Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. Although studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in PE remains controversial. LMWH may convey beneficial effects in PE independent of their anticoagulant activity, possibly by inhibiting inflammation. Here, we evaluated whether LMWH inhibit placental thromboinflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle–induced and platelet-dependent PE-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation, and improves trophoblast proliferation in vivo and in vitro. Moreover, LMWH inhibits platelet-independent trophoblast NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. Mechanistically, LMWH activates via heparin-binding epidermal growth factor (HBEGF) signaling the PI3-kinase-AKT pathway in trophoblasts, thus preventing inflammasome activation. In human PE placental explants, inflammasome activation and PI3-kinase-AKT signaling events were reduced with LMWH treatment compared with those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates PE-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in PE and identify a signaling mechanism through which LMWH ameliorates PE, thus providing a rationale for the use of LMWH in PE.
Background: Parametrial tumor involvement is an important prognostic factor in cervical cancer and is used to guide management. Here, we investigate the diagnostic value of clinical examination under general anesthesia (EUA) and magnetic resonance imaging (MRI) in determining parametrial tumor spread. Methods: Post-operative pathological findings of 400 patients with primary cervical cancer were compared to the respective MRI data and the results from EUA. The gynecological oncologist had access to the MR images during clinical assessment (augmented EUA, aEUA). Results: Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. aEUA exhibited a higher accuracy than MRI alone (83% vs. 76%; McNemar’s odds ratio [OR] = 2.0, 95%CI 1.25–3.27, p = 0.003). Although accuracy was not affected by tumor size in aEUA, MRI was associated with a lower accuracy in tumors ≥2.5 cm (OR for a correct diagnosis compared to smaller tumors 0.22, p < 0.001). There was also a decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥2.5 cm in diameter (p < 0.0001) compared to smaller tumors (< 2.5 cm). Body mass index had no influence on performance of either method. Conclusions: aEUA has the potential to increase the diagnostic accuracy of MRI in determining parametrial tumor involvement in cervical cancer patients.
In this prospective, monocentric study, we investigated the potency of a novel three-dimensional (3D) body scanner for external pelvic assessment in birth planning for intended vaginal breech delivery. Between April 2021 and June 2022, 73 singleton pregnancies with intended vaginal birth from breech presentation (>36.0 weeks of gestation) were measured using a pelvimeter by Martin, a three-dimensional body scanner, and MR-pelvimetry. Measures were related to vaginal birth and intrapartum cesarean section. A total of 26 outer pelvic dimensions and 7 inner pelvic measurements were determined. The rate of successful vaginal breech delivery was 56.9%. The AUC (area under the curve) of the obstetric conjugate (OC) measured by MRI for predicting the primary outcome was 0.62 (OR 0.63; p = 0.22), adjusted for neonatal birth weight 0.66 (OR 0.60; p = 0.19). Of the 22 measured 3D body scanner values, the ratio of waist girth to maternal height showed the best prediction (AUC = 0.71; OR 1.27; p = 0.015). The best predictive pelvimeter value was the distantia spinarum with an AUC of 0.65 (OR = 0.80). The 3D body scanner technique is at least equal to predict successful vaginal breech delivery compared to MRI diagnostics. Further large-scale, prospective studies are needed to verify these results.
Cervical carcinoma is a major cause of morbidity and mortality among women worldwide. Histological subtype, lymphovascular space invasion and tumor grade could have a prognostic and predictive value for patients’ outcome and the knowledge of these histologic characteristics may influence clinical decision making. However, studies evaluating the diagnostic value of various biopsy techniques regarding these parameters of cervical cancer are scarce. We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative core needle biopsy (CNB) assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying LVSI and tumor grade. CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma, 92.9% and 96.6% for adenocarcinoma, 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of LVSI was 61.9% and was positively influenced by tumor size in preoperative magnetic resonance imaging and negatively influenced by strong peritumoral inflammation. High tumor grade (G3) was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. In conclusion, CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques.
Background: We investigated possible parameters that could predict the need for obstetric maneuvers, the duration of the active second stage of labor (i.e., the duration of active pushing), and short‐term neonatal outcome in vaginal breech births.Materials and Methods: We performed a retrospective analysis of 268 successful singleton vaginal breech births in women without previous vaginal births from January 2015 to August 2022. Multivariable regression was used to investigate associations between maternal and fetal characteristics (including antepartum magnetic resonance (MR) pelvimetry) with obstetric maneuvers, the duration of active second stage of labor, pH values, and admission to the neonatal unit. Models for the prediction of obstetric maneuvers were built and internally validated.Results: Obstetric maneuvers were performed in a total of 130 women (48.5%). A total of 32 neonates (11.9%) had to be admitted to the neonatal unit. The intertuberous distance (ITD) (p < 0.001), epidural analgesia (p < 0.001), and birthweight (p = 0.026) were associated with the duration of active second stage of labor. ITD (p = 0.028) and birthweight (p = 0.011) were also independently associated with admission to the neonatal unit, while pH values below 7.10 dropped significantly (p = 0.0034) if ITD was ≥13 cm. Furthermore, ITD (p < 0.001) and biparietal diameter (p = 0.002) were independent predictors for obstetric maneuvers.Conclusions: ITD is independently associated with the duration of active second stage of labor. Thus, it can predict suboptimal birth mechanics in the last stage of birth, which may lead to the need for obstetric maneuvers, lower arterial pH values, and admission to the neonatal unit. Consequently, MR pelvimetry gives additional information for practitioners and birthing people preferring a vaginal breech birth.