Intravascular ultrasound as a novel tool for the diagnosis and targeted treatment of functional popliteal artery entrapment syndrome

Functional popliteal artery entrapment syndrome can be difficult to diagnose, as the imaging modalities presently employed are designed to detect anatomic entrapment. We describe a novel imaging technique to aid in diagnosis in this cohort. A 22-year-old cyclist presented with exercise-limiting claudication. Magnetic resonance angiography with provocative maneuvers was nondiagnostic. Digital subtraction angiography revealed long-segment occlusion of the popliteal artery with plantar flexion; however, the specific site of compression remained unclear. Intravascular ultrasound allowed specific localization of compression and further confirmed the diagnosis. Thus, we report this as an adjunctive imaging modality to definitively diagnose functional popliteal artery entrapment syndrome and to assist in operative planning

The clinical impact of cardiology consultation prior to major vascular surgery

OBJECTIVE: To understand statewide variation in preoperative cardiology consultation prior to major vascular surgery and to determine whether consultation was associated with differences in perioperative myocardial infarction (poMI). SUMMARY BACKGROUND DATA: Medical consultation prior to major vascular surgery is obtained to reduce perioperative risk. Despite perceived benefit of preoperative consultation, evidence is lacking specifically for major vascular surgery on the effect of preoperative cardiac consultation. METHODS: Patient and clinical data were obtained from a statewide vascular surgery registry between January 2012 and December 2014. Patients were risk stratified by revised cardiac risk index category and compared poMI between patients who did or did not receive a preoperative cardiology consultation. We then used logistic regression analysis to compare the rate of poMI across hospitals grouped into quartiles by rate of preoperative cardiology consultation. RESULTS: Our study population comprised 5191 patients undergoing open peripheral arterial bypass (n = 3037), open abdominal aortic aneurysm repair (n = 332), or endovascular aneurysm repair (n = 1822) at 29 hospitals. At the patient level, after risk-stratification by revised cardiac risk index category, there was no association between cardiac consultation and poMI. At the hospital level, preoperative cardiac consultation varied substantially between hospitals (6.9%-87.5%, P \u3c0.001). High preoperative consulting hospitals (rate \u3e66%) had a reduction in poMI (OR, 0.52; confidence interval: 0.28-0.98; P \u3c0.05) compared with all other hospitals. These hospitals also had a statistically greater consultation rate with a variety of medical specialties. CONCLUSIONS: Preoperative cardiology consultation for vascular surgery varies greatly between institutions, and does not appear to impact poMI at the patient level. However, reduction of poMI was noted at the hospitals with the highest rate of preoperative cardiology consultation as well as a variety of medical services, suggesting that other hospital culture effects play a role

Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+) demonstrated delayed early healing (days 1–3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet), improved wound healing was seen at late time points (days 6–7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds

SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair

Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds