The effect of myelopathic symptoms on hospital costs, length of stay, and discharge location in anterior cervical discectomy and fusion.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common clinical degenerative disease treated with anterior cervical discectomy and fusion (ACDF), which seriously impacts quality of life and causes severe disability. The objective of the study was to determine the effect of different characteristics of the neurological deficit found in myelopathic patients undergoing ACDFs on hospital cost, length of stay (LOS), and discharge location. METHODS: This is a retrospective review of ACDF cases performed at a single institution by multiple surgeons from 2011 to 2017. Patient symptomatology, complications, comorbidities, demographics, surgical time, LOS, and discharge location were collected. Patients with readmissions or reoperations were excluded. Symptoms evaluated were based on clinical diagnosis, Japanese Orthopaedic Association classification, Ranawat grade, and Cooper scales. Symptoms were further grouped using principal component analysis. Cost was defined as surgical episode hospital stay costs plus outpatient clinic costs plus discharge disposition cost. Multivariate linear regression models were created to evaluate correlations with outcomes. The primary outcome was total 90-day hospital costs. Secondary outcomes were discharge location and LOS. RESULTS: A total of 250 patients were included in the analyses. Discharge location, neuromonitoring use, number of surgical vertebral levels, cage use, LOS, surgical time, having a complication, and sex were all found to be predictive of total 90-day costs. Myelopathic symptomatology was not found to be associated with increased 90-day costs (p ≥ 0.131) when correcting for these other factors. Lower-extremity functionality was found to be associated with increased LOS (p < 0.0001). Upper-extremity myelopathy was found to be associated with increased discharge location needs (p < 0.0001). CONCLUSIONS: Cervical myelopathy was not found to be predictive of total 90-day costs using symptomatology based on multiple myelopathy grading systems. Lower-extremity functionality was, however, found to predict LOS, while upper-extremity myelopathy was found to predict increased discharge location needs. This implies that preoperative deficits from myelopathy should not be considered in a bundled payment system; however, certain myelopathic symptoms should be considered when determining the cost of care.

Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma.

Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.

Heterogeneous and dynamic lumen remodeling of the entire infrainguinal vein bypass grafts in patients.

OBJECTIVE: To examine the regional variation and temporal change in lumen size along the entire autogenous vein bypass graft used for treating arterial occlusive disease in lower extremity and to explore the factors associated with graft expansive or constrictive remodeling. METHODS: Patients were prospectively scanned using contrast-enhanced computed tomography at 1 week and 1, 6, and 12 months postoperatively to obtain lumen cross-sectional areas at 1-mm intervals along the entire grafts. Graft lumen remodeling characteristics and the associated demographic and clinical factors were examined. RESULTS: Fifty-six patients with at least two consecutive computed tomography scans were analyzed. Patients with a composite or longer graft, or with diabetes, had a larger lumen cross-sectional area variation along the graft. The mean lumen cross-sectional areas of all the grafts demonstrated no significant changes through 12 months. However, individually, graft remodeling was time dependent and there was a more dramatic change in lumen cross-sectional area within the first postoperative month. At 12 months, a near equal distribution between expansive and constrictive grafts existed. A negative relation between the initial lumen diameters and the subsequent lumen diameter changes was observed. Eleven grafts failed within 12 months; failed and patent grafts had similar mean lumen cross-sectional areas at all four time points, but failed grafts had a larger maximal local cross-sectional area reduction from 1 week to 1 month (58.0 ± 6.7% vs 38.1 ± 3.1%, mean ± standard error of the mean, failed vs patent, P = .004). Black patients had a smaller mean lumen cross-sectional area than white patients at all four time points and also had a higher early percent mean area reduction (-20.5 ± 6.3% vs -1.0 ± 3.7%, black vs white, P = .018). Cilostazol use was associated with early expansive graft remodeling. CONCLUSIONS: Vein grafts remodel heterogeneously and dynamically. Remodeling is associated with initial graft lumen size, race, and cilostazol use. It is found that remodeling that produces some critical minimum area or maximal percent reduction during the first postoperative month may predispose to vein graft failure. These findings offer insight into further investigation to examine the underlying mechanisms and opportunities to improve graft remodeling and durability.

Results of chimney endovascular aneurysm repair as used in the PERICLES Registry to treat patients with suprarenal aortic pathologies.

BACKGROUND: The prevailing evidence calls for using chimney/snorkel endovascular repair (ch-EVAR) with one or two chimney grafts. No studies up to now focus on its applicability and results for the treatment of suprarenal aortic pathologies (SRAP). Hence, we evaluated the clinical and radiologic results of ch-EVAR treatment for SRAP placing three or more chimney grafts within the PERICLES Registry. METHODS: Data from 517 patients suffering complex aortic pathologies treated by ch-EVAR between 2008 and 2014 at 13 European and U.S. centers were retrospectively reviewed and analyzed. RESULTS: Sixty-seven ch-EVAR-treated patients (12.9% of the entire PERICLES cohort) presented SRAP (83.5% elective, 16.5% urgent). The majority of patients (95.5%) received three chimney grafts; four patients received four chimney grafts. The Endurant device was the most commonly used (35.8%) followed by the Zenith abdominal endograft (19.4%). Overall, 204 chimney grafts were placed (56.7% covered self-expandable, 40.3% covered balloon-expandable stents, and 10.4% bare metal balloon-expandable stents). At a median follow-up of 24 months (range, 0.1-67.0 days), 30-day mortality was 6.1% (4 patients), and the overall mortality was 16.4% (11 patients). Overall survival was 87.4% (range, 79.5%-96.0%) at 1 year, 81.8% (range, 72.2%-92.2%) at 2 years and thereafter. Type IA endoleak was noted in nine patients (13.4%) intraoperatively and successfully treated in seven cases (97.1% technical success). Aneurysm sac diameter significantly decreased from 70.5 ± 19.3 mm to 66.9 ± 20.6 mm (P < .001) at last follow-up. Ischemic stroke or transient ischemic attack were noted in two patients (2.9%). Chimney occlusion was detected in six renal arteries (9.5%) and two superior mesenteric arteries (3.2%). No patients required chronic hemodialysis. All occluded superior mesenteric artery grafts were successfully rescued using endovascular approaches. CONCLUSIONS: The midterm use of ch-EVAR for the treatment SRAP seems to be safe, highlighting its applicability for the treatment of rupture threatening pathologies and seal zone lengthening as in type IA endoleaks after EVAR. However, the incidence of type IA endoleaks, chimney graft occlusions, and ischemic stroke rates is higher compared with the prevailing single chimney evidence. Longer follow-up with more cases is needed to establish the exact performance of this treatment in SRAP.

Impact of hospital volume on patient safety indicators and failure to rescue following open aortic aneurysm repair.

OBJECTIVE: Failure to rescue (FTR), a patient safety indicator (PSI) defined, codified, and adjudicated by the Agency for Healthcare Research and Quality, is classified as a preventable inpatient death following major complications. FTR has been reported to be a significant driver of postoperative mortality after open abdominal aortic aneurysm (OAAA) repair. The association between hospital volume (HV) and mortality is well known; however, the mechanisms responsible for these improved outcomes and relative contribution to observed interhospital variation is poorly understood. Similarly, HV influence on specific complications predictive of FTR is unknown; therefore, we sought to determine how HV influences risk and contributes to interhospital variation in PSI events leading to FTR and/or in-hospital mortality after OAAA repair. METHODS: The Vizient database (174 academic/nonacademic hospitals) was queried for all OAAA repairs (elective, n = 2827; nonelective, n = 1622) completed from 2012 to 2014. The primary endpoint was combined FTR and/or in-hospital 30-day mortality. Risk-adjusted rates of complications, Agency for Healthcare Research and Quality-designated PSIs, and FTR were determined. Additional modeling identified PSIs associated with FTR, whereas HV effects on PSIs and FTR were evaluated using mixed-effect models accounting for interhospital variation. Proportion of variation attributable to HV was estimated by contrasting hospital random effect variances in the presence/absence of volume effects. RESULTS: The combined overall FTR/in-hospital 30-day mortality rate was 9.3% (n = 414). For elective and nonelective cases, the overall FTR and 30-day mortality rates were: FTR, 1.6%, 4.9%; and 30-day in-hospital mortality, 3.4%, 17.5%, respectively. HV significantly influenced FTR/30-day in-hospital mortality (P < .0001). FTR/30-day mortality odds for hospitals with 3-year volumes of 50, 100, 150, and 200 cases were 1.4, 2.0, 2.7, and 3.0 times lower, respectively, than hospitals performing ≤25 cases/3 years. The proportion of interhospital variation attributed to HV was greatest for FTR/30-day mortality (62%). Procedural volume accounted for 41% and 38% of interhospital variation in postoperative bleeding and myocardial infarction, respectively. Preoperative predictors of FTR included coagulopathy, arrhythmia (nonelective cases); congestive heart failure, obesity (elective cases); and age, neurological disease, hypertension, and valvular disease (all cases). CONCLUSIONS: OAAA FTR/30-day in-hospital mortality strongly correlated with annual case volume with higher volume centers having the lowest risk. Notably, HV accounted for a significant proportion of the observed variation in FTR and specific complications providing direct evidence for how the volume-outcome relationship may influence perioperative mortality. These findings can inform stakeholders to strategically enable them to implement processes of care directed at the most vulnerable patients that are designed to reduce the likelihood of preventable adverse events and death after OAAA repair. Furthermore, these results underscore the need to regionalize OAAA repair and potentially other complex operations, to HV centers because of their improved ability to rescue patients experiencing complications associated with postoperative mortality.

Association of hospital volume with patient selection, risk of complications, and mortality from failure to rescue after open abdominal aortic aneurysm repair.

OBJECTIVE: The association of higher hospital volume with lower mortality after open abdominal aortic aneurysm (OAAA) repair is well known; however, the underlying mechanism for improved outcomes is poorly understood. Better patient selection, lower risk of complications, and improved ability to rescue patients after adverse events are assumed mechanisms, but few data exist to validate this hypothesis. The purpose of this analysis was to determine the association of hospital volume with patient selection, incidence of complications, and failure to rescue (FTR) after adverse events resulting from OAAA repair. METHODS: The Vizient (Irving, Tex) database (>95% of all academic hospitals) was reviewed for OAAA repairs (elective, n = 2827; nonelective, n = 1622) performed from 2012 to 2014. Presentation type (elective vs nonelective) was considered in all analyses. Elixhauser comorbidity index and van Walraven weighted scores were assigned to patients and volume-outcome relationships explored. By use of logistic regression, risk-adjusted complications (including preventable complications; Agency for Healthcare Research and Quality patient safety indicators [PSIs]) and FTR rates were determined. Predicted risk scores were assigned to delineate hospital volume association with these outcomes. RESULTS: Overall, no relationship between hospital volume and composite patient comorbidity severity score was identified (Elixhauser comorbidity index and van Walraven weighted scores: Pearson [ρ, 0.02], P = .2; [ρ, -0.01], P = .4; Spearman correlation coefficient [ρ, 0.02], P = .4; [ρ, -0.02], P = .2). The lack of correlation persisted in considering elective vs nonelective status. However, for elective cases, differences in specific comorbidities were noted because high-volume hospitals were more likely to repair patients with a history of peripheral vascular disease (P = .01), diabetes (P = .07), obesity (P = .004), and alcohol abuse (P = .05). Lower volume hospitals more frequently repaired patients with hypothyroidism (P = .05), fluid and electrolyte disorders (P = .007), and chronic blood loss anemia (P = .05). No specific individual comorbidity differences were detected for nonelective cases. In examining hospital volume effects on the likelihood for development of any complication (45%), PSIs (12%), and FTR (9%), a significant risk reduction was noted in high-volume institutions. Specifically, a nonlinear relationship between hospital volume and risk of any complication (P = .0004), PSI (P = .0004), and FTR (P =. 0003) was present. In exploring the risk of specific complications or PSI events, greater hospital volume was strongly correlated to a lower likelihood of multiple adverse outcomes. CONCLUSIONS: Although high-volume institutions performing OAAA repair do not necessarily operate on patients with more comorbidities, there are important differences in the patients selected compared with lower volume hospitals. The risk for development of multiple specific postoperative complications as well as for preventable adverse events preceding FTR is significantly lower in high-volume centers. These findings provide benchmarks for multiple selected quality indicators and further support national initiatives to incentivize regionalization of OAAA care.

National incidence, mortality outcomes, and predictors of spinal cord ischemia after thoracic endovascular aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) is a dreaded complication of thoracic endovascular aortic repair (TEVAR). There are limited national data describing the incidence and influence of in-hospital SCI recovery on survival. Moreover, no robust preoperative SCI risk assessment models currently exist. The purpose of this analysis was to analyze the Vascular Quality Initiative to determine the national incidence, survival association, and preoperative predictors of SCI after TEVAR. METHODS: All Vascular Quality Initiative TEVAR procedures (June 2014-June 2019) were reviewed. The primary end point was development of in-hospital SCI, defined as any new neurologic deficit or paralysis not attributable to intracranial disease. Secondary end points were disease-specific SCI rates and long-term out-of-hospital survival. Functional outcomes (transient vs permanent SCI) were independently determined by treating physicians. Kaplan-Meier analysis and Cox proportional hazards methodology were used to assess the association of SCI with survival. A logistic regression model of candidate preoperative SCI predictors was created, and bootstrapped backward elimination (retaining predictors with ≥50% selection frequency) was used for model reduction. Model fit and performance statistics were validated by adjustment for Efron's optimism. RESULTS: The overall rate of SCI was 3.7% (n = 422/11,473; transient, 1.6% [n = 179]; permanent, 2.1% [n = 243]). Patients who developed any SCI had significantly lower Kaplan-Meier survival estimate compared with those without SCI (1-year survival: SCI, 65%; no SCI, 87%; P < .0001), and patients with permanent SCI had notably worse survival than patients with transient SCI (1-year survival: permanent SCI, 54%; transient SCI, 80%; P < .0001). Disease-specific incidence of any SCI was as follows: aneurysm, 3.4%; dissection, 5.3%; aneurysm from dissection, 4.1%; trauma, 1.1%; penetrating ulceration, 2.4%; intramural hematoma, 5.7%; penetrating ulceration and intramural hematoma, 4.3%; and aortic thrombus, 4.8%. Several factors were selected on multivariable analysis as the most robust preoperative predictors of any SCI, including distal landing zone 5 to zone 10, nonelective case, creatinine concentration >1.38 mg/dL, smoking history, American Society of Anesthesiologists class, adjunctive procedure, nonwhite race, and preoperative hypertension (area under the curve = 0.72; Nagelkerke R2 = 0.06). CONCLUSIONS: SCI is a devastating complication after TEVAR that is associated with worse overall survival, particularly when no functional recovery occurs by hospital discharge. Disease-specific, real-world benchmarks for SCI rates are provided that may inform quality initiatives focused on reducing this complication. Importantly, this analysis is the first description of a preoperative prediction model derived from national data for determining SCI risk after TEVAR. These predictors should be used to identify high-risk patients to balance the risk of SCI and its associated increased short-term mortality with the risk of the underlying disease. Furthermore, all available adjunctive measures should be implemented in these high-risk patients to reduce risk of SCI.

Comparative outcomes of open, hybrid, and fenestrated branched endovascular repair of extent II and III thoracoabdominal aortic aneurysms.

OBJECTIVE: Open repair of extent II and III thoracoabdominal aortic aneurysms (TAAA) is associated with substantial morbidity. Alternative strategies, such as hybrid operations combining proximal thoracic endovascular aortic repair with either staged open distal TAAA repair or visceral debranching (hybrid), as well as fenestrated/branched endografts (FEVAR), have been increasingly reported; however, benefits of these approaches compared with direct open surgery remain unclear. The purpose of this study was to compare outcomes of these three different strategies in the management of extent II/III TAAA. METHODS: All extent II/III TAAA repairs (2002-2018) for nonmycotic, degenerative aneurysm or chronic dissection at a single institution were reviewed. The primary end point was 30-day mortality. Secondary end points included incidence of spinal cord ischemia (SCI), complications, unplanned re-operation, 90-day readmission, and out-of-hospital survival. To mitigate impact of covariate imbalance and selection bias, intergroup comparisons were made using inverse probability weighted-propensity analysis. Cox regression was used to estimate survival while cumulative incidence was used to determine reoperation risk. RESULTS: One hundred ninety-eight patients (FEVAR, 92; hybrid, 40; open, 66) underwent repair. In unadjusted analysis, compared with hybrid/open patients, FEVAR patients were significantly older with more cardiovascular risk factors, but less likely to have a connective tissue disorder or dissection-related indication. Unadjusted 30-day mortality and complication rates were: 30-day mortality, FEVAR 4%, hybrid 13%, open 12% (P = .01); and complications, FEVAR 36%, hybrid 33%, open 50% (P = .11). Permanent SCI was not different among groups (FEVAR 3%, hybrid 3%, open 6%; P = .64). In adjusted analysis, 30-day mortality risk was greater for open vs FEVAR (hazard ratio, 3.6; 95% confidence interval, 1.4-9.2; P = .01) with no difference for hybrid vs open/FEVAR. There was significantly lower risk of any SCI for open vs FEVAR (hazard ratio, 0.3; 95% confidence interval, 0.09-0.96; P = .04); however, no difference in risk of permanent SCI was detected among the three groups. There was no difference in complications or unplanned reoperation, but open patients had the greatest risk of unplanned 90-day readmission. There was a time-varying effect on survival probability, with open repair having a significant survival disadvantage in the first 1 to 6 months after the procedure compared with hybrid/FEVAR patients (Cox model P = .03), but no difference in survival at 1 and 5 years (1- and 5-year survival: FEVAR, 86 ± 3%, 55 ± 8%; hybrid, 86 ± 5%, 60 ± 11%; open 69 ± 7%, 59 ± 8%; Cox-model P = .10). CONCLUSIONS: Extent II/III TAAA repair, regardless of operative strategy, is associated with significant morbidity risk. FEVAR is associated with the lowest 30-day mortality risk compared with hybrid and open repair when estimates are adjusted for preoperative risk factors. These data support greater adoption of FEVAR as first-line therapy to treat complex TAAA disease in anatomically suitable patients who present electively.

Editor's Choice - Protamine Reduces Serious Bleeding Complications Associated with Carotid Endarterectomy in Asymptomatic Patients without Increasing the Risk of Stroke, Myocardial Infarction, or Death in a Large National Analysis.

OBJECTIVE: Controversy persists regarding the use of protamine during carotid endarterectomy (CEA), despite real world evidence to support its use. The purpose of this study was to determine the impact of protamine reversal of heparin anticoagulation on the outcome of CEA in the USA. METHODS: A prospective national registry (Society for Vascular Surgery Vascular Quality Initiative) of 72 787 patients undergoing elective asymptomatic CEA by 1879 surgeons from 316 centres in the USA and Canada from 2012 to 2018 was reviewed. Protamine use varied by both surgeon (20% rare use [< 10%], 30% variable use [11%-79%], 50% routine use [> 80% cases]) and geographical region (44% vs. 96%). Temporal trends in protamine use were also determined. End points included post-operative re-operation for bleeding, as well as potential protamine related thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of end points were determined by multivariable logistic regression. Propensity matching was additionally used to control for differences between groups. RESULTS: Of the 72 787 patients who underwent CEA, 69% received protamine, while 31% did not. Protamine use increased over time from 60% (2012) to 73% (2018). In total, 378 patients (0.7%) in the protamine treated group underwent re-operation for bleeding vs. 342 patients (1.4%) in the untreated cohort (p < .001). Protamine use did not affect the rate of MI (0.7% vs. 0.8%; p = .023), stroke (1.1% vs. 1.0%; p = .20), or in hospital death (0.2% vs. 0.2%; p = 0.70) between treated and untreated patients, respectively. On multivariable analysis, protamine use was independently associated with reduced risk of re-operation for bleeding (odds ratio 0.5, 95% confidence interval 0.39-0.55; p < .001). Independent of protamine exposure, the consequences of a return to the operating room (RTOR) for bleeding were statistically significant, with a sevenfold increase in MI (RTOR 4.9% vs. no RTOR 0.7%; p < .001), an eightfold increase in stroke (RTOR 7.2% vs. no RTOR 0.9%; p < .001), and a 13 fold increase in death (RTOR 2.4% vs. no RTOR 0.2%; p < .001). CONCLUSION: Protamine reduces serious bleeding complications at the time of CEA without increasing the risk of MI, stroke, or death, in this large North American analysis. Based on this and previous regional work regarding protamine use in CEA, it is believed that there is now sufficient evidence to support its routine use, and it should be considered as a benchmark for quality during CEA.

Interaction between frailty and sex on mortality after elective abdominal aortic aneurysm repair.

BACKGROUND: Controversy exists surrounding gender outcome disparity and abdominal aortic aneurysm (AAA) repair. Previous reports have demonstrated worse outcomes for women undergoing open aneurysm repair (OAR); however, these differences are less evident with endovascular aneurysm repair (EVAR). Epidemiologic studies have documented that women score higher on most frailty assessment scales but paradoxically have longer life expectancy compared to men. The interaction of gender/frailty and the influence on outcomes and practice patterns surrounding EVAR and OAR is poorly described. This analysis characterizes the association of frailty/sex interactions on mortality as well as patient selection surrounding elective AAA repair in the Society for Vascular Surgery Vascular Quality Initiative. METHODS: All elective infrarenal AAA (EVAR + OAR; 2003-2017) cases were queried from the Vascular Quality Initiative database. Each patient was assigned a previously published modified frailty index (mFI) score derived from comorbidity and preoperative functional status data. Cox proportional hazard models, adjusted for statistically significant covariates, including procedural complexity, determined associations within full models and sex-stratified models. RESULTS: A total of 20,750 elective AAA cases were analyzed (EVAR 15,893 [77%]; OAR 4857 [23%]). Thirty-day mortality for EVAR and OAR was 0.7% (n = 115) and 3.5% (n = 169), respectively. Patients who died were significantly more likely to be older (EVAR, 78 vs 73 years; OAR, 74 vs 69 years; P < .0001), have larger AAA diameters (EVAR, 59 vs 56 mm; P = .005; OAR, 62 vs 59 mm; P = .001), higher mFI scores (EVAR, 3.2 vs 2.4; OAR, 3.1 vs 2.2; P < .0001), and be of female sex (EVAR hazard ratio = 1.66 [95% confidence interval, 1.10-2.52]; P = .007; OAR-1.43 [1.02-1.99]; P = .003). Significant differences in the gender distribution of frailty scores among EVAR patients were evident (mean mFI: male 2.42 vs female 2.34; P = .02), but no difference was detected for OAR (male 2.17 vs female 2.22; P = .38). The mFI was a strong independent predictor of mortality (30 days: EVAR hazard ratio = 1.36 [1.22-1.53] and OAR 1.46 [1.32-1.60]; 1 year: EVAR 1.32 [1.25-1.39] and OAR-1.38 [1.28-1.48]). There was no interaction between mFI and gender on the association with mortality. Across frailty strata, male patients were nearly twofold more likely to undergo either elective EVAR or OAR for an AAA below recommended minimum diameter thresholds (male, <5.5 cm; female, <5.0 cm). Greater mFI score did not alter OAR selection but was associated with less frequent EVAR of small AAA. CONCLUSIONS: Given the strong association between frailty and postoperative mortality, mFI can be used as a predictive tool to aid in surgical planning of patients undergoing elective AAA repair. While mFI can predict postoperative mortality for both men and women, it does not account for the survival disparity between sexes, and further research is warranted to explain this difference. There appear to be significant gender differences in patient selection based on current Society for Vascular Surgery-endorsed treatment thresholds that may have important implications on the appropriateness of AAA care delivery nationally.

Outcomes of antegrade and retrograde open mesenteric bypass for acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is a challenging clinical problem associated with significant morbidity and mortality. Few contemporary reports focus specifically on patients undergoing open mesenteric bypass (OMB) or delineate outcome differences based on bypass configuration. This is notable, because there is a subset of patients who are poor candidates for endovascular intervention including those with flush mesenteric vessel occlusion, long segment occlusive disease, and a thrombosed mesenteric stent and/or bypass. This analysis reviewed our experience with OMB in the treatment of AMI and compared outcomes between patients undergoing either antegrade or retrograde bypass. METHODS: A single-center, retrospective review was performed to identify all patients who underwent OMB for AMI from 2002 to 2016. A preoperative history of mesenteric revascularization, demographics, comorbidities, operative details, and outcomes were abstracted. The primary end point was in-hospital mortality. Secondary end points included complications, reintervention, and overall survival. Kaplan-Meier estimation and Cox proportional hazards regression were used to analyze all end points. RESULTS: Eighty-two patients (female 54%; age 63 ± 12 years) underwent aortomesenteric bypass (aortoceliac/superior mesenteric, n = 44; aortomesenteric, n = 38) for AMI. A history of prior stent/bypass was present in 20% (n = 16). A majority (76%; n = 62) underwent antegrade bypass and the remainder received retrograde infrarenal aortoiliac inflow. Patients receiving antegrade OMB were more likely to be male (53% vs 25%; P = .02), have coronary artery disease (48% vs 25%; P = .06), chronic obstructive pulmonary disease (52% vs 25%; P = .03), and peripheral arterial disease (60% vs 35%; P = .05). Concurrent bowel resection was evenly distributed (antegrade, 45%; retrograde, 45%; P = .9) and 37% (n = 30) underwent subsequent resection during second look operations. The median duration of stay was 16 days (interquartile range, 9-35 days) and 78% (n = 64) experienced at least one major complication with no difference in rates between antegrade/retrograde configurations. In-hospital mortality was 37% (n = 30; multiple organ dysfunction, 22; bowel infarction, 4; hemorrhage/anemia, 2; arrhythmia, 1; stroke, 1; 30-day mortality, 26%). The median follow-up was 8 months (interquartile range, 1-26 months). The 1- and 3-year primary patency rates were both 82% ± 6% (95% confidence interval, 71%-95%), with 10 patients requiring reintervention. Estimated survival at 1 and 5 years was 57% ± 6% and 50% ± 6%, respectively. Bypass configuration was not associated with complication rates (P > .10), in-hospital mortality (log-rank, P = .3), or overall survival (log-rank, P = .9). However, a higher risk of reintervention was observed in patients undergoing retrograde bypass (hazard ratio, 3.0; 95% confidence interval, 0.9-11.0; P = .08). CONCLUSIONS: OMB for AMI results in significant morbidity and mortality, irrespective of bypass configuration. Antegrade OMB is associated with comparable outcomes as retrograde OMB. The bypass configuration choice should be predicated on patient presentation, anatomy, physiology, and surgeon preference; however, an antegrade configuration may provide a lower risk of reintervention.

Impact of aortic stent-graft oversizing on outcomes of the chimney endovascular technique based on a new analysis of the PERICLES Registry.

OBJECTIVE: Chimney endovascular aortic aneurysm repair is gaining ever greater acceptance. However, persistent gutters leading to type IA endoleaks represent an unsolved issue. The aim of the current study was to analyze the impact of abdominal endograft oversizing to the occurrence of this phenomenon. METHODS: The PERformance of the snorkel/chImney endovascular teChnique in the treatment of compLex aortic PathologiesES registry includes the largest experience with chimney endovascular aortic aneurysm repair from 13 vascular centers in Europe and the U.S. Prospectively collected data from centers with standard use of the Endurant stent-graft and balloon-expandable covered stents as chimney grafts only were included in the present analysis. The parameter which varied was the degree of oversizing of the aortic stent-graft classifying the cohort in two groups, group A (20% and less oversizing) and group B (>20% of oversizing). The primary endpoint was the incidence of persistent type IA endoleak needed reintervention. Secondary endpoints were all-cause mortality and freedom from reintervention. RESULTS: Group A included 21 patients while group B 144. The mean preoperative pathology's neck length and diameter was 5.8 mm (±4.4) versus 4.9 mm (±3.8) and 27.6 mm (±4.7) versus 24.9 mm (±3.7) for group A and group B, respectively. The mean length of the new sealing zone after chimney graft placement was similar for both groups (group A versus group B; 17.9 mm versus 18.3 mm, respectively, P = .21). The percentage of oversizing of the aortic stent-graft ranged between 13.8 and 20% versus 22.2 and 30%, for group A and group B, respectively. Patients of group A had more type 1A endoleaks, (14.3%) versus patients of group B (2.1%) based on the first follow-up imaging, P = .02. The incidence of persistent type IA endoleaks needing a reintervention was 14.3 and 1.4% for the group A and group B, respectively, P = .01. The mean volume of contrast medium used was greater in group A versus group B with 239 ml versus150 ml, P = .05. Additionally, 14.3% of patients of group A experienced acute renal failure compared to those in group B which was 1.0%, P = .01. CONCLUSIONS: Oversizing of ideally 30% of the Endurant stent-graft is associated with significant lower incidence of type IA endoleaks requiring reintervention for patients treated by chimney endovascular aortic aneurysm repair.

Implementation of a bundled protocol significantly reduces risk of spinal cord ischemia after branched or fenestrated endovascular aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication after branched or fenestrated endovascular aortic repair (B/FEVAR) for thoracoabdominal aortic disease. The purpose of this analysis was to describe the impact of a bundled clinical care protocol designed to reduce the risk of SCI in this population of patients. METHODS: A bundled SCI prevention protocol including cerebrospinal fluid drainage, blood pressure parameters, transfusion goals, and pharmacologic adjuncts (steroids, naloxone) was initiated in May 2015. Before that date, portions of the protocol (cerebrospinal fluid drainage in particular) were used in an informal fashion in patients perceived to be at high risk. B/FEVAR cases completed from January 2012 to May 2016 were reviewed, and outcomes before (n = 223) and after (n = 70) SCI bundle application were compared. The primary end point was the incidence of SCI events. Secondary end points included length of stay, complications, and survival. High-risk patients for SCI were defined as those undergoing B/FEVAR resulting in aortic coverage equivalent to open Crawford extent I to III thoracoabdominal aortic aneurysm (TAAA) repair. Survival was estimated using Kaplan-Meier life-table analysis. RESULTS: Postprotocol patients were more likely to be older (75 ± 7 vs 72 ± 8 years; P = .03), to have an American Society of Anesthesiologists class 4 designation (94% vs 81%; P = .04), and to be treated for TAAA (67% vs 56%; P = .004). Postprotocol pre-emptive spinal drain use was greater in high-risk patients (100% vs 87%; P = .04) but significantly decreased in lower risk patients (suprarenal aneurysm or extent IV TAAA: 5% after protocol implementation vs 21% before protocol implementation; P = .04). Rates of any SCI before and after implementation of the bundled protocol were 13% (n = 29 of 223) and 3% (n = 2 of 70; P = .007), respectively. In comparing high-risk patients, protocol use resulted in an even more significant reduction in SCI rate (19% [28 of 144] vs 4% [2 of 50]; P = .004). Postoperative morbidity (41% vs 33%; P = .2) and 30-day mortality (5% vs 1%; P = .3) were not different between groups. However, patients treated on protocol had significantly improved 1-year survival (99% ± 1% after protocol implementation vs 90% ± 2% before protocol implementation; log-rank, P = .05). CONCLUSIONS: Implementation of a bundled multimodal protocol may significantly reduce risk of SCI after B/FEVAR, with the greatest risk reduction occurring in the most vulnerable patients. Interestingly, reduction in SCI risk was associated with improvement in 1-year survival.

Identification of optimal device combinations for the chimney endovascular aneurysm repair technique within the PERICLES registry.

OBJECTIVE: The ideal stent combination for chimney endovascular aneurysm repair remains undetermined. Therefore, we sought to identify optimal aortic and chimney stent combinations that are associated with the best outcomes by analyzing the worldwide collected experience in the PERformance of chImney technique for the treatment of Complex aortic pathoLogiES (PERICLES) registry. METHODS: The PERICLES registry was reviewed for patients with pararenal aortic disease electively treated from 2008 to 2014. Eleven different aortic devices were identified with three distinct subgroups: group A (n = 224), nitinol/polyester; group B (n = 105), stainless steel/polyester; and group C (n = 69), nitinol/expanded polytetrafluoroethylene. The various chimney stent subtypes included the balloon-expandable covered stent (BECS), self-expanding covered stent, and bare-metal stent. Deidentified aortic and chimney device combinations were compared for risk of chimney occlusion, type IA endoleak, and survival. Effects of high-volume centers (>100 cases), use of an internal lining chimney stent, number of chimney stents, and number of chimney stent subtypes deployed were also considered. We considered demographics, comorbidities, and aortic anatomic features as potential confounders in all models. RESULTS: The 1- and 3-year freedom from BECS chimney occlusion was not different between groups (group A, 96% ± 2% and 87% ± 5%; groups B and C, 93% ± 3% and 76% ± 10%; Cox model, P = .33). Similarly, when non-BECS chimney stents were used, no difference in occlusion risk was noted for the three aortic device groupings; however, group C patients receiving BECS did have a trend toward higher occlusion risk relative to group C patients not receiving a BECS chimney stent (hazard ratio [HR], 4.0; 95% confidence interval [CI], 0.85-18.84; P = .08). Patients receiving multiple chimney stents, irrespective of stent subtype, had a 1.8-fold increased risk of occlusion for each additional stent (HR, 1.8; 95% CI, 1.2-2.9; P = .01). Use of a bare-metal endolining stent doubled the occlusion hazard (HR, 2.1; 95% CI, 1.0-4.5; P = .05). Risk of type IA endoleak (intraoperatively and postoperatively) did not significantly differ for the aortic devices with BECS use; however, group C patients had higher risk relative to groups A/B without BECS (C vs B: odds ratio [OR], 3.2 [95% CI, 1-11; P = .05]; C vs A/B: OR, 2.4 [95% CI, 0.9-6.4; P = .08]). Patients treated at high-volume centers had significantly lower odds for development of type IA endoleak (OR, 0.2; 95% CI, 0.1-0.7; P = .01) irrespective of aortic or chimney device combination. Mortality risk was significantly higher in group C + BECS vs group A + BECS (HR, 5.3; 95% CI, 1.6-17.5; P = .006). The 1- and 3-year survival for groups A, B, and C (+BECS) was as follows: group A, 97% ± 1% and 92% ± 3%; group B, 93% ± 3% and 83% ± 7%; and group C, 84% ± 7% and 63% ± 14%. Use of more than one chimney subtype was associated with increased mortality (HR, 3.2; 95% CI, 1.4-7.5; P = .006). CONCLUSIONS: Within the PERICLES registry, use of nitinol/polyester stent graft devices with BECS during chimney endovascular aneurysm repair is associated with improved survival compared with other aortic endografts. However, this advantage was not observed for non-BECS repairs. Repairs incorporating multiple chimney subtypes were also associated with increased mortality risk. Importantly, increasing chimney stent number and bare-metal endolining stents increase chimney occlusion risk, whereas patients treated at low-volume centers have higher risk of type IA endoleak.

Analysis of immunobiologic markers in primary and recurrent glioblastoma.

Glioblastoma (GBM) generates a varied immune response and understanding the immune microenvironment may lead to novel immunotherapy treatments modalities. The goal of this study was to evaluate the expression of immunologic markers of potential clinical significance in primary versus recurrent GBM and assess the relationship between these markers and molecular characteristics of GBM. Human GBM samples were evaluated and analyzed with immunohistochemistry for multiple immunobiologic markers (CD3, CD8, FoxP3, CD68, CD163, PD1, PDL1, CTLA4, CD70). Immunoreactivity was analyzed using Aperio software. Degree of strong positive immunoreactivity within the tumor was compared to patient and tumor characteristics including age, gender, MGMT promoter methylation status, and ATRX, p53, and IDH1 mutation status. Additionally, the TCGA database was used to perform similar analysis of these factors in GBM using RNA-seq by expectation-maximization. Using odds ratios, IDH1 mutated GBM had statistically significant decreased expression of CD163 and CD70 and a trend for decreased PD1, CTLA4, and Foxp3. ATRX-mutated GBMs exhibited statistically significant increased CD3 immunoreactivity, while those with p53 mutations were found to have significantly increased CTLA4 immunoreactivity. The odds of having strong CD8 and CD68 reactivity was significantly less in MGMT methylated tumors. No significant difference was identified in any immune marker between the primary and recurrent GBM, nor was a significant change in immunoreactivity identified among age intervals. TCGA analysis corroborated findings related to the differential immune profile of IDH1 mutant, p53 mutant, and MGMT unmethylated tumors. Immunobiologic markers have greater association with the molecular characteristics of the tumor than with primary/recurrent status or age.

Collected Transatlantic Experience From the PERICLES Registry: Use of Chimney Grafts to Treat Post-EVAR Type Ia Endoleaks Shows Good Midterm Results.

PURPOSE: The aim of this retrospective analysis was to evaluate the performance of the chimney (ch) technique in the treatment of type Ia endoleaks after standard endovascular aneurysm repair (EVAR). METHODS: Between January 2008 and December 2014, 517 chEVAR procedures were performed in 13 US and European vascular centers (PERICLES registry). Thirty-nine patients (mean age 76.9±7.1 years; 33 men) were treated for persistent type Ia endoleak and had computed tomography angiography or magnetic resonance angiography follow-up at >1 month. Endurant abdominal stent-grafts were used in the 20 cases. Single chimney graft placement was performed in 18 (46%) patients and multiple in 21 (54%). Overall, 70 visceral vessels were targeted for revascularization. RESULTS: Technical success was achieved in 35 (89.7%) cases; 3 persistent type Ia endoleaks and 1 chimney graft occlusion were detected within the first 30 days. Thirty-day mortality was 2.6%. Two other deaths (not aneurysm related) occurred during a mean follow-up of 21.9 months (0.23-71.3). Primary patency of the chimney grafts was 94.3% at 36 months. In a subgroup analysis comparing Endurant to other stent-grafts, no significant differences were observed regarding persistent endoleak [1/20 (5%) vs 2/19 (11%), p=0.6] or reintervention [1/20 (5%) vs 0/19 (0%)]. CONCLUSION: The present series demonstrates that chEVAR in the treatment of post-EVAR type Ia endoleaks has satisfactory results independent of the abdominal and chimney graft combinations. Midterm results show that chEVAR is an effective method for treating type Ia endoleaks.

Outcomes of Thoracic Endovascular Aortic Repair for Acute Type B Dissection in Patients With Intractable Pain or Refractory Hypertension.

PURPOSE: To compare uncomplicated acute type B aortic dissection (UATBAD) patients with intractable pain/refractory hypertension treated with thoracic endovascular aortic repair (TEVAR) to UATBAD subjects without these features receiving best medical therapy (BMT). METHODS: Interrogation of the hospital database identified 101 consecutive UATBAD patients admitted between January 2011 and December 2014. Of these, 74 patients (mean age 62±13 years; 44 men) were treated with BMT; the other 27 UATBAD patients (mean age 63±13 years; 17 men) were subsequently treated with TEVAR for intractable pain (24, 89%) and/or refractory hypertension (3, 11%) at a mean 2.4±3.3 days (median 1, range 0-12) after admission. Mixed models were employed to determine differences in centerline measured aortic remodeling. Propensity analysis was employed to mitigate selection bias. Kaplan-Meier methodology was used to estimate reintervention and survival. RESULTS: The groups were well matched; there was no difference in demographics, comorbidities, or proportion with visceral involvement (70% for TEVAR vs 86% for BMT, p=0.08). There was no significant difference in length of stay (9.6±6.3 for TEVAR vs 10.3±7.8 for BMT, p=0.3), complications (19% for TEVAR vs 24% for BMT, p=0.6), or 30-day mortality (0 for TEVAR vs 7% for BMT, p=0.1). One (4%) TEVAR patient experienced retrograde dissection. BMT resulted in greater mean increase in discharge antihypertensive medications (1.7±1.9 vs 0.7±1.7 for TEVAR, p=0.03), but there was no difference in narcotic utilization. Mean follow-up was greater in the TEVAR group (17.9±16.0 months) compared with BMT patients (11.5±10.8 months, p=0.05). TEVAR significantly improved rates of aortic diameter change (1.5% vs 12.9% for BMT, p=0.007), complete false lumen thrombosis (41% vs 11% for BMT, p=0.004), and true lumen expansion (85% vs 7% for BMT, p<0.01). However, there was no difference in reintervention (25.9% for TEVAR vs 23% for BMT, p=0.2) or survival (log-rank p=0.8). CONCLUSION: TEVAR for UATBAD with intractable pain/refractory hypertension is safe but offers no short-term outcome advantage when compared to UATBAD patients without these features receiving BMT. A significant improvement in aortic remodeling was identified after TEVAR. The potential long-term reintervention and aorta-related mortality benefits of this favorable remodeling have yet to be defined and randomized trials are warranted.

American Muslim Physician Attitudes Toward Organ Donation.

Religious beliefs and values impact Muslim patients' attitudes toward a variety of healthcare decisions, including organ donation. Muslim physician attitudes toward organ donation, however, are less well studied. Utilizing a national survey of physician members of the Islamic Medical Association of North America, relationships between religiosity, patterns of bioethics resource utilization, and sociodemographic characteristics with attitudes toward organ donation were assessed. Of 255 respondents, 251 answered the target question, "in your understanding, does Islamic bioethics and law permit organ donation?." 177 respondents (70%) answered positively, 30 (12%) negatively, and 46 (18%) did not know. Despite the overwhelming majority of respondents believing organ donation to be permitted by Islamic bioethics and law, fewer than one-third (n = 72, 30%) are registered donors. Several sociodemographic features had a positive association with believing organ donation to be permitted: ethnic descent other than that of South Asian, having immigrated to the USA as an adult, and male sex. When using a logistic regression model controlling for these three variables as potential confounders, the best predictor of Muslim physicians believing organ donation to be permissible was utilization of an Imam as a bioethical resource (odds ratio 5.9, p = 0.02). Religiosity variables were not found to be associated with views on the Islamic permissibility of organ donation. While Muslim American physicians appear to believe there is religious support for organ donation, only a minority sign up to be donors. Greater study is needed to understand how physicians' attitudes regarding donation impact discussions between patients and physicians regarding the possibility of donating and of receiving a transplant.

Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM.

Development of a refill pattern method to measure polypharmacy in administrative claims databases.

PURPOSE: The purposes of the study were to develop a refill pattern method to identify polypharmacy in pharmacy billing records and to compare the method with traditional days' supply overlap algorithms. METHODS: This method is characterized by the assessment of prescription refill pattern. Concomitant therapy is assumed when two drugs are dispensed repeatedly during the active days' supply of each other. We tested the refill pattern method in a simplified scenario in which two drugs (methylphenidate/dexmethylphenidate and atomoxetine) for attention deficit/hyperactivity disorder (ADHD) were considered. Children who had at least one prescription of methylphenidate/dexmethylphenidate or atomoxetine in 2008 were included for the calculation of 2-year prevalence of ADHD treatment polypharmacy. Results were compared with traditional method that requires a minimum overlap of 30, 60 or 90 days of filled prescriptions. We compared polypharmacy prevalence estimated by the two methods and explored reasons for disagreement. RESULTS: Among 131 385 children who had at least one prescription of methylphenidate/dexmethylphenidate or atomoxetine, the refill pattern method identified 4021 patients who had ADHD treatment polypharmacy (2-year prevalence = 3.1%). This prevalence estimate fell between those from a 30- to 60-day overlap method. The Cohen's kappa regarding determination of polypharmacy was 0.83, 0.92 and 0.80 considering 90-, 60- and 30-day overlap method, respectively. CONCLUSIONS: The refill pattern method can be used as another way to measure polypharmacy in administrative claims databases and can be adapted to a wide variety of research questions, diseases and study populations. Copyright © 2016 John Wiley & Sons, Ltd.