Search

Cell-cell interaction dictates cell morphology and organization, which play a crucial role in the micro-architecture of tissues that guides their biological and mechanical functioning. Here, we investigate the effect of cell density on the responses of cells seeded on flat substrates using a novel statistical thermodynamics framework. The framework recognizes the existence of nonthermal fluctuations in cellular response and thereby naturally captures entropic interactions between cells in monolayers. In line with observations, the model predicts that cell area and elongation decrease with increasing cell seeding density-both are a direct outcome of the fluctuating nature of the cellular response that gives rise to enhanced cell-cell interactions with increasing cell crowding. The modeling framework also predicts the increase in cell alignment with increasing cell density: this cellular ordering is also due to enhanced entropic interactions and is akin to nematic ordering in liquid crystals. Our simulations provide physical insights that suggest that entropic cell-cell interactions play a crucial role in governing the responses of cell monolayers.

Frailty is a clinical syndrome characterized by a reduction in metabolic reserves leading to increased susceptibility to adverse outcomes following invasive surgical interventions. The 5-item modified frailty index (mFI-5) validated in prior studies has shown high predictive accuracy for all surgical specialties, including vascular procedures. In this study, we aim to utilize the mFI-5 to predict outcomes in Transcarotid Revascularization (TCAR).All patients who underwent TCAR from November 2016 to April 2021 in the Vascular Quality Initiative (VQI) Database were included. The mFI-5 was calculated as a cumulative score divided by 5 with 1 point each for poor functional status, presence of diabetes, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and hypertension. Patients were stratified into two groups based on prior studies: low mFI-5 (0.6) and high (≥0.6). Primary outcomes included in-hospital death, extended length of postoperative stay (1 day), and nonhome discharge. Secondary outcomes included in-hospital stroke, transient ischemic attack (TIA), myocardial infarction (MI), a composite endpoint of stroke/death, stroke/TIA, and stroke/death/MI. Univariate and multivariable logistic regression were used to assess the association between mFI-5 and postoperative outcomes. Secondary analysis stratified by symptomatic status was performed.Out of the 17,983 patients who underwent TCAR, 4526(25.2%) had mFI-5 score of ≥0.6 and considered clinically frail. Compared to the nonfrail group, frail patients were more likely to be female (38.7% vs. 35.6%, P 0.001), have poor functional status (43.6 vs. 8.3%, P 0.001), and present with significant comorbidities, including diabetes (75.3% vs. 26.1%, P 0.001), hypertension (98.9% vs. 88.5%, P 0.001), CHF (52.2% vs. 5.6, P 0.001), and COPD (60.3% vs. 14.2%, P 0.001). They were also more likely to be active smokers (25.4% vs. 20.4%, P 0.001) and symptomatic prior to intervention (28.7% vs. 25.3%, P 0.001). On univariate analysis, frail patients were at significantly higher risk to experience adverse outcomes, including in-hospital mortality, TIA, MI, stroke/death, stroke/TIA, stroke/death/MI, discharge to nonhome facility, and extended LOS. After adjusting for potential confounders, frail patients remained at significantly higher risk of in-hospital mortality [aOR 2.26(1.41,3.61), P = 0.001], TIA [aOR 1.65(1.08, 2.54), P = 0.040], nonhome discharge [aOR 1.99(1.71,2.32) P 0.001], and extended LOS [aOR 1.41(1.27, 1.55) P 0.001]. On further stratified analysis based on symptomatic status, the increased risk of stroke/death, TIA, and death was observed only in symptomatic patients.Modified Frailty Index is a reliable tool that can be used to identify high-risk patients for TCAR prior to intervention. This could help vascular surgeons, patients, and families in informed decision making to further optimize perioperative care and medical management in frail patients.

Strategies of balloon dilation during transfemoral carotid artery stenting include prestent dilation only (PRE), post-stent dilation only (POST), or both predilation and postdilation (PRE+POST). Concerns over higher neurological risk have been raised with POST and PRE+POST during transfemoral carotid artery stenting. Whether these concerns are applicable to transcarotid artery revascularization (TCAR), which uses proximal clamping and cerebral blood flow reversal during stent deployment and balloon angioplasty remains unknown. Our aim is to analyze outcomes of PRE, POST, or PRE+POST balloon dilation strategies during TCAR.We analyzed the prospectively collected data from the ROADSTER1 (pivotal), ROADSTER2 (US Food and Drug Administration indicated postmarket), and ROADSTER Extended Access TCAR trials. All trial patients had a high risk anatomic or clinical factors for carotid endarterectomy and were included, unless they did not undergo stent deployment or balloon dilation. For trial inclusion, asymptomatic patients had a carotid stenosis of more than 80%, and symptomatic patients had stenosis of more than 50%. Primary outcome measures were stroke, death, and myocardial infarction (MI) at 30 days. Data were statistically analyzed with χThere were 851 patients (566 male) who underwent dilation by PRE (n = 216), POST (n = 249), or PRE+POST (n = 386). Patients had carotid stenosis of greater than 70% (n = 828, 97%), and 207 (24%) were symptomatic. Flow reversal times were longer in the PRE+POST group (PRE 10.2 minutes, POST 9.8 minutes, and PRE+POST 13.3 minutes; P .001). The 30-day stroke rate for the whole cohort was 1.9%, mortality was 0.5%, and MI rate was 0.94%. Stroke rates for the PRE cohort (1.9%), POST cohort (2.0%), and PRE+POST cohort (1.8%; P = .98) were similar. Also, death rates at 30 days, and composite stroke, death, and MI rates were similar in the three cohorts. No significant differences in adverse outcomes were noted among the various dilation strategies for both symptomatic and asymptomatic patients.Based on these prospective trial data, there is no difference in neurological complications owing to balloon dilation strategy during TCAR. The balloon dilation technique best suited to the patient's specific lesion morphology should be used. Further studies are needed to evaluate the relationship of these dilation strategies to long-term outcomes, including stent patency, restenosis, and reintervention.

Objective The optimal antiplatelet regimen after lower extremity revascularization in patients with chronic limb-threatening ischemia (CLTI) is unknown because current recommendations are based on extrapolation of data from trials in coronary artery disease and stroke. Methods We identified all patients undergoing an elective lower extremity revascularization for CLTI in the Vascular Quality Initiative registry discharged on a mono antiplatelet agent (MAPT) or dual antiplatelet therapy (DAPT). Results From 2003 to 2018, 50,890 patients underwent revascularization procedures for CLTI, and were discharged on MAPT or DAPT. Of these, 33,781 patients underwent endovascular therapy (EVT), and 17,109 patients underwent open surgery (OS) procedures. The rate of major amputation at 30 days in the target limb in the EVT group was 0.3% and 0.4% in the OS group (P = .22). On Kaplan-Meier analyses, patients on MAPT at discharge had a higher risk of 1-year major amputation compared with DAPT after EVT but not after OS procedures. Patients on MAPT had lower overall survival and amputation-free survival at 30 days and 1 year compared with DAPT after both EVT and OS. At 1 year, the MAPT group was at higher risk for target lesion reintervention after EVT compared with the DAPT group (15.9% vs 13%; P = .0012). There was no significant difference in thrombosis at 1 year between the MAPT and DAPT groups either after EVT (3.9% vs 3.7%; P = .3048) or OS (3.1% vs 3.2%; P = .2893). On Cox regression analysis, DAPT was associated with improved survival but not major amputation after both EVT and OS. Conclusions In patients with CLTI, DAPT at the time of discharge has a positive impact on amputation-free survival and overall survival after both EVT and OS as well as target lesion reintervention after EVT. DAPT was not associated with a positive impact on major amputation after either EVT or OS.

Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost.A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with10 patients were included in the present study.We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient.Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within 10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.

Renal failure can be divided into acute kidney injury and chronic kidney disease. Both are common and result in increased patient morbidity and mortality. The etiology is multifactorial and differentiation of acute kidney injury from chronic kidney disease includes clinical evaluation, laboratory tests, and imaging. The main role of imaging is to detect treatable causes of renal failure such as ureteral obstruction or renovascular disease and to evaluate renal size and morphology. Ultrasound is the modality of choice for initial imaging, with duplex Doppler reserved for suspected renal artery stenosis or thrombosis. CT and MRI may be appropriate, particularly for urinary tract obstruction. However, the use of iodinated and gadolinium-based contrast should be evaluated critically depending on specific patient factors and cost-benefit ratio. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Paclitaxel-coated devices have been shown to decrease restenosis when used in the femoropopliteal artery. Recent reports have suggested a possible risk of increased late mortality in patients treated with paclitaxel. It has been suggested that younger patients and those with limited comorbidities may be at higher risk. Our objective was to analyze long-term mortality based on patient age comparing treatment with paclitaxel to uncoated devices.We performed a retrospective review of 1,170 consecutive patients who underwent femoropopliteal percutaneous intervention by angioplasty, atherectomy, stent placement, or combination between 2011 and 2018. Patients were grouped by age at the time of procedure:60 years old (n = 244, 20.9%), 60-80 years old (n = 635, 54.3%), and80 years old (n = 291, 24.9%). Within each group, patients were further divided by use of paclitaxel. The primary outcome measure was survival assessed by Kaplan-Meier analysis. Differences between the groups were analyzed with analysis of variance. Multivariable analysis was performed using Cox proportional hazard models.Of the 1,170 patients who underwent femoropopliteal percutaneous intervention, 654 (55.9%) received a paclitaxel-coated device during treatment and 516 (44.1%) did not. Mean age of the overall patient cohort was 70.4 ± 12.6 years and 663 (56.7%) were male. When comparing the groups by age we found an increase in age but a decrease in the proportion of patients who smoke. The use of paclitaxel-coated devices was similar across the groups (60 years old, 56.2%; 60-80 years old, 57.0%;80 years old, 52.6%; P = 0.45). Demographics and comorbidities were similar between the patients treated with and without paclitaxel within each age group except more males in the60-year-old group treated without paclitaxel and more patients with chronic limb threatening ischemia in the80-year-old group treated with paclitaxel. In patients60 and 60-80 years old paclitaxel use was associated with increased survival at 4 years:60 (80.7% vs. 64.4%; P = 0.04); 60-80 (63.2% vs. 55.1%; P = 0.04). Survival was similar in the80-year-old group (46.6% vs. 32.8%; P = 0.65).Our data suggest that the use of paclitaxel-coated arterial devices is not associated with increased mortality. On the contrary, our data show that younger patients treated with paclitaxel show improved survival compared with those treated without paclitaxel. Paclitaxel-coated devices may be used with continued caution especially in patients at high risk for restenosis.