The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer.
OBJECTIVE: To perform a systematic review of the literature on the effect of simulation training of operative vaginal delivery on learner technique and knowledge, operator comfort, and patient-centered outcomes. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, ERIC, The Cochrane Library, and ClinicalTrials.gov were searched from inception through April 2017. The search criteria used MeSH terms (“simulation training,” “high fidelity simulation training,” “teaching,” “obstetrical extraction,” “obstetrical forceps,” “vaginal delivery,” “clinical competence,” and “internship and residency”). METHODS OF STUDY SELECTION: A total of 30,813 articles were reviewed for inclusion. Studies detailing operative vaginal delivery simulation using forceps or vacuums and reporting health care provider or patient outcomes were eligible. TABULATION, INTEGRATION, AND RESULTS: All studies were independently reviewed by two investigators for inclusion. Only eight articles assessed the effect of simulation on trainee skill and comfort or patient outcomes and were included. Four were pretest–posttest studies, two were cross-sectional studies, one was a case–control study, and one was a cohort study. No randomized trials were identified. Simulation was associated with improved forceps placement accuracy and generated force during extraction, as well as increased operator knowledge and comfort with operative vaginal delivery. Additionally, simulation had no association with forceps failure rates, but there was an association with decreased rates of maternal lacerations and neonatal injury. The quality of the included studies was assessed with the Medical Education Research Study Quality Instrument, with a median score of 9.75 (range 9.0–13.5), indicating low-to-moderate quality. CONCLUSION: The available evidence suggests that improved technique, comfort, knowledge, and patient outcomes are associated with operative vaginal delivery simulation, but additional studies are required to further characterize such benefits for both forceps and vacuum. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018087343.
BACKGROUND: Standard treatment for placental site trophoblastic tumor is hysterectomy. This may be unacceptable to women desiring fertility. Cells aberrant in placental site trophoblastic tumor display an ability to invade normal tissue while evading the immune system. CASE: We present a case of a 23-year-old woman with stage I placental site trophoblastic tumor who declined hysterectomy. Tumor assay for program cell death-ligand 1 staining was performed and suggestive of an immune-responsive tumor. The patient initiated intravenous pembrolizumab 200 mg every 2 weeks, and by cycle 3 her β-hCG level fell to undetectable. She subsequently conceived and went on to have an uncomplicated term vaginal birth after cesarean. At 6 weeks postpartum, she remained without evidence of disease. CONCLUSION: Immunotherapy can eliminate early program cell death-ligand 1–positive placental site trophoblastic tumor with subsequent normal pregnancy.
Up to 30% of term labor deliveries experience fetal acidemia, a condition usually caused by hypoxia that is associated with adverse neonatal outcomes. The American College of Obstetricians and Gynecologists and American Academy of Pediatrics recommend assessing fetal umbilical artery (UA) blood gases at delivery when fetal metabolic status is in question. Although a UA pH of 7.24 to 7.28 is considered normal, the degree of acidemia associated with neonatal death is unclear. Recent data suggest that mild acidemia (UA pH of 7.0–7.2) and certain types of acidemia (metabolic, mixed, or respiratory) also indicate increased risk for adverse outcomes. Most cases of acidemia follow labor when the placental gas exchange is interrupted during contractions. But fetal acidemia is rare in cases of scheduled prelabor cesarean delivery (CD) and not well described in the literature. This study aims to determine if fetal acidemia at the time of scheduled, prelabor CD is associated with neonatal morbidity.This was a retrospective cohort study comparing patients with and without fetal acidemia, defined as a UA pH <7.2. Included were singleton neonates delivered via scheduled CD at a single tertiary care center from June 2004 to December 2014. Excluded were those who delivered before 37 weeks of gestation, were diagnosed with major anomalies, or underwent CD due to labor, rupture of membranes, or nonreassuring fetal status. Also excluded were cases in which data on validated umbilical cord gases were unavailable. The primary outcome was a composite of neonatal outcomes, including neonatal death, encephalopathy, therapeutic hypothermia, seizures, intubation, and respiratory distress.A total of 2081 neonates met the inclusion criteria, with fetal acidemia present at the time of delivery in 252 cases (12.1%). Acidemia occurred more frequently in breech neonates and those born to mothers with gestational diabetes mellitus or obesity. Intraoperative maternal hypotension, use of vasopressor therapy, and increased times from anesthesia induction and skin incision to delivery were also more likely to occur in cases of acidemia. The primary composite outcome was observed in 176 (8.5%) of neonates. This outcome was significantly higher in those with acidemia than those without (7.6% vs 15.1%; adjusted risk ratio [aRR], 2.95; 95% confidence interval [CI], 2.03 to 4.12). Intubation (aRR 3.50; 95% CI, 1.27–9.13) and respiratory distress (aRR, 2.93; 95% CI, 2.00–4.13) also occurred more frequently among those with acidemia. As the rate of UA pH categories decreased, the proportion of neonates with the primary outcome increased: 13.5% morbidity if UA pH was 7.0 to 7.19 versus 42.9% morbidity if UA pH was <7.0. Compared with neonates with a UA pH ≥7.2, the risk for adverse outcomes rose 3.2-fold in those with a UA pH <7.1 (aRR, 3.23; 95% CI, 1.73–5.24) and 6.6-fold in those with a UA pH <7.0 (aRR, 6.64; 95% CI, 3.23–8.96). The primary outcome was observed in 24.7% of neonates with respiratory acidemia, 27.5% with mixed, and 25% with other ac...
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