Pravastatin Effects on Placental Prosurvival Molecular Pathways in a Mouse Model of Preeclampsia.

OBJECTIVE: Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta. METHODS: Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean ± standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value < .05 was considered statistically significant. RESULTS: The sFlt-1 + Pravastatin mice had significantly higher placental protein concentrations of prosurvival/ antiapoptotic factors (activating transcription factor 2, pp38, phosphorylated c-jun N-terminal kinase, and phosphorylated extracellular signal-regulated kinase) and of heat-shock protein 27 and signal transducer and activator of transcription 3, 2 factors crucial for embryonic and placental development during oxidative stress, compared to sFlt-1 mice (P < .05) and similar to the mFc control group. No differences were noted in substrates of the proapoptotic pp53 pathway. CONCLUSION: Pravastatin ability to prevent preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia.

Early versus Late Feeding after Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: This study aims to evaluate whether early feeding after cesarean delivery (CD) shortens the time to pass flatus and bowel movement. METHODS: Women at term undergoing CD were randomly assigned to start oral intake either within 6 hours (early feeding) or after 12 hours (late feeding) from surgery completion. Women with preeclampsia, or requiring emergent CD, additional bowel surgery, or the use of general anesthesia were excluded. Our primary outcome was time of passing first flatus following surgery completion. Secondary outcomes included time of first bowel sounds, time of first bowel movement, nausea/vomiting, and length of maternal hospital stay (clinicaltrials.gov identifier NCT02396485). RESULTS: A total of 177 women were randomized to early (n = 85) or late feeding (n = 82). There was no loss to follow-up, and outcomes were available for all patients. There were no differences in baseline characteristics between the two groups. Early feeding resulted in shorter time to pass flatus (median [interquartile range], 715 [485-1,208] minutes vs. 1,300 [820-1,760] minutes; p < 0.001) and to have bowel sounds (232 [168-537.8] minutes vs. 554.5 [202-706] minutes; p = 0.001). Time to pass bowel movement was shorter in the early-feeding group, but did not reach significance. The groups did not differ in length of stay or in rates of nausea, vomiting, or ileus. CONCLUSION: In women undergoing CD, early oral intake is well tolerated and results in earlier return of bowel function.

Enmeshed in Controversy: Use of Vaginal Mesh in the Current Medicolegal Environment.

UNLABELLED: Vaginal mesh has been a valuable tool in the treatment of stress urinary incontinence and pelvic organ prolapse. As our knowledge of the long-term outcomes and complications of this product has evolved, however, vaginal mesh has become the subject of legal scrutiny. Therefore, it is imperative that physicians understand pertinent litigation techniques to optimize their informed consent and documentation processes and protect themselves. OBJECTIVES: Our objective is to familiarize physicians who use vaginal mesh with how law suits involving transvaginal mesh are construed. We also describe the current medicolegal environment surrounding the use of these products. METHODS: The food and drug administration public safety communications, food and drug administration Manufacturer and User Facility Device Experience database, and LexisNexis legal search engine were used to review data relevant to current vaginal mesh litigation. This information was used to create a medicolegal review. RESULTS: Litigation involving transvaginal mesh follows 3 paths. The first consists of claims against the manufacture of transvaginal mesh with allegations, such as design defects, failure to warn, and misrepresentation. The second is a defensive legal strategy called the learned intermediary doctrine, used by manufacturers to shift liability from themselves to surgeons. The manufacturers claim that the duty to inform patients of potential complications lies with the surgeon. The third involves claims by patients against surgeons for lack of informed consent, alleging that they were not sufficiently informed of potential complications associated with transvaginal mesh before insertion. CONCLUSIONS: To lessen the liability, a surgeon using transvaginal mesh should inform patients of potential complications associated with the products and document informed consent in their medical records.