Racial disparities in postoperative outcomes persist for patients with inflammatory bowel disease under a colorectal enhanced recovery program.

INTRODUCTION: Enhanced recovery programs (ERPs) reduce racial disparities in surgical outcomes for general colorectal surgery populations. It is unclear, however, if disparities in IBD populations are impacted by ERPs. METHODS: Retrospective study comparing IBD patients undergoing major elective colorectal operations before (2006-2014) and after (2015-2021) ERP implementation using ACS-NSQIP data. The primary outcome of length of stay (LOS) was analyzed by negative binomial regression, and secondary outcomes (complications and readmissions) by logistic regression. RESULTS: Of 466 IBD patients, 47% were pre-ERP and 53% were ERP patients. In multivariable analysis stratified by ERP period, Black race was associated with increased odds of complications in the pre-ERP (OR 3.6, 95%CI 1.4-9.3) and ERP groups (OR 3.1 95%CI 1.3-7.6). Race was not a predictor of LOS or readmission in either group. High social vulnerability was associated with increased odds of readmission pre-ERP (OR 15.1, 95%CI 2.1-136.3), but this disparity was mitigated under ERPs (OR 1.4, 95%CI 0.4-5.6). CONCLUSION: While ERPs mitigated some disparities by social vulnerability, racial disparities persist in IBD populations even under ERPs. Further work is needed to achieve surgical equity for IBD patients.

The effects of focal adhesion kinase and platelet-derived growth factor receptor beta inhibition in a patient-derived xenograft model of primary and metastatic Wilms tumor.

Aggressive therapies for patients with metastatic Wilms tumor (WT) with subsequent severe late effects warrant the search for novel therapies. The role of focal adhesion kinase (FAK), a non-receptor tyrosine kinase important in pediatric solid tumor development and progression, has not been examined in metastatic WT. Using a novel patient-derived xenograft (PDX) of a primary and matched, isogenic, metastatic WT, the hypothesis of the current study was that FAK would contribute to metastatic WT and small molecule inhibition would decrease tumor growth. Immunohistochemical staining, immunoblotting, cell viability and proliferation assays, cell cycle analysis, and cellular motility and attachment-independent growth assays were performed. FAK was present and phosphorylated in both WT PDXs and in the human samples from which they were derived. FAK inhibition decreased cellular survival, proliferation, and cell cycle progression in both PDXs but only significantly decreased migration, invasion, and attachment-independent growth in the primary WT PDX. Kinomic profiling revealed that platelet-derived growth factor receptor beta (PDGFRß) may be affected by FAK inhibition in WT. Pharmacologic inhibition of FAK and PDGFRß was synergistic in primary WT PDX cells. These findings broaden the knowledge of metastatic WT and support further investigations on the potential use of FAK and PDGFRß inhibitors.

The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival.

PURPOSE: Hepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival. METHODS: The hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed. RESULTS: PIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival. CONCLUSIONS: PIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma.

Timed Stair Climbing Is the Single Strongest Predictor of Perioperative Complications in Patients Undergoing Abdominal Surgery.

BACKGROUND: Current methods to predict patients' perioperative morbidity use complex algorithms with multiple clinical variables focusing primarily on organ-specific compromise. The aim of the current study was to determine the value of a timed stair climb in predicting perioperative complications for patients undergoing abdominal surgery. STUDY DESIGN: From March 2014 to July 2015, three hundred and sixty-two patients attempted stair climbing while being timed before undergoing elective abdominal surgery. Vital signs were measured before and after stair climb. Ninety-day postoperative complications were assessed by the Accordion Severity Grading System. The prognostic value of stair climb was compared with the American College of Surgeons NSQIP risk calculator. RESULTS: A total of 264 (97.4%) patients were able to complete the stair climb. Stair climb time directly correlated to changes in both mean arterial pressure and heart rate as an indicator of stress. An Accordion grade 2 or higher complication occurred in 84 (25%) patients. There were 8 mortalities (2.4%). Patients with slower stair climb times had increased complication rates (p < 0.0001). In multivariable analysis, stair climb time was the single strongest predictor of complications (odds ratio = 1.029; p < 0.0001), and no other clinical comorbidity reached statistical significance. Receiver operative characteristic curves predicting postoperative morbidity by stair climb time was superior to that of the American College of Surgeons risk calculator (area under the curve = 0.81 vs 0.62; p < 0.0001). Additionally, slower patients had greater deviations from predicted length of hospital stay (p = 0.034). CONCLUSIONS: Stair climb provides measurable stress, accurately predicts postoperative complications, and is easy to administer in patients undergoing abdominal surgery. Larger patient populations with a diverse group of operations will be needed to validate the use of stair climbing in risk-prediction models.