result of the described factors, but mainly due to the new protocols, both the rate and the success rate of labour inductions increased significantly, while the cesarean rate decreased with improving perinatal mortality and morbidity. Orv Hetil. 2021; 162(21): 811-823.

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.

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.

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.

Standardized measurement in uterine ultrasonography / Standardizált mérési technika a méh ultrahang-diagnosztikájában.

Összefoglaló. Bevezetés: Jelenleg a méh méretének pontos megítélése meglehetosen szubjektív, az azt leíró ultrahangleletek igen nagy eltérést mutatnak. Számos klinikai szituációban azonban nagyon fontos az eltérések méretének, elhelyezkedésének, meghatározott anatómiai pontokhoz való viszonyának pontos leírása. Célkituzés: Célunk egy egységes mérési módszer kifejlesztése, mellyel sorvezetot adunk a vizsgálók kezébe, így csökkentve az egyéni variabilitásból adódó eltéréseket. A standardizált adatok lehetoséget adnak a szisztematikus gyujtésre, azok egységes feldolgozására, rendszerbe foglalására, tudományos értékelésére, segítséget nyújtva a mindennapi klinikai gyakorlatban és kutatásokban. Módszer: A méh általunk végzett ultrahangvizsgálatait, valamint a nemzetközi tanulmányokat alapul véve kívánunk javaslatot tenni egy egységes mérési módszer kialakítására, mellyel egyértelmu, pontos, reprodukálható adatokat kaphatunk a méhrol. Eredmények: Létrehoztunk egy standardizált paraméterekkel rendelkezo mérési eljárást Uteromap néven, melyet alkalmazva objektív méretadatokat kaphatunk a méh ultrahangvizsgálata során. Külön figyelmet fordítottunk arra, hogy az általunk létrehozni kívánt standardizált mérési eljárás alkalmas legyen minden általános, valamint speciális esetben is. A kipróbálás során a legelso 253 páciens adatait elemeztük retrospektív módon. Eredményeink szerint az idosebb életkor megnövekedett méhmagassággal és nagyobb hátsó falvastagsággal korrelált. Következtetés: Arra a következtetésre jutottunk, hogy standardizált mérési módszerünk alkalmazásával a méhrol és elváltozásairól sokkal pontosabb, objektívebb és egységesebb adatokat nyerhetünk anélkül, hogy a vizsgálathoz szükséges ido szignifikánsan hosszabb lenne. Munkánk folytatásaként minél több vizsgáló bevonásával szeretnénk a standardizált módszert a mindennapi gyakorlatra kiterjeszteni, a felmerülo igények, javaslatok alapján fejleszteni és létrehozni egy nemzetközileg elfogadott, standardizált mérési eljárást, mellyel az ultrahangvizsgálatok minoségét növelhetnénk, azzal a végso céllal, hogy javítsuk a betegek biztonságát és az ellátás eredményességét. Orv Hetil. 2020; 161(48): 2029-2036. INTRODUCTION: Currently, the accurate assessment of the size of the uterus is rather subjective as the related ultrasound findings show an immense difference. However, in several clinical situations it is crucial to accurately describe the size and location of abnormalities and their relationship to specific anatomical positions. OBJECTIVE: We aim to develop a unified measurement method that can serve as a guide for the examiners, thus reducing variances due to individual variability. Standardized data provide an opportunity for systematic collection, unified processing, systematization, and scientific evaluation, assisting in everyday clinical practice and research. METHOD: Based on our ultrasound examinations and the international studies, we propose a unified measurement method that can provide precise, accurate and reproducible data on the uterus. RESULTS: We have established a measurement procedure with standardized parameters called Uteromap, which obtained objective size data during the ultrasound examination of the uterus. Special attention was given to creating a standardized measurement procedure suitable for general and special cases, too. According to our results, older age was correlated with increased uterine height and greater posterior wall thickness. During the trial, the data of the first 253 patients were analyzed retrospectively. CONCLUSION: We concluded that our standardized measurement method could obtain more accurate, objective, and consistent data about the uterus and its lesions without significantly increasing the time of the examination. Continuing our work, we would like to extend the standardized method to everyday practice, develop and create an internationally accepted standardized measurement procedure based on the emerging needs and recommendations, with the ultimate aim of improving patient safety and effectiveness of care. Orv Hetil. 2020; 161(48): 2029-2036.

Vaginal elasticity is significantly decreased in vaginal atrophy: a strain elastography study.

OBJECTIVES: Strain elastography is a novel method to assess the elasticity of tissues. We aimed to evaluate the value of vaginal strain elastography in women with vulvovaginal atrophy (VVA). METHODS: Women with or without VVA were enrolled in this prospective study. Participants underwent vaginal cytology and vaginal wall elastography. Vaginal Health Index (VHI) was calculated. Based on Vaginal Maturation Value (VMV), participants were divided into atrophic and nonatrophic groups. Elastography parameters of the vaginal walls were measured in nine regions of interest (ROI). Elastography Index (EI) was defined by the average color score of nine ROIs. Groups were compared with unpaired t test or Mann-Whitney U test. Pearson correlation was used to determine the strength of association between EI and selected parameters. Multiple regression was used to evaluate the association between EI and age, VMV, and vaginal atrophy. RESULTS: Ten women were diagnosed with VVA, and twenty had no cytological signs of vaginal atrophy (age-range 38-79 y). VHI score was significantly lower in the atrophic group (mean ±â€ŠSD, 9.4 ±â€Š2.011 vs 16.6 ±â€Š4.22, P < 0.0001). In the atrophic group, EI was significantly lower than in nonatrophic group (mean ±â€ŠSD, 20 ±â€Š21 vs 47 ±â€Š4, P < 0.01). We found a strong negative correlation between EI and vaginal atrophy (r =  -0.706, P < 0.0001; 95% CI: 0.8501 to -0.4639). In the multiple regression model, only atrophy remained statistically significant for the prediction of EI (P = 0.004). CONCLUSIONS: Vaginal elasticity is significantly decreased in women with vaginal atrophy, measured by EI. Our results suggest that strain elastography might be useful in the diagnosis of vaginal atrophy.

Predictive value of bubble sign for tubal patency during office hysteroscopy.

OBJECTIVE: Our purpose was to investigate the predictive value of visible air bubble sign for real tubal patency during hysteroscopic procedures. METHODS: In this cross-sectional study, clinical data of 61 infertile women who underwent diagnostic hysteroscopy and laparoscopy have been analysed. RESULTS: Mean age of patients was 33.45 ± 3.25 years. Bubble sign for the detection of patency demonstrated 73 % (95 % CI: 57-86 %) sensitivity, 70 % (95 % CI: 46-88 %) specificity, a positive predictive value of 83 % (95 % CI: 67-94 %), and a negative predictive value of 56 % (95 % CI: 35-76 %). CONCLUSIONS: A visible tubal "flow" of air bubbles during hysteroscopy was not accurate in the prediction of tubal patency.

Randomized controlled trial for improved recovery of the pelvic floor after vaginal delivery with a specially formulated postpartum supplement.

OBJECTIVE: To improve pelvic floor recovery after vaginal delivery with daily supplementation of a specially formulated postpartum recovery supplement. METHODS: Within 48 hours of vaginal delivery, primipara women were randomized in a 1:1 ratio to receive daily oral supplementation for 6 weeks with either a combination of regular prenatal vitamin (PNV), leucine (4 g/day), zinc (30 mg/day) and omega-3 fatty acid (900 mg/day) (treatment group), or only a PNV daily (control group). Co-primary outcomes were vaginal squeeze pressure as measured by perineometer and levator muscle injury as measured by transperineal 3-dimensional tomographic ultrasound at 6 weeks postpartum. RESULTS: Twenty-six women in the control group and 27 in the treatment group completed the trial. Weak pelvic floor muscle strength was significantly less frequent in the treatment group compared to the control group at 6 weeks after delivery (28% vs. 58%, P=0.03). Both right and left-sided levator-urethra gap was significantly larger in the control group compared to the treatment group indicating more levator injury being present in the control group at 6 weeks after delivery. Anterior vaginal wall prolapse at or beyond the hymenal ring was significantly more common in the control group compared to the treatment group (19% vs. 0%, P=0.02). Significantly more women reported bothersome bulge symptoms in the control group compared to the treatment group at 6 weeks postpartum (19% vs. 0%, P=0.02). CONCLUSION: Postpartum women who received a specially formulated postpartum recovery supplement had improved recovery of the pelvic floor after vaginal delivery.

Fallopian tubal obstruction is associated with increased pain experienced during office hysteroscopy: a retrospective study.

This study aimed at evaluating the pain experienced during office hysteroscopy, with selective tubal cannulation and chromopertubation, by women with and without tubal obstruction in order to determine if such condition would be associated with increased pain during the examination. Women with a history of infertility underwent in-office hysteroscopy with selective chromopertubation using a continuous flow office hysteroscope with a 5 Fr operating channel fitted with a 4 Fr catheter for the injection of methylene blue dye. Experienced pain was recorded on a Visual Analog Scale (VAS) during diagnostic hysteroscopy after access to the uterine cavity. Of 90 women, 58 (66.4%) were found with at least one patent fallopian tube and inserted in the group "any", meanwhile 32 (33.6%) were categorized into group "none" as both tubes were judged obstructed. There was no significant difference between groups in BMI and primary infertility rate, but the difference was significant concerning mean age (32.6 vs. 35.8; p < 0.001). The mean VAS score was 3.34 (± 1.07) in the group "any" and 4.25 (± 1.11) in "none". Comparing the VAS score of the two groups, the difference was significant (p < 0.001). Tubal occlusion may have a potential role in the pain experienced by women undergoing in-office hysteroscopy. Women with bilateral tubal occlusion experienced a higher level of pain compared with patients with at least one patent fallopian tube. Operators may use milder intrauterine pressure of fluid distension medium when these patients are undergoing in-office hysteroscopy to reduce discomfort.