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Intermittent claudication (IC) is a commonly treated vascular condition. Patient sex has been shown to influence outcomes of interventions for other vascular disorders; however, whether outcomes of interventions for IC vary by sex is unclear. We sought to assess the association of patient sex with outcomes after IC interventions.The Vascular Quality Initiative was queried from 2010-2020 for all peripheral endovascular interventions (PVI), infra-inguinal bypasses (IIB), and supra-inguinal bypasses (SIB) for any degree IC. Univariable and multivariable analyses compared peri-operative and long-term outcomes by patient sex.There were 24,701 female and 40,051 male patients undergoing PVI, 2,789 female and 6,525 male patients undergoing IIB, and 1,695 female and 2,370 male patients undergoing SIB for IC. Guideline-recommended pre-operative medical therapy differed with female patients less often prescribed aspirin for PVI (73.4% vs. 77.3%), IIB (71.5% vs. 74.8%), and SIB (70.9% vs. 74.3%) or statins for PVI (71.8% vs. 76.7%) and IIB (73.1% vs. 76.0%) (all P 0.05). Female compared with male patients had lower 1-year reintervention-free survival after PVI (84.4% ± 0.3% vs. 86.3% ± 0.2%, P 0.001), IIB (79.0% ± 0.9% vs. 81.2% ± 0.6%, P = 0.04), and SIB (89.4% ± 0.9% vs. 92.6% ± 0.7%, P = 0.005), but similar amputation-free survival and survival across all procedures. Multivariable analysis confirmed that female sex was associated with increased 1-year reintervention for PVI (HR 1.16, 95% CI 1.09-1.24, P 0.001), IIB, (HR 1.16, 95% CI 1.03-1.31, P = 0.02), and SIB (HR 1.60, 95% CI 1.20-2.13, P = 0.001).Female patients undergoing interventions for IC were less often pre-operatively medically optimized than male patients, though the difference was small. Furthermore, female sex was associated with more reinterventions after interventions. Interventionists treating female patients should increase their efforts to maximize medical therapy. Future research should clarify reasons for poorer intervention durability in female patients.

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10−11), rs12454712 (BCL2; P = 2.7 × 10−8), and rs10506418 (FAM19A2; P = 1.9 × 10−8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.

Patients who are obese or underweight are traditionally at higher risk for perioperative morbidity and mortality. The effect of body mass index (BMI) on outcomes after carotid endarterectomy (CEA) is unclear. Our goal was to analyze the association of BMI with perioperative and long-term outcomes after elective CEA.The Vascular Quality Initiative (VQI) database was queried from 2003-2018 for patients undergoing elective CEAs. Patients were categorized into 5 BMI cohorts - underweight (UW, BMI18.5 kg/mThere were 89,079 patients included: 2% UW, 26% NW, 38.4% OW, 29.9% OB, and 3.6% MO. Overall, the mean age was 70.6 years, 60% were male, and 91.8% were of white race. There were significant differences among the BMI cohorts in regards to age, sex, smoking status, and comorbidities (all P0.05). For perioperative outcomes, the BMI cohorts differed significantly in reoperation for bleeding and 30-day mortality. On multivariable analysis, BMI was not associated with stroke or perioperative mortality. MO was associated with perioperative cardiac complications (Odds Ratios [OR] 1.26, 95% CI 1-1.57, P = 0.05). UW status was associated with increased return to the operating room (OR 1.89, 95% confidence interval [95% CI] 1.28-2.78, P = 0.001), 30-day mortality (OR 1.68, 95% CI 1-2.86, P =0.05), 1-year mortality (Hazard ratio [HR] 1.37, 95% CI 1.08-1.74, P = 0.01), and 5-year mortality (HR 1.22, 95% CI 1.06-1.41, P =0.005).BMI status was not associated with perioperative stroke, cranial nerve injury, or surgical site infections. Patients with MO had higher perioperative cardiac complications. UW patients have lower short and long-term survival and should be a focus for long-term targeted risk factor stratification and modification.

Intensive care unit (ICU) admission after endovascular aortic aneurysm repair (EVAR) varies across medical centers. We evaluated the association of postoperative ICU use with perioperative and long-term outcomes after EVAR.The Vascular Quality Initiative (2003-2019) was queried for index elective EVARs. Included centers were categorized by percentage of patients with EVARs postoperatively admitted to the ICU; routine ICU (rICU) centers as ≥80% ICU admissions and nonroutine ICU (nrICU) centers as ≤20% ICU admissions. Patients admitted preoperatively or with same day discharge were excluded. Perioperative outcomes and survival were compared between rICU and nrICU centers.Of 45,310 EVARs in the database, 35,617 were performed at rICU or nrICU centers - 5,443 (15.3%) at 71 rICU centers and 30,174 (84.7%) at 200 nrICU centers. Overall, mean age was 73.4 years and 81.6% were male. Postoperative myocardial infarction, pulmonary complications, stroke, leg ischemia, and in-hospital mortality were similar between rICU and nrICU centers (all p0.05). Postoperative length of stay (LOS) was prolonged at rICU centers (mean) (2.2 ± 3.6 vs 2 ± 4.2 days, p0.001). One-year survival was similar between rICU and nrICU centers, respectively, (94.9% vs 95.4%, p = 0.085). When compared with nrICU centers, rICU centers had similar 1-year mortality risk (hazard ratio [HR] 1.15, 95% CI 0.99-1.34, p = 0.076), but were associated with longer postoperative LOS (means ratio 1.1, 95% CI 1.08-1.13, p0.001).Routine ICU use after EVAR was associated with prolonged postoperative LOS, without improved perioperative/long-term morbidity or mortality. Updated care pathways to include postoperative admission to lower acuity care units may reduce costs without compromising care.

The choice of intervention for treating suprainguinal arterial disease, open bypass vs endovascular intervention, is often tempered by patient age and comorbidities. In the present study, we compared the association of patient age with 1-year major adverse limb events (MALE)-free survival and reintervention-free survival (RFS) rates among patients undergoing intervention for suprainguinal arterial disease.The Vascular Quality Initiative datasets for bypass and peripheral endovascular intervention (PVI; aorta and iliac only) were queried from 2010 to 2017. The patients were divided into two age groups: 60 and ≥60 years at the procedure. Age-stratified propensity matching of patients in bypass and endovascular procedure groups by demographic characteristics, comorbidities, and disease severity was used to identify the analysis samples. The 1-year MALE-free survival and RFS rates were compared using the log-rank test and Kaplan-Meier plots. Proportional hazard Cox regression was used to perform propensity score-adjusted comparisons of MALE-free survival and RFS.A total of 14,301 cases from the Vascular Quality Initiative datasets were included in the present study. Propensity matching led to 3062 cases in the ≥60-year group (1021 bypass; 2041 PVI) and 2548 cases in the 60-year group (1697 bypass; 851 PVI). In the crude comparison of the matched samples, the older patients undergoing bypass had had significantly greater in-hospital (4.6% vs 0.9%; P .001) and 1-year (10.5% vs 7.5%; P = .005) mortality compared with those who had undergone endovascular intervention. The rates of MALE (7.5% vs 14.3%; P .001) and reintervention (6.7% vs 12.7%; P .001) or death were significantly higher for the younger group undergoing PVI than bypass at 1 year. However, the rates of MALE (12.9% vs 14.3%; P = .298) and reintervention (12.7% vs 12.9%; P = .881) or death for were similar both procedures for the older group. Both log-rank analyses and the adjusted propensity score analyses of MALE-free survival and RFS in the two age groups confirmed these findings. The adjusted comparison of outcomes using propensity score matching favored PVI at 1-year survival (hazard ratio, 1.4; 95% confidence interval, 1.1-1.9; P = .003) for the older group but was not different for the younger group (hazard ratio, 0.6; 95% confidence interval, 0.3-1.0; P = .054).Among the patients aged 60 years undergoing intervention for suprainguinal arterial disease, the choice of therapy should be open surgical intervention given the higher risk of reintervention and MALE with endovascular intervention. Endovascular intervention should be favored for patients aged ≥60 years because of reduced perioperative mortality.

Background Limited information exists regarding the factor IX (FIX) coagulant activity (FIX:C) measured by different assays following FIX‐Padua gene therapy. Objective Assess for the first time FIX:C in five commonly used coagulation assays in plasma samples from hemophilia B subjects receiving FIX‐Padua gene transfer. Methods FIX:C was compared between central (n = 1) and local laboratories (n = 5) in the study, and across four commonly used FIX:C one‐stage assays and one FIX:C chromogenic assay. For comparison, samples of pooled congenital FIX‐deficient plasma spiked with purified recombinant human FIX (rHFIX)‐Padua protein or rHFIX (nonacog alfa) to obtain FIX:C concentrations from ~20% to ~40% were tested. Results FIX:C results at local laboratories strongly correlated with central laboratory results. However, absolute values at the central laboratory were consistently lower than those at local laboratories. Across five different FIX:C assays, a consistent pattern of FIX:C was observed for subjects receiving fidanacogene elaparvovec‐expressed gene transfer. Use of Actin FSL activated partial thromboplastin time (APTT) reagent in the central laboratory resulted in lower FIX:C values compared with other APTT reagents tested. The chromogenic assay determined lower FIX:C than any of the one‐stage assays. The rHFIX‐Padua protein–spiked samples showed similar results. In contrast, FIX:C results for rHFIX‐nonacog alfa measured within 25% of expected for all one‐stage assays and below 25% in the chromogenic assay. Conclusions Assay‐based differences in FIX:C were observed for fidanacogene elaparvovec transgene product and rHFIX‐Padua protein, suggesting the variable FIX:C determined with different assay reagents is inherent to the FIX‐Padua protein and is not specific to gene therapy–derived FIX‐Padua.

Background The day of the week (DOW) for performing procedures and operations has been shown to affect clinical and resource utilization outcomes. Limited published data are available on vascular surgery operations. Our primary objective was to assess outcomes by DOW for infrainguinal lower extremity bypass (LEB) performed for claudication or rest pain. The secondary objective was to assess outcomes by DOW for LEBs performed for tissue loss. Methods The Vascular Quality Initiative was queried from 2003 to 2018 for all elective index infrainguinal LEBs performed for claudication or rest pain. Cases performed for acute limb ischemia as well as concomitant peripheral vascular intervention, nonelective LEBs, sequential grafts, and weekend cases were excluded. LEBs were grouped by DOW: Monday–Tuesday (early weekdays) versus Wednesday–Friday (later weekdays). Baseline data, operative details, and outcomes were collected. Univariate and multivariable analyses were performed. LEBs performed for claudication/rest pain were analyzed together while tissue loss was assessed separately. Results There were 12,084 LEBs identified—44.5% performed on Monday–Tuesday and 55.5% on Wednesday–Friday. Overall, the mean age was 65.6 years, 68.6% were male, and 82.8% were Caucasian. LEBs were performed for claudication in 57.4% of cases. An autogenous great saphenous vein was used in 58.8% of cases, whereas a prosthetic graft was used in 35.1% of cases. The most common bypass origin was the femoral artery (94.1%), and target was the popliteal artery (70.1%). Significant differences between Monday–Tuesday versus Wednesday–Friday, respectively, were mean body mass index (27.8 kg/m2 vs. 28 kg/m2), preoperative aspirin use (74.2% vs. 72.5%), continuous vein harvest technique (41.9% vs. 44%), and mean operative time (mins) (216.2 vs. 222.6) (all P 0.05). However, LEBs performed for tissue loss on Wednesday–Friday versus Monday–Tuesday had similar cardiac complications (P > 0.05). Conclusions Elective LEBs performed on later weekdays for claudication/rest pain were associated with cardiac complications and prolonged LOS, whereas tissue loss confirmed association with prolonged LOS. Further investigations are needed to identify whether increased resources or allocation of resources should be focused on later weekdays to optimize patient outcomes.

There are limited data on access type when treating ruptured abdominal aortic aneurysms (AAAs) with endovascular aneurysm repair (EVAR). Our study's objective was to evaluate if the type of access in ruptured AAAs affected outcomes.The Vascular Quality Initiative was queried from 2009 to 2018 for all ruptured AAAs treated with an index EVAR. Procedures were grouped by access type: percutaneous, open, and failed percutaneous that converted to open access. Patients with iliac access, both percutaneous and open access, and concurrent bypass were excluded. Baseline characteristics, procedure details, and outcomes were collected. Univariable and multivariable analyses were performed.There were 1,206 ruptured AAAs identified-739 (61.3%) was performed by percutaneous access, 416 (34.5%) by open access, and 51 (4.2%) by failed percutaneous that converted to open access. Percutaneous access, compared with open access and failed percutaneous access, respectively, had the shortest operative time (min, median) (111 vs. 138 vs. 180, P 0.001) and was most often performed under local anesthesia (16.7% vs. 5% vs. 9.8%, P 0.001). The amount of contrast used was similar between the approaches. Univariable analysis comparing percutaneous access, open access, and failed percutaneous access showed differences in 30-day mortality (19.9% vs. 24.8% vs. 39.2%, P = 0.002), postoperative complications (33.7% vs. 40.2% vs. 54%, P = 0.003), and cardiac complications (18.2% vs. 19.8% vs. 34.7%, P = 0.018). However, multivariable analysis did not show access type to have a significant effect on cardiac complications, pulmonary complications, any complications, return to the operating room, or perioperative mortality. Open access was independently associated with a prolonged length of stay (means ratio 1.17, 95% confidence interval (CI) 1.04-1.33, P = 0.012). Factors independently associated with failed percutaneous were prior bypass (odds ratio (OR) 9.77, 95% CI 2.44-39.16, P = 0.001) and altered mental status (OR 2.45, 95% CI 1.17-5.15, P = 0.018).Access type for ruptured AAAs was not independently associated with major morbidity or mortality but did have a differential effect on length of stay. Access during these emergent procedures should be based on surgeon preference and experience.

Objective Maintenance of functional arteriovenous grafts (AVGs) for dialysis is difficult secondary to low primary patency, need for reinterventions, and limited alternative dialysis access options. We assessed our experience with percutaneous thrombectomy for treatment of occluded AVGs. Methods We performed a retrospective analysis of all percutaneous thrombectomies for AVGs from 2015 to 2017. These were generally performed using mechanical thrombectomy and occasional chemical tissue plasminogen activator thrombolysis, over-the-wire balloon embolectomy for inflow, and adjunctive inflow and outflow interventions as necessary. Perioperative outcomes, long-term patency, reinterventions, and need for new permanent access placement were analyzed. Results There were 218 percutaneous thrombectomies performed on 86 AVGs in 77 patients. Approximately half (53.2%) of the patients were male and 68.8% were black. Mean age was 61.1 ± 13.0 years. At the time of thrombectomy, 73.8% underwent venous outflow interventions and 4.5% underwent arterial inflow interventions. Within 30 days, 24.8% of declotted grafts underwent repeated percutaneous thrombectomy, 14.3% required tunneled dialysis catheter placement, 4% developed minor access site or graft infections, and one patient underwent surgical arterial thrombectomy for arm ischemia. There were no venous thromboembolic, cardiopulmonary, or cerebrovascular complications or clinically significant pulmonary embolism. At 1 year and 3 years after percutaneous thrombectomy, freedom from repeated thrombosis was 37% and 18%, respectively, and freedom from new dialysis access placement was 66% and 51%, respectively. Overall patient survival was 82% at 3 years. Conclusions Percutaneous thrombectomy of AVGs is safe and is associated with acceptable patency rates. This minimally invasive method extends AVG use for these high-risk patients with limited dialysis access options.

Despite improvements in treating human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the risk of end-stage renal disease and need for long-term arteriovenous (AV) access for hemodialysis remain high in HIV-infected patients. Associations of HIV/AIDS with AV access creation complications have been conflicting. Our goal was to clarify short- and long-term outcomes of patients with HIV/AIDS undergoing AV access creation.The Vascular Quality Initiative registry was queried from 2011 to 2018 for all patients undergoing AV access creation. Documentation of HIV infection status with or without AIDS was recorded. Data were propensity score matched (4:1) between non-HIV-infected patients and HIV/AIDS patients. Subsequent multivariable analysis and Kaplan-Meier analysis were performed for short- and long-term outcomes.There were 25,711 upper extremity AV access creations identified: 25,186 without HIV infection (98%), 424 (1.6%) with HIV infection, and 101 (.4%) with AIDS. Mean age was 61.8 years, and 55.8% were male. Patients with HIV/AIDS were more often younger, male, nonwhite, nonobese, and current smokers; they were more often on Medicaid and more likely to have a history of intravenous drug use, and they were less often diabetic and less likely to have cardiac comorbidities (P .05 for all). There was no significant difference in autogenous or prosthetic access used in these cohorts. Wound infection requiring incision and drainage or explantation within 90 days was low for all groups (0.6% vs 1.9 vs 0%; P = .11) of non-HIV-infected patients vs HIV-infected patients vs AIDS patients. Kaplan-Meier analysis showed no significant difference in 1-year freedom from primary patency loss (43.9% vs 46.3%; P =.6), 1-year freedom from reintervention (61% vs 60.7%,; P = .81), or 3-year survival (83% vs 83.8%; P = .57) for those with and without HIV/AIDS, respectively. Multivariable analysis demonstrated that patients with HIV/AIDS were not at significantly higher risk for access reintervention (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.76-1.24; P = .81), occlusion (HR, 1.06; 95% CI, 0.86-1.29; P = .6), or mortality (HR, 1.08; 95% CI, 0.83-1.43; P = .57).Patients with HIV/AIDS undergoing AV access creation have outcomes similar to those of patients without HIV infection, including long-term survival. Patients with HIV/AIDS had fewer traditional end-stage renal disease risk factors compared with non-HIV-infected patients. Our findings show that the contemporary approach for creation and management of AV access in patients with HIV/AIDS should be continued; however, further research is needed to identify risk factors in this population.

Background: We compared the outcomes of upper arm arteriovenous grafts (AVGs) in a large, prospectively collected data set to determine if there are clinically significant differences in axillary artery-based and brachial artery-based AVGs. Methods: Patients who received upper arm AVGs within the Society of Vascular Surgery Vascular Quality Initiative (VQI) dataset were identified. The primary outcome measures were primary and secondary patency loss at 12-month follow-up. Other outcomes included were wound infection, steal syndrome, and arm swelling at 6-month follow-up. The log-rank test was used to evaluate patency loss using Kaplan–Meier analysis, and Cox proportional hazards models were used to examine adjusted association between inflow artery (brachial artery vs axillary artery) and outcomes, adjusting for configuration (straight vs looped). Results: Among 3637 upper extremity AVGs in the VQI (2010-2017), there were 510 upper arm brachial artery AVGs and 394 upper arm axillary artery AVGs. Patients with axillary artery AVGs were more likely to be female (72% vs 56%, p Conclusions: From this observational study analyzing the outcomes of upper extremity hemodialysis access, axillary artery AVGs were associated with significantly lower patency rates and higher risk of steal syndrome than brachial artery AVGs.

Brachiocephalic arteriovenous fistulas (BCFs) are commonly placed in outpatient settings. The impact of general anesthesia (GA), regional anesthesia (RA), or local anesthesia (LA) on perioperative recovery and fistula maturation/patency after outpatient BCF creations is unknown. We evaluated whether outcomes of outpatient BCF creations vary based on anesthesia modality.The Vascular Quality Initiative (2011-2018) national database was queried for outpatient BCF creations. Anesthesia modalities included GA, RA, and LA. Perioperative, 3-month, and 1-year outcomes were compared between GA versus RA/LA anesthesia types.Among 3,527 outpatient BCF creations, anesthesia types were GA in 1,043 (29.6%), RA in 1,150 (32.6%), and LA in 1,334 (37.8%). Patients receiving GA were more often younger, obese, Medicaid recipients, without coronary artery disease, and treated in non-office-based settings (P 0.05 for all). GA compared with RA/LA cohorts were more often admitted postoperatively (5.3% vs. 2.4%, P 0.001) but had similar rates of thirty-day mortality (0.9 vs. 0.6%, P = 0.39). 3-month access utilization for hemodialysis was lower in GA than in RA/LA cohorts (12.6% vs. 23.6%, P 0.001). The Kaplan-Meier analysis showed that GA and RA/LA cohorts had similar 1-year primary access occlusion-free survival (43.6% vs. 47.1%, P = 0.24) and endovascular/open reintervention-free survival (57.2% vs. 57.6%, P = 0.98). On multivariable analysis, GA compared with RA/LA use was independently associated with increased postoperative admission (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.08-2.67, P = 0.02) and decreased 3-month access utilization (OR: 0.39, 95% CI: 0.25-0.61, P 0.001) but had similar 1-year access occlusion (hazard ratio [HR]: 1.09, 95% CI: 0.9-1.32, P = 0.36) and reintervention (HR: 1.02, 95% CI: 0.82-1.26, P = 0.88). On subgroup analysis of the RA/LA cohort, RA compared with LA was associated with increased 3-month access utilization (OR: 1.6, 95% CI: 1.01-2.5; P = 0.04) and 1-year access reintervention (HR: 1.46, 95% CI: 1.12-1.89), but had similar 1-year access occlusion (HR: 1.2, 95% CI: 0.95-1.51, P = 0.13).Compared with RA/LA use, GA use in patients undergoing outpatient BCF creations was associated with increased hospital admissions, decreased access utilization at 3 months, and similar 1-year access occlusion and reintervention. RA/LA is preferable to expedite recovery and access utilization.

Treatment of asymptomatic internal carotid artery (ICA) stenosis, particularly for moderate to severe (70%-80%) disease, is controversial. The goal was to assess the clinical course of patients with moderate to severe carotid stenosis.A single institution retrospective analysis of patients with asymptomatic ICA stenosis identified on duplex ultrasound as moderate to severe (70%-80%) from 2003 to 2018 were analysed. Duplex criteria for 70%-80% stenosis was a systolic velocity of ≥325 cm/s or an ICA:common carotid artery ratio of ≥4, and an end diastolic velocity of140 cm/s. Asymptomatic status was defined as no stroke/transient ischaemic attack (TIA) within six months of index duplex. Primary outcomes were progression of stenosis to80%, ipsilateral stroke/TIA without documented progression, and death.In total, 206 carotid arteries were identified in 182 patients meeting the inclusion criteria. Mean patient age was 71.5 years, 57.7% were male, and 67% were white. There were 19 stenoses removed from analysis except for survival analysis as they initially underwent carotid endarterectomy or carotid artery stent based on surgeon/patient preference. Documented progression occurred in 24.1% of stenoses. There were 5.3% of stenoses associated with an ipsilateral stroke/TIA without documented progression, which occurred at a mean of 26.4 months. Kaplan-Meier analysis demonstrated a 60.3% five year freedom from stenosis progression, 92.5% five year freedom from stroke/TIA without documented progression, and 83.7% five year survival. Risk factors associated with stroke/TIA without documented progression at five years were atrial fibrillation (hazard ratio [HR] 14.87, 95% confidence interval [CI] 2.72-81.16; p = .002) and clopidogrel use at index duplex (HR 6.19, 95% CI 1.33-28.83; p = .020). Risk factors associated with death at five years were end stage renal disease (HR 9.67, 95% CI 2.05-45.6; p = .004), atrial fibrillation (HR 7.55, 95% CI 2.48-23; p .001), prior head/neck radiation (HR 6.37, 95% CI 1.39-29.31; p = .017), non-obese patients (HR 5.49, 95% CI 1.52-20; p = .009), and non-aspirin use at index duplex (HR 3.05, 95% CI 1.12-8.33; p = .030).Patients with asymptomatic moderate to severe carotid stenosis had a low rate of stroke/TIA without documented progression. However, there was a high rate of stenosis progression reinforcing the need to follow these patients closely.

Objective Interventional approaches to managing intermittent claudication vary widely. According to Society for Vascular Surgery guidelines, any invasive treatment of claudication must offer long-term benefit at low risk of complications. Our aim was to evaluate contemporary claudication intervention patterns and functional outcomes. Methods The Vascular Study Group of New England database (2003-2018) was queried for peripheral vascular interventions (PVIs), infrainguinal bypasses, and suprainguinal bypasses for claudication. Perioperative and 1-year outcomes were evaluated. Results There were 7051 PVIs, 2527 infrainguinal bypasses, and 849 suprainguinal bypasses performed for claudication. Treatment levels were iliac (52.2%), femoral-popliteal (54%), and tibial (5.7%). Isolated tibial interventions were completed in 1.7% of patients. Infrainguinal bypasses were most often to the popliteal artery (81.2%); however, in 18.8% of cases, bypasses were to tibial targets. Suprainguinal bypasses originated primarily from the abdominal aorta (88.6%) but also from the axillary artery (10.6%) and thoracic aorta (0.8%). Common perioperative complications were access site hematoma in 4.9% of PVIs and cardiac complications in 3.7% of infrainguinal bypasses and 11.3% of suprainguinal bypasses. Overall, 30-day mortality was 0.4% to 2%. After 1 year, of patients initially ambulating without assistance, 2.4% to 3.6% required assistance and 0.3% to 1.3% were nonambulatory. Ipsilateral reintervention/amputation-free survival, major amputation-free survival, and survival at 1 year were 81.4% to 90.6%, 92.9% to 94.1%, and 95.3% to 97%, respectively. Conclusions Multisegment PVI was the most commonly performed intervention for claudication; however, a subset of patients received treatments supported by limited evidence, including isolated tibial PVI and bypasses with axillary inflow and tibial outflow. Interventions had low perioperative morbidity and mortality, yet patients were still at risk for worse functional status and limb loss at 1 year, emphasizing the importance of careful patient selection, medical optimization, and informed consent.

It has been suggested that more bypass outflow targets for bypass grafts improve patency and outcomes. Our objective was to examine this in a multicenter contemporary series of axillary to femoral artery grafts.The Vascular Quality Initiative database was queried for all axillary-unifemoral (AxUF) and axillary-bifemoral (AxBF) bypass grafts performed between 2010 and 2017 for claudication, rest pain, and tissue loss. Patients with acute limb ischemia were excluded. Patients' demographics and comorbidities as well as operative details and outcomes were recorded. Univariable, multivariable, and Kaplan-Meier analyses were used to assess long-term outcomes.There were 412 (32.9%) AxUF grafts and 839 (67.1%) AxBF grafts identified. Overall, the mean age of the patients was 68.3 years, 51.1% were male, and 84.7% were white. Compared with AxBF grafts, AxUF grafts were more often performed for urgent cases; in patients who were younger, male, nonambulatory, and diabetic; and in those with preoperative anticoagulation, critical limb ischemia, prior bypass, aneurysm repair, peripheral vascular intervention, and major amputation (P .05 for all). There were no significant differences between AxUF and AxBF grafts in perioperative wound complications (4.2% vs 2.9%; P = .23), cardiac complications (7.3% vs 10.4%; P = .08), pulmonary complications (4.1% vs 6%, P = .18), early stenosis/occlusion (0.2% vs 0.8%; P = .22), perioperative mortality (2.9% vs 3.2%; P = .77), and length of stay (6.4 ± 5.6 days vs 6.7 ± 8 days; P = .29). The mean estimated blood loss (268.1 mL vs 348.6 mL; P .001) and mean operative time (201 minutes vs 224.1 minutes; P .001) were significantly lower for AxUF grafts. Kaplan-Meier analysis showed that AxUF and AxBF grafts had similar freedom from graft occlusion (62.6% vs 71.8%; P = .074), major adverse limb event-free survival (57.1% vs 66.6%; P = .052), and survival (86% vs 86%; P = .897) at 1 year. Major amputation-free survival was lower for AxUF grafts (63.7% vs 73%; P = .028). Multivariable analysis also showed that the type of graft configuration did not independently predict occlusion/death (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.77-1.46; P = .72), amputation/death (HR, 1.12; 95% CI, 0.83-1.51; P = .45), major adverse limb event/death (HR, 0.97; 95% CI, 0.73-1.3; P = .85), or mortality (HR, 0.91; 95% CI, 0.65-1.26; P = .55). Three-year survival after placement of AxUF and AxBF grafts was similar (75.1% vs 78.2%; P = .414).AxUF and AxBF grafts have similar perioperative and 1-year outcomes. Graft patency was not significantly different between an AxBF graft and an AxUF graft at 1 year. Overall, patients treated with these reconstructions have many comorbidities and low long-term survival.

Mutations in thedystrophingene cause the most common and currently incurable Duchenne muscular dystrophy (DMD) characterized by progressive muscle wasting. Although abnormal Ca2+handling is a pathological feature of DMD, mechanisms underlying defective Ca2+homeostasis remain unclear. Here we generate a novel DMD patient-derived pluripotent stem cell (PSC) model of skeletal muscle with an isogenic control using clustered regularly interspaced short palindromic repeat (CRISPR)- mediated precise gene correction. Transcriptome analysis identifies dysregulated gene sets in the absence of dystrophin, including genes involved in Ca2+handling, excitation-contraction coupling and muscle contraction. Specifically, analysis of intracellular Ca2+transients and mathematical modeling of Ca2+dynamics reveal significantly reduced cytosolic Ca2+clearance rates in DMD-PSC derived myotubes. Pharmacological assays demonstrate Ca2+flux in myotubes is determined by both intracellular and extracellular sources. DMD-PSC derived myotubes display significantly reduced velocity of contractility. Compared with a non-isogenic wild type PSC line, these pathophysiological defects could be rescued by CRISPR-mediated precise gene correction. Our study provides new insights into abnormal Ca2+homeostasis in DMD and suggests that Ca2+signaling pathways amenable to pharmacological modulation are potential therapeutic targets. Importantly, we have established a human physiology-relevantin vitromodel enabling rapid pre-clinical testing of potential therapies for DMD.

Objective Lower extremity arteriovenous (AV) access is an alternative when upper extremity access options have been exhausted. Our goal was to assess short- and medium-term outcomes of lower extremity hemodialysis access. Methods The Vascular Quality Initiative was reviewed for all lower extremity AV hemodialysis cases. Patient and case details were recorded. Multivariable analysis was used to analyze outcomes. Results We identified 463 lower extremity AV access cases in the VQI registry. There were 56 AVF (12.1%) and 407 AVG (87.9%). The mean age was 56 ± 15 years, 46.9% were male, and 40.7% were Caucasian. The majority (90%) had a previous upper extremity AV access and 25.4% had a prior lower extremity access. More than one-half (57.9%) had a tunneled line at the time of the procedure. Patients undergoing an AVF vs AVG creation were younger, more often ambulatory, and less often with peripheral arterial disease. For AVF, the superficial femoral artery was more often used for access inflow (76.8% vs 49.4%; P Conclusions In our contemporary multicenter analysis, patients undergoing lower extremity AV access creation have low primary access patency and almost 20% mortality at 1 year. These results should be considered when suggesting a lower extremity dialysis access, as well as other dialysis alternatives when available.

Percutaneous radial artery access has been increasingly used for peripheral vascular interventions (PVIs). Our goal was to characterize the practice patterns and perioperative outcomes among patients treated using PVI performed via radial artery access.The Vascular Quality Initiative was queried from 2016 to 2020 for PVI performed via upper extremity access. Univariable and multivariable analyses were used to evaluate the periprocedure outcomes of radial artery access cases. A separate sample of brachial artery access cases was used as a comparator.A total of 520 radial artery access cases were identified. The mean age was 69 ± 10 years, and 41.3% were women. Most procedures were performed in the hospital outpatient setting (71.7%). The sheath size was ≤5F for 10%, 6F for 78%, and 7F for 12%. Ultrasound-guided access and protamine were used in 68.3% and 17.3% of cases, respectively. The interventions were aortoiliac (55%), femoropopliteal (55%), and infrapopliteal (9%). Stenting and atherectomy were performed in 55% and 19% of cases, respectively, and more often with 7F sheaths. Access site complications were any hematoma (4.8%), including hematomas resulting in intervention (0.8%), pseudoaneurysms (1%), and access stenosis or occlusion (0.8%). On multivariable analysis, sheath size was not associated with access site complications. Percutaneous brachial artery access (n = 1135) compared with radial access was independently associated with more overall hematomas (odds ratio, 1.73; 95% confidence interval, 1.06-2.81; P = .03). However, access type was not associated with hematomas resulting in intervention (odds ratio, 2.15; 95% confidence interval, 0.69-6.72; P = .19).PVIs via radial artery access exhibited a low prevalence of postprocedural access site complications and were associated with fewer minor hematoma complications compared with interventions performed using brachial artery access. Radial artery access compared with brachial artery access should be the preferred technique for PVIs.

Vascular closure devices (VCDs) and manual compression (MC) are used to achieve hemostasis after peripheral vascular interventions (PVIs). We sought to compare perioperative outcomes between MC and four VCDs after PVI in a multicenter setting.The Vascular Quality Initiative was queried for all lower extremity PVIs with common femoral artery access performed from 2010 to 2020. The VCDs included were MynxGrip (Cordis, Santa Clara, CA), StarClose SE (Abbott Vascular, Redwood City, CA), Angio-Seal (Terumo, Somerset, NJ), and Perclose ProGlide (Abbott Vascular). In a blinded fashion, these four VCDs (labeled A, B, C, and D) were compared to MC for baseline characteristics, procedural details, and outcomes (access site hematoma and stenosis/occlusion). Those with a sheath size8F were excluded. Propensity score matching (1:1) was performed. Univariable and multivariable analyses were completed for unmatched and matched data.A total of 84,172 lower extremity PVIs were identified. Of these, 32,013 (38%) had used MC and 52,159 (62%) had used VCDs (A, 12,675; B, 6224; C, 19,872; D, 13,388). The average age was 68.7 years, and 60.4% of the patients were men. The most common indications for intervention were claudication (43.8%) and tissue loss (40.1%). Compared with MC, VCDs were used more often for patients with obesity, diabetes, and end-stage renal disease (P .001 for all). VCDs were used less often for patients with hypertension, chronic obstructive pulmonary disease, coronary artery disease, prior percutaneous coronary and extremity interventions, and major amputation (P .001 for all). VCD use was more common than MC during femoropopliteal (73% vs 63.8%) and tibial (33.8% vs 22.3%) interventions but less common with iliac interventions (20.6% vs 34.7%; P .001 for all). Protamine was used less often with VCDs (19.1% vs 25.6%; P .001). Overall, 2003 hematomas had developed (2.4%), of which 278 (13.9%) had required thrombin or surgical intervention. Compared with MC, the use of any VCD had resulted in fewer hematomas (1.7% vs 3.6%; P .001) and fewer hematomas requiring intervention (0.2% vs 0.5%; P .001). When divided by hemostatic technique, the rate of the development of any hematoma was as follows: MC, 3.6%; VCD A, 1.4%; VCD B, 1.2%; VCD C, 2.3%; and VCD D, 1.1% (P .001). The rate of hematomas requiring intervention was as follows: MC, 0.5%; VCD A, 0.2%; VCD B, 0.2%; VCD C, 0.3%; and VCD D, 0.1% (P .001). Access site stenosis/occlusion was similar between the MC and any VCD groups (0.2% vs 0.2%; P = .12). Multivariable analysis demonstrated that any VCD use and the use of the individual VCDs compared with MC were independently associated with the development of fewer hematomas. The incidence of access site stenosis/occlusion was similar between the use of any VCD and MC. The matched analysis revealed similar findings.Although the overall rates of hematomas requiring intervention were low regardless of hemostatic technique, VCD use, irrespective of type, compared favorably with MC, with significantly fewer access site complications after PVI.

Although endovascular therapy is often the first-line option for medically refractory intermittent claudication (IC) caused by aortofemoral disease, suprainguinal bypass is often performed. Although this will often be aortofemoral bypass (AoFB), axillofemoral bypass (AxFB) is still sometimes performed despite limited data evaluating its utility in the management of IC. Our goal was to assess the safety and durability of AxFB performed for IC.The Vascular Quality Initiative (2009-2019) was queried for suprainguinal bypass performed for IC. Univariable and multivariable analyses were used to compare the perioperative and 1-year outcomes between AxFB and a comparison cohort of AoFB.We identified 3261 suprainguinal bypasses performed for IC: 436 AxFBs and 2825 AoFBs. The mean age was 61.4 ± 9.1 years, 58.8% of the patients were men, and 59.7% currently smoked. Patients undergoing AxFB, compared with AoFB, were more often older, male, never smokers and ambulated with assistance (P .001 for all). They had more often had hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and end-stage renal disease and had more often undergone previous outflow peripheral endovascular interventions and previous inflow or outflow bypass. The AxFBs, compared with the AoFBs, were more often unifemoral (P .05). Patients who had undergone AxFB, compared with AoFB, had had a shorter postoperative length of stay (median, 4 vs 6 days) and fewer perioperative pulmonary (3% vs 7.9%) and renal (5.5% vs 9.9%) complications but had required more perioperative ipsilateral major amputations (0.9% vs 0.04%; P .05 for all). No significant differences were found in the incidence of perioperative myocardial infarction (2.8% vs 2.7%), stroke (0.7% vs 1.1%), or death (1.8% vs 1.7%). At 1 year, the Kaplan-Meier analysis demonstrated that the AxFB cohort, compared with the AoFB cohort, had had higher rates of death (7.3% vs 3.6%; P = .002), graft occlusion or death (14.3% vs 7.2%; P = .001), ipsilateral major amputation or death (12.5% vs 5.6%; P .001), and reintervention, amputation, or death (19% vs 8.6%; P .001). On multivariable analysis, AxFB was independently associated with an increased risk of 1-year reintervention, amputation, or death (hazard ratio, 1.6; 95% confidence interval, 1.03-2.4; P = .04).The results from the present retrospective analysis suggest that long-term complications were more frequent in patients who had undergone AxFB compared with AoFB, although patients treated with AxFB had had a greater risk with more comorbidities. Because AxFB was associated with significant perioperative morbidity, mortality, and long-term complications, serious consideration should be given before its use to treat IC.

The lack of stable housing can impair access and continuity of care for patients living with human immunodeficiency virus (HIV). This study investigated the relationship between housing status assessed at multiple time points and several core HIV-related outcomes within the same group of HIV patients experiencing homelessness. Patients with consistently stable housing (CSH) during the year were compared to patients who lacked CSH (non-CSH group). The study outcomes included HIV viral load (VL), CD4 counts, and health care utilization. Multivariable and propensity weighted analyses were used to assess outcomes adjusting for potential group differences. Of 208 patients, 88 (42%) had CSH and 120 (58%) were non-CSH. Patients with CSH had significantly higher proportion of VL suppression and higher mean CD4 counts. The frequency of nurse visits in the CSH group was less than a half of that in the non-CSH group. Patients with CSH were less likely to be admitted to the medical respite facility, and if admitted, their length of stay was about a half of that for the non-CSH group. Our study findings show that patients with CSH had significantly better HIV virologic control and immune status as well as improved health care utilization.

The choice for surgical revascularisation for aortoiliac occlusive disease is often tempered by patient comorbidities. This study compares peri-operative outcomes and the association between choice of operation and one year major adverse limb event (MALE) free survival and five year mortality.The Vascular Study Group of New England (VSGNE) dataset for supra-inguinal bypass operations from 2009 to 2015 was queried. This study excluded cases with bypass other than aortofemoral (AFB), axillofemoral (AXB), and femorofemoral (FFB), and those with endovascular interventions or femoral endarterectomy. Cases combined with other procedures, indications other than occlusive disease, and missing pathology were also excluded. Patients were divided into three groups: AFB, AXB, and FFB. Thirty day post-operative death (POD) and adverse events were compared using univariable and multivariable analyses. One year MALE free survival was compared between groups with log rank test and Kaplan-Meier plot. Proportional hazard Cox regression was used for adjusted comparison of MALE free and five year survival.In total, 1,602 cases were included: 207 (12.9%) AXB; 872 (54.4%) AFB; 523 (32.6%) FFB. AXB patients were older with more comorbidities. Post-operative complications and POD rates were significantly higher for AXB (p .05). On adjusted analyses, AXB increased the hazard of one year MALE (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.12-2.78; p = .014) and five year mortality (HR 1.54; 95% CI 1.11-2.41; p = .009). Both FFB and AFB had similar one year MALE free survival but significantly better one year MALE free survival than AXB.After adjusting for confounding variables, and while acknowledging limitations related to the VSGNE data set, FFB led to significantly lower rates of post-operative complications than AXB. FFB may serve as the extra-anatomical operation of choice in high risk patients with extensive disease, who cannot undergo AFB, provided that anatomy permits. AFB should be performed preferentially in low risk patients with appropriate anatomy. Owing to its higher complications rates, the study suggests that AXB should be limited to patients with no other option for revascularisation.

Objective Radial artery-based wrist arteriovenous fistulas (AVFs) are commonly created as an initial upper extremity arteriovenous access. A more distal access site, such as the anatomic snuffbox AVF, can also be created. Although much has been written about wrist AVFs, outcomes of snuffbox AVFs are unclear. Our goal was to compare perioperative and midterm outcomes between these two types of distal access. Methods The Vascular Quality Initiative database was queried for all patients undergoing snuffbox AVFs and wrist AVFs from 2011 to 2017. Unmatched and matched analyses were performed for baseline characteristics and outcomes at 6 months for ischemic steal, wound infection, and arm swelling. Multivariable analysis was performed for unmatched and matched analyses for primary patency, surgical or endovascular repair, and patient survival. Kaplan-Meier matched analysis was performed for primary patency, freedom from surgical or endovascular intervention, and survival. Results We identified 4525 distal forearm fistulas: 179 (4%) snuffbox AVFs and 4346 (96%) wrist AVFs. The average age was 59 ± 14.7 years, and 72.3% of patients were male. There were no significant differences in baseline demographics or comorbidities of patients with snuffbox AVFs and wrist AVFs except that patients with snuffbox AVFs had fewer tunneled lines at access creation (70.2% vs 65.2%; P = .046) and had a lower American Society of Anesthesiologists class. There were no significant differences in unmatched outcomes at 6 months for ischemic steal (0.8% vs 1.9%; P = .336), wound infection (0% vs 0.2%; P = .649), and arm swelling (0.8% vs 1.3%; P = .592). Matched analysis showed no significant differences in baseline characteristics and outcomes at 6 months for ischemic steal (0% vs 1.8%; P = .146), wound infection (0% vs 0%), and arm swelling (0.9% vs 1.2%; P = .789). Kaplan-Meier matched analysis showed no significant differences between snuffbox AVFs and wrist AVFs at 6 months for primary patency (51% vs 48%; P = .61), freedom from endovascular intervention (84.5% vs 82.5%; P = .98), freedom from surgical intervention (90% vs 86%; P = .08), and survival (92% vs 96%; P = .1). In multivariable analysis of unmatched data, snuffbox AVFs and wrist AVFs had similar primary patency (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.26; P = .83), likelihood of surgical intervention (HR, 0.61; 95% CI, 0.35-1.05; P = .074) and endovascular intervention (HR, 0.96; 95% CI, 0.65-1.42; P = .83), and survival (HR, 1.47; 95% CI, 0.9-2.4; P = .128). Conclusions Snuffbox AVFs have midterm results similar to those of wrist AVFs.

Two-way enriched design (TED) is a novel approach addressing placebo response in clinical trials. It is a two-stage, randomized, placebo-controlled trial design with enrichment in placebo non-responders and treatment responders at the second stage. All data from the first stage and data from placebo non-responders and treatment responders in the second stage are used for the final analysis of the treatment effect. The existing methods for the analysis of TED data include score tests with one, two, and three degrees of freedom. All these methods are only applicable to binary outcomes. However, there is an interest in continuous outcomes in clinical trials in psychiatry. In this manuscript, we apply some novel methods, including a repeated measures model, a weighted repeated measures model with weights from propensity score, and weights from K-means clustering, to analyze TED data for both binary outcomes and continuous outcomes. The simulation study indicates that the repeated measures model performs consistently well in preserving the type I error and achieving the minimum mean standard error as well as a higher power. The performance of the weighted repeated measures model with weights from K-means clustering improves with increasing sample size. Investigators can choose from these analytic approaches under different scenarios.

Although tapered dialysis access grafts are often used in an effort to prevent ischemic steal, their efficacy is uncertain. Our goal was to use real-world data to assess the performance of these grafts with respect to primary patency and ischemic steal.The Vascular Quality Initiative database was queried from 2010 to 2017 for all patients undergoing tapered dialysis grafts in the upper arm. Multivariable analysis was performed to analyze primary patency, ischemic steal, and reinterventions.We identified 3608 patients who received dialysis access grafts, 1473 tapered grafts and 2135 nontapered grafts. The mean age was 64.8 years, and 43.4% of the patients were male. Tapered grafts were used more often in female patients (60.5% vs 54%), nonwhite patients (53.3% vs 47.7%), patients with no previous access (28% vs 26.3%), grafts with an antecubital brachial artery origin (50% vs 44.4%), and grafts with an antecubital cephalic vein target (7.4% vs 3.7%; P .05). Three-month outcomes between tapered and nontapered grafts were similar for wound infection (1.4% vs 2%; P = .31), ischemic steal (4.1% vs 4.6%; P = .58), and arm swelling (3.5% vs 2.9%; P = .38). Multivariable analyses revealed that in comparison to nontapered grafts, tapered grafts did not affect primary patency rates (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.96-1.42; P = .11), ischemic steal (HR, 1.03; 95% CI, 0.64-1.65; P = .92), difference in endovascular reintervention (HR, 1.08; 95% CI, 0.74-1.16; P = .5), or operative reintervention (HR, 1.25; 95% CI, 0.86-1.82; P = .24).Tapered grafts for upper extremity arteriovenous access do not affect primary patency, development of steal, or endovascular reintervention in comparison to nontapered grafts. Our findings do not support the routine use of these grafts in dialysis access to improve outcomes.

According to the Center for Disease Control and Prevention, trauma is the leading cause of death in children aged1 year in the United States (US). Although vascular injuries occur in only 0.6-1% of pediatric patients with trauma, they are a major mortality contributor. This study aims to examine epidemiology and outcomes after pediatric vascular injuries (PedVIs) in the US.The National Trauma Data Bank (2002-2012) was queried to identify children (0-16) with PedVIs. Patients were categorized based on their demographics, location, and mechanism and presenting trauma severity (injury severity score [ISS] and shock). Study was divided into two 5-year periods (P1: 2002-2006; P2: 2007-2012) to study the trends in pediatric vascular trauma presentation and outcomes (hospital death and extended length of stay [LOS 8 days]) using adjusted analyses.Analyses were performed on 3,408 cases; who were male (73.7%) and Caucasian (52.8%) with a mean age of 10.5 ± 4.5 years. The Southern region of the US saw the highest increase in PedVIs (P2 versus P1: 38.3% vs. 25.0%, P 0.05). Blunt injuries constituted most of these injuries (57%). Firearm (36.9%) and motor vehicle crash (MVC) (34%) were the most common lethal mechanisms of injury. Despite the significant decrease in MVC rates (P2 versus P1: 17.4% vs. 22.6%, P 0.05), firearm rates were unchanged. Upper extremity injuries were the most common anatomically (34.9%). ISS and shock were significantly decreased during P2. Mortality occurred in 7.9% of patients, which significantly decreased (P2 versus P1: 6.3% vs. 10.9%, P 0.001) without a significant change in LOS. Odds of mortality decreased by 32% during P2 (P = 0.08) and was independently associated with penetrating mechanism of injury (odds ratio [OR]: 1.97; 95% confidence interval [CI]: 1.22-3.19, P = 0.006), shock at presentation (OR: 5.48; 95% CI: 3.55-8.46, P 0.001); ISS (OR: 1.08; 95% CI: 1.06-1.27, P 0.001), and Glasgow Coma Score 9 (OR: 11.21; 95% CI: 7.18-17.49, P 0.001).We observed a significant decrease in the overall severity of injury and in-hospital mortality concurrent with the observation of a significant decrease in the rates of pediatric MVC vascular injuries. Public health policies directed toward firearm safety may further decrease PedVIs and mortality among this vulnerable population.

Background There are conflicting data about the effect of heparin use on perioperative outcomes during upper extremity arteriovenous (AV) access creation. Our goal was to assess the effect of the use and degree of intraoperative heparin on perioperative outcomes after AV access creation. Methods All upper extremity AV access cases performed at a tertiary academic medical center between 2014 and 2017 were reviewed. Patient and procedural details including intraoperative heparin use and dosing as well as protamine use were analyzed. Full heparin dose was defined as 80–100 U/kg and partial heparin dose as less than 80 U/kg. Perioperative arterial thrombosis or distal embolism, hematoma, and early loss of primary patency within 30 days were evaluated. Multivariate analysis was performed to assess the effect of heparin use. Results There were 550 AV access cases identified: brachiocephalic (37.5%), brachiobasilic (29.3%), and radiocephalic fistulas (12.9%), and AV grafts (16.9%). Average patient age was 62.6 years and 58.9% were male. Full heparinization was used in 21.3%, partial heparinization in 58.7%, and no heparin was used in 20% of cases. Protamine was used in 94.9% of full heparin cases and 51.4% of partial heparin cases. No perioperative arterial thrombosis or distal embolism was observed. Perioperative wound hematoma rate was 3.4%, 3.1%, and 0.9% in full heparin, partial heparin, and no heparin cohorts, respectively (P = 0.42). Early loss of primary patency was 11.1%, 7.7%, and 6.4% for full heparin, partial heparin, and no heparin cases, respectively (P = 0.39). There were no differences in return to the operating room or perioperative survival. On multivariable analysis, full heparin use (odds ratio [OR] 3.82, 95% confidence interval [CI] 0.41–35.9, P = 0.24) and partial heparin (OR 4.03, 95% CI 0.5–32.6, P = 0.19) use were not significantly different from no heparin cases with respect to 30-day perioperative hematoma rate. Full heparin (OR 1.76, 95% CI 0.65–4.78, P = 0.26) and partial heparin (OR 1.13, 95% CI 0.46–2.75, P = 0.79) were not significantly different from no heparin cases with respect to early loss of primary patency. Conclusions Intraoperative heparin use, at full or partial doses, did not affect perioperative outcomes after AV access creation. Overall complication event rate was low for all groups. AV access can be safely performed without intraoperative heparin use.

Patients with critical limb ischemia (CLI) utilize hospital resources at high rates. One major driver for resource utilization is emergency department (ED) visits. Our goal was to assess perioperative ED visits after lower extremity bypass (LEB) for CLI.All patients undergoing LEB for CLI from 2008 to 2017 at our institution were analyzed. ED visits and details of the visit within 30 and 90 days of discharge from index admission were recorded. Multivariable analysis was performed to identify risk factors for any ED presentation and ED presentation without hospital admission.There were 317 patients identified who underwent infrainguinal LEB for CLI. Average age was 66 years, and 60.6% of patients were male. Within 30 and 90 days, 24.3% and 36.3% presented to the ED overall, and 16.7% and 26.5% of all postoperative patients had an ED presentation without hospital admission, respectively. Most common reasons for any ED visits and for ED visits without admission within 30 days were wound complications (22.1% and 20.8%), cardiac complications (16.9% and 17%), and ipsilateral leg pain (10.4% and 11.3%), respectively. Cryopreserved vein bypass (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.02-8.84, P = 0.046) and index length of stay (LOS) (OR 1.09, 95% CI 1.04-1.15, P 0.001) predicted any 30-day ED visit. Active leg infection at the time of bypass (OR 2.35, 95% CI 1.21-4.58, P = 0.012) and index LOS (OR 1.05, 95% CI 1.004-1.09, P = 0.033) predicted 30-day ED presentation without hospital admission. Most common reasons for any ED visit and for ED visits without admission within 90 days were surgical wound complications (15.8% and 14.3%), cardiac complications (14.9% and 14.3%), and nonsurgical wounds (9.6% and 9.5%), respectively. Chronic renal insufficiency (CRI) (OR 2.73, 95% CI 1.52-4.93, P = 0.001) and index LOS (OR 1.07, 95% CI 1.01-1.12, P = 0.017) predicted any 90-day ED visit. CRI (OR 3.34, 95% CI 1.81-6.17, P = 0.001) predicted 90-day ED presentation without hospital admission. For multiple ED visits within 90 days, there were 5 patients each with 5 ED visits, 12 each with 4 ED visits, 26 each with 3 ED visits, and 47 each with 2 ED visits.There is a high rate of ED utilization in CLI patients after LEB. Targeting these patients with closer follow-up and improved outpatient ambulatory access could assist in decreasing the frequency of postoperative ED visits. Particular areas of targeted improvement are those patients who presented to the ED and were not admitted.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

Publisher's version (útgefin grein), Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p, WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The grant funding of WHI are R21 HL123677, R56 DK104806 and R01 MD012765 to NF. The FamHS was funded by R01HL118305 and R01HL117078 NHLBI grants, and 5R01DK07568102 and 5R01DK089256 NIDDK grant." and "The Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (project # Z01-AG000513 and human subjects protocol number 09-AGN248). Support for GENOA was provided by the National Heart, Lung and Blood Institute (HL119443, HL087660, HL054464, HL054457, and HL054481) of the National Institutes of Health. Ruth loos is supported by the NIH (R01DK110113, U01HG007417, R01DK101855, R01DK107786). The Rotterdam Study GWAS datasets are supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), and the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project nr. 050-060-810. The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006- 01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme "Quality of Life and Management of the Living Resources" of 5th Framework Programme (no. QLG2-CT-2002- 01254). The ERF study was further supported by ENGAGE consortium and CMSB. Highthroughput analysis of the ERF data was supported by joint grant from Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWORFBR 047.017.043).ERF was further supported by the ZonMw grant (project 91111025), and this work was partially supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6- 4278). This study is also supported by National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616 to Drs. Meigs, Dupuis and Florez, NIDDK K24 DK080140 to Dr. Meigs, and a Doris Duke Charitable Foundation Clinical Scientist Development Award to Dr. Florez. The HERITAGE Family Study was supported by National Heart, Lung, and Blood Institute grant HL-45670. The Women's Genome Health Study is supported by the National Heart, Lung, and Blood Instutute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913). Additional support for endpoint collection was provided by the National Heart, Lung, and Blood Institute under ARRA funding (HL099355). HyperGEN (Hypertension Genetic Epidemiology Network): The hypertension network is funded by cooperative agreements (U10) with NHLBI: HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515, and 2 R01 HL55673- 12. The AGES study has been funded by NIH contracts N01-AG-1-2100 and 271201200022C. Caroline Hayward is supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease)”and “Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6, the Scottish Funding Council HR03006 and the Wellcome Trust through a Strategic Award (reference 104036/Z/14/Z) for Stratifying Resilience and Depression Longitudinally (STRADL). Genotyping was funded by the UK's Medical Research Council. Jose C. Florez, NIDDK K24 DK110550 The MESA project is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Additionally, one or more authors are affiliated with the following commercial entities: Interleukin Genetics, GlaxoSmithKline, Daiichi-Sankyo, AstraZeneca, Data Tecnica International LLC, Illumina Inc., University of California Healthcare, Janssen Pharmaceuticals, Goldfinch Bio, and Novo Nordisk. Please see the Competing Interests Statement for additional details. The funders provided support in the form of salaries for authors but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.