Clinical Outcomes of Celiac Artery Coverage vs Preservation During Thoracic Endovascular Aortic Repair.

BACKGROUND: Adequate proximal and distal seal zones are necessary for successful Thoracic Endovascular Aortic Repair (TEVAR). Often, the achievement of an adequate distal seal zone requires celiac artery (CA) coverage by endograft with or without preservation of CA blood flow. The outcomes of CA coverage without its flow preservation were studied only in small case series. This study aims to determine the difference in outcomes between CA coverage with vs without preservation of CA blood flow during TEVAR using a multi-institutional national database. METHODS: Vascular Quality Initiative (VQI) was reviewed for all TEVAR patients distally landing in Zone 6. The cohort was divided into TEVAR with vs without CA flow preservation. Demographic, clinical, and perioperative characteristics, as well as post-operative mortality, morbidities, and complications, were compared between the groups. Univariate and multivariate regression analyses were performed. RESULTS: Out of 25,549 reviewed patients, 772 had a distal landing in zone 6, 212 of which (27.5%) had TEVAR without CA flow preservation, whereas 560 (72.5%) underwent TEVAR with CA flow preservation. Indications for TEVAR were: aneurysm in 431 (55.8%), dissection in 247 (32.0%), or other in 94 (12.2%) cases. Patients who underwent TEVAR without CA flow preservation had statistically significantly higher rates of 30-day mortality (11.3% vs 5.9%, p=0.010), 30-day disease/treatment-related mortality (8.0% vs 4.3%, p=0.039), as well as a tendency of increased intestinal ischemia requiring intervention (1.9% vs 0.5%, p=0.077). After adjusting for potential confounders, CA coverage without flow preservation was associated with more than a two-fold increase in the overall 30-day mortality (OR: 2.83, 95%CI: 1.35-5.92, p=0.006) and 30-day disease/treatment-related mortality (OR: 2.72, 95%CI: 1.11-6.72, p=0.029). In a sub-group analysis based on disease pathology, these results persisted only in the aneurysm group (30-day mortality (OR: 2.36, 95%CI: 1.01-5.48, p=0.047), 30-day disease/treatment-related mortality (OR: 2.88, 95%CI: 1.08-7.67, p=0.034)), whereas there was no significant association between CA flow preservation status and the endpoints in the dissection subgroup (30-day mortality (OR: 1.16, 95%CI: 0.22-6.05, p=0.856), 30-day disease/treatment-related mortality (OR: 0.90, 95%CI: 0.16-5.19, p=0.911)). CONCLUSIONS: CA coverage during TEVAR without preservation of its blood flow is associated with significantly higher mortality in patients with aortic aneurysm, but not dissection. In patients with aortic aneurysm CA flow should be preserved during TEVAR whenever feasible, whereas in patients with dissection, it may be safe to cover CA without preservation of its flow. Prospective studies should be done to confirm these findings and compare the open vs endovascular revascularization techniques on outcomes.

Analysis of Surgeon and Center Case Volume and Stroke or Death after Transcarotid Artery Revascularization.

BACKGROUND: It has been suggested that the annual hospital volume of cases may affect the number of adverse events following carotid endarterectomy (CEA). We aim to study the associations between hospital as well as surgeon volume and the risk of stroke/death following TCAR. STUDY DESIGN: Retrospective review of the Vascular Quality Initiative data of patients undergoing TCAR from 2016 to 2021. Surgeon and center volume were calculated based on the mean number of cases (MNC) performed yearly by each surgeon and center. The primary outcome was a composite endpoint of in-hospital stroke/death. RESULTS: A total of 22,624 cases were included. Surgeon volume was divided into three quantiles: low (MNC=4), medium (MNC=10), and high (MNC=26). Center volume was also divided into low (MNC=14), medium (MNC=32), and high (MNC=64). After adjusting for potential confounders, and when compared to high volume centers, low and medium center volume was not associated with any increased odds of in-hospital stroke/death, stroke, death, or stroke/TIA. Compared to high volume surgeons, low surgeons' volume was associated with a higher odd of stroke (OR: 1.5, 95%CI (1.1-2.04), P=0.008), and stroke/TIA (OR: 1.5, 95%CI (1.2-1.9), P=.002). However, medium surgeon volume was not associated with higher odds of stroke/death, stroke, and stroke/TIA. Neither low nor medium surgeon volume was associated with a difference in mortality compared to high surgeon volume. CONCLUSIONS: In this retrospective study, center volume was not associated with any differences in outcomes among patients undergoing TCAR. On the other hand, surgeons with low volume were associated with a higher risk of stroke/death/MI and stroke/TIA when compared to high surgeon volume. There was no difference in outcomes between medium and high surgeon volume.

Long-Term Patency Between Brachiocephalic and Brachiobasilic Fistulas: A Single Institution Review.

OBJECTIVE: Dialysis access is a fundamental procedure performed by vascular surgeons. Commonly, upper extremity access is utilized via a brachiobasilic fistula (BBF) or brachiocephalic fistula (BCF). BCF is preferred due to ease compared to BBF without documented improved function. Few studies compare patency outcomes between BBF and BCF over time. Our goal was to evaluate the difference in outcomes between BBF and BCF. METHODS: This is a retrospective review of patients with BCF or BBF between 2019-2022. Patients were split by procedure: BCF and BBF. Data collected included demographics, vein size, tunneled catheter, and previous access. Primary outcomes included primary patency (PP), primary assisted patency (PAP) and secondary patency (SP). Secondary outcomes included 30-day complications, access abandonment, interventions and mortality. Linear regression, Kaplan-Meier and log-rank test were performed. RESULTS: Our study had 184 patients, 109 (59%) with BCF and 75 (41%) with BBF. There were no differences in demographics except for BMI and vein size (BBF: 4 vs BCF: 3.6mm, p=0.020). There was no difference in PP at one year (41% vs 47%, p=0.547) or SP at two years (73% vs 84%, p=0.058) in BBF vs BCF. However, PAP was significantly greater in BCF (80% vs 67%, p=0.030) at one year. Secondary outcomes revealed no difference in wound complications (1% vs 0%, p=0.408), access abandonment (35% vs 28%, p=0.260), or number of interventions (1 vs 1, p=0.712) in BBF vs BCF. Mortality was significantly greater in the BBF patients (19% vs 6%, p=0.005). On adjusted analysis, BBF had 43 minutes longer operative time (p<0.001) and 22cc greater blood loss (p<0.0001). CONCLUSION: In this single center review comparing BBF and BCF, no difference was seen between BBF and BCF in terms of primary patency or secondary patency. Even with larger vein size, BBF did not confer a benefit in long term patency or access abandonment. Additionally, BBF did not confer decreased procedures to maintain patency and BBF had greater operative length and blood loss, as well as mortality. We believe this study demonstrates that for patients who must use an upper extremity location, when the cephalic vein is satisfactory, using the cephalic vein is preferred as it does not negatively impact long-term patency.

Investigation of the Weekend Effect on Peri-Operative Complications and Mortality Following Carotid Revascularization.

OBJECTIVE: Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications compared to weekday interventions. While prior investigations have reported the 'weekend effect' for carotid endarterectomy (CEA), this association remains unclear for Transcarotid Artery Revascularization (TCAR) and Transfemoral Carotid Artery Stenting (TFCAS). We investigated the weekend effect for all three carotid revascularization methods. METHODS: We queried the Vascular Quality Initiative (VQI) for patients undergoing CEA, TCAR, and TFCAS between 2016-2022. Chi-square and logistic regression modeling analyzed outcomes including in-hospital stroke, death, MI, and 30-day mortality by weekend vs. weekday intervention. Backward stepwise regression was utilized to identify significant confounding variables and were ultimately included in each final logistic regression model. Logistic regression of outcomes was substratified by symptomatic status. Secondary multivariable analysis compared outcomes between the three revascularization methods by weekend vs. weekday interventions. RESULTS: 155,962 procedures were analyzed including 103,790 CEA, 31,666 TCAR and 20,506 TFCAS. Of these, 1988 CEA, 246 TCAR and 820 TFCAS received weekend interventions. Logistic regression demonstrated no significant differences for TCAR, and increased odds of in-hospital stroke/death/MI for CEA [OR:1.31,(1.04-1.65)] and TFCAS [OR:1.46,(1.09-1.96)] weekend procedures. Asymptomatic TCAR patients had nearly triple the odds of 30-day mortality [OR:2.85,(1.06-7.68), P=0.038]. Similarly, odds of in-hospital death were nearly tripled for asymptomatic CEA [OR:2.89,(1.30-6.43), P=0.009] and asymptomatic TFCAS [OR:2.78,(1.34-5.76), P=0.006] patients. Secondary analysis demonstrated that CEA and TCAR had no significant differences for all outcomes. TFCAS was associated with increased odds of stroke and death compared to CEA and TCAR. CONCLUSION: In this observational cohort study, we found that weekend carotid revascularization is associated with increased odds of complications and mortality. Furthermore, asymptomatic weekend patients perform worse in the CEA and TFCAS procedural groups. Among the three revascularization methods, TFCAS is associated with the highest odds of perioperative stroke and mortality. As such, our findings suggest that TFCAS procedures should be avoided over the weekend, in favor of CEA or TCAR. In patients who are poor candidates for CEA, TCAR offers the lowest morbidity and mortality for weekend procedures.

Synthesis and in vitro antitumor evaluation of new thieno[2,3-d]pyrimidine derivatives as EGFR and DHFR inhibitors.

New thienopyrimidine derivatives 2-16 have been synthesized and their in vitro cytotoxicity was evaluated against five different human cancer cell lines HCT-116, Hela, MDA-MB-231, MCF7 and PC3. Compounds 6e, 7a, 7b, 7d, 10c and 10e displayed the highest antitumor activity against all tested cell lines compared to Doxorubicin. Enzyme inhibition assay revealed that compounds 6e and 10e showed high inhibitory activity against EGFR-TK, with IC50 values of 0.133 and 0.151 µM, compared to Olmutinib (IC50 = 0.028 µM); while the highest DHFR inhibitory activity was shown by compounds 7d and 10e with IC50 values of 0.462 and 0.541 µM, compared to Methotrexate (IC50 = 0.117 µM). Cell cycle analysis following a flow cytometric study using colorectal HCT-116 cancer cell line proved that compound 6e induced cell cycle arrest in G0-G1 phase, while compound 10e arrested the cell cycle at both G0-G1 and S phases. Additionally, both compounds (6e and 10e) were potently able to induce apoptosis in HCT-116 cell line. Docking results of compounds 6e and 10e into the pocket of EGFR active site showed their similar main binding features with Olmutinib, while compounds 7d and 10e showed only moderate fitting into DHFR compared to methotrexate. In silico studies revealed that most of the tested compounds obeyed Lipinski's RO5 and showed positive drug likeness scores.

Non-White Patients Have a Higher Risk of Stroke Following Transcarotid Artery Revascularization.

INTRODUCTION: Carotid artery revascularization has traditionally been performed by either a carotid endarterectomy or carotid artery stent. Large data analysis has suggested there are differences in perioperative outcomes with regards to race, with non-White patients (NWP) having worse outcomes of stroke, restenosis and return to the operating room (RTOR). The introduction of transcarotid artery revascularization (TCAR) has started to shift the paradigm of carotid disease treatment. However, to date, there have been no studies assessing the difference in postoperative outcomes after TCAR between racial groups. METHODS: All patients from 2016 to 2021 in the Vascular Quality Initiative who underwent TCAR were included in our analysis. Patients were split into two groups based on race: individuals who identified as White and a second group that comprised all other races. Demographic and clinical variables were compared using Student's t-Test and chi-square test of independence. Logistic regression analysis was performed to determine the impact of race on perioperative outcomes of stroke, myocardial infarction (MI), death, restenosis, RTOR, and transient ischemic attack (TIA). RESULTS: The cohort consisted of 22,609 patients: 20,424 (90.3%) White patients and 2185 (9.7%) NWP. After adjusting for sex, diabetes, hypertension, coronary artery disease, history of prior stroke or TIA, symptomatic status, and high-risk criteria at time of TCAR, there was a significant difference in postoperative stroke, with 63% increased risk in NWP (odds ratio = 1.63, 95% confidence interval: 1.11-2.40, P = 0.014). However, we found no significant difference in the odds of MI, death, postoperative TIA, restenosis, or RTOR when comparing NWP to White patients. CONCLUSIONS: This study demonstrates that NWP have increased risk of stroke but similar outcomes of death, MI, RTOR and restenosis following TCAR. Future studies are needed to elucidate and address the underlying causes of racial disparity in carotid revascularization.

Endovascular therapy versus bypass for chronic limb-threatening ischemia in a real-world practice.

OBJECTIVE: The recent Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) study showed that bypass was superior to endovascular therapy (ET) in patients with chronic limb-threatening ischemia (CLTI) deemed suitable for either approach who had an available single-segment great saphenous vein (GSV). However, the superiority of bypass among those lacking GSV was not established. We aimed to examine comparative treatment outcomes from a real-world CLTI population using the Vascular Quality Initiative-Medicare-linked database. METHODS: We queried the Vascular Quality Initiative-Medicare-linked database for patients with CLTI who underwent first-time lower extremity revascularization (2010-2019). We performed two one-to-one propensity score matchings (PSMs): ET vs bypass with GSV (BWGSV) and ET vs bypass with a prosthetic graft (BWPG). The primary outcome was amputation-free survival. Secondary outcomes were freedom from amputation and overall survival (OS). RESULTS: Three cohorts were queried: BWGSV (N = 5279, 14.7%), BWPG (N = 2778, 7.7%), and ET (N = 27,977, 77.6%). PSM produced two sets of well-matched cohorts: 4705 pairs of ET vs BWGSV and 2583 pairs of ET vs BWPG. In the matched cohorts of ET vs BWGSV, ET was associated with greater hazards of death (hazard ratio [HR] = 1.34, 95% confidence interval [CI], 1.25-1.43; P < .001), amputation (HR = 1.30, 95% CI, 1.17-1.44; P < .001), and amputation/death (HR = 1.32, 95% CI, 1.24-1.40; P < .001) up to 4 years. In the matched cohorts of ET vs BWPG, ET was associated with greater hazards of death up to 2 years (HR = 1.11, 95% CI, 1.00-1.22; P = .042) but not amputation or amputation/death. CONCLUSIONS: In this real-world multi-institutional Medicare-linked PSM analysis, we found that BWGSV is superior to ET in terms of OS, freedom from amputation, and amputation-free survival up to 4 years. Moreover, BWPG was superior to ET in terms of OS up to 2 years. Our study confirms the superiority of BWGSV to ET as observed in the BEST-CLI trial.

Seven years of the transcarotid artery revascularization surveillance project, comparison to transfemoral stenting and endarterectomy.

OBJECTIVE: This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques. METHODS: Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury. RESULTS: A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared with both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%; adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.65-2.06; P < .001) and CEA (2.9% vs 1.3%; aOR, 2.21; 95% CI, 2.01-2.43; P < .001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%; aOR, 0.83; 95% CI, 0.76-0.91; P < .001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%; aOR, 0.00; 95% CI, 0.00-0.00; P < .001) and CEA (0.0% vs 2.3%; aOR, 0.00; 95% CI, 0.0-0.0; P < .001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%; aOR, 0.67; 95% CI, 0.54-0.84; P < .001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%; aOR, 1.31; 95% CI, 1.13-1.54; P < .001) and cranial nerve injury (2.3% vs 0.3%; aOR, 9.42; 95% CI, 7.78-11.4; P < .001). CONCLUSIONS: Although tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it is important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis.

The obesity paradox exists for perioperative complications and mortality following lower extremity arterial bypass surgery.

OBJECTIVE: The obesity paradox refers to a phenomenon by which obese individuals experience lower risk of mortality and even protective associations from chronic disease sequelae when compared with the non-obese and underweight population. Prior literature has demonstrated an obesity paradox after cardiac and other surgical procedures. However, the relationship between body mass index (BMI) and perioperative complications for patients undergoing major open lower extremity arterial revascularization is unclear. METHODS: We queried the Vascular Quality Initiative for individuals receiving unilateral infrainguinal bypass between 2003 and 2020. We used multivariable logistic regression to assess the relationship of BMI categories (underweight [<18.5 kg/m2], non-obese [18.5-24.9 kg/m2], overweight [25-29.9 kg/m2], Class 1 obesity [30-34.9 kg/m2], Class 2 obesity [35-39.9 kg/m2], and Class 3 obesity [>40 kg/m2]) with 30-day mortality, surgical site infection, and adverse cardiovascular events. We adjusted the models for key patient demographics, comorbidities, and technical and perioperative characteristics. RESULTS: From 2003 to 2020, 60,588 arterial bypass procedures met inclusion criteria for analysis. Upon multivariable logistic regression with the non-obese category as the reference group, odds of 30-day mortality were significantly decreased among the overweight (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.78), Class 1 obese (OR, 0.65; 95% CI, 0.52-0.81), Class 2 obese (OR, 0.66; 95% CI, 0.48-0.90), and Class 3 obese (OR, 0.61; 95% CI, 0.39-0.97) patient categories. Conversely, odds of 30-day mortality were increased in the underweight patient group (OR, 1.58; 95% CI, 1.16-2.13). Furthermore, a BMI-dependent positive association was present, with odds of surgical site infections with patients in Class 3 obesity having the highest odds (OR, 2.10; 95% CI, 1.60-2.76). Finally, among the adverse cardiovascular event outcomes assessed, only myocardial infarction (MI) demonstrated decreased odds among overweight (OR, 0.82; 95% CI, 0.71-0.96), Class 1 obese (OR, 0.78; 95% CI, 0.65-0.93), and Class 2 obese (OR, 0.66; 95% CI, 0.51-0.86) patient populations. Odds of MI among the underweight and Class 3 obesity groups were not significant. CONCLUSIONS: The obesity paradox is evident in patients undergoing lower extremity bypass procedures, particularly with odds of 30-day mortality and MI. Our findings suggest that having higher BMI (overweight and Class 1-3 obesity) is not associated with increased mortality and should not be interpreted as a contraindication for lower extremity arterial bypass surgery. However, these patients should be under vigilant surveillance for surgical site infections. Finally, patients that are underweight have a significantly increased odds of 30-day mortality and may be more suitable candidates for endovascular therapy.

The Double Burden: Deciphering Chronic Limb-Threatening Ischemia in End-Stage Renal Disease.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) in patients with end-stage renal disease (ESRD) poses significant challenges in clinical management due to its unique pathology and poor treatment outcomes. This review calls for a tailored classification and risk assessment for these patients to guide better revascularization choices with early minor amputation as a first-line strategy in advanced stages. METHODS: This review consolidates key findings from recent literature on CLTI in ESRD, focusing on disease mechanisms, treatment options, and patient outcomes. It evaluates the literature to clarify the decision-making process for managing CLTI in ESRD. RESULTS: CLTI in ESRD patients often results in worse clinical outcomes, such as nonhealing wounds, increased limb loss, and higher mortality rates. While the literature reveals ongoing debates regarding the optimal revascularization method, recent retrospective studies and meta-analyses suggest potential benefits of endovascular treatment (EVT) over open bypass surgery (OB) in reducing mortality and wound complications, with comparable amputation-free survival rates. CONCLUSIONS: The selection of revascularization methods in ESRD patients with CLTI is complex, necessitating individualized strategies. The importance of early detection and timely intervention is critical to decelerate disease progression and improve revascularization outcomes. There is a shift in these treatment strategies toward less invasive endovascular procedures, acknowledging the limitations these patients face with open revascularization surgeries. Considering early minor amputations after revascularization could prevent worse consequences, reflecting a shift in the approach to managing CLTI in ESRD patients.

Long-term outcomes in the smoking claudicant after peripheral vascular interventions.

OBJECTIVE: Emphasis on tobacco cessation, given the urgent and emergent nature of vascular surgery, is less prevalent than standard elective cases such as hernia repairs, cosmetic surgery, and bariatric procedures. The goal of this study is to determine the effect of active smoking on claudicating individuals undergoing peripheral vascular interventions (PVIs). Our goal is to determine if a greater emphasis on education should be placed on smoking cessation in nonurgent cases scheduled through clinic visits and not the Emergency Department. METHODS: This study was performed using the multi-institution de-identified Vascular Quality Initiative/Medicare-linked database (Vascular Implant Surveillance and Interventional Outcomes Network [VISION]). Claudicants who underwent PVI for peripheral arterial occlusive disease between 2004 and 2019 were included in our study. Our final sample consisted of a total of 18,726 patients: 3617 nonsmokers (19.3%) (NSs), 9975 former smokers (53.3%) (FSs), and 5134 current smokers (27.4%) (CSs). We performed propensity score matching on 29 variables (age, gender, race, ethnicity, treatment setting [outpatient or inpatient], obesity, insurance, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, previous coronary artery bypass graft, carotid endarterectomy, major amputation, inflow treatment, prior bypass or PVI, preoperative medications, level of treatment, concomitant endarterectomy, and treatment type [atherectomy, angioplasty, stent]) between NS vs FS and FS vs CS. Outcomes were long-term (5-year) overall survival (OS), limb salvage (LS), freedom from reintervention (FR), and amputation-free survival (AFS). RESULTS: Propensity score matching resulted in 3160 well-matched pairs of NS and FS and 3750 well-matched pairs of FS and CS. There was no difference between FS and NS in terms of OS (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.82-1.09; P = .43), FR (HR, 0.96; 95% CI, 0.89-1.04; P = .35), or AFS (HR, 0.90; 95% CI, 0.79-1.03; P = .12). However, when compared with CS, we found FS to have a higher OS (HR, 1.18; 95% CI, 1.04-1.33; P = .01), less FR (HR, 0.89; 95% CI, 0.83-0.96; P = .003), and greater AFS (HR, 1.16; 95% CI, 1.03-1.31; P = .01). CONCLUSIONS: This multi-institutional Medicare-linked study looking at elective PVI cases in patients with peripheral artery disease presenting with claudication found that FSs have similar 5-year outcomes in comparison to NSs in terms of OS, FR, and AFS. Additionally, CSs have lower OS and AFS when compared with FSs. Overall, this suggests that smoking claudicants should be highly encouraged and referred to structured smoking cessation programs or even required to stop smoking prior to elective PVI due to the perceived 5-year benefit.

Outcomes following carotid revascularization for stroke stratified by Modified Rankin Scale and time of intervention.

OBJECTIVES: The relationship between baseline Modified Rankin Scale (mRS) in patients with prior stroke and optimal timing of carotid revascularization is unclear. Therefore, we evaluated the timing of transfemoral carotid artery stenting (tfCAS), transcarotid artery revascularization (TCAR), and carotid endarterectomy (CEA) after prior stroke, stratified by preoperative mRS. METHODS: We identified patients with recent stroke who underwent tfCAS, TCAR, or CEA between 2012 and 2021. Patients were stratified by preoperative mRS (0-1, 2, 3-4, or 5) and days from symptom onset to intervention (time to intervention; ≤2 days, 3-14 days, 15-90 days, and 91-180 days). First, we performed univariate analyses comparing in-hospital outcomes between separate mRS or time-to-intervention cohorts for all carotid intervention methods. Afterward, multivariable logistic regression was used to adjust for demographics and comorbidities across groups, and outcomes between the various intervention methods were compared. Primary outcome was the in-hospital stroke/death rate. RESULTS: We identified 4260 patients who underwent tfCAS, 3130 patients who underwent TCAR, and 20,012 patients who underwent CEA. Patients were most likely to have minimal disability (mRS, 0-1 [61%]) and least likely to have severe disability (mRS, 5 [1.5%]). Patients most often underwent revascularization in 3 to 14 days (45%). Across all intervention methods, increasing preoperative mRS was associated with higher procedural in-hospital stroke/death (all P < .03), whereas increasing time to intervention was associated with lower stroke/death rates (all P < .01). After adjustment for demographics and comorbidities, undergoing tfCAS was associated with higher stroke/death compared with undergoing CEA (adjusted odds ratio, 1.6; 95% confidence interval, 1.3-1.9; P < .01) or undergoing TCAR (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.8; P = .03). CONCLUSIONS: In patients with preoperative stroke, optimal timing for carotid revascularization varies with stroke severity. Increasing preoperative mRS was associated with higher procedural in-hospital stroke/death rates, whereas increasing time to-intervention was associated with lower stroke/death rates. Overall, patients undergoing CEA were associated with lower in-hospital stroke/deaths. To determine benefit for delayed intervention, these results should be weighed against the risk of recurrent stroke during the interval before intervention.

In Silico Identification of a Potential TNF-Alpha Binder Using a Structural Similarity: A Potential Drug Repurposing Approach to the Management of Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder with no conclusive remedy. Yohimbine, found in Rauwolfia vomitoria, may reduce brain inflammation by targeting tumour necrosis factor-alpha (TNFα), implicated in AD pathogenesis. Metoserpate, a synthetic compound, may inhibit TNFα. The study is aimed at assessing the potential utility of repurposing metoserpate for TNFα inhibition to reduce neuronal damage and inflammation in AD. The development of safe and effective treatments for AD is crucial to address the growing burden of the disease, which is projected to double over the next two decades. Methods: Our study repurposed an FDA-approved drug as TNFα inhibitor for AD management using structural similarity studies, molecular docking, and molecular dynamics simulations. Yohimbine was used as a reference compound. Molecular docking used SeeSAR, and molecular dynamics simulation used GROMACS. Results: Metoserpate was selected from 10 compounds similar to yohimbine based on pharmacokinetic properties and FDA approval status. Molecular docking and simulation studies showed a stable interaction between metoserpate and TNFα over 100 ns (100000 ps). This suggests a reliable and robust interaction between the protein and ligand, supporting the potential utility of repurposing metoserpate for TNFα inhibition in AD treatment. Conclusion: Our study has identified metoserpate, a previously FDA-approved antihypertensive agent, as a promising candidate for inhibiting TNFα in the management of AD.

Association of stroke or death with severity of carotid lesion calcification in patients undergoing carotid artery stenting.

OBJECTIVE: Carotid artery stenting (CAS) for heavily calcified lesions is controversial due to concern for stent failure and increased perioperative stroke risk. However, the degree to which calcification affects outcomes is poorly understood, particularly in transcarotid artery revascularization (TCAR). With the precipitous increase in TCAR use and its expansion to standard surgical-risk patients, we aimed to determine the impact of lesion calcification on CAS outcomes to ensure its safe and appropriate use. METHODS: We identified patients in the Vascular Quality Initiative who underwent first-time transfemoral CAS (tfCAS) and TCAR between 2016 and 2021. Patients were stratified into groups based on degree of lesion calcification: no calcification, 1% to 50% calcification, 51% to 99% calcification, and 100% circumferential calcification or intraluminal protrusion. Outcomes included in-hospital and 1-year composite stroke/death, as well as individual stroke, death, and myocardial infarction outcomes. Logistic regression was used to evaluate associations between degree of calcification and these outcomes. RESULTS: Among 21,860 patients undergoing CAS, 28% patients had no calcification, 34% had 1% to 50% calcification, 35% had 51% to 99% calcification, and 3% had 100% circumferential calcification/protrusion. Patients with 51% to 99% and circumferential calcification/protrusion had higher odds of in-hospital stroke/death (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.02-1.6; P = .034; OR, 1.9; 95% CI, 1.1-2.9; P = .004, respectively) compared with those with no calcification. Circumferential calcification was also associated with increased risk for in-hospital myocardial infarction (OR, 3.5; 95% CI, 1.5-8.0; P = .003). In tfCAS patients, only circumferential calcification/protrusion was associated with higher in-hospital stroke/death odds (OR, 2.0; 95% CI, 1.2-3.4; P = .013), whereas for TCAR patients, 51% to 99% calcification was associated with increased odds of in-hospital stroke/death (OR, 1.5; 95% CI, 1.1-2.2; P = .025). At 1 year, circumferential calcification/protrusion was associated with higher odds of ipsilateral stroke/death (12.4% vs 6.6%; hazard ratio, 1.64; P = .002). CONCLUSIONS: Among patients undergoing CAS, there is an increased risk of in-hospital stroke/death for lesions with >50% calcification or circumferential/protruding plaques. Increasing severity of carotid lesion calcification is a significant risk factor for stroke/death in patients undergoing CAS, regardless of approach.

Small Arteriovenous Anastomosis in Fistula Creation: Establishing a Functional Vascular Access while Minimizing Steal Syndrome.

BACKGROUND: The size selection of the arteriovenous (AV) anastomosis in dialysis access creation requires a careful balance: the diameter must be large enough to accommodate sufficient flow for hemodialysis but small enough to minimize the complication of steal syndrome. Steal syndrome affects up to 10% of patients after creation of dialysis access with sometimes devastating consequences. Conventional teaching recommends a 7-10 mm anastomosis. We sought to assess the efficacy of using a smaller (5-6 mm) anastomosis in new arteriovenous fistula (AVF) creation. METHODS: We conducted a comparative retrospective analysis of patients who underwent fistula creation with a small versus regular size anastomosis at any upper extremity anatomic site between March 2019 and October 2020 at our institution. Anatomic sites included radiocephalic, brachiocephalic, and brachiobasilic. All AV anastomoses were measured intraoperatively to be 5-6 mm in diameter for the small size groups and 8-10 mm for the regular size group. Endpoints included steal syndrome, functional patency, primary patency, and secondary patency. RESULTS: Out of 110 patients who underwent an AVF creation, 59.1% received a 5-6 mm anastomosis with a median follow-up time of 10 ± 6 months. Patients' demographics and comorbidities were relatively similar between the 2 groups except for a higher rate of hyperlipidemia (55.4% vs. 28.9%, P = 0.008) in the small size group. Patients in the small size group were more likely to undergo a radiocephalic fistula (40% vs. 4.5%, P < 0.001) and to have a smaller mean vein diameter on preoperative duplex ultrasound (3.2±1 mm vs. 3.9±1 mm, P = 0.0016) when compared to their regular size counterparts. During follow-up, none of the patients in the small group developed steal syndrome (0% vs. 9%, P = 0.015). At 1 year, patients in the regular size group achieved higher rates of primary patency (67.9% vs. 46.9%, P = 0.02); however, no difference was seen in 1-year primary-assisted patency (84.9% vs. 73.6%, P = 0.3), secondary patency (89.6% vs. 79.5%, P = 0.3), or functional patency (87.7% vs. 82.2%, P = 0.64) between the small and regular size groups, respectively. CONCLUSIONS: The use of a 5-6 mm anastomosis in the creation of new AVFs of the upper extremities appears to be a technically safe option for dialysis access. Our experience suggests that smaller anastomosis still creates enough flow to maintain a functional AV access while minimizing the incidence of steal syndrome. Additionally, even with smaller vein sizes preoperative, adequate dialysis access can be created via a small sized anastomosis, including distal arm access. Larger studies with longer follow-up are needed to evaluate long-term outcomes of small anastomosis fistulas.

Postoperative Outcomes and One-Year Mortality of Patients on Chronic Anticoagulation Medications Undergoing Infrainguinal Bypass.

BACKGROUND: Patients requiring open infrainguinal bypass (IIB) frequently are taking chronic anticoagulation (AC) medications. Taking these medications in the preoperative setting may affect the outcomes of surgery. This study aims to evaluate postoperative outcomes and 1-year mortality of patients taking chronic AC medications that undergo IIB. METHODS: Using data obtained from the Vascular Quality Initiative from January 2011 to October 2021, patients on warfarin or any direct oral anticoagulants (DOAC) within 30 days of IIB were compared with patients not taking chronic AC medications. The primary outcomes were in-hospital, 30-day, and 1-year mortality. The secondary outcomes included total procedure time, need for perioperative packed red blood cell transfusion, prolonged length of hospital stay, postoperative myocardial infarction or stroke, and graft patency at discharge. A subgroup analysis was performed comparing patients taking warfarin with those taking DOACs. Univariate analyses and multivariate logistic regression, Kaplan Meier survival, and Cox regression analyses were used to analyze the data for postoperative and 1-year outcomes, respectively. RESULTS: A total of 55,076 patients underwent IIB during the study period, and 11,547 (20.97%) were on chronic AC prior to surgery. The 2 cohorts differed significantly in almost every demographic and clinical characteristic. Multivariate analyses adjusting for 45 potential confounders revealed that there was no significant difference in in-hospital, 30-day, and 1-year mortality. The total procedure time for the chronic AC cohort was on average 11.46 ± 2.16 min longer (P ≤ 0.001) and there was a greater risk of prolonged length of stay in the hospital (adjusted odds ratio [aOR]: 1.19, 95% confidence interval [CI]: 1.13-1.26, P < 0.001). These patients also returned to the operating room (OR) at a greater rate (aOR: 1.12, 95% CI: 1.05-1.19; P = 0.016) and demonstrated a significantly lower rate of graft patency at discharge (aOR: 0.73, 95% CI: 0.62-0.86, P = 0.001). On subgroup analysis, multivariate analysis demonstrated lower 30-day mortality for the DOAC group in comparison to the warfarin group (aOR: 0.74, 95% CI: 0.57-0.94, P = 0.015), but no significant differences in in-hospital and 1-year mortality. CONCLUSIONS: Patients taking AC medications within 30 days prior to IIBs may require more perioperative red blood cell transfusions, longer hospitalizations, and return to the OR at a greater rate. They are also at an increased risk for loss of graft patency at discharge. However, these patients are not at increased risk of in-hospital, 30-day, or 1-year mortality. IIB can, therefore, be performed safely in patients taking chronic AC medications.

Age-related morphological and ultrastructural changes in the palate and pharyngeal masticatory apparatus of grass carp (Ctenopharyngodon idella) juveniles.

Grass carp (Ctenopharyngodon idella or C. idella) is a Cyprinid fish frequently utilized for aquaculture, medical, and research purposes. In C. idella, the palate is followed by a well-developed pharyngeal masticatory apparatus. The latter consists of an upper chewing pad superimposing a paired set of teeth. The present study investigated morphological, morphometric, histochemical, and surface ultrastructural changes involving these structures in C. idella juveniles at three different timepoints namely 35 mm total length (TL; 59 days posthatching (dph); fry-fingerling transition), 70 mm TL (90 dph; fingerling), and 210 mm TL ( 365 dph: yearling). The palatal epithelium revealed a constant number of taste buds. However, the height and width of these buds revealed an age-dependent increase. The number of palatal acidic goblet cells increased gradually with age. Enhanced keratinization of pad epithelium, and increased teeth dimensions were age-associated characteristics. Ultrastructurally, the palatal surface of C. idella was slightly papillated at 35 mm TL after which it formed brick-like structural units that tended to cluster into longitudinally paralleled rows toward the palate-pad junction. Goblet cell openings appeared oval at 35 mm TL and became club-shaped by 210 mm TL at which the epithelium appeared compact and heavily coated in mucus. Indentations of pad surface and signs of dental wear and tear were evident ultrastructurally at 70 mm TL and onwards. The current study reports for the first time age-related developmental features of the palate and pharyngeal masticatory apparatus of grass carp. Results of the present work will help to understand aging-associated factors involving the studied fish and other related aquatic species.