Associations between lipoprotein(a), oxidized phospholipids, and extracoronary vascular disease.

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) in the development and progression of coronary disease is known, but their influence on extracoronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extracoronary vascular disease and incident major adverse limb events (MALEs). Four hundred forty-six participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extracoronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (odds ratio: 2.14, 95% confidence interval: 1.03, 4.44), and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extracoronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extracoronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries.

Percent Thrombus Predicts Popliteal Artery Aneurysm Related Limb Threatening Events.

OBJECTIVE: The objective of this study was to identify clinical and anatomic characteristics of Popliteal artery aneurysms (PAAs) associated with acutely limb threatening events. SUMMARY BACKGROUND DATA: Popliteal artery aneurysms (PAAs) are associated with high morbidity and mortality. Current guidelines recommend operative repair for PAAs with a diameter greater than 20 mm based on very limited evidence. METHODS: This retrospective cross-sectional cohort was derived from a multi-institutional database queried for all patients with a PAA from 2008 to 2022. Duplex ultrasound (DUS) characteristics of PAAs were abstracted by registered physicians in vascular interpretation. Symptom status at the time of DUS was divided into three categories: asymptomatic PAA, symptomatic PAA with claudication or chronic limb ischemia, and acutely limb threatening PAAs with a thromboembolic event, acute limb ischemia, or rupture. RESULTS: There were 470 PAAs identified in 331 patients. The mean age was 74 years at diagnosis, 94% of patients were white, and 97% of patients were male. In a univariate analysis, patient comorbidities and medications were not associated with symptom status. In a multivariate analysis including age, higher percent thrombus was significantly associated with symptomatic PAAs (RRR 15.2; CI 2.69-72.3; P<0.01) and PAAs with an acutely limb threatening event (RRR 17.9; CI 3.76-85.0; P<0.01). All other anatomic characteristics were not associated with symptom status. CONCLUSION: Percent thrombus was significantly associated with symptomatic PAAs and acutely limb threatening events, whereas diameter was not significantly associated with any symptom group. This analysis supports the use of percent thrombus in identifying high risk PAAs that warrant repair.

A comprehensive analysis of leadership attributes, discrepancies, and implications for gender equity in vascular surgery.

OBJECTIVE: Well-developed leadership skills have been associated with a better understanding of health care context, increased team performance, and improved patient outcomes. Surgeons, in particular, stand to benefit from leadership development. Although studies have focused on investigating knowledge gaps and needs of surgeons in leadership roles, there is a noticeable gap in the literature concerning leadership in vascular surgery. The goal of this study was to characterize current leadership attributes of vascular surgeons and understand demographic influences on leadership patterns. METHODS: This retrospective cohort study was a descriptive analysis of vascular surgeons and their observers who took the Leadership Practices Inventory (LPI) from 2020 to 2023. The LPI is a 30-question inventory that measures the frequency of specific leadership behaviors across five practices of leadership. RESULTS: A total of 110 vascular surgeons completed the LPI. The majority of participants were White (56%) and identified as male (60%). Vascular surgeons most frequently observed the "enabling others to act" leadership practice style (8.90 ± 0.74) by all evaluators. Vascular surgeons were most frequently above the 70th percentile in the "challenge the process" leadership practice style (49%) compared with the average of other leaders worldwide. Observers rated vascular surgeons as displaying significantly more frequent leadership behaviors than vascular surgeons rated themselves in every leadership practice style (P < .01). The only demographic variable associated with a significantly increased occurrence of achieving 70th percentile across all five leadership practice styles was the male gender: a multivariable model adjusting for objective experience showed that men were at least 3.5 times more likely to be rated above the 70th percentile than women. CONCLUSIONS: Vascular surgeons under-report the frequency at which they practice leadership skills across all five leadership practice styles and should recognize their strengths of enabling others to act and challenging the process. Men are recognized as exhibiting all five leadership practices more frequently than women, regardless of current position or experience level. This observation may reflect the limited leadership positions available for women, thereby restricting their opportunities to demonstrate leadership practices as frequently or recognizably as their male counterparts.

Identifying risk factors for postoperative ileus following open abdominal aortic aneurysm repair.

INTRODUCTION: Postoperative ileus (POI) is a common complication following major abdominal surgery. The majority of the data available regarding POI following abdominal surgery is from the gastrointestinal and urologic literature. These data have been extrapolated to vascular surgery, especially with regards to enhanced recovery programs for open abdominal aortic aneurysm (AAA) surgery. However, vascular patients are a unique patient population and extrapolation of gastrointestinal and urological data may not necessarily be appropriate. Therefore, the purpose of this study was to delineate the prevalence and risk factors of POI in patients undergoing open AAA surgery. METHODS: This was a retrospective, single-institution study of patients who underwent open AAA surgery from January 2016 to July 2023. Patients were excluded if they had undergone non-elective repairs or had expired within 72 hours of their index operation. The primary outcome was rates of POI, which was defined as the presence of two or more of the following after the third postoperative day: nausea and/or vomiting, inability to tolerate oral food intake, absence of flatus, abdominal distension, or radiological evidence of ileus. RESULTS: A total of 123 patients met study criteria with an overall POI rate of 8.9% (n=11). Patients who developed a POI had significantly lower BMIs (24.3 kg/m2 versus 27.1 kg/m2, P=.003), were more likely to undergo a transperitoneal approach (81.8% versus 42.0%, P=.022), midline laparotomy (81.8% versus 37.5%, P=.008), longer total clamp times (151.6 minutes versus 97.7 minutes, P=.018), larger amounts of intraoperative crystalloid infusion (3495 mL versus 2628 mL, P=.029), and were more likely to return to the operating room (27.3% versus 3.6%, P=.016). Proximal clamp site was not associated with POI (P=.463). POI patients also had higher rates of post-operative vasopressor use (100% versus 61.1%, P=.014) and larger amounts of oral morphine equivalents in the first 3 post-operative days (488.0 mg + 216.0 versus 203.8 mg + 29.6 P=.016). Patients who developed POI had longer lengths of stay (12.5 days versus 7.6 days, P<.001), longer duration of NGT decompression (5.9 days versus 2.2 days, P<.001), and a longer period of time before diet tolerance (9.1 days versus 3.7 days, P<.001). Of those that developed a POI (n=11), 4 (36.4%) required total parental nutrition during the admission. CONCLUSION: POI is a morbid complication amongst patients undergoing elective open AAA surgery that significantly prolongs hospital stay. Patients at risk for developing a POI are those with lower BMIs, had an operative repair via a transperitoneal approach, midline laparotomy, longer clamp times, larger amounts of intraoperative crystalloid infusion, a return to the operating room, post-operative vasopressor use, and higher amounts of oral morphine equivalents. These data highlight important peri-operative opportunities to reduce the prevalence of POI.

Popliteal artery aneurysm ultrasound criteria for reporting characteristics.

INTRODUCTION: Duplex ultrasound (DUS) is the modality of choice for surveillance of popliteal artery aneurysms (PAAs). However, noninvasive vascular laboratories have no standard guidelines for reporting results. This study assessed reports of PAA DUS for inclusion of information pertinent to operative decision-making and timing of surveillance. METHODS: This study was a retrospective review of a multi-institutional repository that was queried for all patients with a PAA from 2008 to 2022 and confirmed via manual chart review. DUS reports were abstracted and images were individually annotated for features of interest including dimensions, flow abnormalities, and percent thrombus burden. RESULTS: A total of 166 PAAs in 130 patients had at least one DUS available for viewing. Postoperative surveillance of PAAs was performed at several intervals: the first at 30 months (IQR 3.7-113, n = 44), the second at 64 months (IQR 20-172, n = 31), and the third at 152 months (IQR 46-217, n = 16) after the operation. The largest diameter of operative PAAs (median 27.5 mm, IQR 21.8-38.0) was significantly greater than nonoperative PAAs (median 20.9 mm, IQR 16.7-27.3); p < 0.01. Fewer than 33 (21%) reports commented on patency of distal runoff. We calculated an average percent thrombus of 60% (IQR 19-81) in nonoperative PAAs, which is significantly smaller than 75% (IQR 58-89) in operative PAAs; p < 0.01. CONCLUSION: In this multi-institutional retrospective study, PAAs are often not followed at intervals recommended by the Society for Vascular Surgery guidelines and do not include all measurements necessary for clinical decision-making in the multi-institutional repository studied. There should be standardization of PAA DUS protocols performed by all noninvasive vascular laboratories to ensure completeness of PAA DUS images and inclusion of characteristics pertinent to clinical decision-making in radiology reports.

Complications of Carotid Interventions for Symptomatic Lesions after Systemic Thrombolysis.

BACKGROUND: Series detailing complications after carotid endarterectomy (CEA) and transfemoral carotid stenting (tfCAS) for patients presenting with neurologic symptoms that are treated with systemic thrombolysis (ST) are sparse. We sought to determine if treatment with ST was associated with a higher rate of post-carotid intervention complications. METHODS: A multispecialty, institutional, prospectively maintained database was queried for symptomatic patients treated with CEA or tfCAS from 2007 to 2019. The primary outcomes of interest were bleeding complications (access/wound complications, hematuria, intracranial hemorrhage) or need for reintervention, stroke, and death. We compared rates of these outcomes between patients who were and were not treated with ST. To adjust for preoperative patient factors and confounding variables, propensity scores for assignment to ST and non-ST were calculated. RESULTS: There were 1,139 patients included (949 [82%] CEA and 190 [17%] tfCAS. All treated lesions were symptomatic (550 [48%] stroke, 603 [52%] transient ischemic attack). Fifty-six patients (5%) were treated with ST. Fifteen of 56 patients also underwent catheter-based intervention for stroke. ST was administered 0 to 1 day preoperatively in 21 (38%) patients, 2 to 6 days preoperatively in 27 (48%) patients, and greater than 6 days preoperatively in 8 (14%) patients. ST patients were more likely to present with stroke (93% vs. 45%; P < 0.001) and have higher preoperative Rankin scores. Unadjusted rate of bleeding/return to operating room was 3% for ST group and 3% for non-ST group (P = 0.60). Unadjusted rate of stroke was 4% for ST group and 3% for the non-ST group (P = 0.91), while perioperative mortality was 5% for ST group and 1% for non-ST group (P = 0.009). After adjusting for patient factors, preoperative antiplatelet/anticoagulation, and operative factors, ST was not associated with an increased odds of perioperative bleeding/return to the operating room (odds ratio 0.37; 95% confidence interval: 0.02-1.63; P = 0.309) or stroke (odds ratio 0.62; 95% confidence interval: 0.16-2.40; P = 0.493). CONCLUSIONS: ST does not convey a higher risk of complications after CEA or tfCAS. After controlling for other factors, patients that received ST had similar rates of local complications and stroke when compared to non-ST patients. Early carotid intervention is safe in patients that have received ST, and delays should be avoided in symptomatic patients given the high risk of recurrent stroke.

Local Anesthesia for Endovascular Repair of Abdominal Aortic Aneurysm Allows for Accurate Graft Deployment with Durable Results.

BACKGROUND: Local anesthesia (LA) is sparsely used in endovascular aneurysm repair (EVAR) despite short-term benefit, likely secondary to concerns over patient movement preventing accurate endograft deployment. The objective of this study is to examine the association between anesthesia type and endoleak, sac regression, reintervention, and mortality. METHODS: The Vascular Quality Initiative database was queried for all EVAR cases from 2014 to 2022. Patients were included if they underwent percutaneous elective EVAR with anatomical criteria within instructions for use of commercially approved endografts. Multivariable logistic regression with propensity score weighting was used to determine the association between anesthesia type on the risk of any endoleak noted by intraoperative completion angiogram and sac regression. Multivariable survival analysis with propensity score weighting was used to determine the association between anesthesia type and endoleak at 1 year, long-term reintervention, and mortality. RESULTS: Thirteen thousand nine hundred thirty two EVARs met inclusion criteria: 1,075 (8%) LA and 12,857 (92%) general anesthesia (GA). On completion angiogram, LA was associated with fewer rates of any endoleaks overall (16% vs. 24%, P < 0.001). On multivariable analysis with propensity score weighting, LA was associated with similar adjusted odds of any endoleak on intraoperative completion angiogram (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.47-0.68) as well as combined type 1a and type 1b endoleaks (OR 0.72, 95% CI 0.47-1.09). Follow-up computed tomography imaging at 1 year was available for 4,892 patients, 377 (8%) LA and 4,515 (92%) GA. At 1 year, LA was associated with similar rate of freedom from any endoleaks compared to GA (0.66 [95% CI 0.63-0.69] vs. 0.71 [95% CI 0.70-0.72], P = 0.663) and increased rates of sac regression (50% vs. 45%, P = 0.040). On multivariable analysis with propensity score weighting, LA and GA were associated with similar adjusted odds of sac regression (OR 1.22, 95% CI 0.97-1.55). LA and GA had similar rates of endoleak at 1 year (hazard ratio [HR] 0.14, 95% CI 0.63-1.07); however, LA was associated with decreased hazards of combined type 1a and 1b endoleaks at 1 year (HR 0.87, 95% CI 0.80-0.96). LA and GA had similar adjusted long-term reintervention rate (HR 0.77, 95% CI 0.44-1.38) and long-term mortality (HR 1.100, 95% CI 079-1.25). CONCLUSIONS: LA is not associated with increased adjusted rates of any endoleak on completion angiogram or at 1-year follow-up compared to GA. LA is associated with decreased adjusted rates of type 1a and type 1b endoleak at 1 year, but similar rates of sac regression, long-term reintervention, and mortality. Concerns for accurate graft deployment should not preclude use of LA and LA should be increasingly considered when deciding on anesthetic type for standard elective EVAR.

Analysis of Female Participant Representation in Registered Oncology Clinical Trials in the United States from 2008 to 2020.

BACKGROUND: Female underrepresentation in oncology clinical trials can result in outcome disparities. We evaluated female participant representation in US oncology trials by intervention type, cancer site, and funding. MATERIALS AND METHODS: Data were extracted from the publicly available Aggregate Analysis of ClinicalTrials.gov database. Initially, 270,172 studies were identified. Following the exclusion of trials using Medical Subject Heading terms, manual review, those with incomplete status, non-US location, sex-specific organ cancers, or lacking participant sex data, 1650 trials consisting of 240,776 participants remained. The primary outcome was participation to prevalence ratio (PPR): percent females among trial participants divided by percent females in the disease population per US Surveillance, Epidemiology, and End Results Program data. PPRs of 0.8-1.2 reflect proportional female representation. RESULTS: Females represented 46.9% of participants (95% CI, 45.4-48.4); mean PPR for all trials was 0.912. Females were underrepresented in surgical (PPR 0.74) and other invasive (PPR 0.69) oncology trials. Among cancer sites, females were underrepresented in bladder (odds ratio [OR] 0.48, 95% CI 0.26-0.91, P = .02), head/neck (OR 0.44, 95% CI 0.29-0.68, P < .01), stomach (OR 0.40, 95% CI 0.23-0.70, P < .01), and esophageal (OR 0.40 95% CI 0.22-0.74, P < .01) trials. Hematologic (OR 1.78, 95% CI 1.09-1.82, P < .01) and pancreatic (OR 2.18, 95% CI 1.46-3.26, P < .01) trials had higher odds of proportional female representation. Industry-funded trials had greater odds of proportional female representation (OR 1.41, 95% CI 1.09-1.82, P = .01) than US government and academic-funded trials. CONCLUSIONS: Stakeholders should look to hematologic, pancreatic, and industry-funded cancer trials as exemplars of female participant representation and consider female representation when interpreting trial results.

Outcomes of symptomatic penetrating aortic ulcer and intramural hematoma in the endovascular era.

BACKGROUND: Although endovascular technology has resulted in a paradigm shift in treatment, medical management remains the standard of care for penetrating aortic ulcer (PAU) and intramural hematoma (IMH). This study aimed to detail the short- and long-term outcomes of symptomatic PAU/IMH. METHODS: Institutional data on symptomatic PAU/IMH were gathered (2005-2020). The primary outcome was the composite of recurrent symptoms, radiographic progression, intervention, rupture, and death from related or unknown cause. Factors associated with the primary outcome were determined using a Fine-Gray model with death from an unrelated cause as a competing risk. RESULTS: A total of 83 symptomatic patients treated with medical management aside from ruptures and type A dissections: 21 isolated PAU, 30 isolated IMH, and 32 IMH and PAU. Adverse outcomes included symptom recurrence in 14 (16.9%), radiographic progression to dissection or saccular aneurysm in 17 (20.5%), surgery in 20 (24.1%) (17 thoracic endovascular aortic repair, 1 endovascular aortic repair, 1 frozen elephant trunk, and 1 open repair), and rupture in 4 (4.8%). Twenty-seven patients (32.5%) died during follow-up: 6 from IMH treatment complications, 8 from an unknown cause, and 13 from other causes. The 30-day, 1-year, and 5-year cumulative incidences of the primary outcome was 26.5% (95% confidence interval [CI], 16.9%-37.0%), 44.9% (95% CI, 32.8%-56.2%), and 57.5% (95% CI, 42.4%-69.9%), respectively. IMH with PAU was associated with a significantly higher risk of the primary outcome compared with isolated IMH (subdistribution hazard ratio, 2.21; 95% CI, 1.09-4.50; P = .027) and isolated PAU (subdistribution hazard ratio, 3.58; 95% CI, 1.44-8.88; P = .006). CONCLUSIONS: Complications from symptomatic PAU and IMH are frequent, with intervention, recurrent symptoms, radiographic progression, rupture, or death affecting 25% of patients at 30 days after diagnosis and almost one-half of patients 1 year after diagnosis. Given the high rate of adverse events in this population, investigation into a more aggressive interventional strategy may warranted, especially in patients with a combined IMH and PAU.

Routine Completion Angiography for Infrainguinal Bypasses Using Prosthetic Conduit: No Effect on Postoperative Patency.

BACKGROUND: Recent studies have demonstrated increased postoperative patency with the use of routine completion angiography for bypass using venous conduit. Compared to vein conduits, however, prosthetic conduits are less plagued by technical issues such as unlysed valves or arteriovenous fistulae. The effect of routine completion angiography on bypass patency in prosthetic bypasses has yet to be compared to the more traditional selective use of completion imaging. METHODS: A retrospective review of all infrainguinal bypass procedures using prosthetic conduit completed at a single hospital system from 2001 to 2018 was performed. Demographics, comorbidities, intraoperative reintervention rates, and 30-day rates of graft thrombosis were analyzed. Statistical analysis included t-tests, chi-square tests, and cox regression. RESULTS: Four hundred and ninety-eight bypasses that were performed in 426 patients met inclusion criteria. Fifty-six (11.2%) bypasses were classified into the routine completion angiogram group compared to 442 (88.8%) into the no completion angiogram group. Patients who underwent routine completion angiograms had a rate of intraoperative reintervention of 21.4%. When comparing bypasses that underwent routine completion angiography versus no completion angiography, there were no significant differences in rates of reintervention (3.5% vs. 4.5%, P = 0.74) or graft occlusion (3.5% vs. 4.7%, P = 0.69) at 30-days postoperatively. CONCLUSIONS: Almost one-quarter of lower extremity bypasses using prosthetic conduit that undergo routine completion angiography undergo postangiogram bypass revision; however, this is not associated with an increased graft patency at 30 days postoperatively.

Increased anti-thrombotic therapy is associated with decreased major adverse limb events in patients with low wound and foot infection scores.

INTRODUCTION: The optimal anti-thrombotic management of patients after lower extremity bypass has yet to be fully elucidated, in part due to significant heterogeneity in patient presentation and practice patterns. The Wound, Ischemia, and foot Infection (WIfI) score is a validated scoring system to assist in the management of patients with chronic limb threatening ischemia (CLTI). We hypothesized that performing a restriction analysis based on WIFI scores would assist in the postoperative anti-thrombotic management of patients undergoing infrainguinal bypass. METHODS: A retrospective cohort of infrainguinal bypass procedures completed at a single hospital system between January 2018 and January 2021 was selected, and preoperative WIfI scores were extracted for each patient. Patients with either Wound scores of 2 and 3, or Ischemia Scores of 0 and 1, or Foot Infection Scores of 3 were excluded. Based on the type of anti-thrombotic regimen on discharge, demographics, comorbidities, type of bypass, 30-day rates of graft occlusion, major amputation, mortality, and major adverse limb events (MALE) were analyzed. Statistical analysis included t-tests, chi square tests, and time-to-event survival analysis. RESULTS: 230 procedures were included in the study. 69 (30.0%) patients were discharged on single antiplatelet therapy (SAPT), compared to 161 (70.0%) who were discharged on either dual antiplatelet therapy or anticoagulation (DAPT/AC). There was a higher prevalence of bypasses using prosthetic conduit in the DAPT/AC group (45.9 vs 31.8%, p = .047); no other demographic or procedural variable analyzed had any significant differences. At 30-days postoperatively, there was no significant difference in postoperative reintervention rates, however, the DAPT/AC group had significantly lower rates of mortality (1.2 vs 7.2%, p = .01), major amputation (1.2% vs 5.8%, p = .04), and MALE (3.7 vs 13.0%, p < .01). There were no significant differences in bleeding complications. Survival analysis demonstrated that MALE-free survival was higher in the DAPT/AC group compared to the SAPT group (p < .01). On Cox regression analysis, DAPT/AC was associated with significantly decreased rates of MALE + mortality (Hazard Ratio (HR) 0.20 [0.06 - 0.66]). CONCLUSION: Lower extremity bypasses patients with low Wound and low foot Infection scores who are discharged on DAPT/AC postoperatively have a significantly higher 30-day MALE-free survival rate compared to patients discharged on SAPT; consideration could be made to preferentially discharge such post-bypass patients on DAPT/AC.

Wall shear rate and energy loss coefficient measures using conventional Doppler ultrasound do not predict carotid plaque progression.

Background: The rate of carotid plaque progression is believed to be related to blood flow hemodynamics and shear stress. Our objective was to determine if wall shear rate (WSR) and the energy loss coefficient (ELC) measured by Doppler ultrasound could predict atherosclerotic carotid disease progression. Patients and methods: Patients at a large tertiary center with an initial ultrasound between 2016 and 2018 with a significant carotid plaque were included if they had at least one 6 months follow-up comparative study. Stenosis progression was assessed according to the NASCET (The North American Symptomatic Carotid Endarterectomy Trial) percentage criterion. Results: The average annual progression rate for the 74 plaques included was 5.7% NASCET per year. We identified 18 plaques with ≥10% NASCET progression and 56 plaques without significant progression <10% NASCET. Among the plaques with progression, only four plaques had progression greater than 20% NASCET. Median WSR was 6266 s-1 [5813-8974] in plaques with progression and 6564 s-1 [5285-8766] in stable plaques (p=0.643). Median ELC was 3.86 m2 [2.78-5.53] in plaque with progression and 4.32 m2 [3.42-6.81] in stable plaques (p=0.296). Conclusions: Although it is a widely accepted hypothesis that shear stress and hemodynamics of the carotid bifurcation contribute to plaque progression, we found that WSR and ELC estimated by Doppler ultrasound do not reliably predict atherosclerotic plaque progression in the carotid artery. Other ultrasound modalities, such as 3D imaging, may be used to assess the influence of plaque geometry and hemodynamics in plaque progression.

Development of a GalNAc-Tyrosine-Specific Monoclonal Antibody and Detection of Tyrosine O-GalNAcylation in Numerous Human Tissues and Cell Lines.

Glycosylation is a vital post-translational modification involved in a range of biological processes including protein folding, signaling, and cell-cell interactions. In 2011, a new type of O-linked glycosylation was discovered, wherein the side-chain oxygen of tyrosine is modified with a GalNAc residue (GalNAc-Tyr). At present, very little is known about GalNAc-Tyr prevalence, function, or biosynthesis. Herein, we describe the design and synthesis of a GalNAc-Tyr-derived hapten and its use in generating a GalNAc-Tyr selective monoclonal antibody. The antibody, G10C, has an unusually high affinity (app KD = 100 pM) and excellent selectivity for GalNAc-Tyr. We also obtained a crystal structure of the G10C Fab region in complex with 4-nitrophenyl-N-acetyl-α-d-galactosaminide (a small molecule mimic of GalNAc-Tyr) providing insights into the structural basis for high affinity and selectivity. Using this antibody, we discovered that GalNAc-Tyr is widely expressed in most human tissues, indicating that it is a ubiquitous and underappreciated post-translational modification. Localization to specific cell types and organ substructures within those tissues indicates that GalNAc-Tyr is likely regulated in a cell-specific manner. GalNAc-Tyr was also observed in a variety of cell lines and primary cells but was only present on the external cell surface in certain cancer cell lines, suggesting that GalNAc-Tyr localization may be altered in cancer cells. Collectively, the results shed new light on this under-studied form of glycosylation and provide access to new tools that will enable expanded biochemical and clinical investigations.

A systematic review of thromboelastography utilization in vascular and endovascular surgery.

OBJECTIVE: Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS: Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS: This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.

Identifying Strategies for Struggling Surgery Residents.

BACKGROUND: Struggling residents are not uncommon in general surgery. Early identification of these residents and effective remediation remain imperfect. MATERIALS AND METHODS: We performed a survey of program directors (PD) across all general surgery residencies. Survey questions included the following: demographic information about the program and PD, 10 vignettes about hypothetical residents struggling in various ACGME milestones to assess how PDs would address these deficiencies, and self-reported PD preparedness and availability of resources to support struggling residents. RESULTS: In total, we received 82 responses to our survey. All PDs who participated in our study reported having struggling residents in their program. The three most common ways struggling residents are identified were faculty word-of-mouth, formal evaluations such as milestones and ABSITE performance, and resident word-of-mouth. Over 18% of PDs reported having little to no relevant training in addressing the needs of a struggling resident, and 65.9% of PDs did not feel that their program had 'completely adequate' resources to address these needs. In the majority of cases, PDs offer mentorship with themselves or other faculty as a remediation strategy with infrequent use of other resources. CONCLUSIONS: Strategies to identify struggling residents and remediation strategies varied widely across programs. Diversifying remediation approaches should be considered for more effective remediation.

Understanding motivations behind medical student involvement in COVID-19 pandemic relief efforts.

BACKGROUND: Although students were removed from patient-facing settings at the beginning of the COVID-19 pandemic due to concerns of burdening teaching physicians and depleting personal protective equipment, some leaders suggest students can be effectively utilized when personnel resources may be scarce. There have been narrative discussions surrounding medical student involvement, but no studies exploring the attitudes of these students. The authors aim to quantify the degree to which factors influenced a medical student's decision to or to not volunteer during the pandemic and to characterize medical students' attitudes towards medical professionals' duty to serve in a pandemic. METHODS: The authors developed and tested a secure web-based survey before distribution to students at 23 different US allopathic medical schools that did not graduate medical students early to aid in pandemic efforts between April and June 2020. Of the 599 students who completed the survey, 65.5% self-identified as female and were on average 25.94 years old (SD = 2.5). Multiple comparisons were made based on volunteer status. Ordinal scale questions were compared with the Mann Whitney U test, and the Chi-Squared test was used for categorical variables using R version 3.62. RESULTS: 67.6% of students volunteered in pandemic relief activities and a majority of those students volunteered in non-patient-facing roles. Community service, new skills, and time commitment were top 3 influencing factors for students who volunteered, while risk to other, time commitment, and risk to self were top 3 influencing factors for students who chose not to volunteer. Compared to other specialties, students interested in primary care specialties agreed to a greater degree that physicians have a duty to serve in pandemic relief efforts. CONCLUSIONS: Medical students who volunteered cited self-serving factors and altruistic values as significant motivators. Students who did not volunteer were significantly more concerned with risks of COVID-19 exposure. However, medical students in general agreed that students should be allowed to volunteer in COVID-19 related relief efforts. As large areas of the United States continue to experience increases in COVID-19 cases, institutions should involve medical students in balancing the level of acceptable risk with the educational benefits.

Industry Compensation to Physician Vascular Specialist Authors of Highly-referenced Aortic Aneurysm Studies.

BACKGROUND: Industry payments to physicians may influence their attitudes toward medical devices and products. Disclosure of industry compensation by authors of scientific manuscripts usually occurs at the authors' discretion and is seldom audited as part of the peer review process. The purpose of this analysis was to characterize industry compensation among highly cited research articles related to aortic aneurysm. METHODS: A Web of Science search for English language articles published from 2013-2017 using the search term "aortic aneurysm" identified publications for this study. The top 99 most-cited publications were abstracted by author. Physician authors with reported industry compensation from 2013-2016 were identified using the ProPublica Dollars for Docs search tool (linked to Centers for Medicare and Medicaid Services Open Payments data), based on provider name, medical specialty, and geographic location. Statistical analysis included descriptive statistics and categorical tests. RESULTS: The 99 articles had 1,264 unique authors, of whom 105 physicians (8.3%) received industry compensation during the study period. Fourteen of the 105 authors self-reported having received industry compensation. The remaining 91 authors (86.7%) did not disclose their industry-reported compensation. Industry payments during the study period totaled $6,082,574 paid through 13,489 transactions from 169 different manufacturers. In-kind items and services were the most common form of payment (65.3%). The median transaction amount was $58.32. [$138.34]. Food and beverage accounted for the largest number of transactions (N=9653), followed by travel and lodging (N=2365), consulting (N=513), and promotional speaking (N=436). Consulting accounted for the most total dollars over the study period ($1,970,606), followed by travel and lodging ($1,122,276), promotional speaking ($972,894), food and beverage ($568,251), royalty or license ($504,631), honoraria ($452,167), and education ($428,489). Royalty and license payments had the highest median transaction amount ($15,418. [$29,049]), and was the only category with a median transaction amount greater than $5,000. In contrast, several categories had median transaction amounts under $50, including food and beverage ($32. [$77]), gifts ($34. [$86]), and entertainment ($30. [$69]). No significant difference in payment amounts by medical specialty was identified (P=0.071). CONCLUSIONS: Only 8.3% of physician authors of highly cited aortic aneurysm studies received industry compensation, but 86.7% of those physician authors receiving payments did not disclose industry compensation within the manuscripts. Potential bias associated with industry compensation may be underestimated and conservatively biased based on author self-reporting.

Industry compensation and self-reported financial conflicts of interest among authors of highly cited peripheral artery disease studies.

OBJECTIVE: Industry compensation to authors may influence the interpretation of study results. Scientific journals often require author disclosure of a relevant financial conflict of interest (FCOI) but seldom quantify compensation and leave reporting up to the author's discretion. Professional and public concerns related to potential bias introduced into medical research by FCOI have arisen, especially when physician compensation from manufacturers is not disclosed. Little is known, however, about the prevalence of industry compensation to authors of related publications, payment amounts, or how this information compares with self-reported FCOI. The objective of this study was to compare industry compensation and disclosed FCOI among highly referenced publications related to treatment of peripheral artery disease, a disease that affects approximately 8.5 million Americans and is often treated with medications and devices. METHODS: "Peripheral artery disease" was used as a Web of Science search term to identify publications from 2013 to 2016, excluding review articles, conference proceedings, book chapters, abstract publications, and non-English language publications. The top 99 most cited publications were abstracted for self-reported FCOI by author. Industry compensation to authors was queried using a ProPublica Dollars for Docs custom data set based on Centers for Medicare and Medicaid Services Open Payments data. Providers practicing in the United States in any of the following specialties were included: cardiology, cardiothoracic surgery, vascular and interventional radiology, or vascular surgery. Payment transactions were matched to physician authors on the basis of provider name, specialty, and geographic location. Statistical analysis included descriptive statistics and categorical tests. Descriptive statistics are reported as frequency (percentage) or median (interquartile range). RESULTS: Among 1008 vascular specialist authors identified, 218 (22%) self-reported FCOI. Fifty-six physician authors had compensation reported to the Centers for Medicare and Medicaid Services by industry during the study period. Among those identified as recipients of industry compensation, 28 (50%) self-reported FCOI. Industry payments to the 56 authors totaled $11,139,987, with a median total payment of $18,827 (interquartile range, $152,084) per author. Food and beverage was the most frequently identified nature of payment (n = 8981 [74%]), promotional speaking involved the largest total amount of payments ($3,256,431), and royalty or license was the highest median payment ($51,431 [$72,215]). Physicians reporting FCOI received a total of $9,435,340 during the study period vs $1,706,647 for those who did not report any FCOI. Median total payments were higher among authors reporting FCOI vs not ($81,224 [$324,171] vs $9494 [$43,448]; P < .001). CONCLUSIONS: Nondisclosed author compensation from industry is relatively uncommon among highly cited peripheral artery disease research studies but may be associated with substantial payments. These results suggest that self-reported FCOI does not provide a comprehensive overview of industry compensation. Reporting all payments rather than only those deemed relevant by the author might provide a more complete and transparent report of potential FCOI, allowing independent assessment of relevance in interpreting study findings.

Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101.

Numerous candidate biomarkers in urine extracellular vesicles (EVs) have been described for kidney diseases, but none are yet in clinical use, possibly due to a lack of proper normalization. Proper normalization corrects for normal biological variation in urine flow rate or concentration, which can vary by over one order of magnitude. Here, we observed inter- and intra-animal variation in urine excretion rates of small EVs (<200 nm in diameter) in healthy rats as a series of six 4-h fractions. To visualize intra-animal variation, we normalized a small EV excretion rate to a peak excretion rate, revealing a circadian pattern for each rat. This circadian pattern was distinct from urine volume, urine albumin, urine creatinine, and urine albumin-to-creatinine ratio. Furthermore, urine small EV excretion was not significantly altered by sex, food/water deprivation, or ischemic acute kidney injury. Urine excretion of the exosomal/small EV marker protein tumor susceptibility gene 101 (TSG101) displayed a similar circadian pattern to urine small EV excretion; both measurements were highly correlated (R2 = 0.85), with an average stoichiometry of 10.0 molecules of TSG101/vesicle in healthy rats. The observed stoichiometry of TSG101/vesicle in rat urine translated to human spot urine samples (10.2 molecules/vesicle) and cultured kidney-derived cell lines (human embryonic kidney-293 and normal rat kidney 52E cells). Small EV number and its surrogate, TSG101 protein, can normalize for circadian variation when testing candidate biomarkers in small EVs. Just as creatinine has emerged as the customary normalization factor for liquid-phase urine biomarkers, vesicle number and its surrogate, molecules of exosome/small EV-associated TSG101, should be considered as viable, normalizing factors for small EV biomarkers.

The role of adenosine 1a receptor signaling on GFR early after the induction of sepsis.

Sepsis and acute kidney injury (AKI) synergistically increase morbidity and mortality in the ICU. How sepsis reduces glomerular filtration rate (GFR) and causes AKI is poorly understood; one proposed mechanism includes tubuloglomerular feedback (TGF). When sodium reabsorption by the proximal tubules is reduced in normal animals, the macula densa senses increased luminal sodium chloride, and then adenosine-1a receptor (A1aR) signaling triggers tubuloglomerular feedback, reducing GFR through afferent arteriole vasoconstriction. We measured GFR and systemic hemodynamics early during cecal ligation and puncture-induced sepsis in wild-type and A1aR-knockout mice. A miniaturized fluorometer was attached to the back of each mouse and recorded the clearance of FITC-sinistrin via transcutaneous fluorescence to monitor GFR. Clinical organ injury markers and cytokines were measured and hemodynamics monitored using implantable transducer telemetry devices. In wild-type mice, GFR was stable within 1 h after surgery, declined by 43% in the next hour, and then fell to less than 10% of baseline after 2 h and 45 min. In contrast, in A1aR-knockout mice GFR was 37% below baseline immediately after surgery and then gradually declined over 4 h. A1aR-knockout mice had similar organ injury and inflammatory responses, albeit with lower heart rate. We conclude that transcutaneous fluorescence can accurately monitor GFR and detect changes rapidly during sepsis. Tubuloglomerular feedback plays a complex role in sepsis; initially, TGF helps maintain GFR in the 1st hour, and over the subsequent 3 h, TGF causes GFR to plummet. By 18 h, TGF has no cumulative effect on renal or extrarenal organ damage.