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Summary: Background: Current models for predicting intraoperative hemorrhage in cesarean scar ectopic pregnancy (CSEP) are constrained by known risk factors and conventional statistical methods. Our objective is to develop an interpretable prediction model using machine learning (ML) techniques to assess the risk of intraoperative hemorrhage during CSEP in women, followed by external validation and clinical application. Methods: This multicenter retrospective study utilized electronic medical record (EMR) data from four tertiary medical institutions. The model was developed using data from 1680 patients with CSEP diagnosed and treated at Qilu Hospital of Shandong University, Chongqing Health Center for Women and Children, and Dezhou Maternal and Child Health Care Hospital between January 1, 2008, and December 31, 2023. External validation data were obtained from Liao Cheng Dong Chang Fu District Maternal and Child Health Care Hospital between January 1, 2021, and December 31, 2023. Random forest (RF), Lasso, Boruta, and Extreme Gradient Boosting (XGBoost) were employed to identify the most influential variables in the model development data set; the best variables were selected based on reaching the λmin value. Model development involved eight machine learning methods with ten-fold cross-validation. Accuracy and decision curve analysis (DCA) were used to assess model performance for selection of the optimal model. Internal validation of the model utilized area under the receiver operating characteristic curve (AUC), sensitivity, specificity, Matthews correlation coefficient, and F1 score. These same indicators were also applied to evaluate external validation performance of the model. Finally, visualization techniques were used to present the optimal model which was then deployed for clinical application via network applications. Findings: Setting λmin at the value of 0.003, the optimal variable combination containing 9 variables was selected for model development. The optimal prediction model (Bayes) had an accuracy of 0.879 (95% CI: 0.857–0.901) an AUC of 0.882 (95% CI: 0.860–0.904), a DCA curve maximum threshold probability of 0.41, and a maximum return of 7.86%. The internal validation accuracy was 0.869 (95% CI: 0.847–0.891), an AUC of 0.822 (95% CI: 0.801–0.843), a sensitivity of 0.938, a specificity of 0.422, a Matthews correlation coefficient of 0.392, and an F1 score of 0.925. In the external validation, the accuracy was 0.936 (95% CI: 0.913–0.959), an AUC of 0.853 (95% CI: 0.832–0.874), a sensitivity of 0.954, a specificity of 0.5, a Matthews correlation coefficient of 0.365, and an F1 score of 0.966. This indicates that the prediction model performed well in both internal and external validation. Interpretation: The developed prediction model, deployed in the network application, is capable of forecasting the risk of intraoperative hemorrhage during CSEP. This tool can facilitate targeted preoperative assessment and clinical decision-making for clinicians. Prospective data should be utilized in future studies to further validate the extended applicability of the model. Funding: Natural Science Foundation of Shandong Province; Qilu Hospital of Shandong University.

Abstract Background Uterine arteriovenous malformation (UAVM) is a relatively rare but potentially life-threatening situations abnormal vascular connections between the uterine arterial and venous systems. Lack of recognized guidelines and clinic experience, there is a lot of clinic problems about diagnosis and treatment. By analyzing the clinical data of patients with pregnancy-related UAVM, we aim to confirm the safety of direct surgeries and the benefit of pretreatment (uterine artery embolization or medical therapy) before surgery, and to explore more optimal therapies for patients with pregnancy-related UAVM. Methods A total of 106 patients in Qilu Hospital of Shandong University from January 2011 to December 2021 diagnosed of pregnancy-related UAVM were involved in this study. Depending on whether preoperative intervention was performed, the patients were divided into direct surgery group and pretreatment group (uterine artery embolization or medical management). Clinical characteristics, operative related factors and prognosis were analyzed. Results The most common symptom of pregnancy-related UAVM was vaginal bleeding (82.5%), which could also be accompanied by abdominal pain. Pretreatments (uterine artery embolization or medical therapy) had no obvious benefit to the subsequent surgeries, but increased the hospital stay and hospital cost. Direct surgery group had satisfactory success rate and prognosis compared to pretreatment group. Conclusion For pregnancy-related UAVM, direct surgery has good effects and high safety with shorter hospital stays and less hospital cost. What is more, without uterine artery embolization and other medical therapy, patients could remain better fertility in future.

Abstract Background The aim of this study was to evaluate the effectiveness and safety of different treatment strategies for endogenic caesarean scar pregnancy (CSP) patients. Methods According to Vial’s standard, we defined endogenic-type CSP as (1) the gestational sac growing towards the uterine cavity and (2) a greater than 0.3 cm thickness of myometrial tissue at the caesarean scar. A total of 447 endogenic CSP patients out of 527 patients from 4 medical centres in China were enrolled in this study. A total of 120 patients were treated with methotrexate (MTX) followed by surgery, 106 received ultrasound-guided curettage directly and 221 received curettage combined with hysteroscopy. The clinical information and clinical outcomes of these patients were reviewed. Successful treatment was defined as (1) no additional treatment needed, (2) no retained mass of conception and (3) serum β subunit of human chorionic gonadotropin (β-hCG) level returning to a normal level within 4 weeks. The success rate was analysed based on these factors. Result Among 447 patients, no significant difference was observed in baseline characteristics between groups except for foetal heartbeat. The success rate was significantly different (p

Mullerian adenosarcoma (MAS) is a biphasic tumor with malignant stroma. It is most commonly of endometrial origin but occasionally originates in the cervix, ovary, or other pelvic/peritoneal sites. The typical MAS is low grade with an indolent clinical course; however, tumors with sarcomatous overgrowth (SO) or a high-grade sarcoma tend to be aggressive. Tumor etiology is largely unknown. To better understand the global genome alterations and gene mutations in MAS, whole-genome sequencing (WGS) and target validation analysis were performed. MAS showed remarkable chromosome (chr) copy number variation (CNV), specifically, gains in chr 1q, 5p, 12p, 12q, and 17q and losses in chr 3p, 3q, 9p, and 11q. Gain of chr 12q13-15 was present in 50% of cases. The selected gene products in gain regions were upregulated as measured by immunohistochemistry. HMGA2 overexpression was significantly correlated with SO. While the structural variation (SV) rate was relatively low overall, a disproportionally high rate of break-ends at chr 7 was noted involving 6 in-frame rearrangement fusion genes. Among 40 frequently mutated genes detected by WGS and validated in 29 MAS by next generation sequencing (NGS), KMT2C, and BCOR were frequently seen in MAS both with and without SO, while MAGEC1 and KDM6B were strongly associated with SO. Overall, a higher rate of frequently mutated genes was found in MAS with SO (33%) than MAS without (11%). This study uncovers the complex and specific genetic alterations in this malignancy. The findings provide a tool for future investigation of these molecular changes in tumorigenesis and target therapies.

NK cells accumulate at the maternal-fetal interface (MFI) and play essential roles in maintaining immune tolerance during pregnancy. The mechanisms that facilitate NK cells tolerance to fetal tissue are largely unknown. T cell Ig and mucin domain-containing protein 3 (Tim-3) is a newly defined molecule with essential immunological function in many physiological and pathological processes. Recent study showed that Tim-3 was involved in the regulation of immune tolerance at MFI. However, whether Tim-3 regulates NK cells cytotoxicity toward trophoblasts is unclear. Here, we showed Tim-3 was mainly expressed by decidual NK cells (dNK) and Tim-3 level in dNK was higher than peripheral NK cells (pNK). Tim-3(+) dNK expressed more levels of mature markers CD94 and CD69 than Tim-3- dNK cells and blocking Tim-3 significantly inhibited dNK IFN-γ and TNF-α secretion. Furthermore, we found TGF-β1 may contribute to such up-regulation of Tim-3 in NK cells. Interestingly, blocking Tim-3 enhanced NK cytotoxicity toward trophoblast cell line HTR-8 but not K562. We found HTR-8 expressed Tim-3 ligand Galectin-9, in contrast K562 did not. Small interfering RNA-mediated silencing of Galectin-9 expression enhanced NK cytotoxicity toward HTR-8. We further showed Tim-3/Galecin-9 inhibited NK cytotoxicity toward trophoblast partially via impairing the degranulation process. In addition, clinical data showed that abnormal Tim-3 level on pNK might be associated with recurrent spontaneous abortion (RSA). Thus, our data demonstrate Tim-3/Galectin-9 pathway maintains local tolerance by suppressing NK cytotoxicity toward trophoblasts which may represent a new immunologic tolerance mechanism at MFI.