Mutant FOXO1 controls an oncogenic network via enhancer accessibility.

Transcriptional dysregulation is a hallmark of diffuse large B cell lymphoma (DLBCL), as transcriptional regulators are frequently mutated. However, our mechanistic understanding of how normal transcriptional programs are co-opted in DLBCL has been hindered by a lack of methodologies that provide the temporal resolution required to separate direct and indirect effects on transcriptional control. We applied a chemical-genetic approach to engineer the inducible degradation of the transcription factor FOXO1, which is recurrently mutated (mFOXO1) in DLBCL. The combination of rapid degradation of mFOXO1, nascent transcript detection, and assessment of chromatin accessibility allowed us to identify the direct targets of mFOXO1. mFOXO1 was required to maintain accessibility at specific enhancers associated with multiple oncogenes, and mFOXO1 degradation impaired RNA polymerase pause-release at some targets. Wild-type FOXO1 appeared to weakly regulate many of the same targets as mFOXO1 and was able to complement the degradation of mFOXO1 in the context of AKT inhibition.

Risk factors for unexpected readmission and reoperation following open procedures for shoulder instability: a national database study of 1,942 cases.

BACKGROUND: The purpose of this study was to identify demographics and risk factors associated with unplanned 30-day readmission and reoperation following open procedures for shoulder instability and examine recent trends in open shoulder instability procedures. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried using current procedural terminology (CPT) codes 23455, 23460, and 23462 to find patients who underwent shoulder instability surgery from 2015 to 2019. Independent sample Student t-tests and chi-square tests were used in univariate analyses to identify demographic, lifestyle, and perioperative variables related to 30-day readmission following repair for shoulder instability. Multivariate logistic regression modeling was subsequently performed. RESULTS: In total, 1,942 cases of open surgical procedures for shoulder instability were identified. Within our study sample, 1.27% of patients were readmitted within 30 days of surgery, and 0.85% required reoperation. Multivariate logistic regression modeling confirmed that the following patient variables were associated with a statistically significant increase in the odds of readmission: open anterior bone block/Latarjet-Bristow procedure, being a current smoker, and a long hospital stay (all P<0.05). Multivariate logistic regression modeling confirmed statistically significant increased odds of reoperation with an open anterior bone block or Latarjet-Bristow procedure (P<0.05). CONCLUSIONS: Unplanned 30-day readmission and reoperation after open shoulder instability surgery is infrequent. Patients who are current smokers, have an open anterior bone block or Latarjet-Bristow procedure, or a longer than average hospital stay have higher odds of readmission than others. Patients who undergo an open anterior bone block or Latarjet-Bristow procedure have higher odds of reoperation than those who undergo an open soft-tissue procedure. Level of evidence: III.