Resolvin D2/GPR18 signaling enhances monocytic myeloid-derived suppressor cell function to mitigate abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is a chronic vascular pathology characterized by inflammation, leukocyte infiltration and vascular remodeling. The aim of this study was to delineate the protective role of Resolvin D2 (RvD2), a bioactive isoform of specialized proresolving lipid mediators, via G-protein coupled receptor 18 (GPR18) receptor signaling in attenuating AAAs. Importantly, RvD2 and GPR18 levels were significantly decreased in aortic tissue of AAA patients compared with controls. Furthermore, using an established murine model of AAA in C57BL/6 (WT) mice, we observed that treatment with RvD2 significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), elastic fiber disruption and increased smooth muscle cell α-actin expression as well as increased TGF-ß2 and IL-10 expressions compared to untreated mice. Moreover, the RvD2-mediated protection from vascular remodeling and AAA formation was blocked when mice were previously treated with siRNA for GPR18 signifying the importance of RvD2/GPR18 signaling in vascular inflammation. Mechanistically, RvD2-mediated protection significantly enhanced infiltration and activation of monocytic myeloid-derived suppressor cells (M-MDSCs) by increasing TGF-ß2 and IL-10 secretions that mitigated smooth muscle cell activation in a GPR18-dependent manner to attenuate aortic inflammation and vascular remodeling via this intercellular crosstalk. Collectively, this study demonstrates RvD2 treatment induces an expansion of myeloid-lineage committed progenitors, such as M-MDSCs, and activates GPR18-dependent signaling to enhance TGF-ß2 and IL-10 secretion that contributes to resolution of aortic inflammation and remodeling during AAA formation.

Intraoperative hypotension and complications after vascular surgery: A scoping review.

BACKGROUND: Intraoperative hypotension during major surgery is associated with adverse health outcomes. This phenomenon represents a potentially important therapeutic target for vascular surgery patients, who may be uniquely vulnerable to intraoperative hypotension. This review summarizes current evidence regarding the impact of intraoperative hypotension on postoperative complications in patients undergoing vascular surgery, focusing on potentially modifiable procedure- and patient-specific risk factors. METHODS: A scoping review of the literature from Embase, MEDLINE, and PubMed databases was conducted from inception to December 2019 to identify articles related to the effects of intraoperative hypotension on patients undergoing vascular surgery. RESULTS: Ninety-two studies met screening criteria; 9 studies met quality and inclusion criteria. Among the 9 studies that defined intraoperative hypotension objectively, there were 9 different definitions. Accordingly, the reported incidence of intraoperative hypotension ranged from 8% to 88% (when defined as a fall in systolic blood pressure of >30 mm Hg or mean arterial pressure <65). The results demonstrated that intraoperative hypotension is an independent risk factor for longer hospital length of stay, myocardial injury, acute kidney injury, postoperative mechanical ventilation, and early mortality. Vascular surgery patients with comorbid conditions that confer increased vulnerability to hypoperfusion and ischemia appear to be susceptible to the adverse effects of intraoperative hypotension. CONCLUSION: There is no validated, consensus definition of intraoperative hypotension or other hemodynamic parameters associated with increased risk for adverse outcomes. Despite these limitations, the weight of evidence suggests that intraoperative hypotension is common and associated with major postoperative complications in vascular surgery patients.

Antibiotics May be Safely Discontinued Within One Week of Percutaneous Cholecystostomy.

BACKGROUND: For patients with acute cholecystitis managed with percutaneous cholecystostomy (PC), the optimal duration of post-procedural antibiotic therapy is unknown. Our objective was to compare short versus long courses of antibiotics with the hypothesis that patients with persistent signs of systemic inflammation 72 h following PC would receive prolonged antibiotic therapy and that antibiotic duration would not affect outcomes. METHODS: We performed a retrospective cohort analysis of 81 patients who underwent PC for acute cholecystitis at two hospitals during a 41-month period ending November 2014. Patients who received short (≤7 day) courses of post-procedural antibiotics were compared to patients who received long (>7 day) courses. Treatment response to PC was evaluated by systemic inflammatory response syndrome (SIRS) criteria. Logistic and linear regressions were used to evaluate associations between antibiotic duration and outcomes. RESULTS: Patients who received short (n = 30) and long courses (n = 51) of antibiotics had similar age, comorbidities, severity of cholecystitis, pre-procedural vital signs, treatment response, and culture results. There were no differences in recurrent cholecystitis (13 vs. 12%), requirement for open/converted to open cholecystectomy (23 vs. 22%), or 1-year mortality (20 vs. 18%). On logistic and linear regressions, antibiotic duration as a continuous variable was not predictive of any salient outcomes. CONCLUSIONS: Patients who received short and long courses of post-PC antibiotics had similar baseline characteristics and outcomes. Antibiotic duration did not predict recurrent cholecystitis, interval open cholecystectomy, or mortality. These findings suggest that antibiotics may be safely discontinued within one week of uncomplicated PC.

Intubated Trauma Patients Receiving Prolonged Antibiotics for Pneumonia despite Negative Cultures: Predictors and Outcomes.

BACKGROUND: Despite the excellent negative predictive value of sterile respiratory cultures, antibiotics often are continued after negative endotracheal aspirate (ETA) or bronchoalveolar lavage (BAL) for critically ill trauma patients. We hypothesized that persistent elevation of the Clinical Pulmonary Infection Score (CPIS) would predict continued antibiotic therapy after a negative respiratory culture for intubated trauma patients, and that prolonged antibiotics would provide no benefit. METHODS: We performed a four-year retrospective cohort analysis (May 1, 2011-September 30, 2015), including patients from our trauma database with ETA or BAL, excluding patients with any infection other than pneumonia or bacteremia. Cultures with <2+ organisms on gram stain and <2+ or 104 organisms on culture were considered negative. The CPIS was assessed at the time of culture and five days later, when all cultures were final. Multiple logistic regression was used to identify predictors of long-term antibiotic therapy. RESULTS: A series of 106 patients with negative cultures were included, of whom 61 had ≤5 d of antibiotics and 45 had >5 d of antibiotics. There were no differences in injury severity, head or chest trauma, initial CPIS, or subsequent culture results between the groups. Long-term antibiotic therapy did not affect intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, or death. Factors predicting long-term antibiotic therapy included development of a localized chest radiograph infiltrate (odds ratio [OR] 6.8; 95% confidence interval [CI] 1.7-28), CPIS >5 five days after culture (OR 6.1; 95% CI 1.2-32), and a colonized culture (OR 3.3; 95% CI 1.3-8.3). CONCLUSIONS: Long-term antibiotic therapy for intubated trauma patients with negative respiratory cultures provided no benefit and was predicted by development of a localized chest radiograph infiltrate, persistently elevated CPIS, and a contaminated/colonized culture. Although long-term antibiotic use did not worsen outcomes, better strategies are needed to diagnose pneumonia accurately and ensure timely discontinuation of antibiotics when appropriate.

The effects of renal transplantation on peripheral blood dendritic cells.

Recent advances allow accurate quantification of peripheral blood (PB) myeloid and plasmacytoid dendritic cell (DC) populations (mDC and pDC, respectively), although the response to renal transplantation (RT) remains unknown. Using flow cytometry, PBDC levels were quantified in patients with end stage renal disease (ESRD) undergoing RT. PBDC levels were significantly reduced in ESRD patients pre-RT compared to healthy controls, with further reduction noted immediately following a hemodialysis session. RT resulted in a dramatic decrease in both subsets, with a greater reduction of pDC levels. Both subset levels were significantly lower than in control patients undergoing abdominal surgery without RT. Subgroup analysis revealed significantly greater mDC reduction in RT recipients receiving anti-lymphocyte therapy, with preferential binding of antibody preparation to this subset. Samples from later time points revealed a gradual return of PBDC levels back to pre-transplant values concurrent with overall reduction of immunosuppression (IS). Finally, PBDC levels were significantly reduced in patients with BK virus nephropathy compared to recipients with stable graft function, despite lower overall IS. Our findings suggest that PBDC levels reflect the degree of IS in renal allograft recipients. Furthermore, PBDC monitoring may represent a novel strategy to predict important outcomes such as acute rejection, long-term graft loss and infectious complications.