Vein interposition cuffs decrease the intimal hyperplastic response of polytetrafluoroethylene bypass grafts

AbstractPurpose: The modification of the distal anastomosis of polytetrafluoroethylene (PTFE) bypass grafts with vein interposition cuffs (VCs) has been reported to increase graft patency. However, the mechanisms that are responsible for this improved patency are unclear. Because intimal hyperplasia (IH) is a primary cause of prosthetic graft failure, we hypothesized that VCs affect the distal anastomosis by decreasing the IH response of the outflow artery. Methods: Twenty-three female domestic Yorkshire pigs (mean weight, 35 kg) underwent 42 femoral PTFE bypass grafting procedures. The PTFE bypass grafts were separated into the following three groups according to distal anastomotic configuration: end-to-side anastomoses (ES), VCs, and cuffs constructed with PTFE (PCs). Four femoral arteries from two pigs served as healthy controls. At sacrifice, the grafts were perfusion fixed, and the distal anastomoses harvested at 1 and 4 weeks. The specimens were hemisected and serially sectioned to identify the heel, toe, and mid-anastomotic regions. The sections were cut into 5-μm segments and analyzed for intima and media thickness and area, intima/media area ratio, and the distribution of IH in the vein cuff. The roles of transforming growth factor–β1 and platelet-derived growth factor–BB in IH development were assessed with immunohistochemistry. Results: IH development was significantly lower at all areas of the anastomosis, with VCs compared with ES and PCs at 4 weeks (P ≤ .001). IH decreased in VCs from 1 to 4 weeks in all areas of the anastomosis (P ≤ .001). PCs showed pronounced IH at the mid-anastomosis as compared with VCs and ES (P ≤ .001). IH was most pronounced at the toe with ES and PCs (P ≤ .001). Qualitatively, VCs altered the site of IH development, sparing the recipient artery with preferential thickening of the vein cuff and formation of a pseudointima at the vein-PTFE interface. Immunohistochemistry results showed positive staining for transforming growth factor–β1, platelet-derived growth factor–BB, and smooth muscle α-actin in the hyperplastic intima. Conclusion: PTFE bypass grafts with VCs had less IH develop than did grafts with ES and PC anastomoses. IH regression in VCs at 4 weeks suggests compensatory vessel wall remodeling mediated by the presence of the VC. Furthermore, VCs caused a redistribution of hyperplasia to the vein-PTFE interface, delaying IH-induced outflow obstruction in the recipient artery. The marked increase in IH with PCs, despite a similar geometric configuration to VCs, suggests that the biologic properties of autogenous tissue dissipate IH development. Similarly, the flow patterns in PCs and VCs should be identical, which suggests a less important role of hemodynamic forces in VC-mediated protection. (J Vasc Surg 2000;31:69-83.

A multicenter, randomized, controlled trial of totally percutaneous access versus open femoral exposure for endovascular aortic aneurysm repair (the PEVAR trial)

ObjectiveThe first multicenter randomized controlled trial was designed and conducted to assess the safety and effectiveness of totally percutaneous endovascular aortic aneurysm repair (PEVAR) with use of a 21F endovascular stent graft system and either an 8F or 10F suture-mediated closure system (the PEVAR trial, NCT01070069). A noninferiority trial design was chosen to compare percutaneous access with standard open femoral exposure.MethodsBetween 2010 and 2012, 20 U.S. institutions participated in a prospective, Food and Drug Administration–approved randomized trial to evaluate percutaneous femoral artery access and closure by a “preclose” technique in conjunction with endovascular abdominal aortic aneurysm repair. A total of 151 patients were allocated by a 2:1 design to percutaneous access/closure (n = 101) or open femoral exposure (n = 50 [FE]). PEVAR procedures were performed with either the 8F Perclose ProGlide (n = 50 [PG]) or the 10F Prostar XL (n = 51 [PS]) closure devices. All endovascular abdominal aortic aneurysm repair procedures were performed with the Endologix 21F profile (outer diameter) sheath-based system. Patients were screened by computed tomography with three-dimensional reconstruction and independent physician review for anatomic suitability and adequate femoral artery anatomy for percutaneous access. The primary trial end point (treatment success) was defined as procedural technical success and absence of major adverse events and vascular complications at 30 days. An independent access closure substudy evaluated major access-related complications. Clinical utility and procedural outcomes, ankle-brachial index, blood laboratory analyses, and quality of life were also evaluated with continuing follow-up to 6 months.ResultsBaseline characteristics were similar among groups. Procedural technical success was 94% (PG), 88% (PS), and 98% (FE). One-month primary treatment success was 88% (PG), 78% (PS), and 78% (FE), demonstrating noninferiority vs FE for PG (P = .004) but not for PS (P = .102). Failure rates in the access closure substudy analyses demonstrated noninferiority of PG (6%; P = .005), but not of PS (12%; P = .100), vs FE (10%). Compared with FE, PG and PS yielded significantly shorter times to hemostasis and procedure completion and favorable trends in blood loss, groin pain, and overall quality of life. Initial noninferiority test results persist to 6 months, and no aneurysm rupture, conversion to open repair, device migration, or stent graft occlusion occurred.ConclusionsAmong trained operators, PEVAR with an adjunctive preclose technique using the ProGlide closure device is safe and effective, with minimal access-related complications, and it is noninferior to standard open femoral exposure. Training, experience, and careful application of the preclose technique are of paramount importance in ensuring successful, sustainable outcomes

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Alohamora: Reviving HTTP/2 Push and Preload by Adapting Policies On-the-Fly

Despite their promise of improved performance, HTTP/2's server push and link preload features have seen minimal adoption, largely because designing performant push/preload policies requires complex reasoning about the subtle relationships between page content, browser state, device resources, and network conditions. Static policies and guidelines that sufficiently generalize across these diverse conditions remain elusive.We present Alohamora, a system that automatically generates push/preload policies using Reinforcement Learning (RL). Alohamora trains a neural network that, given inputs that characterize the page structure and execution environment, outputs a push/preload policy for the page load at hand. To ensure efficient and practical training despite the large space of potential policies, number of pages served by a given site, and high mobile page load times, Alohamora introduces several key innovations: a faithful page load simulator that can evaluate a policy in several milliseconds (compared to 10s of seconds for a regular page load), and a page clustering strategy that appropriately balances insights for push/preload with the number of pages required during training. Experiments across a wide range of pages and mobile execution environments reveal that Alohamora is able to accelerate page loads by 19-57% and 12-34% for page load time and Speed Index, respectively

Mortality and Clinical Outcomes among Patients with COVID-19 and Diabetes

Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact of DM on mortality and other clinical outcomes of COVID-19 infection from this region. Aims The primary objective of our study was to analyze the mortality rate in people with DM infected with COVID-19. The secondary objectives were to assess the effect of various comorbidities on mortality and study the impact of DM on other clinical outcomes. Methods This is a retrospective study of COVID-19 infected patients admitted to a tertiary care hospital in north India in the early phase of the pandemic. Results Of the 1211 cases admitted, 19 were excluded because of incomplete data, and 1192 cases were finally considered for analysis. DM constituted 26.8% of total patients. The overall mortality rate was 6.1%, and the rate was 10.7% in the presence of diabetes (p 2 at presentation, extensive involvement in CXR, and elevated ANC/ALC ratio were also significantly associated with mortality. Conclusions The presence of comorbidities such as DM, hypertension, CAD, CKD, and cancer strongly predict the risk of mortality in COVID-19 infection. Early triaging and aggressive therapy of patients with these comorbidities can optimize clinical outcomes

Effect of adjunct femoral endarterectomy in lower extremity bypass on perioperative and 1-year outcomes.

BACKGROUND: Isolated common femoral endarterectomy was recently reported to have a 30-day mortality of 3.4%. The effect of adjunctive femoral endarterectomy at the time of lower extremity bypass is not well described, and therefore, the purpose of this study was to determine its associated perioperative and long-term risk. METHODS: Vascular Study Group of New England registry data were used to identify patients undergoing initial lower extremity bypass from 2003 to 2015. After univariate analysis, multivariable logistic regression was used to identify the independent association of endarterectomy with adverse perioperative events. Kaplan-Meier and Cox hazard models were used for the 1-year analysis. RESULTS: After exclusions, 4496 patients were identified as undergoing infrainguinal bypass (33% with endarterectomy). There was no difference in the proportion with chronic limb-threatening ischemia (CLI; 68% vs 67%; P = .24) or tissue loss of those with CLI (65% vs 63%; P = .34) between the adjunctive endarterectomy group and bypass alone, respectively. Patients undergoing adjunctive endarterectomy were older (mean 68 years vs 67 years; P = .02), more likely white (95% vs 93%; P = .02), smokers (91% vs 87%; P = .001), and more often had prior coronary artery bypass grafting/percutaneous coronary intervention (34% vs 31%; P = .02). The endarterectomy cohort had similar 30-day mortality (CLI: 2.6% vs 2.9%; P = .60; claudication: 0.2% vs 0.4%; P = 1.0) despite a longer operative time (median, 268 minutes vs 210 minutes; P \u3c .001) and increased blood loss (median, 250 mL vs 180 mL; P \u3c .001). Patients with CLI undergoing adjunctive endarterectomy had more in-hospital myocardial infarctions (MIs; 6.2% vs 3.8%; P = .003) and transfusions (11% vs 6.8%; P \u3c .001). At 1-year, this group had a suggestion of improved freedom from major amputation (91% vs 87%; P = .049) and amputation-free survival (80% vs 76%; P = .03) that did not reach significance after adjustment. For patients with claudication and adjunctive endarterectomy, rates of MI (2.4% vs 0.9%; P = .02), renal dysfunction (3.6% vs 1.4%; P = .01), surgical site infection (SSI; 5.0% vs 2.6%; P = .02), and transfusion (4.6% vs 1.8%; P = .002) were higher. After adjustment, all patients undergoing adjunctive endarterectomy were at increased risk of MI (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2), SSI (OR, 1.5; 95% CI, 1.1-2.0), and bleeding requiring transfusion (OR, 1.8; 95% CI, 1.4-2.3). There were no differences in 1-year survival for CLI or claudication groups and no difference in all 1-year end points for patients with claudication. CONCLUSIONS: Adjunctive femoral endarterectomy with bypass is safe, with no difference in perioperative or 1-year mortality compared with bypass. However, surgeons should be aware that adjunctive endarterectomy is associated with an increased risk of bleeding, SSI, and MI, likely from these patients\u27 disease burden and presumed more extensive atherosclerosis