Effects of a New Hospital-Wide Surgical Consultation Protocol in Patients with Clostridium difficile Colitis.

BACKGROUND: Fulminant Clostridium difficile colitis (fCDC) occurs in 2%-8% of patients with CDC and carries a high death rate. Prompt operation may reduce death. Our aim was to determine whether a standardized hospital-wide protocol for surgical referral in CDC would result in earlier surgical consultation, earlier identification of patients who could benefit from surgical therapy, and reduced deaths from fCDC. METHODS: A multidisciplinary team developed consensus criteria for surgical consultation. Compliance was evaluated by prospective review of all inpatient CDC cases. Outcomes of the prospective cohort (POST) were compared to an historic control group (PRE). RESULTS: From November 1, 2010 to October 31, 2012, we identified 1,106 inpatients with CDC; 339 patients matched the consultation criteria, of whom 213 received a surgical consultation, resulting in an overall compliance rate of 62.8%. All those with fCDC received a surgical consultation, with a median time to surgical referral of three hours. Of 46 patients with fCDC, 11 (23.9%) died, compared with 34.8% in the historical control group (p = 0.15). The death rate was 14.7% in the POST group, when excluding patients with limitations of care and those transferred to our institution in a fulminant state. There was a shorter interval between admission and surgical intervention for those who required operation in the POST group-three (1-11) days versus 1.5 (0-3) days, respectively, in the PRE and POST groups (p = 0.018), and a shorter adjusted median hospital length of stay (adjusted difference 9.0, 95% CI 2.2-12.3, p = 0.007) Conclusions: A hospital-wide protocol with established criteria for surgical consultation resulted in faster intervention and a shorter adjusted median hospital length of stay. The overall death rate for fCDC patients without limitations of life-sustaining treatment who presented to our emergency department or in whom fCDC developed while they were admitted to our hospital was 14.7%.

Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin.

BACKGROUND: The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been specifically investigated. The aim of this study was to identify genetic variants contributing to ALI/ARDS from pulmonary or extrapulmonary causes. METHODS: We conducted a multistage genetic association study. We first performed a large-scale genotyping (50K ITMAT-Broad_CARe Chip) in 1717 critically ill Caucasian patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p≤0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n=765) and pneumonia/pulmonary sepsis (Population II; n=838), as causes for ALI/ARDS. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second trauma-associated ALI population (n=224, Stage III). RESULTS: In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p<0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p<0.006, Stage II; p<0.05, Stage III). Meta-analysis confirmed these associations. CONCLUSIONS: Different genetic variants may influence ARDS susceptibility depending on direct versus indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI/ARDS, respectively.