Relationship between maternal serum sFlt-1 level and placenta accreta spectrum disorders in the third trimester.

PURPOSE: This study aims to evaluate whether the third-trimester soluble fms-like tyrosine kinase-1 (sFlt-1) serum levels could be related to placenta accreta spectrum (PAS) disorders and the severity of postpartum blood loss. METHODS: This was a nested case-control study which compared serum sFlt-1 level between gravid women with or without PAS disorders. Spearman correlation analysis was conducted to explore the relationship between sFlt-1 level and the volume of postpartum blood loss. Confounding factors were adjusted to avoid the impact on the results. RESULTS: Sixty gravid women were enrolled: 36 women in the PAS group and 24 women in the non-PAS group. Women in the PAS group had a median sFlt-1 level of 9407.1 [2745.9-21,691.5] pg/ml, whereas women in the non-PAS group had a median sFlt-1 level of 25,779.2 [14317.1-35,626.7] pg/ml, (p < 0.001). The sFlt-1 level was negatively related to the volume of postpartum blood loss (r = - 0.358, p = 0.041). After adjusting for maternal age and gestational age at blood taking, sFlt-1 level showed no significant relationship with PAS disorders (p = 0.245) and postpartum blood loss (p = 0.526). CONCLUSION: Third-trimester sFlt-1 serum level is not independently associated with PAS disorders or postpartum blood loss after adjusting for confounding factors.

Risk factors for placenta accreta spectrum without prior cesarean section: A case-control study in China.

OBJECTIVE: To identify the risk factors for placenta accreta spectrum (PAS) disorders in women without prior cesarean section (CS). METHODS: This retrospective case-control study investigated patients without prior CS who gave birth at Peking University Third Hospital between January 1, 2015 and December 31, 2021. Patients diagnosed with PAS according to the clinical diagnostic criteria of the 2019 International Federation of Gynecology and Obstetrics (FIGO) classification were included as the study group. Patients were matched as the control group according to delivery date and placenta previa, in a 1:2 allocation ratio. Maternal characteristics were compared between the two groups. RESULTS: The study included 348 patients in the study group and 696 in the control group. The multivariate analysis showed that the independent risk factors of PAS consisted of operative hysteroscopy (once: adjusted odds ratio [aOR] 2.38, 95% CI 1.28-4.24, P = 0.006; twice or more: aOR 5.43, 95% CI 1.04-28.32, P = 0.045), uterine curettage (once: aOR 2.54, 95% CI 1.80-3.58, P < 0.001; twice: aOR 3.01, 95% CI 1.81-5.02, P < 0.001; three or more times: aOR 9.18, 95% CI 4.64-18.18, P < 0.001), multifetal pregnancy (aOR 5.64, 95% CI 3.01-10.57, P < 0.001), adenomyosis (aOR 2.77, 95% CI 1.23-6.22, P = 0.014), in vitro fertilization (aOR 1.51, 95% CI 1.04-2.20, P = 0.030) and pre-eclampsia (aOR 2.72, 95% CI 1.36-5.45, P = 0.005), and the independent protective factor was being multiparous (aOR 0.37, 95% CI 0.25-0.54, P < 0.001). CONCLUSION: After controlling the effect of placenta previa, we found that patients with PAS without prior CS had unique maternal characteristics. Classification and quantification of the intrauterine surgeries they have undergone is essential for identifying high-risk patients. Early identification of high-risk groups by risk factors has the potential to improve the prognosis considerably.

Exosomal microRNAs induce tumor-associated macrophages via PPARγ during tumor progression in SHH medulloblastoma.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is composed of at least four molecular subgroups with distinct clinical characteristics. The sonic hedgehog (SHH) subgroup exhibits the most abundant tumor-associated microglia/macrophages (TAMs) infiltration. SHH-MB patients treated by anti-SHH drugs showed high drug resistance. However, the comprehensive role of TAMs in SHH-MB remains enigma. The aim of this study is to explore the mechanism of TAM activation/polarization in SHH-MB and discover a potential immunotherapeutic target to reduce drug resistance. We first analyzed expression profiles of immuno-microenvironment (IME) in four subgroups of 48 MB tumors using NanoString PanCancer IO360 panel and found TAMs were the major component of IME in SHH-MBs. We further distinguished M1/M2-like TAMs in tumors and found M2-like macrophages, rather than microglia, were enriched in SHH-MBs. In transgenic SHH-MB mice, these TAMs had close relationship with tumor progression. Polarization of the TAMs could be induced by MB-derived exosomes in vitro. We then screened SHH MB-derived exosomal miRNAs and their target genes using RNA sequencing and luciferase assay to clarify their roles in regulating TAM polarization. We found down-regulated let-7i-5p and miR-221-3p can induce M2-like polarization of TAMs via upregulating peroxisome proliferator activated receptor gamma (PPARγ). Finally, we demonstrated the PPARγ antagonist efficiently improved the antitumor activity of SMO inhibitor in vivo, which may be related to inhibition of M2-like TAMs. Our findings suggest a potential therapeutic strategy for SHH-MB by targeting tumor-supportive M2-like TAMs to enhance the therapeutic effect of SMO inhibitors.