Expanding the Whipple Accelerated Recovery Pathway (WARP) To All Patients Undergoing Pancreaticoduodenectomy (PD)

Introduction: Pancreaticoduodenectomy (PD) is a complex abdominal procedure with high rates of perioperative morbidity. The Whipple Accelerated Recovery Pathway (WARP) was developed for highly selected patients undergoing PD to reduce hospital length of stay (LOS) and time to adjuvant therapy (TTAT), without increasing post-operative complications (POC) or readmission rates (RR). The purpose of this study was to determine if WARP could be implemented for all-risk patients undergoing PD. Methods: A single-institution, retrospective analysis of 281 patients implemented on the WARP between 2017-2020 was performed. 119 patients were categorized as WARP-eligible (WEPs) according to original inclusion criteria, and 162 were deemed WARP-ineligible (WIPs). Primary endpoints include LOS, TTAT, RR, and POC. Data was collected from Epic and a multivariate analysis with logistic regression was performed. Results: 28 POC were found in WEPs (23.5%) compared to 73 POC in WIPs (45.1%) (p\u3c0.05). Delayed gastric emptying (DGE) and post-operative pancreatic fistulas (POPF) were higher in WIPs: DGE was found in 10.2% of WEPs vs. 26.2% of WIPs (p\u3c0.05), while POPF was found in 5.1% of WEPs vs. 21% of WIPs (p\u3c0.05). Mean LOS was 5 days for WEPs vs. 6 days for WIPs (p\u3c0.05). TTAT was 55 days for WEPs, compared to 63 days in WIPs (p\u3c0.05). RR was 12.6% for WEPs and 23.5% for WIPs (p\u3c0.05). Discussion: WARP results in lowered POC, TTAT, LOS, and RR, cutting costs to patients. WARP may be expanded to all PD patients; however, WIPs may benefit from additional modifications that are specific for patient risk factor

Immunogenetics associated with severe coccidioidomycosis

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis