Carotid Endarterectomy for Asymptomatic Stenosis Based on Duplex Ultrasound Alone Achieves Equivalent Perioperative and Long-Term Outcomes Relative to Advanced Imaging Based Endarterectomy.

BACKGROUND: The purpose of this study is to compare both perioperative as well as long-term outcomes of patients undergoing carotid endarterectomy (CEA) for asymptomatic carotid bifurcation stenosis based on duplex ultrasound in isolation relative to a combination of duplex and more advanced imaging. METHODS: All CEA in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEAs in the database. Exclusions were symptomatic carotid lesion (57,742), lack of imaging documentation (908), lack of advanced imaging status (1,816), simultaneous additional arterial intervention in the carotid, coronary, or peripheral arterial system (n = 4,118), and anatomic high-risk status for CEA (n = 4,071). Included patients were then placed into 1 of 2 cohorts: patients undergoing CEA based on duplex imaging alone (n = 33,437) and those undergoing CEA based on advanced imaging (CTA, MRA, or invasive angiography) with or without duplex (n = 69,715). We performed multivariable analysis for the following outcomes utilizing CEA based on duplex in isolation as 1 of the variables: perioperative neurological ischemic event utilizing binary logistic regression; combined 90-day mortality and neurological ischemic event utilizing binary logistic regression; neurological event in long-term follow-up with date of surgery serving as time zero; time dependent Cox regression analysis; mortality in long-term follow-up utilizing time-dependent Cox regression. RESULTS: Carotid endarterectomy based on duplex alone and CEA based on advanced imaging had essentially equivalent rates of 90-day mortality (0.9% vs. 1.0%, P = 0.108); combined perioperative neurological event and 90-day mortality (2.0% vs. 2.2%, P = 0.042); and, return to the operating room (1.6% vs. 1.7%, P = 0.154). On multivariable analysis CEA based on advanced imaging was noted to have a slightly higher absolute rate of perioperative neurological event without achieving multivariable significance (1.3% vs. 1.2%, adjusted odds ratio 1.11 (0.98-1.25), P = 0.092. CEA based on advanced imaging had a higher rate of neurological event after index hospital admission relative to duplex in isolation (hazard ratio (HR) 1.44 (1.31-1.60), P < 0.001). However, the absolute percentage difference was just 0.5% (1.6% vs. 2.1%). CEA based on duplex alone was associated with a slightly increased risk of mortality in LTFU (HR 1.16 (1.11-1.21), P < 0.001). At 5 years the absolute risk of mortality was less than 1% different between the cohorts. CONCLUSIONS: Performing CEA for asymptomatic bifurcation stenosis based on duplex ultrasound alone is a safe practice which achieves clinically equivalent perioperative and long-term freedom from cerebral ischemia and mortality relative to CEA based on advanced imaging. This has potential implications for health care cost saving as well as avoidance of radiation and iodinated contrast.

PDZ Domains from the Junctional Proteins Afadin and ZO-1 Act as Mechanosensors.

Intercellular adhesion complexes must withstand mechanical forces to maintain tissue cohesion, while also retaining the capacity for dynamic remodeling during tissue morphogenesis and repair. Most cell-cell adhesion complexes contain at least one PSD95/Dlg/ZO-1 (PDZ) domain situated between the adhesion molecule and the actin cytoskeleton. However, PDZ-mediated interactions are characteristically nonspecific, weak, and transient, with several binding partners per PDZ domain, micromolar dissociation constants, and bond lifetimes of seconds or less. Here, we demonstrate that the bonds between the PDZ domain of the cytoskeletal adaptor protein afadin and the intracellular domains of the adhesion molecules nectin-1 and JAM-A form molecular catch bonds that reinforce in response to mechanical load. In contrast, the bond between the PDZ3-SH3-GUK (PSG) domain of the cytoskeletal adaptor ZO-1 and the JAM-A intracellular domain becomes dramatically weaker in response to ∼2 pN of load, the amount generated by single molecules of the cytoskeletal motor protein myosin II. These results suggest that PDZ domains can serve as force-responsive mechanical anchors at cell-cell adhesion complexes, and that mechanical load can enhance the selectivity of PDZ-peptide interactions. These results suggest that PDZ mechanosensitivity may help to generate the intricate molecular organization of cell-cell junctions and allow junctional complexes to dynamically remodel in response to mechanical load.

Objective assessment of physician work in infrainguinal arterial bypass surgery.

OBJECTIVE: The purpose of this study is obtain robust objective data from the Vascular Quality Initiative on physician work in infrainguinal artery bypass surgery. Operative time, patient comorbidities, anatomical complexity, consequences of adverse outcomes, and postoperative length of stay all factor into procedure relative value unit assignment and physician reimbursement. METHODS: Baseline demographics and comorbidities were identified among 74,920 infrainguinal bypass surgeries in Vascular Quality Initiative between 2003 and 2022. Investigation into areas of progressive complexity over time was conducted. Bypasses were divided into 10 cohorts based on inflow and target arteries and conduit type. Mean operative times, lengths of stay, major morbidity rates, and 90-day mortality rates were identified across the various bypasses. Comparison of relative value unit per minute service time during the acute inpatient hospital admission was performed between the most 4 common bypasses and 14 commonly performed highly invasive major surgeries across several subdisciplines. RESULTS: Patients undergoing infrainguinal arterial bypass have an advanced combination of medical complexities highlighted by diabetes mellitus in 40%, hypertension in 88%, body mass index >30 in 30%, coronary artery disease that has clinically manifested in 31%, renal insufficiency in 19%, chronic obstructive pulmonary disease in 27%, and prior lower extremity arterial intervention (endovascular and open combined) in >50%. The need for concomitant endarterectomy at the proximal anastomosis site of infrainguinal bypasses has increased over time (P < .001). The indication for bypass being limb-threatening ischemia as defined by ischemic rest pain, pedal tissue loss, or acute ischemia has also increased over time (P < .001), indicating more advanced extent of arterial occlusion in patients undergoing infrainguinal bypass. Finally, there has been a significant (P < .001) progression in the percentage of patients who have undergone a prior ipsilateral lower extremity endovascular intervention at the time of their bypass (increasing from 9.9% in 2003-2010 to 31.9% in the 2018-2022 eras). Among the 18 procedures investigated, the 4 most commonly performed infrainguinal bypasses were included in the analysis. These ranked 14th, 16th, 17th and 18th as the most poorly compensated per minute service time during the acute operative inpatient stay. CONCLUSIONS: Infrainguinal arterial bypass surgery has an objectively undervalued physician work relative value unit compared with other highly invasive major surgeries across several subdisciplines. There are elements of progressive complexity in infrainguinal bypass patients over the past 20 years among a patient cohort with a very high comorbidity rate, indicating escalating intensity for infrainguinal bypass.

Investigation of Combined Carotid Endarterectomy and Coronary Artery Bypass Graft Surgery Outcomes and Adverse Event Risk Factors in the Vascular Quality Initiative.

OBJECTIVE: The purpose of this study was to investigate outcomes of simultaneous CEA and CABG utilizing the Vascular Quality Initiative (VQI). Additionally, we seek to investigate risks for both perioperative and long-term mortality and adverse neurological outcomes. METHODS: All carotid endarterectomies in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEA in the database. We extracted 2 cohorts from these CEA. The first group was patients who underwent simultaneous carotid endarterectomy (CEA) and coronary artery bypass (CABG) (N = 3137). The second group encompassed patients who underwent CABG or percutaneous coronary artery angioplasty/stent within 5 years of ultimately undergoing CEA (N = 27,387). We investigated the following outcomes in a multivariable fashion: 1. Risks for mortality in long term follow-up for both cohorts combined; 2. Risks for ischemic event in the cerebral hemisphere ipsilateral to the CEA site after index hospital admission in follow up for both cohorts combined. Tertiary outcomes are also investigated in the manuscript. RESULTS: On multivariable analysis, patients undergoing simultaneous combined CEA and CABG had equivalent long-term survival to patients who underwent coronary revascularization within 5 years of ultimately undergoing CEA. Five-year survival is noted to be 84.5% vs 86% with a Cox regression non-significant P-value (.203). Significant multivariable risks for reduced long term survival (P < .03 for all) included: advancing age (HR 2.48/year); smoking history (HR 1.26); Diabetes (HR 1.33); history of CHF (HR 1.66); history of COPD (HR 1.54); baseline renal insufficiency at the time of surgery (HR 1.30); anemia (HR1.64); lack of preoperative aspirin (HR 1.12); and lack of preoperative statin (HR 1.32); lack of patch placement at CEA site (HR 1.16); perioperative MI (HR 2.04); perioperative CHF (1.66); perioperative dysrhythmia (HR 1.36); cerebral reperfusion injury (HR 2.23); perioperative ischemic neurological event (HR 2.48); and lack of statin at discharge (HR 2.04). Amongst patients with documented neurological status in follow up, combined CEA and CABG had over 99% freedom from ischemic cerebral event ipsilateral to the CEA site after discharge. CONCLUSIONS: Combined CEA and CABG provides excellent long-term mortality prevention in patients with co-existing severe coronary and carotid atherosclerosis. Simultaneous CEA and CABG provides equivalent stroke prevention and long-term survival to both a cohort of patients undergoing coronary revascularization within 5 years of CEA and patients undergoing isolated CEA or CABG in the literature. The two most impactful modifiable risk factors towards long-term stroke and mortality prevention for patients undergoing simultaneous CEA-CABG are patch placement at CEA site and adherence to statin medication therapy.

The Impact of Perioperative Morbidities, Lack of Discharge Aspirin, and Lack of Discharge Statin on Long Term Survival Following EVAR.

OBJECTIVE: Adverse perioperative events and discharge medications both have the potential to impact survival following endovascular abdominal aortic aneurysm repair (EVAR). We hypothesize that variables such as blood loss, reoperation in the same hospital admission, and lack of discharge statin/aspirin have significant effect on long term survival following EVAR. Similarly, other perioperative morbidities, are hypothesized to affect long term mortality. Quantifying the mortality effect of perioperative events and treatment emphasizes to physicians the critical nature of preoperative optimization, case planning, operative execution and postoperative patient management. METHODS: All EVAR in the Vascular Quality Initiative between 2003 and 2021 were queried. Exclusions were: ruptured/symptomatic aneurysm; concomitant renal artery or supra-renal intervention at the time of EVAR; conversion to open aneurysm repair at the time of initial operation; and undocumented mortality status at the 5 year mark postoperatively. 18,710 patients met inclusion criteria. Multivariable Cox regression time dependent analysis was performed to investigate the strength of mortality association of the exposure variables. Standard demographic variables and pre-existing major co-morbidities were included in the regression analysis to account for disproportionate, deleterious co-variables amongst those experiencing the various morbidities. Kaplan-Meier survival analysis was performed to provide survival curves for the key variables. RESULTS: Mean follow up was 5.99 years and 5-year survival for included patients was 69.2%. Cox regression revealed increased long term mortality to be associated with the following perioperative events: reoperation during the index hospital admission (HR 1.21, P = .034), perioperative leg ischemia (HR 1.34, P = .014), perioperative acute renal insufficiency (HR 1.24, P = .013), perioperative myocardial infarction (HR 1.87, P < .001), perioperative intestinal ischemia (HR 2.13, P < .001), perioperative respiratory failure (HR 2.15, P < .001), lack of discharge aspirin (HR 1.26, P < .001), and lack of discharge statin (HR 1.26, P < .001). The following pre-existing co-morbidities correlated with increased long term mortality (P < .001 for all) : body mass index under 20 kg/m2, hypertension, diabetes, coronary artery disease, reported history congestive heart failure, chronic obstructive pulmonary disease, peripheral artery disease, advancing age, baseline renal insufficiency and left ventricular ejection fraction less than 50%. Females were more likely to have EBL >300 mL, reoperation, perioperative MI, limb ischemia and acute renal insufficiency than males (P < .01 for all). Female sex trended but was not associated with increased long term mortality risk (HR 1.06, 95% CI .995-1.14, P = .072). CONCLUSIONS: Survival after EVAR is improved with optimal operative planning to facilitate evading the need for reoperation and ensuring patients without contra-indication are discharged with aspirin and statin medications. Females and patients with pre-existing co-morbidity are at particularly higher risk for perioperative limb ischemia, renal insufficiency, intestinal ischemia and myocardial ischemia necessitating appropriate preparation and preventative measures.

Investigation of Renal Decline and New Onset Dialysis Following Endovascular Aneurysm Repair in the Vascular Quality Initiative.

INTRODUCTION: The purpose of this study is to identify variables significantly associated with renal function decline after elective endovascular infra-renal abdominal aortic aneurysm repair and to identify the rate and risks of subsequent progression to dialysis. Specifically, we investigate the long-term impact of supra-renal fixation, female gender, and physiologically stressful perioperative events on renal function following endovascular aneurysm repair (EVAR). METHODS: Review of all EVAR cases in the Vascular Quality Initiative between 2003 and 2021 was conducted to investigate variable associations with three primary outcomes: postoperative acute renal insufficiency (ARI); greater than 30% decline in glomerular filtration rate (GFR) in patients beyond 1 year of follow up; and new onset dialysis requirement at any point in follow up. Binary logistic regression analysis was performed for the events of acute renal insufficiency and new onset dialysis requirement. Cox proportional hazard regression was performed regarding long term GFR decline. RESULTS: Postoperative ARI occurred in 3.4% (1692/49 772) of patients. Significant (P < .05) association with postoperative ARI was noted for: age (OR 1.014/year, 95% CI 1.008-1.021); female gender (OR 1.44, 95% CI 1.27-1.67); hypertension (OR 1.22, 95% CI 1.04-1.44); chronic obstructive pulmonary disease (OR 1.34, 95% CI 1.20-1.50); anemia (OR 4.24, 95% CI 3.71-4.84); reoperation at index admission (OR 7.86, 95% CI 6.47-9.54); baseline renal insufficiency (OR 2.29, 95% CI 2.03-2.56); larger aneurysm diameter; increased blood loss; and higher volumes of intra-operative crystalloid. Risk factors (P < .05) correlating with a decline of 30% in GFR at any time beyond 1 year were: female gender (HR 1.43, 95% CI 1.24-1.65); body mass index (BMI) less than 20 (HR 1.34, 95% CI 1.03-1.74); hypertension (HR 1.38, 95% CI 1.15-1.64); diabetes (HR 1.34, 95% CI 1.17-1.53); COPD (HR 1.21, 95% CI 1.07-1.37); anemia (HR 1.92, 95% CI 1.52-2.42); baseline renal insufficiency (HR 1.31, 95% CI 1.15-1.49); absence of discharge ace-inhibitor (HR 1.27, 95% CI 1.13-1.42); long term re-intervention (HR 2.43, 95% CI 1.84-3.21) and larger AAA diameter. Patients who experienced long term GRF decline had a significantly higher long-term morality. New onset dialysis following EVAR occurred in .47% (234/49 772) of those meeting inclusion criteria. Higher rate (P < .05) of new onset dialysis was associated with age (OR 1.03/year, 95% CI 1.02-1.05); diabetes (OR 1.376, 95% CI 1.005-1.885); baseline renal insufficiency (OR 6.32, 95% CI4.59-8.72); Reoperation at index admission (OR 2.41, 95% CI 1.03-5.67); postoperative ARI (OR 23.29, 95% CI 16.99-31.91); absence of beta blocker (OR 1.67, 95% CI 1.12-2.49); long term graft encroachment on renal arteries (OR 4.91, 95% CI 1.49-16.14). CONCLUSIONS: New onset dialysis following EVAR is a rare event. Perioperative variables influencing renal function following EVAR include blood loss, arterial injury, and reoperation. Supra-renal fixation is not associated with postoperative acute renal insufficiency or new onset dialysis in long term follow up. Renal protective measures are recommended for patients with baseline renal insufficiency undergoing EVAR as acute renal insufficiency following EVAR portends a 20-fold increased risk of new onset dialysis in long term follow up.

The Effect of Smoking Status on Perioperative Morbidity and Mortality after Open and Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: This study quantifies the extent to which active tobacco smoking is deleterious toward outcomes following open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Open and endovascular AAA repairs between January 2003 and June 2020 in the Vascular Quality Initiative were queried. Rupture, symptomatic status, and lack of 90 day follow-up were exclusions. Patients were then placed into 1 of 6 groups: open AAA with active smoking (n = 3,788), open AAA with prior smoking (n = 4,614), open AAA never smokers (817), endovascular AAA active smokers (n = 14,173), endovascular AAA former smokers (n = 25,831), and endovascular AAA never smokers (n = 6,064). Comparison of baseline characteristics, comorbidities, and adverse outcomes across each of the 6 cohorts was performed with open AAA in active smokers serving as the reference. Subanalysis investigating open AAA repair in active smokers relative to open AAA in patients confirmed in Vascular Quality Initiative to have quit smoking between 30 and 90 days before surgery was performed. Smoking cessation for a minimum of 30 days before surgery was required to fall into the former smoker category. RESULTS: In comparing open AAA in active smokers to open AAA in former and never smokers, the active smokers experienced significantly higher rates of pneumonia (P < 0.001). Combined additive morbidity and mortality was highest (54%) in active smokers (P < 0.001) relative to all cohorts other than open AAA former smokers (P = 0.21). Smoking status did not impact morbidity or mortality incidence across individuals undergoing endovascular aneurysm repair. Binary logistic regression for all AAA patients (open and endovascular combined) revealed those with any history of smoking to be more likely to experience 90 day mortality (adjusted odds ratio [OR] 2.5 [2.2-2.9], P < 0.001) relative to never smokers. Active smokers were similarly more likely to experience 90 day mortality than prior/never smokers combined (OR 1.23 [1.07-1.38], P < 0.001). Mortality within 90 days was significantly more likely (P < 0.001) with aging, female gender, larger aneurysms, preoperative history of congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency, peripheral artery disease, and body mass index less than 20 and more than 35 mg/kg2. Diabetes and coronary artery disease were also associated with 90 day mortality (P = 0.045 and 0.049, respectively). Quitting smoking between 30 and 90 days before open repair reduced combined additive morbidity and mortality relative to active smokers (OR 1.34, P = 0.038). CONCLUSIONS: Smoking cessation 30 days before open AAA repair reduces perioperative morbidity and mortality. Smoking status does not impact morbidity and mortality in patients undergoing endovascular AAA repair. When combining all patients (open and endovascular), higher rates of 90 day mortality are associated with any history of smoking, aging, female gender, and advanced pre-existing comorbidities on a multivariable analysis.

Extent of mural thrombus is not associated with increased 5-year mortality following elective AAA repair.

BACKGROUND: Mural thrombus in abdominal aortic aneurysm (AAA) has been associated with increased rates of aneurysm growth as well as adverse cardiovascular events. The extent of mural thrombus in thoracoabdominal aortic aneurysms has recently been linked to 1-year mortality following endovascular repair and has been hypothesized as a marker for reduced cardiac reserve. This study investigates whether the extent of mural thrombus in infra-renal AAA is associated with 5-year mortality following elective repair. METHODS: Retrospective review of all patients undergoing elective infra-renal AAA repair at a single academic medical center between 2007 and 2016 was performed. The following variables at the time of surgery were investigated for association with 5-year mortality: age, sex, ethnicity, insurance status and co-morbidities, repair type, renal insufficiency, end-stage renal disease on dialysis, history of smoking, coronary artery disease, congestive heart failure, diabetes mellitus, hypertension, stroke, chronic obstructive pulmonary disease, body mass index category, AAA diameter, and ratio of aortic thrombus to total aneurysm diameter. RESULTS: Amongst 427 patients undergoing infra-renal AAA repair during the study period, 232 met extensive inclusion criteria. Univariate analysis found mean age (76 vs 72, p < 0.01), age cohort over 72 years (OR = 1.9, p = 0.04), renal insufficiency (OR = 3.1, p < 0.01), ESRD (OR = 6.5, p < 0.01), AAA diameter 6 cm or greater (OR = 2.3, p < 0.01), and mean AAA diameter (61.36 vs 56.99 mm, p < 0.01) all predictive of 5-year mortality. Multivariate analysis revealed renal insufficiency (p < 0.01) and AAA diameter 6 cm or greater (p = 0.03) to be significantly associated with 5-year mortality. The extent of mural thrombus was identical between 5-year survivors and non-survivors. The mean inner to outer AAA diameter was 0.65 in the survivor cohort and 0.64 in the mortality cohort. Inner to outer ratio of < 0.5 was identified in 23% of 5-year survivors and 27% of the mortality group. CONCLUSIONS: In our experience, the extent of mural thrombus in AAA does not influence long-term survival after elective repair. AAA repair may provide protection against circulating components of mural thrombus which have the potential to promote atherosclerotic-related adverse events. Patients with renal insufficiency and larger AAA have increased risk of mortality 5 years after elective repair.

Modifiable risk factors for occurrence of ipsilateral ischemic events after carotid endarterectomy beyond perioperative period.

OBJECTIVE: The purpose of this study was to quantify the effects of several modifiable variables on the occurrence of stroke after the initial perioperative period for patients who had undergone carotid endarterectomy (CEA). METHODS: The primary outcome for the present study was the development of an ischemic stroke or transient ischemic attack (TIA) in the cerebral hemisphere ipsilateral to CEA after the initial hospitalization. All CEAs in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEAs in the database. The exclusion criteria for the study were the lack of follow-up data for >30 days, concomitant coronary artery bypass surgery, concomitant proximal or distal carotid intervention at CEA, other arterial interventions at CEA, and stroke or TIA during the initial hospital admission, leaving 126,290 patients for analysis. We used the χ2 test for statistical analysis of the outcome of ipsilateral ischemic stroke or TIA after the initial CEA hospital admission to determine the relevant variables. Age was evaluated as an ordinal variable using the Student t test. Variables with P ≤ .05 on univariable analysis were included in the multivariable Cox regression time-to-event analysis for the primary outcome. Kaplan-Meier curves were constructed of the most significant variables on Cox regression as a visual aid. RESULTS: The following variables achieved significance on Cox regression for an association with development of ipsilateral hemispheric ischemic events after the index CEA hospital admission: lack of patch placement at CEA site (hazard ratio [HR], 18.24; P < .0001), lack of antiplatelet therapy at long-term follow-up (LTFU; HR, 9.75; P < .0001), lack of statin therapy at LTFU (HR, 3.18; P < .001), lack of statin therapy at hospital discharge (HR, 1.25; P = .015), anticoagulation at LTFU (HR, 1.53; P < .001), development of >70% recurrent stenosis (HR, 2.15; P < .001), and shunt use at surgery (HR, 1.20; P = .007). Patients with patch placement at surgery and patients with confirmed antiplatelet therapy at LTFU had had 99.8% and 99.6% freedom from an ischemic event ipsilateral to the side of the CEA at LTFU, respectively. This finding is in contrast to the 5.7% and 4.7% positivity for ischemic events for those without patch placement at surgery and those not receiving antiplatelet therapy at LTFU, respectively (P < .0001 for both). CONCLUSIONS: Performance of patch angioplasty arterial closure was remarkably protective against ipsilateral cerebral ischemic events at LTFU after CEA. Discharging and maintaining patients with antiplatelet and statin medication after CEA significantly reduces the incidence of future ipsilateral ischemic events. Thus, a significant opportunity exists for enhanced outcomes with improved implementation of these measures.

Strain Transfer Mechanisms and Mechanical Properties of Optical Fiber Cables.

Understanding the strain transfer mechanism is required to interpret strain sensing results for fiber optic cables. The strain transfer mechanism for fiber optic cables embedded in cementitious materials has yet to be thoroughly investigated experimentally. Interpretation of fiber optic sensing results is of particular concern when there is a displacement discontinuity. This study investigates the strain transfer mechanism for different types of fiber optic cables while embedded in concrete cubes, sustaining a boundary condition which features a displacement discontinuity. The strain transfer mechanisms for different cables are compared under increasing strain levels. Under cyclic loading, the nonlinear behavior of the force-displacement relation and of the strain distribution in the fiber optic cable are discussed. The mechanical properties of the fiber optic cables are presented and discussed. A parameter is proposed to quantify the strain transfer length. The results of this study will assist researchers and engineers to select appropriate cables for strain sensing and interpret the fiber optic sensing results.

Distributed Fiber-Optic Strain Sensing of an Innovative Reinforced Concrete Beam-Column Connection.

Distributed fiber-optic sensing (DFOS) technologies have been used for decades to detect damage in infrastructure. One recent DFOS technology, Optical Frequency Domain Reflectometry (OFDR), has attracted attention from the structural engineering community because its high spatial resolution and refined accuracy could enable new monitoring possibilities and new insight regarding the behavior of reinforced concrete (RC) structures. The current research project explores the ability and potential of OFDR to measure distributed strain in RC structures through laboratory tests on an innovative beam-column connection, in which a partial slot joint was introduced between the beam and the column to control damage. In the test specimen, fiber-optic cables were embedded in both the steel reinforcement and concrete. The specimen was tested under quasi-static cyclic loading with increasing displacement demand at the structural laboratory of the Pacific Earthquake Engineering Research (PEER) Center of UC Berkeley. Different types of fiber-optic cables were embedded both in the concrete and the rebar. The influence of the cable coating and cable position are discussed. The DFOS results are compared with traditional measurements (DIC and LVDT). The high resolution of DFOS at small deformations provides new insights regarding the mechanical behavior of the slotted RC beam-column connection, including direct measurement of beam curvature, rebar deformation, and slot opening and closing. A major contribution of this work is the quantification of the performance and limitations of the DFOS system under large cyclic strains. Performance is quantified in terms of non-valid points (which occur in large strains when the DFOS analyzer does not return a strain value), maximum strain that can be reliably measured, crack width that causes cable rupture, and the effect of the cable coating on the measurements. Structural damage indices are also proposed based on the DFOS results. These damage indices correlate reasonably well with the maximum sustained drift, indicating the potential of using DFOS for RC structural damage assessment. The experimental data set is made publicly available.

Risk factors for mortality within 5 years of carotid endarterectomy for asymptomatic stenosis.

OBJECTIVE: The current Society for Vascular Surgery guidelines for the treatment of patients with asymptomatic carotid stenosis recommend endarterectomy for patients with >70% stenosis and acceptable surgical risk. The reduced rate of stroke with modern medical therapy has increased the importance of careful selection in deciding which patients should undergo elective carotid endarterectomy (CEA) for asymptomatic disease. It would, therefore, be very prudent to investigate preexisting variables predictive of 5-year mortality for patients meeting the criteria to undergo CEA. METHODS: The Vascular Quality Initiative was queried from 2003 onward for all cases of CEA. Inclusion in the study required the following: (1) documentation of survival status; (2) complete data on all incorporated demographic study variables; and (3) asymptomatic neurologic status. The variables present at surgery were investigated using binary logistic regression to identify multivariate predictors of 5-year mortality. The highest risk variables were then interrogated for an additive effect regarding long-term mortality. A subanalysis was performed for patients aged >80 years. RESULTS: A total of 30,615 patients met the inclusion criteria, 5414 (18%) of whom had died within 5 years. The highest risk variables were classified as those that had had an adjusted odds ratio >1.25, P < .001, and beta coefficient of ≥0.25. These included a body mass index <20 kg/m2, diabetes mellitus, a history of congestive heart failure, renal insufficiency, end-stage renal disease, chronic obstructive pulmonary disease, living status other than home, prior lower extremity bypass, prior major amputation, Black race relative to other races combined, hemoglobin <10 mg/dL, a history of neck irradiation, and a history of smoking. Age had an annual odds ratio of 1.04 (P < .001). Other variables that achieved a statistically significant (P < .05) association with 5-year mortality were coronary artery disease, a positive stress test or the occurrence of myocardial infarction within 2 years, lower extremity arterial intervention, aneurysm repair, and P2Y12 inhibitor therapy at surgery. The use of statin and aspirin therapy at surgery were both protective against 5-year mortality (P < .001). CONCLUSIONS: We identified 12 particularly high-risk variables, which, in combination, progressively predicted for increasing mortality within 5 years of CEA performed for asymptomatic stenosis. Special attention should be given to patients aged >80 years and patients with any history of congestive heart failure regardless of current symptoms, chronic obstructive pulmonary disease, renal insufficiency or end-stage renal disease, peripheral artery disease, diabetes, and variables associated with frailty (BMI under 20, anemia, assisted living status).

Predictors of Decline in Renal Function 5 Years after EVAR.

INTRODUCTION: While there exists copious short-term data regarding renal function following infra-renal endovascular abdominal aortic aneurysm repair (EVAR), long-term analysis is sparse. This is a single institution retrospective review of predictors of renal function decline 5 years after elective EVAR. METHODS: All EVAR between 2007 and 2015 were queried. Patients in whom renal function was documented 5 years postoperatively were included in analysis. Exclusion criteria were ruptured aneurysm, mortality before 56 months, lack of follow-up, ESRD status, and concomitant renal intervention. The primary outcome investigated was a 20% or greater drop in glomerular filtration rate (GFR) 5 years postoperatively. The following variables at the time of surgery were investigated as potential predictors: age, gender, hypertension, hyperlipidemia, diabetes, CAD or prior MI, COPD, prior stroke, baseline eGFR under 60 mL/min/1.73 m2, supra-renal fixation, infra-renal fixation, neck diameter, neck length, and number of contrast CT. RESULTS: 354 EVAR were identified of which 143 met inclusion criteria (211 excluded). Univariate analysis revealed female gender (OR 2.7), hypertension (OR 9.4), baseline renal insufficiency (OR 3.8), larger neck diameter, and supra-renal fixation (OR 2.32) all predictive (P < .05) of GFR drop at 5 years. Multivariate binary logistic regression analysis found female gender (multivariate OR 3.9, P = .023) and baseline renal insufficiency (multivariate OR 3.0, P = .029) as significant predictors of greater than 20% GFR drop at 5 years. Only 2 patients of the 143 progressed to dialysis requirement at 5 years. CONCLUSIONS: Females and patients with baseline renal insufficiency are more vulnerable to significant decline in renal function 5 years following EVAR. Consistent with analogous literature, supra-renal fixation appears moderately deleterious toward renal function with no clinical significance in those with baseline normal renal function. The potential benefit of avoidance of supra-renal fixation in female patients with baseline renal insufficiency is worth further investigation in a more robust multi-center study.

A Platform for Deep Sequence-Activity Mapping and Engineering Antimicrobial Peptides.

Developing potent antimicrobials, and platforms for their study and engineering, is critical as antibiotic resistance grows. A high-throughput method to quantify antimicrobial peptide and protein (AMP) activity across a broad continuum would be powerful to elucidate sequence-activity landscapes and identify potent mutants. Yet the complexity of antimicrobial activity has largely constrained the scope and mechanistic bandwidth of AMP variant analysis. We developed a platform to efficiently perform sequence-activity mapping of AMPs via depletion (SAMP-Dep): a bacterial host culture is transformed with an AMP mutant library, induced to intracellularly express AMPs, grown under selective pressure, and deep sequenced to quantify mutant depletion. The slope of mutant growth rate versus induction level indicates potency. Using SAMP-Dep, we mapped the sequence-activity landscape of 170 000 mutants of oncocin, a proline-rich AMP, for intracellular activity against Escherichia coli. Clonal validation supported the platform's sensitivity and accuracy. The mapped landscape revealed an extended oncocin pharmacophore contrary to earlier structural studies, clarified the C-terminus role in internalization, identified functional epistasis, and guided focused, successful synthetic peptide library design, yielding a mutant with 2-fold enhancement in both intracellular and extracellular activity. The efficiency of SAMP-Dep poises the platform to transform AMP engineering, characterization, and discovery.

HDAC inhibition prevents transgene expression downregulation and loss-of-function in T-cell-receptor-transduced T cells.

T cells that are gene-modified with tumor-specific T cell receptors are a promising treatment for metastatic melanoma patients. In a clinical trial, we treated seven metastatic melanoma patients with autologous T cells transduced to express a tyrosinase-reactive T cell receptor (TCR) (TIL 1383I) and a truncated CD34 molecule as a selection marker. We followed transgene expression in the TCR-transduced T cells after infusion and observed that both lentiviral- and retroviral-transduced T cells lost transgene expression over time, so that by 4 weeks post-transfer, few T cells expressed either lentiviral or retroviral transgenes. Transgene expression was reactivated by stimulation with anti-CD3/anti-CD28 beads and cytokines. TCR-transduced T cell lentiviral and retroviral transgene expression was also downregulated in vitro when T cells were cultured without cytokines. Transduced T cells cultured with interleukin (IL)-15 maintained transgene expression. Culturing gene-modified T cells in the presence of histone deacetylase (HDAC) inhibitors maintained transgene expression and functional TCR-transduced T cell responses to tumor. These results implicate epigenetic processes in the loss of transgene expression in lentiviral- and retroviral-transduced T cells.