Moderate intravenous sedation for first trimester surgical abortion: a comparison of adverse outcomes between obese and normal-weight women.

OBJECTIVE: To determine if obese women experience increased rates of adverse outcomes with moderate intravenous sedation during first trimester surgical abortion compared to normal weight women. STUDY DESIGN: We performed a retrospective cohort study of all first trimester surgical abortions with moderate intravenous sedation at an outpatient facility between September 2010 and June 2015. The primary outcome was supplemental oxygen administration. Secondary outcomes included reversal agent administration, anesthesia-related adverse events, and intraoperative lowest level of consciousness (LLOC). We compared three obesity groups [I (Body Mass Index, BMI=30-34.9), II (BMI=35-39.9), and III (BMI ≥40)] to normal weight women (BMI <25). We exported data from electronic medical records and reviewed adverse outcomes individually. RESULTS: Of 20,381 first trimester surgical abortion procedures, 31 (0.15%) utilized supplemental oxygen, 24 (0.12%) utilized a reversal agent, 40 (0.20%) had a presumed anesthesia-related adverse event and 184 of 19,725 (0.93%) had a documented low intraoperative LLOC. One patient (0.005%) required hospital transfer or hospitalization. Supplemental oxygen administration (obesity versus normal weight: obese I, aOR 0.52, 95% CI 0.12-2.27; II/III, aOR 1.51, 95% CI 0.50-4.54), low intraoperative LLOC, and anesthesia-related adverse events were not associated with obesity. The rate of reversal agent administration was lower among obese I, II and III women combined compared to normal weight women (aOR 0.13, 95% CI 0.02-0.96). CONCLUSIONS: Adverse outcomes were rare across all BMI categories with no detectable increased risk among obese women compared to normal weight women. IMPLICATIONS: With appropriate clinical screening, obese women can safely receive moderate intravenous sedation for first trimester surgical abortion in an outpatient clinical setting. Restrictions on moderate intravenous sedation based on BMI alone may be unnecessary.

Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer.

Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible Kras(G12D)-driven mouse model of PDAC has established a critical role for sustained Kras(G12D) expression in tumor maintenance, providing a model to determine the potential for and the underlying mechanisms of Kras(G12D)-independent PDAC recurrence. Here, we show that some tumors undergo spontaneous relapse and are devoid of Kras(G12D) expression and downstream canonical MAPK signaling and instead acquire amplification and overexpression of the transcriptional coactivator Yap1. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving Kras(G12D)-independent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models, portend a novel mechanism of escape from oncogenic Kras addiction in PDAC.