Psychiatric Diagnoses Are Associated With Postoperative Disparities in Patients Undergoing Major Colorectal Operations.

BACKGROUND: Over 50% of hospitalized patients have comorbid psychiatric diagnoses, resulting in increased risk of morbidity such as longer lengths of stay, worse health-related quality of life, and increased mortality. However, data regarding colorectal surgery postoperative outcomes in patients with psychiatric diagnoses (PD) are limited. METHODS: We queried a single institution's National Surgical Quality Improvement Program from 2013-2019 for major colorectal procedures. Postsurgical outcomes for patients with and without PD were compared. Primary outcomes were prolonged length of stay (pLOS) and 30-day readmission. RESULTS: From a total of 1447 patients, 402 (27.8%) had PD. PD had more smokers (20.9% vs 15%) and higher mean body mass index (29.1 kg/m2 vs 28.2 kg/m2). Bivariate outcomes showed more surgical site infections (SSI) (10.2% vs 6.12%), reoperation (9.45% vs 6.35%), and pLOS (34.8% vs 29.0%) (all P values <.05) in the PD group. On multivariate analysis, PD had higher likelihood of reoperation (OR 1.53, 95% CI: [1.02-2.80]) and SSI (OR 1.82, 95% CI: [1.25-2.66]). DISCUSSION: Psychiatric diagnoses are a risk factor for adverse outcomes after colorectal procedures. Further studies are needed to evaluate the benefit of perioperative mental health support services for these patients.

The Effect of an Enhanced Recovery Program on Elective Right Hemicolectomies for Crohn's Disease vs. Colon Cancer: A Retrospective Cohort Analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are widely employed in colorectal surgery, successful in reducing postoperative morbidities and hospital length of stay (LOS). However, ERAS effects on the inflammatory bowel disease population remain unclear. This study examines the postoperative course of both Crohn's disease (CD) and colon cancer (CC) patients after elective right hemicolectomies and compares the effectiveness of ERAS protocol. METHODS: A retrospective analysis was performed on patients with CD and CC undergoing elective right hemicolectomies and ileocecectomies from January 2014 through June 2016 (pre-ERAS) and January 2017 through April 2019 (post-ERAS) from a single tertiary care center. Patient demographics and perioperative variables were examined, including prolonged postoperative ileus (PPOI), hospital LOS, and 30-day readmission. RESULTS: 98 CC patients and 91 CD patients met the inclusion criteria. The pre-ERAS CC and post-ERAS CC cohorts were significantly different: post-ERAS had fewer patients with congestive heart failure and chronic obstructive pulmonary disease and had higher albumin levels. The pre-ERAS CC cohort had significantly longer operative durations and higher rates of concomitant procedures than the post-ERAS CC cohort. Both patients with CC and CD had a reduction in LOS with implementation of ERAS, decreasing by 2.24 days (P = .002) and 1.21 days (P = .038), respectively. There was a reduction in rates of organ space infections with CD (pre .132, post .00, P = .007). There was a trend towards an increased rate of PPOI with CD (Pre .079, Post .226, P = .062). DISCUSSION: The ERAS protocol significantly reduced LOS for both groups, without increasing 30-day readmission rates or other morbidities.

Signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells lessen E. coli and LPS-induced acute inflammatory injury.

Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by Chrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate E. coli and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR+CD11b+ cells (CD11b is coded by Itgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury. Using both E. coli and LPS-induced lung injury mouse models, we found that vagotomy augmented splenic egress and lung recruitment of α7 nAChR+CD11b+ cells, and consequently worsened lung inflammatory responses. Rescue of vagotomy with an α7 nAChR agonist preserved α7 nAChR+CD11b+ cells in the spleen, suppressed recruitment of these cells to the lung and attenuated lung inflammatory responses. Vagal signals via α7 nAChR promoted serine473 phosphorylation of AKT1 in α7 nAChR+CD11b+ cells and stabilized these cells in the spleen. Deletion of Akt1 enhanced splenic egress and lung recruitment of α7 nAChR+CD11b+ cells, which elicited neutrophil-infiltrated lung inflammation and injury. Vagotomy and double deletion of Chrna7 and Itgam reduced serine473 phosphorylation of AKT1 in the spleen and BAL (bronchoalveolar lavage) Ly6CintGr1hi neutrophils and Ly6Chi monocytes, and they facilitated the recruitment of neutrophils and monocytes to the airspaces of E. coli-injured lungs. Double deletion of Chrna7 and Itgam increased lung recruitment of monocytes and/or neutrophils and deteriorated E. coli and LPS-induced lung injury. Thus, signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells attenuate E. coli and LPS-induced acute lung inflammatory responses. Targeting this signaling pathway could provide novel therapeutic strategies for treating acute lung injury.

Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice.

CFTR (cystic fibrosis transmembrane conductance regulator) is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del) or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2) or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage) during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF) levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase) inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.

Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

Mutation of CFTR (cystic fibrosis transmembrane conductance regulator) leads to cystic fibrosis (CF). Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation) mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels). Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1), platelet activating factor (PAF), and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF), or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.