Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement.

Female genital tract (FGT) microbiota has been associated with the development of gynaecological cancers. Thus, the possibility of whether manipulation of the FGT microbiota can help in the prevention of disease should be investigated. Various prebiotics, probiotics, and other non-clinician prescribed agents have been reported to have therapeutic effects in cervical disease. Numerous studies have reported an association between human papillomavirus infection and subsequent cervical dysplasia and a decrease in the abundance of Lactobacillus species. A continuum of microbiota composition is observed from the vagina to the upper parts of the FGT, but no evidence suggests that manipulation of the vaginal microbiota can help to modify the composition of other FGT compartments. Although prebiotics and probiotics have been reported to be beneficial, the studies are small and of varying design, and high-quality evidence to support their use is lacking. Currently, no studies have examined these therapeutics in other gynaecological malignancies. Thus, recommendation of probiotics, prebiotics, or other over-the-counter supplements for the prevention of gynaecological cancers warrants larger, well designed studies.

Operating during pregnancy: A needs assessment among surgical residents in Austria.

In Austria, female physicians must immediately disrupt their surgical training as soon as their pregnancy is announced. In Germany, surveys on the topic of "female surgeons performing surgery during pregnancy" led to a reform of the German Maternity Protection Act, which came into force on January 1, 2018, and allows female physicians to perform risk-adapted surgery during pregnancy at their own request. However, in Austria, such reform is still pending. The study aimed i) to assess the current situation of how pregnant female surgeons handle their training under the actual restrictive legislature in Austria, especially in context of operative activity, and ii) to identify needs for improvements. Therefore, a nation-wide online survey, initiated by the Austrian Society for Gynecology and Obstetrics and the Young Forum of the Austrian Society of Gynecology and Obstetrics, was performed from June 1 to December 24, 2021, among employed physicians working in surgical specialties. To conduct a general needs assessment, the questionnaire was made available to both female and male physicians in all positions. In total, 503 physicians participated in the survey, of which 70.4% (n = 354) were women and 29.6% (n = 149) were men. The majority of the women (61.3%) were undergoing residency training at the time of their pregnancy. The announcement of the pregnancy to the supervisor(s) occurred on average in the 13th week of gestation (week 2-40). Before that, pregnant female physicians spent an average of 10 h per trimester (first trimester: 0-120 h; second trimester: 0-100 h) in the operating room. The main reason for women to continue surgical activity despite their (yet unreported) pregnancy was "own request". 93% (n = 469) of the participants explicitly wished to be able to perform surgical activities in a safe setting during pregnancy. This response was independent of gender (p = 0.217), age (p = 0.083), specialty (p = 0.351), professional position (p = 0.619), and previous pregnancy (p = 0.142). In conclusion, there is an urgent need to offer female surgeons the possibility of continuing surgical activities during pregnancy. This handling would significantly increase the career opportunities for women who want to build up both a successful career and a family life.

Does mode of delivery impact the course of cervical dysplasia in pregnancy? A review of 219 cases.

OBJECTIVE: The prevalence of cervical intraepithelial neoplasia (CIN) in pregnancy is about 1%. The aim of this study was to analyze the regression, persistence and progression rates of cervical dysplasia in pregnancy and the impact of delivery mode. STUDY DESIGN: In this retrospective study, data from pregnant patients with abnormal cytology findings, who presented to a colposcopic outpatient clinic of a university hospital within the last 10 years, were analyzed. Information on cytology, histology and Human Papillomavirus (HPV) status during pregnancy and postpartum and mode of delivery was collected. RESULTS: 219 women, who were assessed with cytology and /or biopsy antepartum and postpartum between January 2010 and July 2020, were included in the study. Antepartum patients presented with low grade squamous intraepithelial lesions (LSIL) in 37% and high grade squamous intraepithelial lesions (HSIL) in 53%. During pregnancy biopsy was performed in 78 patients (36%). Postpartum evaluation revealed an overall regression rate of 39%. Persistence rates were especially high in the HSIL group with 70 %. HSIL regressed in 28 %. Progression to invasive disease was rare and seen in two patients postpartum only. 141 women delivered vaginally (VD) and 51 received a cesarean section (CS). Regression rates were similar: 36 % and 47 %. There was no significant difference in progression or persistence rates. CONCLUSION: Our study demonstrates that mode of delivery does not influence the course of SIL. SIL show high rates of regression and persistence, progression to invasive disease is rare.

A 10 year comparative study of caesarean deliveries using the Robson 10 group classification system in a university hospital in Austria.

OBJECTIVE: The Robson ten group classification system is used as a global standard for assessing, monitoring and comparing caesarean delivery (CD) rates within and between maternity services. Our objective was to compare the changes of CD rates at our institution between the years 2008-2010 and 2017-2019 using the Robson ten group classification system. STUDY DESIGN: Data was collected retrospectively and all women were classified using the obstetric concepts and parameters described in the Robson ten group classification system. RESULTS: During 2008-2010 7,832 deliveries were performed, increasing to 9,490 in 2017-2019. The CD rate also increased from 29.1% to 32.2% (p<.05) during this 10 year period. In both observed periods group 5 (single cephalic multiparous women at term with a previous CD) was the largest contributor to the overall CD rate accounting for 20.2% of all CD during 2008-2010 and increasing to 26.9% in 2017-2019 (p<.001). The overall size of group 5 also increased from 8.3% to 11.6% (p<.001). Furthermore, an increase in CD rate in group 7 (multiparous women with a single breech pregnancy, including women with a uterine scar) from 92.9% to 98.2% (p = .752) could be observed. In group 8 (women with multiple pregnancies, including women with a uterine scar) a slight shift towards vaginal delivery (VD) can be reported with CD rates decreasing from 82% to 79.2% (p = .784). There was no observed difference with CD rates in group 1 although the group size decreased from 29.4% in 2008-2010 to 24.2% in 2017-2019 (p<.001). The CD rate in group 10 experienced a slight elevation, in 2008-2010 46.2% were delivered per CD and in 2017-2019 48.8% (p = .553). The overall size of group 10 decreased, contributing 8.9% in 2008-2010 and 8% in 2017-2019 (p<.05) to the overall birthrate. CONCLUSION: The biggest contributors to the CD rate in our hospital remain multiparous women at term with a previous CD. The CD rates, as well as the overall size of this group, keep rising, resulting in a need to establish more effective ways to motivate women with one previous CD towards vaginal birth after caesarean delivery (VBAC). Furthermore, the CD rate in preterm deliveries is increasing and approaching 50%. This illustrates the need to discuss whether CD is the appropriate mode of delivery in half of the preterm infants.

Long-term effects of Na+ /Ca2+ exchanger inhibition with ORM-11035 improves cardiac function and remodelling without lowering blood pressure in a model of heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is increasingly common but there is currently no established pharmacological therapy. We hypothesized that ORM-11035, a novel specific Na+ /Ca2+ exchanger (NCX) inhibitor, improves cardiac function and remodelling independent of effects on arterial blood pressure in a model of cardiorenal HFpEF. METHODS AND RESULTS: Rats were subjected to subtotal nephrectomy (NXT) or sham operation. Eight weeks after intervention, treatment for 16 weeks with ORM-11035 (1 mg/kg body weight) or vehicle was initiated. At 24 weeks, blood pressure measurements, echocardiography and pressure-volume loops were performed. Contractile function, Ca2+ transients and NCX-mediated Ca2+ extrusion were measured in isolated ventricular cardiomyocytes. NXT rats (untreated) showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV end-diastolic pressure (LVEDP) elevation, increased brain natriuretic peptide (BNP) levels, preserved ejection fraction and pulmonary congestion. In cardiomyocytes from untreated NXT rats, early relaxation was prolonged and NCX-mediated Ca2+ extrusion was decreased. Chronic treatment with ORM-11035 significantly reduced LV hypertrophy and cardiac remodelling without lowering systolic blood pressure. LVEDP [14 ± 3 vs. 9 ± 2 mmHg; NXT (n = 12) vs. NXT + ORM (n = 12); P = 0.0002] and BNP levels [71 ± 12 vs. 49 ± 11 pg/mL; NXT (n = 12) vs. NXT + ORM (n = 12); P < 0.0001] were reduced after ORM treatment. LV cardiomyocytes from ORM-treated rats showed improved active relaxation and diastolic cytosolic Ca2+ decay as well as restored NCX-mediated Ca2+ removal, indicating NCX modulation with ORM-11035 as a promising target in the treatment of HFpEF. CONCLUSION: Chronic inhibition of NCX with ORM-11035 significantly attenuated cardiac remodelling and diastolic dysfunction without lowering systemic blood pressure in this model of HFpEF. Therefore, long-term treatment with selective NCX inhibitors such as ORM-11035 should be evaluated further in the treatment of heart failure.

Novel pathomechanisms of cardiomyocyte dysfunction in a model of heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is increasingly common, but the underlying cellular mechanisms are not well understood. We investigated cardiomyocyte function and the role of SEA0400, an Na(+) /Ca(2+) exchanger (NCX) inhibitor in a rat model of chronic kidney disease (CKD) with HFpEF. METHODS AND RESULTS: Male Wistar rats were subjected to subtotal nephrectomy (NXT) or sham operation (Sham). After 8 and 24 weeks, in vivo (haemodynamics, echocardiography) and in vitro function (LV cardiomyocyte cell shortening (CS), and Ca(2+) transients (CaT)) were determined without and with SEA0400. In a subgroup of rats, SEA0400 or vehicle was given p.o. (1 mg/kg b.w.) between week 8 and 24. NXT resulted in stable compensated CKD and HFpEF [hypertrophied left ventricle, prolonged LV isovolumetric relaxation constant TAU (IVRc TAU), elevated end diastolic pressure (EDP), increased lung weight (pulmonary congestion), and preserved LV systolic function (EF, dP/dt)]. In NXT cardiomyocytes, the amplitude of CS and CaT were unchanged but relaxation and CaT decay were progressively prolonged at 8 and 24 weeks vs. Sham, individually correlating with diastolic dysfunction in vivo. NCX forward mode activity (caffeine response) was progressively reduced, while NCX protein expression was up-regulated, suggesting increased NCX reverse mode activity in NXT. SEA0400 acutely improved relaxation in NXT in vivo and in cardiomyocytes and improved cardiac remodelling and diastolic function when given chronically. CONCLUSIONS: This model of renal HFpEF is associated with slowed relaxation of LV cardiomyocytes. Treatment with SEA0400 improved cardiomyocyte function, remodelling, and HFpEF.