This article provides a broad overview of the interaction between neuropeptides and inflammatory mediators as it pertains to diabetic wound healing. Abnormal wound healing is a major complication of both type I and type II diabetes and is the most frequent cause of non-traumatic lower limb amputation. Wound healing requires the orchestrated integration of complex biological and molecular events. Inflammation, proliferation and migration of cells followed by angiogenesis and re-epithelization are essential phases of wound healing. The link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. The bidirectional connection between the nervous and the immune systems and the role it plays in wound healing has emerged as one of the focal features of the wound healing dogma. The mediators of this connection include neuropeptides and the cytokines released from different cells including immune and cutaneous cells. Therefore, to develop successful wound healing therapies, it is vital to understand in depth the signaling pathways in the neuro-immune axis and their implication in diabetic wound healing.

Objectives To characterize operative outcomes for ascending aorta and arch replacement on a national scale and develop risk models for mortality and major morbidity. Background Contemporary outcomes for ascending aorta and arch replacement in North America are unknown. Methods We queried the Society of Thoracic Surgeons Database for patients undergoing ascending aorta (+/− root) +/− arch replacement from 2004 to 2009. The database captured 45,894 cases, including 12,702 root, 22,048 supracoronary ascending alone, 6,786 ascending+arch, and 4,358 root+arch. Baseline characteristics and clinical outcomes were analyzed. A parsimonious multivariable logistic regression model was constructed to predict risks of mortality and major morbidity. Results Operative mortality was 3.4% for elective and 15.4% for non-elective cases. A risk model for operative mortality [c-index 0.81] revealed a risk-adjusted odds ratio (OR) for death following emergent vs. elective operation of 5.9 [95% confidence interval (CI) 5.3, 6.6]. Among elective patients, end stage renal disease and re-operative status were the strongest predictors of mortality (adjusted OR 4.0 [95% CI 2.6, 6.4] and 2.3 [95% CI 1.9, 2.7] respectively, p<0.0001). Conclusions Current outcomes for ascending aorta and arch replacement in North America are excellent for elective repair; however, results deteriorate for non-elective status, suggesting that increased screening and/or lowering thresholds for elective intervention could potentially improve outcomes. The predictive models presented may serve clinicians in counseling patients.

Objective Hybrid repair of the transverse aortic arch may allow for aortic arch repair with reduced morbidity in patients who are suboptimal candidates for conventional open surgery. Here, we present our results with an algorithmic approach to hybrid arch repair, based upon the extent of aortic disease and patient comorbidities. Methods Between August 2005 and January 2012, 87 patients underwent hybrid arch repair by three principal procedures: zone 1 endograft coverage with extra-anatomic left carotid revascularization (zone 1, n=19), zone 0 endograft coverage with aortic arch debranching (zone 0, n=48), or total arch replacement with staged stented elephant trunk completion (stented elephant trunk, n=20). Results The mean patient age was 64 years and the mean expected in-hospital mortality rate was 16.3% as calculated by the EuroSCORE II. 22% (n=19) of operations were non-elective. Sternotomy, cardiopulmonary bypass, and deep hypothermic circulatory arrest were required in 78% (n=68), 45% (n=39), and 31% (n=27) of patients, respectively, to allow for total arch replacement, arch debranching, or other concomitant cardiac procedures, including ascending ± hemi-arch replacement in 17% (n=8) of patients undergoing zone 0 repair. All stented elephant trunk procedures (n=20) and 19% (n=9) of zone 0 procedures were staged, with 41% (n=12) of patients undergoing staged repair during a single hospitalization. The 30-day/in-hospital rates of stroke and permanent paraplegia/paraparesis were 4.6% (n=4) and 1.2% (n=1), respectively. Three of 27 (11.1%) patients with native ascending aorta zone 0 proximal landing zone experienced retrograde type A dissection following endograft placement. The overall in-hospital mortality rate was 5.7% (n=5), however, 30-day/in-hospital mortality increased to 14.9% (n=13) due to eight 30-day out-of-hospital deaths. Native ascending aorta zone 0 endograft placement was found to be the only univariate predictor of 30-day/in-hospital mortality (odds ratio, 4.63; 95% confidence interval, 1.35-15.89; P=0.02). Over a mean follow-up of 28.5 ± 22.2 months, 13% (n=11) of patients required reintervention for type 1A (n=4), type 2 (n=6), or type 3 (n=1) endoleak. Kaplan-Meier estimates of survival at 1, 3, and 5 years were 73%, 60%, and 51%, respectivel. Conclusions Hybrid aortic arch repair can be tailored to patient anatomy and comorbid status to allow complete repair of aortic pathology, frequently in a single stage, with acceptable outcomes. However, endograft placement in the native ascending aorta is associated with high rates of retrograde type A dissection and 30-day/in-hospital mortality and should be approached with caution.