Perinatal outcomes comparison between neuraxial and general anesthesia in pregnant women with placenta accreta spectrum: a multicenter retrospective study.

PURPOSE: We investigated the impact of anesthesia mode on perinatal outcomes in patients with placenta accreta spectrum (PAS) undergoing cesarean delivery and identified factors associated with adverse perinatal events. METHODS: The multicenter retrospective analysis was conducted in patients with PAS who delivered at three medical centers. Patients were classified according to whether they received general anesthesia (GA) or neuraxial anesthesia (NA). We compared the basic clinical characteristics of patients in the pre-propensity score matching (PSM) and post-PSM cohorts and identified factors associated with a high risk of adverse maternal outcomes. RESULTS: This study included a total of 425 patients, with 307 (72.2%) in the GA group and 118 (27.8%) in the NA group. After PSM, 162 patients were identified for analysis. In the post-matched cohort, the NA group exhibited shorter total operation time (P = 0.030) and postoperative length of hospital stay (P = 0.037). Additionally, the NA group experienced lower intraoperative blood loss (P < 0.001) and received fewer units of transfused packed red blood cells (PRBC) (P < 0.001). Multivariate logistic regression analysis indicated that GA (P < 0.001), emergency cesarean delivery (P = 0.010), vascular lacunae within the placenta (P < 0.001), hypervascularity of uterine-placental margin (P = 0.002), hypervascularity of the cervix (P = 0.014), and balloon placement in the abdominal aorta (P < 0.001) were associated with a high risk of adverse maternal events. CONCLUSION: In comparison to GA, cesarean delivery with NA in PAS patients appears to be associated with reduced intraoperative blood loss, PRBC transfusion, operating duration, and postoperative hospital stay.

Progress in the Management of Pregnancy with Paroxysmal Nocturnal Hemoglobinuria: A Review.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired complement-mediated hemolytic disease characterized by intravascular hemolysis, thrombosis, smooth muscle dystonia, and so on. Thrombosis is the principal cause of death in PNH patients. During the perinatal period, pregnant PNH patients have increased morbidity and mortality with a heightened risk of complications, including significant preterm birth. The management of pregnancy complicated by PNH is difficult. Therefore, early diagnosis, standardized treatment protocols, and improving perinatal outcomes are crucial. However, there is a lack of consensus on treating patients with PNH during pregnancy. This article reviews 32 studies of pregnancy affected by PNH, focusing on the clinical presentation, diagnosis, and treatment strategies of PNH, to provide guidance for obstetricians on how to handle pregnant patients with PNH, and to offer academic support for the management of PNH patients. We found that Eculizumab has become the primary choice for treating PNH, effectively controlling intravascular hemolysis and reducing the frequency of blood transfusions necessary to stabilize the condition, with no severe threat to the safety of the mother and fetus.

Cinobufacini suppresses malignant behaviors of endometrial cancer by regulating NF-κB pathway.

Cinobufagin has inhibitory effects on various tumors, but there are few studies on gynecological tumors. This study explored the function and molecular mechanism of cinobufagin in endometrial cancer (EC). Different concentrations of cinobufagin treated EC cells (Ishikawa and HEC-1). Clone formation, methyl thiazolyl tetrazolium (MTT), flow cytometry, and transwell assays were used to detect malignant behaviors. A Western blot assay was performed to detect protein expression. Cinobufacini was sensitive to the inhibition of EC cell proliferation in a time- and concentration-dependent manner. Meanwhile, EC cell apoptosis was induced by cinobufacini. In addition, cinobufacini impaired the invasive and migratory abilities of EC cells. More importantly, cinobufacini blocked the nuclear factor kappa beta (NF-κB) pathway in EC by inhibiting p-IkBα and p-p65 expression. Cinobufacini suppresses malignant behaviors of EC by blocking the NF-κB pathway.

Parallel Loop Binding Compression Suture, a Modified Procedure for Pernicious Placenta Previa Complicated With Placenta Increta.

Objective: To evaluate the efficacy and safety of parallel loop binding compression suture of the lower uterus during cesarean section in pernicious placenta previa complicated with placenta increta. Methods: This retrospective study was performed in patients with pernicious placenta previa complicated with placenta increta or percreta between November 2014 and December 2020 at the Qilu Hospital of Shandong University. Patients underwent parallel loop binding compression suture surgery were defined as study group, and patients underwent traditional surgery with figure-of-eight sutures as the main hemostatic method were defined as control group. Postpartum hemorrhage was evaluated as the primary outcome. The secondary outcomes included age, gestational weeks, operative time, fetal childbirth time, prevention of hysterectomy, blood transfusion, duration of postoperative catheterization, duration of antibiotic treatment, and postoperative hospitalization (days). Additionally, neonatal outcomes were evaluated. Results: A total of 124 patients were enrolled in the study, including 38 patients receiving parallel loop binding compression suture surgery in the study group, and 86 patients in the control group. With parallel loop binding compression suture, the average operation time was significantly reduced (109.0 ± 33.5 vs. 134.4 ± 54.2 min, p = 0.00), and the volume of blood lost were also decreased (2152.6 ± 1169.4 vs. 2960.5 ± 1963.6 ml, p = 0.02), which correspondingly reduced RBC transfusion (7.2 ± 3.5 vs. 10.3 ± 8.7 units, p = 0.03) and FFP transfusion (552.6 ± 350.3 vs. 968.0 ± 799.8 ml, p = 0.00). The fetal childbirth time was extended (14.1 ± 5.6 vs. 11.0 ± 8.0 min, p = 0.03), however, there was no increase in NICU admission rates (36.9 vs. 34.9%, p = 0.83). Except for one premature infant (32 weeks) death in the control group, all infants at our hospital were safely discharged after treatment. Conclusion: Parallel loop binding compression suture is an effective, swift, practical, and safe method to reduce postpartum bleeding in women with pernicious placenta previa, complicated with placenta increta. Besides, it has no adverse effects on newborns.

Role of Abdominal Aortic Balloon Placement in Planned Conservative Management of Placenta Previa With Placenta Increta or Percreta.

Background: We investigated the role of balloon placement in the abdominal aorta (BPAA) in planned conservative management of placenta previa with placenta increta or percreta and the effects of BPAA on perinatal adverse maternal events. Methods: This retrospective case-control study included women with placenta previa (increta or percreta), who underwent pregnancy termination at the Qilu Hospital of Shandong University between January 2016 and June 2019. Patients were categorized into the BPAA and non-BPAA groups based on the BPAA placement before delivery. The Chi-square and non-parametric rank-sum tests were used for the intergroup comparison of patient characteristics. The propensity score matching algorithm was used to minimize the intergroup differences in clinical characteristics. Logistic regression analysis was used to identify the factors associated with a high risk of adverse pregnancy outcomes. The area under the receiver operating characteristic curve [area under the curve (AUC)] was used to evaluate the classification of the selected high-risk factors. Results: The study included 260 patients, and 104 patients were identified after propensity score matching. In the post-matched cohort, intraoperative blood loss was significantly lower in the BPAA than in the non-BPAA group (median 1,000 vs. 2,250 ml, P < 0.001). Intraoperative B-Lynch suture was performed in fewer patients in the BPAA (15.4 vs. 34.6%, P = 0.024) than in the non-BPAA group. The packed red blood cell (PRBC) transfusion rate was lower in the BPAA group (median 4 vs. 8 units, P < 0.001). Overall, 46 (45.1%) patients developed adverse maternal events; however, the rate of adverse maternal events was lower in the BPAA group (19.6 vs. 80.4%, P < 0.001). No ligation of the ascending branch of the uterine artery (P = 0.034), no BPAA (P < 0.001), intraplacental vascular lacunae (P = 0.046), and cervical hypervascularity (P = 0.001) were associated with a high risk of adverse perinatal maternal events. The AUC of the high-risk factors was 0.89 in the post-matched and 0.76 in the pre-matched cohorts. Conclusion: Planned conservative management using BPAA significantly minimized the intraoperative blood loss, the need for a B-Lynch suture, and PRBC transfusion in patients with severe placenta accreta spectrum and placenta previa.

Risk Stratification of Early-Stage Cervical Cancer with Intermediate-Risk Factors: Model Development and Validation Based on Machine Learning Algorithm.

BACKGROUND: Adjuvant therapy for patients with cervical cancer (CC) with intermediate-risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early-stage CC with pathological intermediate-risk factors and to provide a reference for adjuvant therapy choice. MATERIALS AND METHODS: This retrospective study included 481 patients with stage IB-IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan-Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high-risk or low-risk groups according to the risk score cutoff value. The Kaplan-Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML-based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63. CONCLUSION: Two prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate-risk factors. Evaluation of long-term survival will be needed to corroborate these findings. IMPLICATIONS FOR PRACTICE: The Sedlis criteria are intermediate-risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate-risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early-stage cervical cancer.

Development and validation of nomograms for predicting blood loss in placenta previa with placenta increta or percreta.

BACKGROUND: To develop the risk prediction model of intraoperative massive blood loss in placenta previa with placenta increta or percreta. METHODS: This study included 260 patients, of whom 179 were allocated to the development group and 81 to the validation group. Univariate and multivariate logistic regression analyses were used to identify characteristics that were associated with massive blood loss (≥2,500 mL) during cesarean section. A nomogram was constructed based on regression coefficients. Receiver-operating characteristic curve, calibration curve, and decision curve analyses were applied to assess the discrimination, calibration, and performance of the model. RESULTS: Two models were constructed. The preoperative feature model (model A) consisted of vascular lacunae within the placenta and hypervascularity of the uterine-placental margin, uterine serosa-bladder wall interface, and cervix. The preoperative and surgical feature model (model B) consisted of an emergency cesarean section, no preoperative balloon placement of the abdominal aorta, and the previously mentioned four ultrasound signs. Model B had better discrimination than model A (area under the curve: development group: 0.839 vs. 0.732; validation group: 0.829 vs. 0.736). Model B showed a higher area under the decision curve than model A in both the training and validation groups. CONCLUSIONS: The preoperative and surgical feature model for placenta previa with placenta increta or percreta can improve the early identification and management of patients who are at high risk of intraoperative massive blood loss.

Prucalopride Inhibits Proliferation of Ovarian Cancer Cells via Phosphatidylinositol 3-Kinase (PI3K) Signaling Pathway.

BACKGROUND Ovarian cancer is the second most common malignant tumor of the female reproductive system and is the leading cause of death of gynecological malignancies, but at present there is no effective and safe therapy. There is no previously published report on the anti-cancer effect of prucalopride, which is a high-affinity 5-HT4 receptor. The aim of the present study was to determine whether prucalopride can inhibit proliferation of ovarian cancer cells. MATERIAL AND METHODS The cell viability was detected by use of the Cell Counting Kit-8 (CCK-8) assay. The invasion and migration of SKOV3 and OVCAR3 cells was detected by Transwell assay. The cell apoptosis was detected by apoptosis flow detection and Caspase-Glo 3/7 Assay Systems. The apoptosis-related proteins, autophagy marker proteins, and the related-factors of phosphatidylinositol 3-kinase (PI3K) were detected by Western blot. RESULTS The CCK-8 proliferation test showed that prucalopride inhibited the growth of ovarian cancer cell lines SKOV3 and OVCAR3. In the Transwell assay, prucalopride inhibited cell invasion and migration. Furthermore, we found the expression of anti-apoptotic protein Bcl-2 decreased, whereas the expression of pro-apoptotic protein Caspase3 and Bax increased in the SKOV3 cell line treated with prucalopride, as well as cleaved PARP. In addition, the expression of p-AKT, p-mTOR, and p70S6K decreased in the prucalopride-treated group, and the expression of autophagy marker protein LC3-II/I and Beclin1 significantly increased, whereas the expression of p62 protein decreased. CONCLUSIONS The present study reveals that in ovarian cancer cells, prucalopride inhibits proliferation, migration, and invasion, and induces apoptosis and autophagy, which may be regulated by the PI3K signaling pathway. These results suggest prucalopride has potential as a new drug for clinical ovarian cancer treatment.

Knockdown of ZEB1 suppressed the formation of vasculogenic mimicry and epithelial-mesenchymal transition in the human breast cancer cell line MDA-MB-231.

Breast cancer is a common malignant tumor in women. It has been suggested that a type of microcirculation pattern that does not rely on host microvascular endothelial cells known as vasculogenic mimicry (VM) may contribute to the poor effect of anti­angiogenesis treatment on some patients with breast cancer. However, the formation and regulatory mechanism of VM in breast cancer are unclear and still require further investigation. The present study examined whether decreasing the expression of zinc finger E­box binding homeobox (ZEB1) using siRNA can inhibit the formation of VM in Triple Negative Breast Cancer (TNBC), and its specific function and molecular mechanism. mRNA and protein expression were detected by RT­qPCR and western blotting. Invasion assay and tube formation assay were also performed. The results demonstrated that ZEB1 small hairpin (sh)RNA inhibited the formation of VM. Knockdown of ZEB1 markedly inhibited the expression of vimentin in MDA­MB­231 cells and markedly increased the expression of E­cadherin. It was suggested that ZEB1 shRNA may have inhibited the epithelial­mesenchymal transition (EMT). In addition, ZEB1 shRNA inhibited the invasion of MDA­MB­231 cells and suppressed the expression of fetal liver kinase 1 (flk­1). The flk­1 inhibitor Semaxanib inhibited the formation of VM; thus, ZEB1 shRNA inhibited EMT and cell invasion, and may have inhibited the formation of VM through flk­1. The present study contributed further understanding on the theory of tumor angiogenesis and provided theoretical basis for novel targeted therapy of TNBC.

Loss of microRNA-145 expression is involved in the development and prognosis of breast cancer complicated by type 2 diabetes mellitus.

OBJECTIVE: To explore the relationships of the expression of miR-145 to the clinicopathological characteristics and prognosis of patients with breast cancer complicated by type 2 diabetes mellitus (T2DM). METHODS: A total of 257 female patients with breast cancer were enrolled for our experiment, including 140 patients with simple breast cancer (control group) and 117 patients with breast cancer complicated by T2DM (observation group). Patients were treated with modified radical mastectomy supplemented with radiotherapy, chemotherapy and endocrine therapy. qRT-PCR was used for the detection of miR-145 expression in patients of both groups. Follow-up lasted 13-60 months. RESULTS: The relative expression of miR-145 in the observation group was significantly lower than that in the control group (p<0.05). The expression of miR-145 in patients with breast cancer complicated by T2DM was related to the history of diabetes, tumor node metastasis (TNM) stage, tumor size, lymph node metastasis (LNM), estrogen receptor (ER) status, and HER2 (all p<0.05). The median disease-free survival (DFS) was significantly longer and the 5-year DFS rate significantly higher in the high-expression group than in the low-expression group. History of diabetes, TNM stage, tumor size, LNM, ER status, and HER2 were risk factors for patients with breast cancer complicated by T2DM (all p<0.05). CONCLUSIONS: Loss of miR-145 expression is related to the development of breast cancer complicated by T2DM, and low miR-145 expression might be an adverse prognostic factor in patients with this disease.

Topotecan plus carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate whether the addition of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. METHODS: Meta-analysis was performed using a random effects model. RESULTS: Four randomized controlled trials with a total of 3632 patients were identified and included in the meta-analysis. No significant differences were observed in terms of progression-free survival (P=0.400), overall survival (P=0.502) and overall response rate (P=0.953) between patients treated with topotecan plus carboplatin and paclitaxel versus carboplatin and paclitaxel. However, there were significantly higher rates of grade 3-4 leucopenia (P=0.024), neutropenia (P<0.001), anaemia (P<0.001), and thrombopenia (P<0.001) in the topotecan plus carboplatin and paclitaxel group. No significant differences were observed in grade 3-4 nausea (P=0.352) and vomiting (P=0.092) between these two groups. CONCLUSION: Topotecan plus carboplatin and paclitaxel did not improve survival outcomes and caused more haematological toxicity for advanced ovarian cancer.