Testing the Limits of Imbalanced CPET Reactivity: Mechanistic Crossover in H-Atom Abstraction by Co(III)-Oxo Complexes.

Transition metal-oxo complexes are key intermediates in a variety of oxidative transformations, notably C-H bond activation. The relative rate of C-H bond activation mediated by transition metal-oxo complexes is typically predicated on substrate bond dissociation free energy in cases with a concerted proton-electron transfer (CPET). However, recent work has demonstrated that alternative stepwise thermodynamic contributions such as acidity/basicity or redox potentials of the substrate/metal-oxo may dominate in some cases. In this context, we have found basicity-governed concerted activation of C-H bonds with the terminal CoIII-oxo complex PhB(tBuIm)3CoIIIO. We have been interested in testing the limits of such basicity-dependent reactivity and have synthesized an analogous, more basic complex, PhB(AdIm)3CoIIIO, and studied its reactivity with H-atom donors. This complex displays a higher degree of imbalanced CPET reactivity than PhB(tBuIm)3CoIIIO with C-H substrates, and O-H activation of phenol substrates displays mechanistic crossover to stepwise proton transfer-electron transfer (PTET) reactivity. Analysis of the thermodynamics of proton transfer (PT) and electron transfer (ET) reveals a distinct thermodynamic crossing point between concerted and stepwise reactivity. Furthermore, the relative rates of stepwise and concerted reactivity suggest that maximally imbalanced systems provide the fastest CPET rates up to the point of mechanistic crossover, which results in slower product formation.

Combining Donor Strength and Oxidative Stability in Scorpionates: A Strongly Donating Fluorinated Mesoionic Tris(imidazol-5-ylidene)borate Ligand.

Strongly donating scorpionate ligands support the study of high-valent transition metal chemistry; however, their use is frequently limited by oxidative degradation. To address this concern, we report the synthesis of a tris(imidazol-5-ylidene)borate ligand featuring trifluoromethyl groups surrounding its coordination pocket. This ligand represents the first example of a chelating poly(imidazol-5-ylidene) mesoionic carbene ligand, a scaffold that is expected to be extremely donating. The {NiNO}10 complex of this ligand, as well as that of a previously reported strongly donating tris(imidazol-2-ylidene)borate, has been synthesized and characterized. This new ligand's strong donor properties, as measured by the υNO of its {NiNO}10 complex and natural bonding orbital second-order perturbative energy analysis, are at par with those of the well-studied alkyl-substituted tris(imidazol-2-ylidene)borates, which are known to effectively stabilize high-valent intermediates. The good donor properties of this ligand, despite the electron-withdrawing trifluoromethyl substituents, arise from the strongly donating imidazol-5-ylidene mesoionic carbene arms. These donor properties, when combined with the robustness of trifluoromethyl groups toward oxidative decomposition, suggest this ligand scaffold will be a useful platform in the study of oxidizing high-valent transition-metal species.

Enzyme-Like Hydroxylation of Aliphatic C-H Bonds From an Isolable Co-Oxo Complex.

The selective hydroxylation of aliphatic C-H bonds remains a challenging but broadly useful transformation. Nature has evolved systems that excel at this reaction, exemplified by cytochrome P450 enzymes, which use an iron-oxo intermediate to activate aliphatic C-H bonds with k1 > 1400 s-1 at 4 °C. Many synthetic catalysts have been inspired by these enzymes and are similarly proposed to use transition metal-oxo intermediates. However, most examples of well-characterized transition metal-oxo species are not capable of reacting with strong, aliphatic C-H bonds, resulting in a lack of understanding of what factors facilitate this reactivity. Here, we report the isolation and characterization of a new terminal CoIII-oxo complex, PhB(AdIm)3CoIIIO. Upon oxidation, a transient CoIV-oxo intermediate is generated that is capable of hydroxylating aliphatic C-H bonds with an extrapolated k1 for C-H activation >130 s-1 at 4 °C, comparable to values observed in cytochrome P450 enzymes. Experimental thermodynamic values and DFT analysis demonstrate that, although the initial C-H activation step in this reaction is endergonic, the overall reaction is driven by an extremely exergonic radical rebound step, similar to what has been proposed in cytochrome P450 enzymes. The rapid C-H hydroxylation reactivity displayed in this well-defined system provides insight into how hydroxylation is accomplished by biological systems and similarly potent synthetic oxidants.

Two, Three, or Not to Be? Elucidating Multiple Bonding in d6 Pseudotetrahedral Oxo and Imide Complexes.

Late-transition-metal oxo and imide complexes play an important role in the catalytic functionalization and activation of small molecules. An emerging theme in this area over the past few decades has been the use of lower coordination numbers, and pseudotetrahedral geometries in particular, to stabilize what would otherwise be highly reactive species. However, the bonding structure in d6 oxo and imide complexes in this geometry is ambiguous. These species are typically depicted with a triple bond; however, recent experimental evidence suggests significant empirical differences between these complexes and other triply bonded complexes with lower d counts. Here we use a suite of computational orbital localization methods and electron density analyses to probe the bonding structure of isoelectronic d6 CoIII oxo and imide complexes. These analyses suggest that a triple-bond description is inaccurate because of a dramatically weakened σ interaction. While the exact bond order in these cases is necessarily dependent on the model used, several metrics suggest that the strength of the metal-O/N bond is most similar to that of other formally doubly bonded complexes.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).

Results of carotid endarterectomy in patients with contralateral internal carotid artery occlusion from the Mid-America Vascular Study Group and the Society for Vascular Surgery Vascular Quality Initiative.

OBJECTIVE: Carotid endarterectomy (CEA) is among the most commonly performed vascular procedures. Some have suggested worse outcomes with contralateral internal carotid artery (ICA) occlusion. We compared patients with and patients without contralateral ICA occlusion using the Society for Vascular Surgery Vascular Quality Initiative database. METHODS: Deidentified data were obtained from the Vascular Quality Initiative. Patients with prior ipsilateral or contralateral CEA, carotid stenting, combined CEA and coronary artery bypass graft, or <1-year follow-up were excluded, yielding 1737 patients with and 45,179 patients without contralateral ICA occlusion. Groups were compared with univariate tests, and differences identified in univariate testing were entered into multivariate models to identify independent predictors of outcomes and in particular whether contralateral ICA occlusion is an independent predictor of outcomes. RESULTS: Patients with contralateral ICA occlusion were younger and more likely to be smokers; they were more likely to have chronic obstructive pulmonary disease, preoperative neurologic symptoms (56% vs 47%), nonelective CEA (16% vs 13%), and shunt placement (75% vs 53%; all P < .001). The 30-day ipsilateral stroke risk was 1.3% with vs 0.7% without contralateral ICA occlusion (P = .004). The 30-day and 1-year survival estimates were 99.0% ± 0.5% and 94.1% ± 1.1% with vs 99.6% ± 0.1% and 96.0% ± 0.2% without contralateral ICA occlusion (log-rank, P < .001). Logistic regression analysis identified prior neurologic event (P = .046), nonelective surgery (P = .047), absence of coronary artery disease (P = .035), and preoperative angiotensin-converting enzyme inhibitor use (P = .029) to be associated with 30-day ipsilateral stroke risk, but contralateral ICA occlusion remained an independent predictor in that model (odds ratio, 2.29; P = .026). However, after adjustment for other factors (Cox proportional hazards), risk of ipsilateral stroke (including perioperative) during follow-up was not significantly greater with contralateral ICA occlusion (hazard ratio, 1.21; P = .32). Results comparing propensity score-matched cohorts mirrored those from the larger data set. CONCLUSIONS: This study demonstrates likely clinically insignificant differences in early stroke or death in comparing CEA patients with and those without contralateral ICA occlusion. After adjustment for other factors, contralateral ICA occlusion was not associated with a greater risk of ipsilateral stroke (including perioperative) in longer follow-up. Mortality was greater with contralateral ICA occlusion, and this difference was more pronounced at 1 year despite younger age of the contralateral ICA occlusion group. CEA risk remains low even in the presence of contralateral ICA occlusion and appears to be explained at least in part by other factors. CEA should still be considered appropriate in the face of contralateral ICA occlusion.

Clinical impact of sex on carotid revascularization.

BACKGROUND: The impact of sex in the management of carotid disease is unclear in the current literature. Therefore, we evaluated the effect of sex on perioperative outcomes following carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: We included patients who underwent CEA or CAS between 2012 and 2017 in the Vascular Quality Initiative database. Our primary outcome was perioperative stroke/death. Secondary outcomes were in-hospital stroke, 30-day mortality, and in-hospital MI. We compared perioperative outcomes between female and male patients, stratified by treatment modality and symptom status, and used multivariable regression to account for differences in baseline characteristics. RESULTS: A total of 83,436 patients underwent either a CEA (71,383) or CAS (12,053). Asymptomatic and symptomatic CEA females were less likely to be on a preoperative antiplatelet agent, when compared to males. Females overall, were less likely to be on a preoperative statin and more likely to have chronic obstructive pulmonary disease. Within the CAS cohort, females were more likely to have a previous ipsilateral CEA. There were no differences between males and females in major adverse events following CEA for asymptomatic disease. Following CEA for symptomatic disease, there was no difference in stroke/death rate or in-hospital stroke. However, females experienced a higher 30-mortality after adjustment (univariate: 1.0% vs 0.7%, P = .04; adjusted: odds ratio [OR], 1.4:1.02-1.94). Following CAS for asymptomatic disease, females experienced a higher rate of perioperative stroke/death (2.9% vs 1.9% P = .02; OR, 1.5: 1.05-2.03) and in-hospital stroke (2.1% vs 1.2% P = .01; OR, 1.8: 1.20-2.60). There were no differences in outcomes for symptomatic females vs males undergoing CAS. CONCLUSIONS: Females with carotid disease less frequently receive optimal medical treatment with antiplatelet agents and statins. This is an important target area for quality improvement issue in both females and males. Furthermore, among symptomatic CEA patients the female sex is associated with higher mortality and among asymptomatic CAS patients, females experience higher rates of stroke/death. These findings suggest that careful patient selection is necessary in the treatment of female patients. Quality improvement projects should be created to further investigate and eliminate the disparities of optimal medical management between the sexes.

Synthesis and Characterization of Cu(II) and Mixed-Valence Cu(I)Cu(II) Clusters Supported by Pyridylamide Ligands.

A group of copper complexes supported by polydentate pyridylamide ligands H2bpda and H2ppda were synthesized and characterized. The two Cu(II) dimers [CuII2(Hbpda)2(ClO4)2] (1) and [CuII2(ppda)2(DMF)2] (2) were constructed by using neutral ligands to react with Cu(II) salts. Although the dimers showed similar structural features, the second-sphere interactions affect the structures differently. With the application of Et3N, the tetranuclear cluster (HNEt3)[CuII4(bpda)2(µ3-OH)2(ClO4)(DMF)3](ClO4)2 (3) and hexanuclear cluster (HNEt3)2[CuII6(ppda)6(H2O)2(CH3OH)2](ClO4)2 (4) were prepared under similar reaction conditions. The symmetrical and unsymmetrical arrangement of the ligand donors in ligands H2bpda and H2ppda led to the dramatic conformation difference of the two Cu(II) complexes. As part of our effort to explore mixed-valence copper chemistry, the triple-decker pentanuclear cluster [CuII3CuI2(bpda)3(µ3-O)] (5) was prepared. XPS examination demonstrated the localized mixed-valence properties of complex 5. Magnetic studies of the clusters with EPR evidence showed either weak ferromagnetic or antiferromagnetic interactions among copper centers. Due to the trigonal-planar conformation of the trinuclear Cu(II) motif with the µ3-O center, complex 5 exhibits geometric spin frustration and engages in antisymmetric exchange interactions. DFT calculations were also performed to better interpret spectroscopic evidence and understand the electronic structures, especially the mixed-valence nature of complex 5.

Outcomes following Eversion versus Conventional Endarterectomy in the Vascular Quality Initiative Database.

BACKGROUND: Although the majority of vascular surgeons perform conventional carotid endarterectomy (c-CEA), others prefer eversion CEA (e-CEA). Despite several randomized controlled trials and single center studies, the advantage of one technique over the other is still not clearly defined. The purpose of this study is to compare the postoperative outcomes and durability of c-CEA versus e-CEA in a nationally representative cohort. METHODS: We performed a retrospective review of the Vascular Quality Initiative database between 2003 and 2018. Patients with prior ipsilateral carotid intervention (CEA and carotid artery stenting) and those undergoing concomitant procedures were excluded. Multivariable logistic and Cox-regression analyses were used to compare risk-adjusted perioperative and 1-year outcomes (stroke, death, and high-grade restenosis [>70%]) between c-CEA (using direct closure or patch angioplasty) and e-CEA. RESULTS: A total of 95,726 CEA cases were included, of which 12,050 (12.6%) were e-CEA and the remaining (87.4%) were c-CEA. Patch angioplasty was used in 94.9% of c-CEA compared with 49.7% of e-CEA (P < 0.001). On univariable analysis, no difference in perioperative outcomes was noted between the 2 approaches except for higher rates of in-hospital dysrhythmia (1.5% vs. 1.3%) and postprocedural hemodynamic instability (27.3% vs. 24.3%) after c-CEA compared with e-CEA (all P < 0.05). On the other hand, e-CEA patients were more likely to return to the operating room for bleeding (1.3% vs. c-CEA: 0.9%, P < 0.001). The outcomes of e-CEA did not differ if the common carotid artery was closed primarily or with a patch. After adjusting for potential confounders and stratifying with respect to patch use, there was no significant difference in outcomes between e-CEA and c-CEA when a patch is used in both procedures. However, when no patching was performed, e-CEA was associated with lower stroke/death at 30 days (odds ratio 0.72, 95% confidence interval [CI] 0.54-0.95, P = 0.02) and at 1 year (hazard ratio 0.75, 95% CI 0.58-0.97, P = 0.03). CONCLUSIONS: Both e-CEA and c-CEA are safe and durable techniques with similar stroke/death and restenosis rates up to 1-year of follow up, as long as c-CEA is performed with patch angioplasty. However, e-CEA is superior to c-CEA without patch angioplasty and is associated with 28% and 25% reduction in 30-day and 1-year stroke/death, respectively.

Trends in Use of Electronic Health Records in Pediatric Office Settings.

OBJECTIVES: To determine the prevalence and functionalities of electronic health records (EHRs) and pediatricians' perceptions of EHRs. STUDY DESIGN: An 8-page self-administered questionnaire sent to 1619 randomly selected nonretired US American Academy of Pediatrics members in 2016 was completed by 709 (43.8%). Responses were compared with surveys in 2009 and 2012. RESULTS: The percent of pediatricians who were using EHRs increased from 58% in 2009 and 79% in 2012 to 94% in 2016. Those with fully functional EHRs, including pediatric functionality, more than doubled from 8.2% in 2012 to 16.9% in 2016 (P = .01). Fully functional EHRs lacking pediatric functionality increased slightly from 7.8% to 11.1% (P = .3), and the percentage of pediatricians with basic EHRs remained stable (30.4% to 31.0%; P < .3). The percentage of pediatricians who lacked basic EHR functionality or who reported no EHR decreased (from 53.6% to 41.0%; P < .001). On average, pediatricians spent 3.4 hours per day documenting care. CONCLUSIONS: Although the adoption of EHRs has increased, >80% of pediatricians are working with EHRs that lack optimal functionality and 41% of pediatricians are not using EHRs with even basic functionality. EHRs lacking pediatric functionality impact the health of children through increased medical errors, missed diagnoses, lack of adherence to guidelines, and reduced availability of child-specific information. The pediatric certification outlined in the 21st Century Cures Act may result in improved EHR products for pediatricians.

Regional variation in patient outcomes in carotid artery disease treatment in the Vascular Quality Initiative.

OBJECTIVE: Quality metrics were developed to improve outcomes after carotid artery revascularization; however, few studies have evaluated regional differences in perioperative outcomes. This study aimed to evaluate regional variation in mortality and perioperative outcomes after carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: We identified all patients who underwent CEA or CAS from 2009 to 2016 in the Vascular Quality Initiative. Patients were analyzed on the basis of their symptom status. We assessed variation in perioperative outcomes using χ2 analysis, Fisher exact test, and t-test, where appropriate. RESULTS: A total of 78,467 carotid interventions were identified; 85% were CEAs, with 69% of those asymptomatic. Within CAS, 39% were asymptomatic. Perioperative stroke/death varied across regions within both CAS groups (asymptomatic, 0%-5.8% [P = .03]; symptomatic, 2.4%-8.1% [P = .1]), and several regions did not meet the American Heart Association (AHA) guidelines of 3% for asymptomatic patients and 6% for symptomatic patients, which persisted after risk adjustment. For CEA, the stroke/death rates fell within the standards set by the AHA guidelines in all regions for both the unadjusted and risk-adjusted models; however, there was significant regional variation in the cohorts (asymptomatic, 0.9%-3.1% [P < .01]; symptomatic, 1.3%-4.9% [P < .01]). Variation in 30-day mortality was significant in symptomatic patients (asymptomatic: CEA, 0%-1.3% [P = .2], CAS, 0%-2.4% [P = .2]; symptomatic: CEA, 0%-1.8% [P < .01], CAS, 0%-4.6% [P = .01]). Rates of in-hospital stroke, postoperative myocardial infarction, prolonged length of stay (>2 days), and use of intravenous blood pressure medications all varied significantly across the regions. After CEA, there was significant variation in the rates of cranial nerve injuries (asymptomatic, 0.9%-4.9% [P < .01]; symptomatic, 1.5%-7.7% [P < .01]), return to the operating room (asymptomatic, 0.9%-3.4% [P < .01]; symptomatic, 0.6%-3.4% [P = .02]), and discharge on antiplatelet and statin (asymptomatic, 75%-87% [P < .01]; symptomatic, 78%-91% [P < .01]). After CAS, significant variation was found in the rates of access site complications (asymptomatic, 2.3%-18.2% [P < .01]; symptomatic, 1.4%-16.9% [P < .01]) and discharge on dual antiplatelet therapy (asymptomatic, 79%-94% [P < .01]; symptomatic, 83%-93% [P < .01]). CONCLUSIONS: Unwarranted regional variation exists in outcomes after carotid artery revascularization across the regions of the VQI. Significant variation was seen in a number of outcomes for which quality metrics currently exist, such as length of stay and discharge medications. In addition, after CAS, several regions failed to meet the AHA guidelines for stroke and death. Given these results, quality improvement projects should be targeted to improve adherence to current guidelines to promote best practices.

Comparison of Direct and Less Invasive Techniques for the Treatment of Severe Aorto-Iliac Occlusive Disease.

BACKGROUND: Severe aorto-iliac occlusive disease (AIOD) is traditionally treated with aorto-bifemoral bypass (ABF) or aorto-unifemoral bypass (AUF). However, cross-femoral bypass (CFB) and hybrid femoral endarterectomy and patch angioplasty with iliac stenting (EPS) have gained popularity as less invasive options. We sought to compare 1-year survival, primary patency, and major amputation rates between open surgical (ABF and AUF) and 2 less invasive reconstruction techniques (CFB and EPS) using a large, multicenter cohort. STUDY DESIGN: This is a retrospective cohort study of patients who underwent either ABF/AUF or CFB/EPS for AIOD between 2006 and 2013 in the Society for Vascular Surgery Vascular Quality Initiative registry. Baseline patient and periprocedural variables were compared. Propensity score matching (PSM) was performed to predict the likelihood of more invasive repair. Kaplan-Meier analysis and Cox models were performed for 1-year survival, primary patency, and major amputation. RESULTS: 1872 patients underwent procedures for AIOD, including 1,133 ABF/AUF and 739 CFB/EPS, during the study period. Indication was critical limb ischemia in 47.3% (n = 886). Median follow-up time was 305 days (range, 10-406). After PSM, the matched cohort included 1,094 ABF/AUF and 711 CFB/EPS patients. Multivariate analysis revealed that patient factors and procedure indication were significant predictors of 1-year mortality and major amputation, but not procedure type. ABF/AUF was associated with improved primary patency over CFB/EPS at 1 year (94.1% ± 1.1% vs. 92.3% ± 1.5%, hazard ratio 0.65, 95% confidence interval 0.45-0.94; P = 0.02). CONCLUSIONS: In a propensity-matched cohort from a multicenter vascular surgery registry, a direct approach to AIOD (ABF/AUF) demonstrated better 1-year primary patency than commonly used less invasive strategies. However, treatment approach was not a predictor of 1-year survival or limb salvage, suggesting that patient factors and procedure indication have a greater impact on outcome.

A comparison of results of carotid endarterectomy in octogenarians and nonagenarians to younger patients from the Mid-America Vascular Study Group and the Society for Vascular Surgery Vascular Quality Initiative.

OBJECTIVE: Carotid endarterectomy (CEA) reduces stroke risk in selected patients. However, CEA risk profile may be different in older patients. We compared characteristics and outcomes of octogenarians and nonagenarians with those of younger patients. METHODS: Deidentified data from CEA patients were obtained from the Society for Vascular Surgery Vascular Quality Initiative (VQI) database. Prior CEA, carotid artery stent, or combined CEA and coronary artery bypass were excluded, yielding 7390 CEAs in octogenarians and nonagenarians (≥80 years of age) and 35,303 CEAs in younger patients (<80 years of age). We compared post-CEA outcomes, including periprocedural cerebral ischemic events and death, and details such as operative time, bleeding, and return to surgery. RESULTS: Octogenarians and nonagenarians were more likely to have pre-CEA neurologic symptoms (51.4% vs 45.6%; P < .001) and to have never smoked (37.8% vs 22.0%; P < .001), and they were slightly more likely to have required urgent CEA (16.1% vs 13.4%; P < .001). Stenosis ≥70% was similar (octogenarians and nonagenarians, 94.2%; younger patients, 94.4%; P = .45). Perioperative ipsilateral neurologic events and ipsilateral stroke were slightly more common among octogenarians and nonagenarians (1.6% vs 1.1% [P < .001] and 1.2% vs 0.8% [P = .002]). Multivariate modeling (logistic regression) showed that pre-CEA neurologic symptoms (odds ratios, 1.35 [P = .005] and 1.42 [P = .007]), pre-CEA ipsilateral cortical ischemic event (odds ratios, 1.18 [P < .001] and 1.20 [P < .001]), and urgency (odds ratios, 1.75 [P < .001] and 1.67 [P < .001]) remained strong predictors of any ipsilateral neurologic event and any ipsilateral stroke, respectively. However, age ≥80 years remained a significant predictor of these outcomes (odds ratios, 1.37 [P = .003] and 1.44 [P = .004]). Kaplan-Meier estimated survival was lower for octogenarians and nonagenarians at 30 days and 1 year (98.6% vs 99.4% and 93.7% vs 97.0%; log-rank, P < .001). Age ≥80 years was also associated with a greater rate of discharge to other than home after CEA, a difference that was only partially explained by comorbidities in multivariate modeling. CONCLUSIONS: CEA was performed with low rates of perioperative neurologic events and mortality. Multivariate testing showed that the higher rate of neurologic complications in octogenarians and nonagenarians appeared partially related to symptomatic status and urgent surgery; but after adjusting for these factors, age ≥80 years still predicted a slightly higher rate. Periprocedural CEA outcomes appear similar in comparing older and younger patients, although longer term survival is lower for older patients, and older patients are at greater risk of discharge to other than home. CEA was associated with slightly higher risk of neurologic complications in older patients but may be considered appropriate for selected octogenarians and nonagenarians.

Variation in hospital costs and reimbursement for endovascular aneurysm repair: A Vascular Quality Initiative pilot project.

OBJECTIVE: Comparing costs between centers is difficult because of the heterogeneity of vascular procedures contained in broad diagnosis-related group (DRG) billing categories. The purpose of this pilot project was to develop a mechanism to merge Vascular Quality Initiative (VQI) clinical data with hospital billing data to allow more accurate cost and reimbursement comparison for endovascular aneurysm repair (EVAR) procedures across centers. METHODS: Eighteen VQI centers volunteered to submit UB04 billing data for 782 primary, elective infrarenal EVAR procedures performed by 108 surgeons in 2014. Procedures were categorized as standard or complex (with femoral-femoral bypass or additional arterial treatment) and without or with complications (arterial injury or embolectomy; bowel or leg ischemia; wound infection; reoperation; or cardiac, pulmonary, or renal complications), yielding four clinical groups for comparison. MedAssets, Inc, using cost to charge ratios, calculated total hospital costs and cost categories. Cost variation analyzed across centers was compared with DRG 237 (with major complication or comorbidity) and 238 (without major complication or comorbidity) coding. A multivariable model to predict DRG 237 coding was developed using VQI clinical data. RESULTS: Of the 782 EVAR procedures, 56% were standard and 15% had complications, with wide variation between centers. Mean total costs ranged from $31,100 for standard EVAR without complications to $47,400 for complex EVAR with complications and varied twofold to threefold among centers. Implant costs for standard EVAR without complications varied from $8100 to $28,200 across centers. Average Medicare reimbursement was less than total cost except for standard EVAR without complications. Only 9% of all procedures with complications in the VQI were reported in the higher reimbursed DRG 237 category (center range, 0%-21%). There was significant variation in hospitals' coding of DRG 237 compared with their expected rates. VQI clinical data accurately predict current DRG coding (C statistic, 0.87). CONCLUSIONS: VQI data allow a more precise EVAR cost comparison by identifying comparable clinical groups compared with DRG-based calculations. Total costs exceeded Medicare reimbursement, especially for patients with complications, although this varied by center. Implant costs also varied more than expected between centers for comparable cases. Incorporation of VQI data elements documenting EVAR case complexity into billing data may allow centers to better align respective DRG reimbursement to total costs.

Regional variation in patient selection and treatment for carotid artery disease in the Vascular Quality Initiative.

OBJECTIVE: Previous studies involving large administrative data sets have revealed regional variation in the demographics of patients selected for carotid endarterectomy (CEA) and carotid artery stenting (CAS) but lacked clinical granularity. This study aimed to evaluate regional variation in patient selection and operative technique for carotid artery revascularization using a detailed clinical registry. METHODS: All patients who underwent CEA or CAS from 2009 to 2015 were identified in the Vascular Quality Initiative (VQI). Deidentified regional groups were used to evaluate variation in patient selection, operative technique, and perioperative management. χ2 analysis was used to identify significant variation across regions. RESULTS: A total of 57,555 carotid artery revascularization procedures were identified. Of these, 49,179 patients underwent CEA (asymptomatic: median, 56%; range, 46%-69%; P < .01) and 8376 patients underwent CAS (asymptomatic: median, 36%; range, 29%-51%; P < .01). There was significant regional variation in the proportion of asymptomatic patients being treated for carotid stenosis <70% in CEA (3%-9%; P < .01) vs CAS (3%-22%; P < .01). There was also significant variation in the rates of intervention for asymptomatic patients older than 80 years (CEA, 12%-27% [P < .01]; CAS, 8%-26% [P < .01]). Preoperative computed tomography angiography or magnetic resonance angiography in the CAS cohort also varied widely (31%-83%; P < .01), as did preoperative medical management with combined aspirin and statin (CEA, 53%-77% [P < .01]; CAS, 62%-80% [P < .01]). In the CEA group, the use of shunt (36%-83%; P < .01), protamine (32%-89%; P < .01), and patch (87%-99%; P < .01) varied widely. Similarly, there was regional variation in frequency of CAS done without a protection device (1%-8%; P < .01). CONCLUSIONS: Despite clinical benchmarks aimed at guiding management of carotid disease, wide variation in clinical practice exists, including the proportion of asymptomatic patients being treated by CAS and preoperative medical management. Additional intraoperative variables, including the use of a patch and protamine during CEA and use of a protection device during CAS, displayed similar variation in spite of clear guidelines. Quality improvement projects could be directed toward improved adherence to benchmarks in these areas.

Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses.

BACKGROUND: The gangliosidoses (Tay-Sachs disease, Sandhoff disease, and GM1-gangliosidosis) are progressive neurodegenerative diseases caused by lysosomal enzyme activity deficiencies and consequent accumulation of gangliosides in the central nervous system (CNS). The infantile forms are distinguished from the juvenile forms by age of onset, rate of disease progression, and age of death. There are no approved treatments for the gangliosidoses. In search of potential biomarkers of disease, we quantified 188 analytes in CSF and serum from living human patients with longitudinal (serial) measurements. Notably, several associated with inflammation were elevated in the CSF of infantile gangliosidosis patients, and less so in more slowly progressing forms of juvenile gangliosidosis, but not in MPS disease. Thirteen CSF and two serum biomarker candidates were identified. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1ß, and TNFR2. Correspondence of abnormal elevation with other variables of disease-i.e., severity of clinical phenotype, differentiation from changes in serum, and lack of abnormality in other neurodegenerative lysosomal diseases-identifies these analytes as biomarkers of neuropathology specific to the gangliosidosis diseases.

A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.

OBJECTIVE: Carotid endarterectomy (CEA) is usually performed with eversion (ECEA) or conventional (CCEA) technique. Previous studies report conflicting results with respect to outcomes for ECEA and CCEA. We compared patient characteristics and outcomes for ECEA and CCEA. METHODS: Deidentified data for CEA patients were obtained from the Society for Vascular Surgery Vascular Quality Initiative (SVS VQI) database for years 2003 to 2013. Second (contralateral) CEA, reoperative CEA, CEA after previous carotid stenting, or CEA concurrent with cardiac surgery were excluded, leaving 2365 ECEA and 17,155 CCEA for comparison. Univariate analysis compared patients, procedures, and outcomes. Survival analysis was also performed for mortality. Multivariate analysis was used selectively to examine the possible independent predictive value of variables on outcomes. RESULTS: Groups were similar with respect to sex, demographics, comorbidities, and preoperative neurologic symptoms, except that ECEA patients tended to be older (71.3 vs 69.8 years; P < .001). CCEA was more often performed with general anesthesia (92% vs 80%; P < .001) and with a shunt (59% vs 24%; P < .001). Immediate perioperative ipsilateral neurologic events (ECEA, 1.3% vs CCEA, 1.2%; P = .86) and any ipsilateral stroke (ECEA, 0.8% vs CCEA, 0.9%; P = .84) were uncommon in both groups. ECEA tended to take less time (median 99 vs 114 minutes; P < .001). However, ECEA more often required a return to the operating room for bleeding (1.4% vs 0.8%; P = .002), a difference that logistic regression analysis showed was only partly explained by differential use of protamine. Life-table estimated 1-year freedom from any cortical neurologic event was similar (96.7% vs 96.7%). Estimated survival was similar comparing ECEA with CCEA at 1 year (96.7% vs 95.9%); however, estimated survival tended to decline more rapidly in ECEA patients after ∼2 years. Cox proportional hazards modeling confirmed that independent predictors of mortality included age, coronary artery disease, chronic obstructive pulmonary disease, and smoking, but also demonstrated that CEA type was not an independent predictor of mortality. The 1-year freedom from recurrent stenosis >50% was lower for ECEA (88.8% vs 94.3%, P < .001). However, ECEA and CCEA both had a very high rate of freedom from reoperation at 1 year (99.5% vs 99.6%; P = .67). CONCLUSIONS: ECEA and CCEA appear to provide similar freedom from neurologic morbidity, death, and reintervention. ECEA was associated with significantly shorter procedure times. Furthermore, ECEA obviates the expenses, including increased operative time, associated with use of a patch in CCEA, and a shunt, more often used in CCEA in this database. These potential benefits may be reduced by a slightly greater requirement for early return to the operating room for bleeding.