Endovascular vs open repair for ruptured abdominal aortic aneurysm.

OBJECTIVE: Endovascular repair (EVAR) of ruptured abdominal aortic aneurysm (rAAA) has become first-line therapy at our institution and is performed under a standardized protocol. We compare perioperative mortality, midterm survival, and morbidity after EVAR and open surgical repair (OSR). METHODS: Records were retrospectively reviewed from May 2000 to September 2010 for repair of infrarenal rAAAs. Primary end points included perioperative mortality and midterm survival. Secondary end points included acute limb ischemia, length of stay, ventilator-dependent respiratory failure, myocardial infarction, renal failure, abdominal compartment syndrome, and secondary intervention. Statistical analysis was performed using the t-test, χ(2) test, the Fisher exact test, and logistic regression calculations. Midterm survival was assessed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Seventy-four infrarenal rAAAs were repaired, 19 by EVAR and 55 by OSR. Despite increased age and comorbidity in the EVAR patients, perioperative mortality was 15.7% for EVAR, which was significantly lower than the 49% for OSR (odds ratio, 0.19; 95% CI, 0.05-0.74; P = .008). Midterm survival also favored EVAR (hazard ratio, 0.40; 95% CI, 0.21-0.77; P = .028, adjusted for age and sex). Mean follow-up was 20 months, and 1-year survival was 60% for EVAR vs 45% for OSR. Mean length of stay for patients surviving >1 day was 10 days for EVAR and 21 days for OSR (P = .004). Ventilator-dependent respiratory failure was 5% in the EVAR group vs 42% for OSR (odds ratio, 0.08; 95% CI, 0.01-0.62; P = .001). CONCLUSIONS: EVAR of rAAA has a superior perioperative survival advantage and decreased morbidity vs OSR. Although not statistically significant, overall survival favors EVAR. We recommend that EVAR be considered as the first-line treatment of rAAAs and practiced as the standard of care.

Results for primary bypass versus primary angioplasty/stent for intermittent claudication due to superficial femoral artery occlusive disease.

BACKGROUND: Percutaneous transluminal angioplasty ± stent (PTA/S) and surgical bypass are both accepted treatments for claudication due to superficial femoral artery (SFA) occlusive disease. However, long-term results comparing these modalities for primary intervention in patients who have had no prior intervention have not been reported. We report our results with 3-year follow-up. METHODS: We reviewed all lower extremity bypass procedures at Beth Israel Deaconess Medical Center from 2001 through 2009 and all PTA/S performed from 2005 through 2009 for claudication. We excluded all limb salvage procedures and included only those that were undergoing their first intervention for claudication due to SFA disease. We recorded patient demographics, comorbidities, perioperative medications, TASC classification, and runoff. Outcomes included complications, restenosis, symptom recurrence, reinterventions, major amputation, and mortality. RESULTS: We identified 113 bypass grafts and 105 PTA/S of femoral-popliteal lesions without prior interventions. Bypasses were above the knee in 62% (45% vein) and below the knee in 38% (100% vein). Mean age was 63 (bypass) versus 69 (PTA/S; P < .01). Mean length of stay (LOS) was 3.9 versus 1.2 days (P < .01). Bypass grafts were used less for TASC A (17% vs 40%; P < .01) and more for TASC C (36% vs 11%; P < .01) and TASC D (13% vs 3%; P < .01) lesions. There were no differences in perioperative (2% vs 0%; not significant [NS]) or 3-year mortality (9% vs 8%; NS). Wound infection was higher with bypass (16% vs 0%; P < .01). None involved grafts. Bypass showed improved freedom from restenosis (73% vs 42% at 3 years; hazard ratio [HR], 0.4; 95% confidence interval [CI], .23-.71), symptom recurrence (70% and 36% at 3 years; HR, 0.37; 95% CI, .2-.56), and freedom from symptoms at last follow-up (83% vs 49%; HR, 0.18; 95% CI, .08-.40). There was no difference in freedom from reintervention (77% vs 66% at 3 years; NS). Multivariable analysis of all patients showed that restenosis was predicted by PTA/S (HR, 2.5; 95% CI, 1.4-4.4) and TASC D (HR, 3.7; 95% CI, 3.5-9) lesions. Recurrence of symptoms was similarly predicted by PTA/S (HR, 3.0; 95% CI, 1.8-5) and TASC D lesions (HR, 3.1; 95% CI, 1.4-7). Statin use postoperatively was predictive of patency (HR, 0.6; 95% CI, .35-.97) and freedom from recurrent symptoms (HR, 0.6; 95% CI, .36-.93). CONCLUSIONS: Surgical bypass for the primary treatment of claudication showed improved freedom from restenosis and symptom relief despite treatment of more extensive disease, but was associated with increased LOS and wound infection. Statins improved freedom from restenosis and symptom recurrence overall.

Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis.

OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) degrades type IV collagen and enables endothelial cell (EC) migration during angiogenesis and wound healing. Peroxisomal biogenesis factor 2 (PEX2), a by-product of activated MMP-2 autocatalysis, competitively inhibits newly activated MMP-2 from EC surface binding and migration. We hypothesize that PEX2 is elevated during limb ischemia and contributes to poor wound healing, with decreased capillary density. METHODS: Western blot was used to identify PEX2 in the hind limbs of FVB/NJ mice with surgically induced ischemia. The PEX2 effect on healing was evaluated by calculating the area of exposed muscle after wounding the dorsum of mice and administering daily injections with human recombinant PEX2 (hrPEX2). Wounds were also injected with lentivirus-expressing PEX2 (PEX2-LV), harvested on postoperative day 7 and processed for staining. Epithelial gap was assessed with light microscopy. Capillary density was evaluated after wounding Tie2-green fluorescent protein (GFP)(+) transgenic FVB mice (ECs labeled green) and viral transduction with PEX2-LV. Wounds were harvested on postoperative day (POD) 7, frozen in liquid nitrogen, sectioned, and stained with Hoechst. Vessel density was assessed via fluorescence microscopy as the average number of capillaries/10 high-powered fields. Paired t test was used to assess differences between the groups. RESULTS: PEX2 was elevated 5.5 ± 2.0-fold (P = .005) on POD 2 and 2.9 ± 0.69-fold (P = .004) on POD 4 in gastrocnemius muscles of ischemic hind limbs. The wound surface area, or lack of granulation tissue and exposed muscle, decreased daily in all mice but was greater in the hrPEX2-treated mice by 12% to 16% (P < .004). Wounds in the control group were completely covered with granulation tissue by POD 3. Wounds injected with hrPEX2 were not completely covered by POD 7 but continued to have exposed muscle. Microscopic examination of wounds after PEX2-LV viral transduction demonstrated an average epithelial gap of 1.6 ± 0.3 vs 0.64 ± 0.3 µm in control wounds (P < .04). Wounds from Tie2-GFP mice had an average number of 3.8 ± 1.1 capillaries vs 6.9 ± 1.2 in control wounds (P < .007). CONCLUSIONS: Our study links elevated PEX2 to ischemia and poor wound healing. We demonstrate comparative PEX2 elevation in ischemic murine hind limbs. Less granulation tissue is produced and healing is retarded in wounds subjected to hrPEX2 or viral transduction with PEX2-LV. Microscopic examination shows the wounds exhibit fewer capillaries, supporting the hypothesis that PEX2 decreases angiogenesis.

A CXCL5- and bFGF-dependent effect of PDGF-B-activated fibroblasts in promoting trafficking and differentiation of bone marrow-derived mesenchymal stem cells.

Adult bone marrow-derived mesenchymal stem cells (MSCs) are able to differentiate into myofibroblasts and be recruited into wound lesions and contribute to wound healing. The cellular and molecular mechanisms responsible for MSC trafficking and differentiation, however, are poorly understood. Local resting resident fibroblasts are activated after injury and play a critical role in recruiting MSCs. We investigated the role of platelet-derived growth factor-B-activated fibroblasts (PDGF-B-aFBs) in regulating recruitment, migration and differentiation of MSCs from GFP transgenic mice in an in vitro wound healing assay and a novel three-dimensional (3D) model. PDGF-B-aFBs caused significant increases in MSC migration velocity compared to control as demonstrated by time-lapse photography in an in vitro wound healing assay. Consistently, invasion/migration of MSCs into 3D collagen gels was enhanced in the presence of PDGF-B-aFBs. In addition, PDGF-B-aFBs induced differentiation of MSCs into myofibroblast. The regulatory effects of PDGF-B-aFBs are likely to be mediated by basic fibroblast growth factor (bFGF) and epithelial neutrophil activating peptide-78 (ENA-78 or CXCL5) as protein array analysis indicated elevated levels of these two soluble factors in culture supernatant of PDGF-B-aFBs. Blocking antibodies against bFGF and CXCL5 were able to inhibit both trafficking and differentiation of MSCs into 3D collagen gels while supplement of exogenous bFGF and/or CXCL5 promoted invasion/migration of MSCs into 3D collagen gels. Our results reveal that PDGF-B-aFBs play a key role in the recruitment/migration and differentiation of MSCs and implicate a bFGF- and CXCL5-dependent mechanism in mediating these effects.