Five-year results of the LEOPARD trial of commercially available endografts.

OBJECTIVE: The LEOPARD (Looking at EVAR Outcomes by Primary Analysis of Randomized Data) trial is a randomized controlled trial comparing the outcomes of endovascular aneurysm repair (EVAR) using commercially available devices in a real-world population. METHODS: A prospective, randomized, multi-center trial was performed to compare the anatomically fixated (AF) AFX/AFX2 endograft system (Endologix) with endografts with proximal fixation (PF) (Cook Medical Zenith Flex; Gore Excluder; and Medtronic Endurant II) in patients with infrarenal abdominal aortic aneurysms. The primary endpoint was freedom from aneurysm-related complications (ARCs), a composite endpoint consisting of perioperative death (≤30 days), aneurysm rupture, conversion to open surgical repair, postoperative endoleaks, endograft migration (≥10 mm), aneurysm enlargement (≥5 mm), endograft limb occlusion, and device- or aneurysm-related reintervention. RESULTS: The study population was 455 patients enrolled at 56 United States centers: 235 patients were treated with AF devices and 220 with PF devices. The primary endpoint supported noninferiority of the AF cohort at 1 year. The 5-year freedom from ARC Kaplan-Meier estimates were 63.8% for AF patients and 55.5% for PF patients (P = .10). Kaplan-Meier estimates for freedom from aneurysm-related mortality were 98.7% and 97.0% in the AF group and 99.5% and 98.5% in the PF group at 1 and 5 years. There was no difference in aneurysm-related mortality, all-cause mortality, rupture, secondary interventions, and type I and type III endoleak between the two cohorts. The type III endoleak rate at 5 years for the AFX cohort was 1.5% and 0.0% for the comparator cohort (P = .11). There was a lower type II endoleak rate in the AF group at 5 years (78.8% vs 68.4%; P = .037). There were zero open surgical conversions (0.0%) in the AF group and four (2.0%) in the PF group. CONCLUSIONS: The 5-year results from the LEOPARD study demonstrated that there was no clinically significant difference in overall aneurysm-related outcomes between patients randomized to the AFX endograft system or commercially available endografts with proximal fixation.

A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis.

OBJECTIVE: Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. METHODS: PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. RESULTS: The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use. CONCLUSIONS: Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.

Decreased National Rate of below the Knee Amputation in Patients with Popliteal Artery Injury.

BACKGROUND: Popliteal arterial injury (PAI) is the second most common infrainguinal arterial injury after femoral artery injury with an incidence < 0.2%. A 2003 analysis of the National Trauma Data Bank (NTDB) reported a below the knee amputation (BKA) rate of 7.1% in patients with PAI as well as higher risk in those with an associated fracture or nerve injury. Given advances in vascular surgical techniques, improved multidisciplinary care, and expeditious diagnosis with computed tomography angiography, we hypothesized that the national rate of BKA in patients with PAI has decreased and sought to identify risk factors for BKA in patients with PAI. METHODS: A retrospective analysis of the NTDB was performed from 2007 to 2015. Patients ≥15 years of age with PAI were included and grouped by mechanism of injury (blunt versus penetrating). Interfacility transfers were excluded. The primary outcome of interest was BKA. Univariable and multivariable analyses were performed to identify predictors of BKA in patients with PAI. RESULTS: From 4,385,698 patients, 5,143 were identified with PAI (<0.2%) with most involved in a blunt mechanism (56.8%). The overall limb loss rate was 5.1% (decreased from 7.1% in 2003, P = 0.0037). After adjusting for covariates, a blunt mechanism (odds ratio [OR] = 3.53, confidence intervals [CI] = 2.49-5.01, P < 0.001) and open proximal tibia/fibula fracture or dislocation (OR = 2.71, CI = 2.08-3.54, P < 0.001) were independent risk factors for BKA in patients with PAI. A combined popliteal vein injury (PVI) did not increase the risk for BKA (P = 0.64). CONCLUSIONS: The national rate of limb loss in trauma patients with PAI has decreased from 7.1 to 5.1%. A blunt mechanism of injury as well as proximal open tibia/fibula fracture or dislocation continue to be the independent risk factors for BKA. Confirming a previous report, we found a combined PVI not to be associated with higher risk for BKA. Future prospective research to determine other possible contributing factors such as intraoperative hemodynamics and utilization of vascular shunt and fasciotomy appears warranted.

Humerus fracture and combined venous injury increases limb loss in axillary or subclavian artery injury.

OBJECTIVE: Axillosubclavian vessel injury is rare, with most cases occurring after penetrating trauma. A prior database (2002-2006) analysis demonstrated an overall limb loss rate of 2.9%, with no difference between isolated arterial axillosubclavian vessel injury and combined artery/vein axillosubclavian vessel injury. Given increases in advanced vascular surgical techniques, as well as improved multidisciplinary care and expeditious diagnosis with computed tomography angiography, we hypothesized the national rate of limb loss in patients with arterial axillosubclavian vessel injury has decreased. In addition, we attempted to identify current predictors for limb loss in arterial axillosubclavian vessel injury. Finally, we hypothesized that combined artery/vein axillosubclavian vessel injury, as well as associated brachial plexus injury will have a higher risk for limb-loss and mortality compared to isolated arterial axillosubclavian vessel injury. METHODS: A retrospective analysis of the National Trauma Data Bank was performed between 2007 and 2015. All patients ≥ 18 years of age with arterial axillosubclavian vessel injury were included. The primary outcome was limb loss. After a univariable logistic regression model identified significant covariates, we performed a multivariable logistic regression for analysis. RESULTS: Of the total 5,494,609 trauma admissions, 3807 patients had arterial axillosubclavian vessel injury (<0.1%). Of these, 3137 (82.4%) had isolated arterial axillosubclavian vessel injury and 670 (17.6%) had combined artery/vein axillosubclavian vessel injury. The overall limb loss rate was 2.4% (from 2.9% in 2006, p = 0.47). After adjusting for covariates, independent risk factors for limb loss included a combined artery/vein axillosubclavian vessel injury (odds ratio = 3.54, confidence interval = 2.06-6.11, p < 0.001), blunt mechanism (odds ratio = 7.81, confidence interval = 4.21-14.48, p < 0.001), open repair (odds ratio = 2.37, confidence interval = 1.47-3.82, p < 0.001), and open proximal humerus fracture (odds ratio = 8.50, confidence interval = 4.97-14.54, p < 0.001). An associated brachial plexus injury was not associated with limb loss ( p = 0.37). Combined artery/vein axillosubclavian vessel injury was associated with higher risk for mortality compared to isolated arterial axillosubclavian vessel injury (odds ratio = 2.17, confidence interval = 1.73-2.71, p < 0.001). CONCLUSIONS: The national rate of limb loss in trauma patients with arterial axillosubclavian vessel injury has not changed in the past decade. A combined artery/vein axillosubclavian vessel injury is an independent risk factor for limb loss, as well as open repair. However, the strongest risk factor is an open proximal humerus fracture. An associated brachial plexus injury is not associated with increased risk of limb loss. Patients with combined artery/vein axillosubclavian vessel injury have a twofold increased risk of death compared to patients with isolated arterial axillosubclavian vessel injury.

Flow Rates at Thirty Days after Construction of Radiocephalic Arteriovenous Fistula Predict Hemodialysis Function.

BACKGROUND: Construction of radiocephalic arteriovenous fistula (RC-AVF) results in successful hemodialysis (HD) in approximately 40% of end-stage renal disease patients. We investigated whether RC-AVF flow measured by ultrasound 30 days postoperative predicted successful HD. METHODS: In this prospective study, color Doppler ultrasound was used to measure cephalic vein outflow volume at 3 forearm sites at 1 and 3 months postoperatively. RESULTS: Of 45 consecutive patients screened for feasibility of RC-AVF by physical examination and US arterial and vein mapping, 41 were considered suitable for construction of RC-AVF. Mean age was 70 (60-78) years. Of the 41 patients who had a forearm RC-AVF, 25 (61%) proceeded to successful AVF dialysis, 4 (10%) had HD via central venous catheter, and 12 (29%) ceased function within the first 30 days postoperatively. The mean flow at 30 days for patent fistulas was 629 ± 305 ml/min and by the third month had increased to 663 ± 367 mL/min. At 1 month, 8/29 (27.6%) patients had a flow rate <400 mL/min. Two (25%) of these clotted, 2 of 3 with closed revisions went on to HD, and 1 died. Of the 21 patients with a flow rate ≥400 mL/min, 19 (90%) functioned for HD, and 2 (10%) AVF occluded before 1 year, resulting in 17 functioning at 1 year (81% 1-year patency). Sixty-two percent of the low-flow fistulas had successful patency within 1 year. CONCLUSIONS: An RC-AVF flow rate of ≥400 mL/min in the first month predicted more successful HD than low flow (<400 mL/min) (81% vs. 62%). Without intervention, low flow rates do not improve significantly and maturation is unlikely. We recommend imaging for all patients at 30 days to identify and promptly correct stenosis in those with low flow rates.

Hospital Teaching Status and Readmission after Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: Readmission after abdominal aortic aneurysm (AAA) repair to a different (nonindex) hospital has been shown to be associated with high mortality rates. Factors influencing this association remain unknown. The objective of this study was to determine the impact of hospital teaching status on nonindex hospital readmission and mortality. METHODS: An observational analysis of the longitudinally linked California Office of Statewide Health Planning and Development database was conducted from 1995 to 2009. Patients who were readmitted within 30 days after open AAA repair were included. The primary outcome measured was mortality on readmission. RESULTS: Over the 15-year study period, 3,475 readmissions after AAA were analyzed, of which 1,020 (29.4%) were to a nonindex hospital. After adjusting for age, race, gender, insurance, comorbidities, perioperative factors, and reason for readmission, nonindex readmission for patients undergoing their initial operation at a teaching hospital did not impact mortality (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.28-2.17, P = 0.63). Nonindex readmission for patients undergoing their initial operation at a nonteaching hospital, however, significantly increased mortality (OR 1.63, 95% CI 1.04-2.54, P = 0.03). CONCLUSIONS: Readmission to a different hospital is associated with a higher mortality rate for patients undergoing AAA repair at nonteaching hospitals. This effect is not seen in patients having their initial operation performed at teaching hospitals, possibly due to infrastructure at these hospitals allowing for decreased impact from fragmentation of care. In cases where triage to an index hospital for readmission is not possible, communication at a high level between the index hospital and readmission hospital is paramount.

The natural history of type 2 endoleaks after endovascular aneurysm repair justifies conservative management.

Objective Management of type 2 endoleaks after endovascular aneurysm repair has been controversial. Some advocate for conservative management, while others believe that intervention is indicated. This study investigated the natural history of type 2 endoleaks in order to derive direction in management. Methods Patients who had endovascular aneurysm repair at the Veterans Affairs Long Beach were retrospectively identified and computerized tomographic angiography was independently reviewed by a radiologist and a vascular surgeon. Type 2 endoleaks were analyzed for the following outcomes: rupture, duration of endoleak, spontaneous resolution, changes in the size of the aneurysm sac, and reintervention rates. Results Of the 160 patients who had completed required follow-up to date (mean 3 years) after endovascular aneurysm repair, 39 (24.4%) patients were identified as having a type 2 endoleak on computerized tomographic angiography imaging. 6 (15.4%) of these 39 patients required repair due to aneurysm sac growth >1 cm. 2 (5.13%) were repaired with an open procedure and 4 (10.3%) with an endovascular approach. Of these 6 aneurysm leaks requiring repair, 4 (66.7%) had a simultaneous endoleak (types 1 or 3) in addition to the identified type 2 endoleak. Spontaneous resolution of type 2 endoleaks occurred in 16 (41.0%) patients. 4 patients (10.3%) had delayed type 2 endoleaks that presented 4, 9, 12, and 23 months after their 30 day post op computed tomography was normal. None of the 4 patients with delayed type 2 endoleaks required reintervention and none had aneurysm sac growth greater than 5 mm. Conclusions Overall, we found that 85% of patients who had type 2 endoleaks did not require intervention after a mean follow-up time of 3 years. The association of a type 1 or 3 endoleak with a type 2 endoleak was more likely to require correction due to aneurysm expansion >1 cm, thus type 2 endoleaks associated with another type of endoleak require more aggressive management.

Postintervention Patency: A Comparison of Stenting versus Patch Angioplasty for Dysfunctional Hemodialysis Access Sites.

BACKGROUND: Arteriovenous access dysfunction is commonly caused by venous outflow stenosis, leading to thrombosis of the conduit. Given that there are limited lifetime hemodialysis access sites, the preservation of existing sites through novel means is of high priority. This study compares the efficacy of balloon angioplasty and stent placement to surgical patch angioplasty for upper arm (brachium) thrombosed or dysfunctional hemodialysis access sites in a group of patients at a single institution. METHODS: Using the operating room log and electronic medical record system, we retrospectively examined the outcomes of 52 consecutive patients (3 were lost to follow-up), who had either stent placement (34 patients) or patch angioplasty (15 patients) for hemodialysis access salvage to calculate postintervention patency. RESULTS: Initial postinterventional patency (PIP1) for patch angioplasty compared with stent placement was not statistically significant at any time during a mean 6-month follow-up (60% vs. 67.65% at 1 month, 33.33% vs. 41.18% at 3 months, and 13.33% vs. 17.65% at 6 months, respectively; P = 0.75). Patency after secondary reintervention (PIP2) was longer for patients who had stent placement as the initial intervention (n = 15) than patients who had patch angioplasty (n = 5; 100% vs. 80% at 1 month, 66.68% vs. 80% at 3 months, and 46.67% vs. 40% at 6 months, respectively), but again there was no statistically significant difference between the 2 groups (P = 0.84). At last, the initial PIP1 of arteriovenous fistula (AVF) and arteriovenous graft (AVG) salvaged before occlusion was significantly different from that of occluded access sites (40% vs. 10% at 6 months, P = 0.024). CONCLUSIONS: Our data suggest that AVF had a longer postinterventional primary patency than AVG though the difference did not reach statistical significance. Stents extended PIP1 for the thrombosed or failing arteriovenous access longer than patch angioplasty, but the difference was not statistically significant. Patency is longer if intervention is made before graft thrombosis. Our data also indicate better prolongation of patency with a second reintervention (PIP2) if the first intervention was a stent placement. Patch angioplasty appears to be a less attractive alternative for correction of venous outflow stenosis given the more invasive and occasionally technically difficult procedure.

Skin and soft-tissue infections: a critical review and the role of telavancin in their treatment.

Skin and soft-tissue infections (SSTIs) are an important cause of morbidity and mortality among hospitalized patients and a major therapeutic challenge for clinicians. Although uncomplicated SSTIs are managed successfully on an outpatient basis, more serious infections extending to the subcutaneous tissue, fascia, or muscle require complex management. Early diagnosis, selection of appropriate antimicrobials, and timely surgical intervention are key to successful treatment. Surgical-site infections, an important category of SSTI, occur in approximately half a million patients in North America annually. SSTIs are also a potential source for life-threatening bacteremia and metastatic abscesses. Gram-positive organisms, such as Staphylococcus aureus and Streptococcus pyogenes, are the dominant organisms isolated early in the infectious process, whereas gram-negative organisms are found in chronic wounds. Methicillin-resistant S. aureus (MRSA) is a potential bloodstream invader that requires aggressive antimicrobial treatment and surgery. Recent concerns regarding vancomycin activity include heteroresistance in MRSA and increase in the minimum inhibitory concentrations (>1 or 2 µg/mL); however, alternative agents, such as telavancin, daptomycin, linezolid, ceftaroline, dalbavancin, oritavancin, and tedizolid, are now available for the treatment of severe MRSA infections. Here, we present a review of the epidemiology, etiology, and available treatment options for the management of SSTIs.

Surveillance computed tomographic arteriogram does not change management before 3 years in patients who have a normal post-EVAR study.

BACKGROUND: Standard surveillance after endovascular abdominal aortic aneurysm repair (EVAR) consists of periodic computed tomographic arteriographies (CTAs) usually performed at postoperative months 1, 6, and 12, and then annually. This imaging regimen is expensive and exposes patients to the hazards of radiation and intravenous contrast. We hypothesized that a normal 1-month CTA after EVAR with no endoleak or other significant abnormality predicts a low rate of future complications, which would justify a reduction in frequency of subsequent CTAs. METHODS: We identified 106 consecutive patients who underwent EVAR at a single hospital from 2003 to 2010 and reviewed all their CTAs. Fifteen patients for whom we could not review a postoperative CTA were excluded. Of the remaining 91 patients, 70 (76.9%) had no abnormality on their CTA at 1 month after EVAR. The medical records of these 70 patients were analyzed for subsequent complications and interventions related to EVAR. RESULTS: The mean patient follow-up was 3.4 ± 2.1 years. Five of the 70 (7.1%) patients with a normal post-EVAR CTA developed late complications consisting of 1 type I endoleak, 3 type II endoleaks, and 1 case of endotension. Only the type I endoleak and one of the type II endoleaks met criteria for intervention, and in both cases, the endoleaks were discovered >3 years after EVAR. Log-rank test showed a statistically significant increased freedom from aneurysm sac expansion in patients with a normal compared with an abnormal 1-month CTA (P < 0.001). CONCLUSIONS: For patients who have a normal CTA with no endoleak 1 month after EVAR, it is reasonable to consider less-frequent CTA surveillance because no significant complications requiring intervention occurred before 3 years. This would decrease unnecessary CTAs and health care expenditures as well as minimize patient exposure to radiation and intravenous contrast.

Source control review in clinical trials of anti-infective agents in complicated intra-abdominal infections.

In clinical trials of complicated intra-abdominal infections, assessment of adequacy of the initial surgical approach to the management of the infection is of considerable importance in determining outcome. Antibiotic therapy would not be expected to adequately treat the infection if the surgical procedure was inadequate with respect to source control. Inclusion of such cases in an efficacy analysis of a particular therapeutic antibiotic may confound the results. We analyzed the source control review process used in double-blind clinical trials of antibiotics in complicated intra-abdominal infections identified through systematic review. We searched MEDLINE (PubMed) and ClinicalTrials.gov databases to identify relevant articles reporting results from double-blind clinical trials that used a source control review process. Eight prospective, randomized, double-blind, multicenter, clinical trials of 5 anti-infective agents in complicated intra-abdominal infections used a source control review process. We provide recommendations for an independent, adjudicated source control review process applicable to future clinical trials.

The comparative effectiveness of surgeons over interventionalists in endovascular repairs of abdominal aortic aneurysm.

OBJECTIVE: Comparative effectiveness research has mostly been focused on comparison of treatment techniques. The goal of the present study was to extend the research to physician specialty. BACKGROUND: Both surgeons and interventionalists (cardiologists and radiologists) are involved in endovascular repairs (EVAR) of aortic aneurysms, with different residency education, operative experience, preoperative assessment and patient selection, and postoperative continuity of care. METHODS: Retrospective analysis was performed using the Nationwide Inpatient Sample from 1998 to 2009. Patients undergoing EVAR for abdominal aortic aneurysm were identified with International Classification of Diseases, Ninth Revision, procedure code 39.71. Using physician identifiers available in the database, surgeons were identified by case experience in the same calendar year with elective open AAA repairs, arteriovenous fistula repairs, or carotid endarderectomy. Multivariate analysis adjusted for physician volume, AAA ruptured status, patient demographic and comorbidities, and hospital characteristics. RESULTS: A total of 28,094 EVARs were analyzed. Unadjusted mortality rates, length of stay, and total hospital charges were significantly higher for patients treated by interventionalists than those by surgeons (all Ps < 0.001). This difference persisted on multivariate analysis, where interventionalists were associated with increased likelihood of mortality (odds ratio = 1.39; 95% confidence interval, 1.04-1.89), longer length of stay (1.32 days; 95% confidence interval, 1.03-1.62), and higher total hospital charges ($19,312; 95% confidence interval, 16,471-22,153). CONCLUSIONS: Physician specialty is associated with patient outcomes. Surgeons are associated with improved outcomes, with lower mortality, shorter length of stay, and lower charges for EVAR cases, when compared with interventionalists. This finding has significant implications for future comparative effectiveness research and potential policy changes in patient referrals or physician admitting privileges.

Hyperspectral image measurements of skin hemoglobin compared with transcutaneous PO2 measurements.

BACKGROUND: Objective measurements of skin blood flow would have predictive value in assessing the potential for wound healing. In this study, we evaluated the relationship between transcutaneous PO(2) (tcPO(2)) measurements and hyperspectral reflectance spectroscopy measurements of oxygenated hemoglobin (OxyHgb), deoxygenated hemoglobin (DeOxyHgb), total hemoglobin (Sum = OxyHgb + DeOxyHgb), and hemoglobin saturation (Sat = 100 × OxyHgb/Sum). The effect of varying tcPO(2) probe temperatures (37 °C, 41 °C, and 45 °C) was also assessed. METHODS: A Hypermed Oxy-Vu system was used for hyperspectral imaging, with measurements performed 2 minutes after removing tcPO(2) probes (Radiometer). Twenty-three sections of foot or wrist skin in four healthy volunteers were measured at 37 °C, 41 °C, and 45 °C using both modalities. RESULTS: TcPO(2) at 37 °C was 23.1 ± 24.8 mm Hg, increasing to 63.0 ± 27.3 mm Hg at 45 °C. OxyHgb levels increased from 52.4 ± 25.4 at 37 °C to 101.3 ± 23.8 at 45 °C. Linear regression analysis of the HSI data at 37 °C showed a positive correlation between tcPO(2) and OxyHgb (r(2) = 0.35, P = 0.003), tcPO(2) and DeOxyHgb (r(2) = 0.63, P < 0.0001), and tcPO(2) and Sum (r(2) = 0.60, P < 0.0001), but not Sat (r(2) = 0.001, P = 0.92). As the probe temperature increased, the correlations of tcPO(2) with OxyHgb, DeoxyHgb, and Sum became progressively much weaker. CONCLUSION: A marked increase in the HSI measurements of OxyHgb in skin exposed to heated tcPO(2) probes was observed, with tcPO(2), Sat, and Sum measurements also observed to increase with temperature. These measurements were influenced by heat inducing vasodilatation in the superficial skin layers. HSI measurements may be clinically useful for measuring wound healing potential, as they correlate with tcPO(2) levels under normal physiological conditions.

PATENCY-2 trial of vonapanitase to promote radiocephalic fistula use for hemodialysis and secondary patency.

OBJECTIVE: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. METHODS: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. RESULTS: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, (p = 0.33). The Kaplan-Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73-82) for vonapanitase and 76% (95% CI, 70-82) for placebo (p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo (p = 0.054). The Kaplan-Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44-55) for vonapanitase and 43% (95% CI, 35-50) for placebo (p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. CONCLUSIONS: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 (https://clinicaltrials.gov/ct2/show/NCT02414841).

Laparoscopic surgery significantly reduces surgical-site infections compared with open surgery.

BACKGROUND: Surgical-site infections (SSIs) are nosocomial infectious complications causing significant morbidity, mortality, and hospital costs. Recently, the US Department of Human Health Services and the Centers for Medicare and Medicare Services outlined measures intended to decrease and prevent hospital-acquired infections such as SSI. This study aimed to compare the incidence of SSI after laparoscopic and open surgery. METHODS: A retrospective analysis of a large administrative, clinical, and financial database (University Health System Consortium) of US Academic Medical Centers and affiliated community hospitals was conducted. Patients who underwent laparoscopic (n = 94,665) or open (n = 36,965) appendectomy, cholecystectomy, antireflux surgery, or gastric bypass between 2004 and 2008 were included in the analysis. The main outcome measure was inpatient diagnosis of SSI after laparoscopic and open surgery. RESULTS: During the 45-month study period, a total of 131,630 patients underwent one of four selected procedures. Overall, the incidence of SSI was significantly lower in laparoscopic (483 of 94,665, 0.5%) than in open (669 of 36,965, 1.8%) surgery (p < 0.01). Largely, laparoscopic techniques offered a protective effect against SSI (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.25-0.31). Patients treated with laparoscopy were 72% less likely to experience an SSI. This protective effect was shown to be sustained after stratification by severity of illness (minor: OR, 0.19; 95% CI, 0.14-0.26; moderate: OR, 0.30; 95% CI, 0.25-0.35; major/extreme: OR, 0.65; 95% CI, 0.54-0.79), admission status (elective: OR, 0.25; 95% CI, 0.20-0.31; urgent: OR, 0.38; 95% CI, 0.28-0.53; emergent: OR, 0.29; 95% CI, 0.25-0.34), and wound classification (dirty wounds: OR, 0.45; 95% CI, 0.37-0.54). CONCLUSIONS: In US academic medical centers, laparoscopy significantly reduces SSI. Patients treated with laparoscopic procedures are less likely to experience SSI. After stratification by severity of illness, admission status, and wound classification, laparoscopic techniques showed a protective effect against SSI.

Is postoperative chronic pain syndrome higher with mesh repair of inguinal hernia?

Chronic postoperative pain has been associated with mesh repair in meta-analysis of clinical trials. We compared the incidence of early complications, recurrence, and chronic pain syndrome in anatomic and mesh repairs in 200 patients. We defined chronic pain syndrome as pain in the inguinal area more than 3 months after inguinal hernia repair, patient referral to pain management, or necessity of a secondary procedure for pain control. The mean follow-up time was 4 years and 2 months for anatomic repair and 3 years and 7 months for mesh repair. The clinical outcomes did not reveal a significant disparity between the 100 consecutive patients who had mesh repair versus the 100 patients who had anatomic repair with regard to the incidence of superficial wound infection (0 vs. 2%, P = 0.497), testicular swelling (12 vs. 7%, P = 0.335), hematoma (1 vs. 0%, P = 0.99), recurrence (3 vs. 2%, P = 0.99), or chronic postoperative pain (4 vs. 1%, P = 0.369). The anatomic procedure without mesh should continue to be offered to patients who have an initial inguinal hernia repair.

Trials of endovascular treatment for superficial femoral artery occlusive lesions: a call for medically managed control patients.

BACKGROUND: The prevalence of occlusive peripheral vascular disease in the superficial femoral artery approaches 20% in patients over the age of 60. Symptomatic peripheral arterial disease (intermittent claudication) is present in 3% to 7% of patients over the age of 60. The attraction of minimally invasive, percutaneous endovascular angioplasty (PTA) for this large number of patients has resulted in multiple trials of new PTA +/- stenting devices. The purpose of this report is to determine whether trials should include controlled patients who have optimal medical management including supervised exercise. METHODS AND RESULTS: In 2007 through 2008, there were 12 active trials of PTA and stent with 9 of the trials randomized and 6 trials using PTA as the control arm. No trial used a medically managed group. Between 1990 and 2008, a search of PubMed disclosed six publications (five randomized trials) comparing PTA +/- stent with medically (exercise) managed claudicants. None of the medically managed patient groups experienced a significant increase in ABI, whereas endovascular patients had an early increase in ABI, which was variably sustained to 1 and 2 years. However, after 6 months, the maximum walking distance was significantly increased in the exercised patients and remained longer than that of the interventional group in four of five trials at 1 to 2 years. CONCLUSION: Endovascular treatment was superior to medical treatment in functional outcome at 1 year in only one of the five randomized trials for claudication. In the other four trials, medical treatment produced a greater maximum walking distance at 1 to 2 years. Current trials lack optimal medical controls. New trials of PTA + stent should include a medically managed group of patients in a supervised exercise program as the comparator arm. The outcome measure should be maximum walking distance to demonstrate added functional benefit of the new device.

Ertapenem versus cefotetan prophylaxis in elective colorectal surgery.

BACKGROUND: Ertapenem, a long-acting carbapenem, may be an alternative to the recommended prophylactic antibiotic cefotetan. METHODS: In this randomized, double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis with ertapenem, as compared with cefotetan, in patients undergoing elective colorectal surgery. A successful outcome was defined as the absence of surgical-site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively. All adverse events were collected until 14 days after the administration of antibiotic prophylaxis. RESULTS: Of the 1002 patients randomly assigned to study groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group and 334 in the cefotetan group) were included in the per-protocol analysis. After adjustment for strata, in the modified intention-to-treat analysis, the rate of overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1 to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%; 95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the superiority of ertapenem. In the modified intention-to-treat analysis, the most common reason for failure of prophylaxis in both groups was surgical-site infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population, the overall incidence of Clostridium difficile infection was 1.7% in the ertapenem group and 0.6% in the cefotetan group (P=0.22). CONCLUSIONS: Ertapenem is more effective than cefotetan in the prevention of surgical-site infection in patients undergoing elective colorectal surgery but may be associated with an increase in C. difficile infection. (ClinicalTrials.gov number, NCT00090272 [ClinicalTrials.gov].).

Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms.

BACKGROUND: Telavancin is an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action. METHODS: We conducted 2 parallel, randomized, double-blind, active-control, phase 3 studies with a prespecified pooled analysis design. Patients aged > or = 18 years who had complicated skin and skin-structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin (10 mg/kg intravenously every 24 h) or vancomycin (1 g intravenously every 12 h). RESULTS: A total of 1867 patients were randomized and received > or = 1 dose of study medication. In the clinically evaluable population, at 7-14 days after receipt of the last antibiotic dose, success was achieved in 88% and 87% of patients who received telavancin and vancomycin, respectively (95% confidence interval for the difference, -2.1 to 4.6). Methicillin-resistant Staphylococcus aureus was isolated at baseline from samples from 579 clinically evaluable patients. Among these patients with methicillin-resistant S. aureus infection, cure rates were 91% among patients who received telavancin and 86% among patients who received vancomycin (95% confidence interval for the difference, -1.1 to 9.3). Microbiologic eradication among patients infected with methicillin-resistant S. aureus was 90% in the telavancin treatment group and 85% in the vancomycin treatment group (95% confidence interval for the difference, -0.9 to 9.8). Therapy was discontinued because of adverse events in 8% and 6% of patients who received telavancin and vancomycin, respectively. Except for mild taste disturbance, nausea, vomiting, and serum creatinine concentration elevation in the telavancin treatment group and pruritus in the vancomycin treatment group, adverse events were similar between groups with regard to type and severity. CONCLUSIONS: Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.