Using the new definition of intraamniotic infection - is there morbidity among the women left out?

BACKGROUND: Recently, ACOG released updated definitions for intraamniotic infection (IAI): maternal fever (≥38.0 °C) and ≥1 symptom (fetal tachycardia, maternal white blood cell count >15,000/mm3 or purulent discharge). Treatment was no longer recommended for women with fever <39.0 °C plus maternal tachycardia or fundal tenderness (previous criteria). The objective of this study was to compare postpartum infectious morbidity among women meeting previous criteria (but not the new IAI criteria) to women meeting new IAI criteria. METHODS: Retrospective cohort of women delivering vaginally at a single academic center. Demographics, antepartum and intrapartum characteristics of women who met diagnostic criteria for chorioamnionitis (previous criteria) compared to those who met IAI criteria using bivariate statistics. The primary outcome was a composite of postpartum infection, including: endometritis, perineal infection, sepsis, urinary tract infection, pyelonephritis. Backward-stepwise elimination used to estimate odds of primary outcome. RESULTS: Of 229 women who met previous IAI criteria, 51 (22.3%) did not meet new IAI criteria. Women no longer meeting IAI criteria were younger (25 versus 27 years, p = .02), more likely to have gestational hypertension (16.0 versus 3.4%, p < .01), and less likely to have third or fourth degree lacerations (2.0 versus 13.4%, p = .02). No difference in antibiotic receipt was observed. Postpartum infection occurred in 16/229 (7.0%) women overall; five (9.8%) in those not meeting new IAI criteria, and 11 (6.2%) meeting new IAI criteria. After adjusting for confounders, there was no difference in odds of postpartum infection (aOR 1.65, 95% CI 0.55-4.99). CONCLUSIONS/IMPLICATIONS: Among women who met old ACOG criteria for IAI, but not the new criteria, postpartum infection occurred in nearly 10%. This number could be higher if these women were not treated with antibiotics.

Risk Factors for Postpartum Maternal Infection Following Spontaneous Vaginal Delivery Complicated by Chorioamnionitis.

Objective Guidelines for the management of chorioamnionitis include intrapartum antibiotics, while postpartum antibiotics after spontaneous vaginal delivery (SVD) are reserved high-risk women. Our objective is to describe the incidence of and risk factors for postpartum infection after SVD complicated by chorioamnionitis. Study Design This is a retrospective study of SVDs with clinically diagnosed chorioamnionitis at a single center. The primary outcome was a composite of postpartum infection. Women who developed the primary outcome were compared with those who did not using bivariate statistics. Regression models were developed to estimate adjusted odds of outcomes. Results In this cohort, 346 women underwent SVD complicated by chorioamnionitis. Of these, 23 (6.6%) developed postpartum infections (endometritis n = 7, urinary tract infection/pyelonephritis n = 6, sepsis n = 4, and perineal wound infection n = 6). Receipt of antibiotics intra- or postpartum did not differ between groups, but women with postpartum infections were more likely to deliver prior to 32 weeks (17.4 vs. 4.9%, p = 0.04). When controlling for antibiotic use, delivery at < 32 weeks was associated with 3.8-fold increased (95% confidence interval: 1.07-13.7) odds of postpartum infection. Conclusion Postpartum infections occur in ∼1/15 women delivering vaginally with chorioamnionitis, with those who deliver at < 32 weeks' gestation being at increased risk.

Adipocyte-Induced FABP4 Expression in Ovarian Cancer Cells Promotes Metastasis and Mediates Carboplatin Resistance.

Adipocytes are critical for ovarian cancer cells to home to the omentum, but the metabolic changes initiated by this interaction are unknown. To this end, we carried out unbiased mass spectrometry-based metabolomic and proteomic profiling of cancer cells cocultured with primary human omental adipocytes. Cancer cells underwent significant proteo-metabolomic alteration(s), typified by changes in the lipidome with corresponding upregulation of lipid metabolism proteins. FABP4, a lipid chaperone protein, was identified as the critical regulator of lipid responses in ovarian cancer cells cocultured with adipocytes. Subsequently, knockdown of FABP4 resulted in increased 5-hydroxymethylcytosine levels in the DNA, downregulation of gene signatures associated with ovarian cancer metastasis, and reduced clonogenic cancer cell survival. In addition, clustered regularly interspaced short palindromic repeats (CRISPR)-mediated knockout of FABP4 in high-grade serous ovarian cancer cells reduced metastatic tumor burden in mice. Consequently, a small-molecule inhibitor of FABP4 (BMS309403) not only significantly reduced tumor burden in a syngeneic orthotopic mouse model but also increased the sensitivity of cancer cells toward carboplatin both in vitro and in vivo. Taken together, these results show that targeting FABP4 in ovarian cancer cells can inhibit their ability to adapt and colonize lipid-rich tumor microenvironments, providing an opportunity for specific metabolic targeting of ovarian cancer metastasis. SIGNIFICANCE: Ovarian cancer metastatic progression can be restricted by targeting a critical regulator of lipid responses, FABP4.