Jeffrey J. Siracuse

Body Mass Index: Surgical Site Infections and Mortality after Lower Extremity Bypass from the National Surgical Quality Improvement Program 2005—2007

BACKGROUNDnPatients undergoing lower extremity bypass are at high risk for surgical site infections (SSI). We examined lower extremity bypasses by graft origin and body mass index (BMI) classification to analyze differences in postoperative mortality and SSI occurrence.nnnMETHODSnThe 2005-2007 National Surgical Quality Improvement Program (NSQIP), a multi-institutional risk-adjusted database, was queried to compare perioperative mortality (30-day), overall morbidity, and SSIs after lower extremity arterial bypass for peripheral arterial disease. Bypass was stratified by graft origin as aortoiliac, femoral, or popliteal. Patient demographics, comorbidities, operative, and postoperative occurrences were analyzed.nnnRESULTSnThere were 7,595 bypasses performed (1,596 aortoiliac, 5,483 femoral, and 516 popliteal). Mortality was similar regardless of bypass origin (2.8%, 2.4%, and 2.7%; p = 0.57). SSIs occurred in 11% of overall cases (10%, 11%, and 11%; p = 0.47). Graft failure was significantly associated with postoperative SSI occurrence (odds ratio [OR] = 2.4, 95% confidence interval [CI] 1.9-3.1, p < 0.001), as was postoperative sepsis (OR = 6.5, 95% CI 5.1-8.3, p < 0.001). Independent predictors of mortality were age, aortoiliac bypass origin, underweight, normal weight, morbid obesity (compared to overweight and obese), end-stage renal disease, poor preoperative functional status, preoperative sepsis, chronic obstructive pulmonary disease, hypoalbuminemia, and cardiac disease. Independent predictors of SSI were obesity, diabetes, poor preoperative functional status, a history of smoking, and female gender.nnnCONCLUSIONnSSIs occur frequently after lower extremity bypass regardless of bypass origin and are associated with early graft failure and sepsis. Obesity predicts postoperative SSI. Mortality risk was greatest in the underweight, followed by morbidly obese and normal-weight patients, while overweight and mild to moderate obesity were associated with the lowest mortality.

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

BACKGROUNDnPercutaneous 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.nnnMETHODSnWe 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.nnnRESULTSnWe 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).nnnCONCLUSIONSnSurgical 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.

Health care and socioeconomic impact of falls in the elderly

BACKGROUNDnElderly falls are associated with long hospital stays, major morbidity, and mortality. We sought to examine the fate of patients ≥75 years of age admitted after falls.nnnMETHODSnWe reviewed all fall admissions in 2008. Causes, comorbidities, injuries, procedures, mortality, readmission, and costs were analyzed.nnnRESULTSnSeven hundred eight patients ≥75 years old were admitted after a fall, with 89% being simple falls. Short-term mortality was 6%. Male sex, atrial fibrillation, acute myocardial infarction, congestive heart failure (CHF), intracranial hemorrhage, hospital-acquired pneumonia, trigger events, Clostridium difficile, and intubation were predictors of death (P < .05). Thirty-day readmission occurred in 14%; CHF, craniotomy, and acute renal failure were predictive. The median cost of hospitalization was

Endovascular vs open repair for ruptured abdominal aortic aneurysm

11,000 with cardiac disease, anemia, major orthopedic and neurosurgical procedures, pneumonia, and intubation as predictive.nnnCONCLUSIONSnSimple falls in the elderly have high morbidity, mortality, and costs. Methodologies for prevention are warranted and should be studied intensively.

O-Glycosylation Regulates Ubiquitination and Degradation of the Anti-Inflammatory Protein A20 to Accelerate Atherosclerosis in Diabetic ApoE-Null Mice

OBJECTIVEnEndovascular 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).nnnMETHODSnRecords 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.nnnRESULTSnSeventy-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).nnnCONCLUSIONSnEVAR 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.

A20 Protects Mice from Lethal Liver Ischemia Reperfusion Injury by Increasing Peroxisome Proliferator-Activated Receptor-α Expression

Background Accelerated atherosclerosis is the leading cause of morbidity and mortality in diabetic patients. Hyperglycemia is a recognized independent risk factor for heightened atherogenesis in diabetes mellitus (DM). However, our understanding of the mechanisms underlying glucose damage to the vasculature remains incomplete. Methodology/Principal Findings High glucose and hyperglycemia reduced upregulation of the NF-κB inhibitory and atheroprotective protein A20 in human coronary endothelial (EC) and smooth muscle cell (SMC) cultures challenged with Tumor Necrosis Factor alpha (TNF), aortae of diabetic mice following Lipopolysaccharide (LPS) injection used as an inflammatory insult and in failed vein-grafts of diabetic patients. Decreased vascular expression of A20 did not relate to defective transcription, as A20 mRNA levels were similar or even higher in EC/SMC cultured in high glucose, in vessels of diabetic C57BL/6 and FBV/N mice, and in failed vein grafts of diabetic patients, when compared to controls. Rather, decreased A20 expression correlated with post-translational O-Glucosamine-N-Acetylation (O-GlcNAcylation) and ubiquitination of A20, targeting it for proteasomal degradation. Restoring A20 levels by inhibiting O-GlcNAcylation, blocking proteasome activity, or overexpressing A20, blocked upregulation of the receptor for advanced glycation end-products (RAGE) and phosphorylation of PKCβII, two prime atherogenic signals triggered by high glucose in EC/SMC. A20 gene transfer to the aortic arch of diabetic ApoE null mice that develop accelerated atherosclerosis, attenuated vascular expression of RAGE and phospho-PKCβII, significantly reducing atherosclerosis. Conclusions High glucose/hyperglycemia regulate vascular A20 expression via O-GlcNAcylation-dependent ubiquitination and proteasomal degradation. This could be key to the pathogenesis of accelerated atherosclerosis in diabetes.

Prosthetic graft infections involving the femoral artery

The nuclear factor‐κB inhibitory protein A20 demonstrates hepatoprotective abilities through combined antiapoptotic, anti‐inflammatory, and pro‐proliferative functions. Accordingly, overexpression of A20 in the liver protects mice from toxic hepatitis and lethal radical hepatectomy, whereas A20 knockout mice die prematurely from unfettered liver inflammation. The effect of A20 on oxidative liver damage, as seen in ischemia/reperfusion injury (IRI), is unknown. In this work, we evaluated the effects of A20 upon IRI using a mouse model of total hepatic ischemia. Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)‐mediated gene transfer. Although only 10%‐25% of control mice injected with saline or the control rAd.β galactosidase survived IRI, the survival rate reached 67% in mice treated with rAd.A20. This significant survival advantage in rAd.A20‐treated mice was associated with improved liver function, pathology, and repair potential. A20‐treated mice had significantly lower bilirubin and aminotransferase levels, decreased hemorrhagic necrosis and steatosis, and increased hepatocyte proliferation. A20 protected against liver IRI by increasing hepatic expression of peroxisome proliferator‐activated receptor alpha (PPARα), a regulator of lipid homeostasis and of oxidative damage. A20‐mediated protection of hepatocytes from hypoxia/reoxygenation and H2O2‐mediated necrosis was reverted by pretreatment with the PPARα inhibitor MK886. In conclusion, we demonstrate that PPARα is a novel target for A20 in hepatocytes, underscoring its novel protective effect against oxidative necrosis. By combining hepatocyte protection from necrosis and promotion of proliferation, A20‐based therapies are well‐poised to protect livers from IRI, especially in the context of small‐for‐size and steatotic liver grafts. Liver Transpl 15:1613–1621, 2009.

Antiplatelet agents, warfarin, and epidemic intracranial hemorrhage

BACKGROUNDnProsthetic graft infection is a major complication of peripheral vascular surgery. We investigated the experience of a single institution over 10 years with bypass grafts involving the femoral artery to determine the incidence and risk factors for prosthetic graft infection.nnnMETHODSnA retrospective cohort single-institution review of prosthetic bypass grafts involving the femoral artery from 2001 to 2010 evaluated patient demographics, body mass index, comorbidities, indications, location of bypass, type of prosthetic material, case urgency, and previous ipsilateral bypass or percutaneous interventions and evaluated the incidence of graft infections, amputations, and mortality.nnnRESULTSnThere were 496 prosthetic grafts identified with a graft infection rate of 3.8% (n = 19) at a mean follow-up of 27 months. Multivariable analysis showed that redo bypass (hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.2-15.0), active infection at the time of bypass (HR, 5.2; 95% CI, 1.9-14.2), female gender (HR, 4.5; 95% CI, 1.6-12.7), and diabetes mellitus (HR, 4.6; 95% CI, 1.5-14.3) were significant predictors of graft infection. Graft infection was predictive of major lower extremity amputation (HR, 9.8; 95% CI, 3.5-27.1), as was preoperative tissue loss (HR, 4.7; 95% CI, 1.8-11.9). Graft infection did not predict long-term mortality; however, chronic renal insufficiency (HR, 2.3; 95% CI, 1.6-3.4), tissue loss (HR, 1.4; 95% CI, 1.0-1.9), and active infection (HR, 2.3; 95% CI, 1.6-3.4) did. Infected grafts were removed 79% of the time. Staphylococcus epidermidis (37%) and methicillin-sensitive Staphylococcus aureus (26%) were the most common pathogens isolated.nnnCONCLUSIONSnRedo bypass, female gender, diabetes, and active infection at the time of bypass are associated with a higher risk for prosthetic graft infection and major extremity amputation but do not confer an increased risk of mortality. Autologous vein for lower extremity bypass and endovascular interventions should be considered when feasible in high-risk patients.

A20-mediated Modulation of Inflammatory and Immune Responses in Aortic Allografts and Development of Transplant Arteriosclerosis

BACKGROUNDnAtrial fibrillation prophylaxis with warfarin and strong antiplatelet agent use in cardiovascular diseases has increased the incidence of anticoagulation in the elderly. We studied traumatic intracranial hemorrhage (TICH) in patients ≥55 years of age on anticoagulation and antiplatelet agents in a stable population.nnnMETHODSnWe used a Level 1 Trauma Center registry study comparing TICH in patients on anticoagulation drugs during the index periods 1999 to 2000 (T1) and 2007 to 2008 (T2).nnnRESULTSnA total of 526 TICH patients were seen in T1 and T2 (age, 77.6 vs 77.5 years; not significant [NS]), with the rate doubling from 6.2% to 12.3% of all trauma activations (P < .01). There was no increase in atrial fibrillation, warfarin use, or CHADS(2) scores in atrial fibrillation patients on anticoagulation therapy. TICH in patients taking antiplatelet agents increased 5-fold (2.2 % vs 10.3%; Pxa0< .01). Overall TICH mortality rate was the same (12.4% vs 12.2%, NS). TICH mortality among patients on therapeutic warfarin was greater in T1 (26%; P < .05), but mortality was similar to TICH in patients not on anticoagulants in T2 (19% vs 12.2%, NS), suggesting treatment improved. Prevalence and mortality of TICH in patients on antiplatelet agents were similar to TICH in patients on warfarin.nnnCONCLUSIONnTICH in patients on anticoagulants is epidemic in patients ≥55 years of age. Despite national trends, our well-served population has not seen an increase in warfarin use for atrial fibrillation. Instead, use of antiplatelet agents has increased and is associated with an increased incidence of TICH.

Time is brain the Gifford factor - or: Why do some civilian gunshot wounds to the head do unexpectedly well? A case series with outcomes analysis and a management guide.

Background. Transplant arteriosclerosis (TA) is the pathognomonic feature of chronic rejection, the primary cause of allograft failure. We have shown that the NF-&kgr;B inhibitory protein A20 exerts vasculoprotective effects in endothelial and smooth muscle cells (SMC), and hence is a candidate to prevent TA. We sought direct proof for this hypothesis. Methods. Fully mismatched, C57BL/6 (H2b) into BALB/c (H2d), aorta to carotid allografts were preperfused with saline, recombinant A20 adenovirus (rAd.A20) or rAd.&bgr;-galactosidase (&bgr;-gal), implanted, harvested 4 weeks after transplantation, and analyzed by histology, immunohistochemistry, and immunofluorescence staining. We measured indoleamine 2,3-dioxygenase, interleukin-6, and transforming growth factor-&bgr; mRNA and protein levels in nontransduced, and rAd.A20 or rAd.&bgr;-gal-transduced human SMC cultures after cytokine treatment. Results. Vascular overexpression of A20 significantly reduced TA lesions. This correlated with decreased graft inflammation and increased apoptosis of neointimal SMC. Paradoxically, T-cell infiltrates increased in A20-expressing allografts, including the immunoprivileged media, which related to A20 preventing indoleamine 2,3-dioxygenase upregulation in SMC. However, infiltrating T cells were predominantly T-regulatory cells (CD25+/Forkhead Box P3 [FoxP3+]). This agrees with A20 inhibiting interleukin-6 and promoting transforming growth factor-&bgr; production by medial SMC and in SMC cultures exposed to cytokines, which favors differentiation of regulatory over pathogenic T cells. Conclusions. In summary, A20 prevents immune-mediated remodeling of vascular allografts, therefore reduces TA lesions by affecting apoptotic and inflammatory signals and modifying the local cytokine milieu to promote an immunoregulatory response within the vessel wall. This highlights a novel function for A20 in local immunosurveillance, which added to its vasculoprotective effects, supports its therapeutic promise in TA.