Polyvascular Disease is Common in Patients Undergoing Carotid Endarterectomy and Lower Extremity Bypass and is Associated With Worse Outcomes.

INTRODUCTION: Polyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. METHODS: The Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in > 1 arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were: (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using chi-square test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. RESULTS: Polyvascular disease was identified in 47% of CEA (39% 2 arterial beds, 7.6% 3 arterial beds; n = 93,736) and 47% of LEB (41% 2 arterial beds, 5.7% 3 arterial beds; n=25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P<0.0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% 1 bed vs 1.5% 2 beds vs 2.7% 3 beds, P<0.001) and LEB (2.2% 1 bed vs 5.3% 2 beds vs 6.6% 3 beds, P<0.001). Polyvascular disease was independently associated with perioperative MI/death after CEA (OR 1.59 (95% CI 1.40-1.81), P<.0001) and LEB (OR 1.78 (95% CI 1.52-2.08), P<.0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% 3 beds vs 88% 2 beds vs 92% 1 bed, P<0.01) and LEB (72% 3 beds vs 75% 2 beds vs 84% 1 bed, P<0.01) in a dose-dependent manner, with the lowest 5 year survival observed in those with 3 arterial beds involved. Polyvascular disease was independently associated with five-year mortality following CEA (HR 1.33 (95% CI 1.24-1.40), P=0.0001) and LEB (HR 1.30 (95% CI 1.20-1.41), P=0.0001). CONCLUSION: Polyvascular disease is common in patients undergoing CEA and LEB and is associated with higher risk of perioperative MI/death and decreased long-term survival. Following revascularization, polyvascular disease patients may be considered for more aggressive cardioprotective medications and closer follow up.

The Association Between Grip Strength, Upper Body Power, and Limb Dominance in a Military Population.

INTRODUCTION: Military service members rely on upper body strength and power to accomplish tasks such as carrying heavy weapons and gear, rappelling, combat grappling, and marksmanship. Early identification of the factors that lead to reduced upper body strength and power would enable leadership to predict and mitigate aspects that decrease military operational readiness and increase injury risk. The purpose of this study was to investigate the relationship between grip strength and upper body power in U.S. Infantry Marines. We hypothesized that dominant arm grip strength would show a strong positive correlation with upper body power and that the dominant arm would be more powerful than the non-dominant arm. MATERIALS AND METHODS: A total of 120 U.S. Marines completed 3 maximum effort isometric grip strength trials with their dominant hand and 3 maximum effort ballistic pushups on a ForceDecks force plate system. Force plate data were used to estimate pushup height and peak power. Maximum grip strength, pushup height, and peak power across the 3 trials were used for analysis. Pearson's correlation was used to test for associations between peak power, pushup height, and grip strength. Paired t-tests were used to test for differences in peak power between the dominant and non-dominant arms. RESULTS: A very weak correlation was found between grip strength and upper body power, but there was no relationship between grip strength and pushup height. Additionally, there were no significant differences in upper body power between the dominant and non-dominant arms. CONCLUSIONS: The results of this study suggest that grip strength is not predictive of upper body power and cannot be used as a stand-alone measure of physical readiness in a military unit. These findings do not, however, degrade the potential of both measures to predict and inform health status and physical readiness. Future prospective research should be conducted to determine if either of these measures can be used as indicators of performance and/or injury susceptibility and if limb dominance plays a role in injury incidence within the upper extremity.

Earned Outcomes Correlate with Reliability-Adjusted Surgical Mortality after Abdominal Aortic Aneurysm Repair and Predict Future Performance.

OBJECTIVES: Cumulative, probability-based metrics are regularly used to measure quality in professional sports, but these methods have not been applied to health care delivery. These techniques have the potential to be particularly useful in describing surgical quality, where case volume is variable and outcomes tend to be dominated by statistical "noise". The established statistical technique used to adjust for differences in case volume is reliability-adjustment which emphasizes statistical "signal"but has several limitations. We sought to validate a novel measure of surgical quality based on earned outcomes methods (deaths above average, DAA) against reliability-adjusted mortality rates, using abdominal aortic aneurysm (AAA) repair outcomes to illustrate the measure's performance. METHODS: Earned outcomes methods were used to calculate the outcome of interest for each patient: deaths above average (DAA). Hospital-level DAA were calculated for non-ruptured open AAA repair and EVAR in the Vascular Quality Initiative (VQI) database from 2016-2019. DAA for each center is the sum of observed - predicted risk of death for each patient; predicted risk of death was calculated using established multivariable logistic regression modeling. Correlations of DAA with reliability-adjusted mortality rates and procedure volume were determined. Because an accurate quality metric should correlate with future results, outcomes from 2016-2017 were used to categorize hospital quality based on (1) risk-adjusted mortality, (2) risk- and reliability-adjusted mortality, and (3) DAA. The best performing quality metric was determined by comparing the ability of these categories to predict 2018-2019 risk-adjusted outcomes. RESULTS: During the study period, 3,734 patients underwent open repair (106 hospitals), and 20,680 patients underwent EVAR (183 hospitals). DAA was closely correlated with reliability-adjusted mortality rates for open repair (r=0.94, P<0.001) and EVAR (r=0.99, P<0.001). DAA also correlated with hospital case volume for open repair (r=-.54, P<0.001), but not EVAR (r=0.07, P=0.3). In 2016-2017, most hospitals had 0% mortality (55% open repair, 57% EVAR), making it impossible to evaluate these hospitals using traditional risk-adjusted mortality rates alone. Further, zero mortality hospitals in 2016-2017 did not demonstrate improved outcomes in 2018-2019 for open repair (3.8% vs 4.6%, P=0.5) or EVAR (0.8% vs 1.0%, P=0.2) compared to all other hospitals. In contrast to traditional risk-adjustment, 2016-2017 DAA evenly divided centers into quality quartiles which predicted 2018-2019 performance with increased mortality rate associated with each decrement in quality quartile (Q1 3.2%, Q2 4.0%, Q3 5.1%, Q4 6.0%). There was a significantly higher risk of mortality at worst quartile open repair hospitals compared to best quartile hospitals (OR 2.01, [95% CI 1.07-3.76], P=0.03). Using 2016-2019 DAA to define quality, highest quality quartile open repair hospitals had lower median DAA compared to lowest quality quartile hospitals (-1.18 DAA vs +1.32 DAA, P<0.001), correlating with lower median reliability-adjusted mortality rates (3.6% vs 5.1%, P<0.001). CONCLUSIONS: Adjustment for differences in hospital volume is essential when measuring hospital-level outcomes. Earned outcomes accurately categorize hospital quality and correlate with reliability-adjustment but are easier to calculate and interpret. From 2016-2019, highest quality open AAA repair hospitals prevented >40 perioperative deaths compared to the average hospital, and >80 perioperative deaths compared to lowest quality hospitals.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Evaluation of Computerized Tomography Utilization in Comparison to Digital Subtraction Angiography in Patients with Peripheral Arterial Disease.

BACKGROUND: Perform literature review to analyze current practices in imaging patient with peripheral arterial disease (PAD) and examine patterns in our practice in order to assess whether a lower extremity computed tomography angiography (CTA) in addition to digital subtraction angiography enhanced the assessment of vessel calcification, percentage of stenosis, and affected outcomes in patients with PAD. METHODS: The study included patients who underwent lower extremity imaging and were followed up to 12 months. This population was divided into cases who had both an angiogram and CTA performed within 30 days (n = 20), and controls who underwent angiography only (n = 19). Baseline characteristics, imaging results, and clinical outcomes were analyzed. RESULTS: Thirty-nine patients met study criteria (mean age was 58.4 years, 69.2% were males, and 33.3% had diabetes). Patients mostly presented with tissue loss/rest pain (10.3%), claudication (15.4%), acute limb (10.3%), and trauma (15.4%). We have not observed any statistically significant differences in various examined blood vessels when their features (e.g., vessel diameter, stenosis, calcifications) were assessed by CTA combined with angiography versus angiography alone. The exceptions were external iliac artery, superficial femoral artery and dorsalis pedis vessels. In external iliac artery percentage of stenosis was 1.11% as determined by computed tomography (CT) scan versus 30% by angiography (P = 0.009). For superficial femoral artery stenosis, the percentage determined by CT was 48.68% vs. 81.41% by angiography, and observed difference between 2 modalities was statistically significant (P = 0.025). For dorsalis pedis percentage of stenosis detected by CT scan was 60.63% vs. 22.73% by angiography, and the differences in findings by these modalities were statistically significant (P = 0.039). The most frequent perioperative complication was cardiac-related (35.5%). Nineteen patients were readmitted and 8 had reinterventions within 12 months. CONCLUSIONS: Both imaging modalities yielded similar results for assessing vessel calcification and percentage of stenosis regardless of anatomic vessel location. Overall, utilization of CTA in addition to angiography for large vessels above the knee (e.g., iliac artery, superficial femoral artery) and below the knee for dorsalis pedis provided more detailed information on the properties of these vessels. Therefore, during preoperative assessments, CTA may be helpful in addition to angiography for planning surgical and endovascular interventions for symptomatic PAD treatment in larger vessels.

"Evolution of Drug-Coated Devices for the Treatment of Chronic Limb Threatening Ischemia".

For patients with Chronic Limb Threatening Ischemia (CLTI), endovascular approaches to revascularization are often employed as a component of multimodality care aimed at limb preservation. However, patients with CLTI are also prone to treatment failure, particularly following balloon angioplasty alone. Drug-coated devices utilizing Paclitaxel were developed to decrease restenosis but have been primarily studied in patients presenting with claudication. In recent years, data have emerged which describe the efficacy of drug-coated devices in the treatment of patients with CLTI. Concurrently, there has been major controversy surrounding the use of drug-coated devices in peripheral arterial disease. A historical narrative of the development and use of drug-coated devices for peripheral arterial disease is presented, along with discussion of major trials. Evidence argues that paclitaxel-based therapies for peripheral arterial disease (PAD) do not increase mortality risk compared to nondrug-coated devices. In CLTI patients, paclitaxel-based balloons and stents provide superior patency and freedom reintervention compared to nondrug-coated devices when treating femoropopliteal disease. However, the use of Paclitaxel-based therapies for below-the-knee (BTK) interventions has not been shown to provide clinically meaningful outcomes compared to nondrug-based therapies. Newer generation antiproliferative agents (Sirolimus, Everolimus) and delivery systems (bioabsorbable scaffolds) hold promise for BTK interventions with early data suggesting decreased rates of major amputation or major adverse limb events.

Age-Related Food Aversion and Anxiety Represent Primary Patient Barriers to Food Oral Immunotherapy.

BACKGROUND: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective. OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians. METHODS: A survey in Canada and the United States involved families currently enrolled in food OIT programs. RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001). CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.

Cold-induced vasodilation during sequential immersions of the hand.

A common practice for those operating in cold environments includes repetitive glove doffing and donning to perform specific tasks, which creates a repetitive cycle of hand cooling and rewarming. This study aimed to determine the influence of intraday repeated hand cooling on cold-induced vasodilation (CIVD), sympathetic activation, and finger/hand temperature recovery. Eight males and two females (mean ± SD age: 28 ± 5 year; height: 181 ± 9 cm; weight: 79.9 ± 10.4 kg) performed two 30-min hand immersions in cold (4.3 ± 0.92 °C) water in an indoor environment (18 °C). Both immersions (Imm1; Imm2) were performed on the same day and both allowed for a 10-min recovery. CIVD components were calculated for each finger (index, middle, ring) during each immersion. CIVD onset time (index, p = 0.546; middle, p = 0.727; ring, p = 0.873), minimum finger temperature (index, p = 0.634; middle, p = 0.493; ring, p = 0.575), and mean finger temperature (index, p = 0.986; middle, p = 0.953; ring, p = 0.637) were all similar between immersions. Recovery rates generally demonstrated similar responses as well. Findings suggest that two sequential CIVD tests analyzing the effect of prior cold exposure of the hand does not impair the CIVD response or recovery. Such findings appear promising for those venturing into cold environments where hands are likely to be repeatedly exposed to cold temperatures.

Investigator attitudes on equipoise and practice patterns in the BEST-CLI trial.

OBJECTIVES: There has been significant variability in practice patterns and equipoise regarding treatment approach for chronic limb-threatening ischemia (CLTI). We aimed to assess treatment preferences of Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) investigators prior to and following the trial. METHODS: An electronic 60-question survey was sent to 1180 BEST-CLI investigators in 2022, after trial conclusion and before announcement of results. Investigators' preferences were assessed across clinical scenarios for both open (OPEN) and endovascular (ENDO) revascularization strategies. Vascular surgeon (VS) surgical and ENDO preferences were compared with a 2010 survey administered to prospective investigators before trial funding. RESULTS: For the 2022 survey, the response rate was 20.2% and was comprised of VSs (76.3%), interventional cardiologists (11.4%) and interventional radiologists (11.6%). The majority (72.6%) were in academic practice and 39.1% were in practice for >20 years. During initial CLTI work-up, 65.8%, 42.6%, and 55.9% of respondents always or usually ordered an arterial duplex, computed tomography angiography, and vein mapping, respectively. The most common practice distribution between ENDO and OPEN procedures was 70/30. Postoperatively, a majority reported performing routine duplex surveillance of vein bypass (99%), prosthetic bypass (81.9%), and ENDO interventions (86%). A minority reported always or usually using the wound, ischemia, and foot infection (WIfI) criteria (25.8%), GLASS (8.3%), and a risk calculator (14.8%). More than one-half (52.9%) agreed that the statement "no bridges are burned with an ENDO-first approach" was false. Intervention choice was influenced by availability of the operating room or ENDO suite, personal schedule, and personal skill set in 30.1%, 18.0%, and 45.9% of respondents, respectively. Most respondents reported routinely using paclitaxel-coated balloons (88.1%) and stents (67.5%); however, 73.3% altered practice when safety concerns were raised. Among surgeons, 17.8%, 2.9%, and 10.3% reported performing >10 annual alternative autogenous vein bypasses, composite vein composite vein bypasses, and bypasses to pedal targets, respectively. Among all interventionalists, 8%, 24%, and 8% reported performing >10 annual radial access procedures, pedal or tibial access procedures, and pedal loop revascularizations. The majority (89.1%) of respondents felt that CLTI teams improved care; however, only 23.2% had a defined team. The effectiveness of the teamwork at institutions was characterized as highly effective in 42.5%. When comparing responses by VSs to the 2010 survey, there were no changes in preferred treatment based on Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) II classification or conduit preference. In 2022, OPEN surgery was preferred more for a popliteal occlusion. For clinical scenarios, there were no differences except a decreased proportion of respondents who felt there was equipoise for major tissue loss for major tissue loss (43.8% vs 31.2%) and increased ENDO choice for minor tissue loss (17.6% vs 30.8%) (P < .05). CONCLUSIONS: There is a wide range of practice patterns among vascular specialists treating CLTI. The majority of investigators in BEST-CLI had experience in both advanced OPEN and ENDO techniques and represent a real-world sample of technical expertise. Over the course of the decade of the BEST-CLI trial, there was overall similar equipoise among VSs.

An expert panel's review on patients with hereditary angioedema switching from attenuated androgens to oral prophylactic therapy.

Background: Hereditary angioedema (HAE) is a rare condition marked by swelling episodes in various body parts, including the extremities, upper airway, face, intestinal tract, and genitals. Long-term prophylaxis (LTP), prescribed to control recurring HAE attacks, is integral to its management. Previously, attenuated androgens (AAs) were the only oral LTP options. However, in 2020, berotralstat, an oral plasma kallikrein inhibitor, was approved in the United States. A 2018 survey of adults with HAE type I or type II showed that almost all the patients who used prophylactic HAE medication preferred oral treatment (98%) and felt that it fit their lifestyle better than injectable treatment (96%). Still, guidelines lack consensus on transitioning patients from AAs to alternative oral prophylactic therapy. Objective: This paper aims to share expert insights and patient feedback on transitioning from AAs to berotralstat, an alternative oral prophylactic therapy, from the perspective of clinicians with extensive experience in treating patients with HAE. Methods: A panel of five HAE specialists convened for a virtual half-day roundtable discussion in April 2023. Results: Discussions about transitioning from AAs to berotralstat were prompted by routine consultations, patient inquiries based on independent research, ineffective current treatment, or worsening AA-related adverse effects. For patients who switched from AAs, the physicians reported that the decision was influenced by the alternative therapy's ability to prevent HAE attacks, its safety, and the once-daily administration schedule. All expert panel members identified fewer AA-related adverse effects; better quality of life; and less severe, shorter, and less frequent HAE attacks as clinical or patient goals they hoped to achieve through the treatment switch. Conclusion: The emergence of new, highly specific LTP drugs for HAE calls for the development of comprehensive recommendations and guidelines for transitioning from AAs to alternative oral prophylactic therapy. The expert panel highlighted key factors to consider during the development of such guidelines.

Prevalence of hypothermia and critical hand temperatures during military cold water immersion training.

Cold-weather military operations can quickly undermine warfighter readiness and performance. Specifically, accidental cold-water immersion (CWI) contributes to rapid body heat loss and impaired motor function. This study evaluated the prevalence of hypothermia and critical hand temperatures during CWI. One-hundred seventeen (N = 117) military personnel (mean ± SD age: 27 ± 6 yr, height: 176 ± 8 cm, weight: 81.5 ± 11.6 kg) completed CWI and rewarming during cold-weather training, which included a 10-min outdoor CWI (1.3 ± 1.4°C) combined with cold air (-4.2 ± 8.5°C) exposure. Following CWI, students removed wet clothing, donned dry clothing, and entered sleeping systems. Core (Tc) and hand (Thand) temperatures were recorded continuously during the training exercise. Tc for 96 students (mean ± SD lowest Tc = 35.6 ± 0.9°C) revealed that 24 students (25%) experienced Tc below 35.0°C. All of 110 students (100%) experienced Thand below 15.0°C, with 71 students (65%) experiencing Thand at or below 8.0°C. Loss of hand function and hypothermia should be anticipated in warfighters who experience CWI in field settings. Given the high prevalence of low Thand, focus should be directed on quickly rewarming hands to recover function.

Sensitivity and specificity of using exercise heart rate in a thermoneutral environment to predict heat tolerance status.

OBJECTIVES: Following heat illness, a return to activity may require passing a heat tolerance test (HTT). However, there are several logistical limitations to the widespread use of the HTT. Thus, it would be advantageous to develop a test that could be conducted in a thermoneutral (~22°C) environment to predict heat tolerance status. The purpose of the current study was to determine the sensitivity and specificity of using the criteria of a heart rate (HR) ≥130 bpm following 30 min of thermoneutral exercise in detecting heat-intolerant and heat-tolerant individuals. MATERIAL AND METHODS: Sixty-five subjects visited the lab on 3 separate days. The first visit consisted of completing a maximal oxygen uptake (VO2 max) test to assess cardiovascular fitness. For lab visits 2 and 3, subjects randomly completed a 2-hour walking treadmill test in either a hot (40°C, 40% relative humidity [RH]) or thermoneutral (22°C, 40% RH) environment. RESULTS: Forty-eight subjects were classified as heat-intolerant and 17 subjects as heat-tolerant. Using the criterion of a HR ≥130 bpm at 30 min of exercise in the thermoneutral environment, specificity (54%) and sensitivity (100%) of passing the HTT was calculated. Secondary analysis using multiple regression revealed 3 significant variables for predicting ending HR during the HTT. They were: 1) absolute VO2 max (l/min), 2) age, and 3) HR at 30 min of exercise during thermoneutral exercise. CONCLUSIONS: Exercise in a thermoneutral environment had a positive predictive value of 100%, thus, if a subject has a HR ≥130 bpm at 30 min of exercise in a thermoneutral environment, they are very likely to fail a subsequent 2-hour HTT in the heat and be classified as heat-intolerant. Therefore, prior screening has the potential to save time and money, along with providing safety to a heat-intolerant subject. Int J Occup Med Environ Health. 2023;36(2):192-200.

Thoracic endovascular aortic repair of metachronous thoracic aortic aneurysms following prior infrarenal abdominal aortic aneurysm repair.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) of metachronous thoracic aortic aneurysms (M-TAAs) following previous infrarenal abdominal aortic aneurysm (AAA) repair has been associated with higher spinal cord ischemia (SCI) risk compared with TEVAR of primary thoracic aortic aneurysms (TAAs). However, data on the impact of the type of prior infrarenal aortic repair on outcomes are scarce. In this study, we examined perioperative outcomes and long-term mortality following TEVAR M-TAA compared with primary TEVAR of TAA. METHODS: We identified all Vascular Quality Initiative (VQI) patients who underwent TEVAR of TAA in the descending thoracic aorta from 2013 to 2022. Only patients undergoing primary TEVAR or TEVAR following infrarenal open (OAR) or endovascular (EVAR) repair were included. We performed univariate analyses to identify differences in baseline and procedural characteristics, and multivariable analyses for perioperative outcomes and 5-year mortality using logistic and Cox regression, respectively. RESULTS: We included 1493 patients who underwent primary TEVAR (81%) or TEVAR following prior OAR (9.0%) or prior EVAR (9.7%). Compared with primary TEVAR, patients undergoing TEVAR M-TAA were older, more commonly male, white, and had higher rates of hypertension, smoking, and renal dysfunction. Patients with M-TAA were more likely to be asymptomatic and have larger diameters at presentation but were exposed to greater contrast volume and procedural times relative to primary TEVAR patients. Following risk-adjustment, compared with primary TEVAR, TEVAR after prior EVAR was associated with higher perioperative mortality (9.7% vs 3.9%; odds ratio [OR], 5.3; 95% confidence interval [CI], 2.3-12; P < .001) and 5-year mortality (40% vs 24%; hazard ratio [HR], 2.1; 95% CI, 1.4-3.1; P = .001). Specifically, among octogenarians (n = 375; 25%), the perioperative and 5-year mortality differences were even more pronounced (perioperative mortality: 17% vs 8.4%; OR, 6.7; 95% CI, 2.2-21; P = .001; 5-year mortality: 50% vs 27%; HR, 3.0; 95% CI, 1.5-5.7; P = .010). However, in-hospital complications, including SCI (2.6% vs 2.8%; OR, 1.2; 95% CI, 0.33-3.3; P = .77), were not notably different. In contrast, TEVAR after previous OAR was associated with comparable perioperative mortality (4.4% vs 3.9%; OR, 1.2; 95% CI, 0.32-3.8; P = .73), 5-year mortality (28% vs 24%; HR, 1.3; 95% CI, 0.80-2.1; P = .54), and in-hospital complications, including SCI (2.6% vs 0.7%; OR, 0.21; 95% CI, 0.01-1.1; P = .16). CONCLUSIONS: Patients undergoing TEVAR of M-TAAs after prior EVAR, particularly octogenarians, have higher perioperative and 5-year mortality and therefore, represent a high-risk group. Future efforts should strive to discern the underlying factors leading to these poorer outcomes; meanwhile, these findings emphasize the need for careful patient selection and appropriate preoperative counseling in these high-risk individuals.

Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor.

Hereditary angioedema (HAE) is a rare, chronic, and debilitating genetic disorder characterized by recurrent and unpredictable swelling episodes that primarily affect the subcutaneous and/or submucosal tissues of the extremities, larynx, face, abdomen, and genitals. Most cases of HAE are caused by mutations in the serpin family G member 1 gene (SERPING1), which encodes C1-esterase inhibitor (C1-INH) protein. Mutations in SERPING1 lead to deficient (type I HAE-C1-INH) or dysfunctional (type II HAE-C1-INH) C1-INH protein and subsequent dysregulation of the kallikrein-bradykinin cascade. However, some patients present with a third type of HAE (HAE-nI-C1-INH), which was first described in the year 2000 and is characterized by an absence of mutations in SERPING1. Although mutations in the coagulation factor XII, angiopoietin-1, plasminogen, kininogen-1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase-6 genes have been identified in some patients with HAE-nI-C1-INH, genetic cause is still unknown in many cases, hindering full elucidation of the pathology of this HAE subtype. Diagnosis of HAE-nI-C1-INH is also further complicated by the fact that patients typically demonstrate normal plasma levels of C1-INH and complement component 4 protein and normal C1-INH functionality during laboratory analysis. Therefore, we review the challenges associated with diagnosing, treating, and living with HAE-nI-C1-INH. We conclude that raising awareness of the presenting features of HAE-nI-C1-INH within the clinical setting and among the general public is critical to aid earlier suspicion and diagnosis of the disease. Furthermore, adopting an individualized approach to HAE-nI-C1-INH treatment is essential to help address the current and significant unmet needs in this patient population.

Symptomatic peripheral artery disease increases risk of perioperative mortality following open abdominal aortic aneurysm repair.

OBJECTIVE: Peripheral artery disease (PAD) is associated with worse survival following abdominal aortic aneurysm (AAA) repair. However, little is known about the impact of PAD and sex on outcomes following open infrarenal AAA repair (OAR). METHODS: All elective open infrarenal AAA cases were queried from the Society for Vascular Surgery Vascular Quality Initiative from 2003 to 2022. PAD was defined as history of non-cardiac arterial bypass, non-coronary percutaneous vascular intervention (PVI), or non-traumatic major amputation. Cohorts were stratified by sex and history of PAD. Multivariable logistic regression and Cox proportional hazards models were constructed to assess the primary endpoints: 30-day and 5-year mortality, respectively. RESULTS: Of 4910 patients who underwent elective OAR, 3421 (69.7%) were men without PAD, 298 (6.1%) were men with PAD, 1098 (22.4%) were women without PAD, and 93 (1.9%) were women with PAD. Men with PAD had prior bypass (45%), PVI (62%), and amputation (6.7%). Women with PAD had prior bypass (32%), PVI (76%), and amputation (5.4%). Thirty-day mortality was significantly higher in men with PAD compared with men without PAD (4.4% vs 1.7%; P = .001) and in women with PAD compared with women without PAD (7.5% vs 2.4%; P = .01). After risk adjustment, when compared with men without PAD, women with PAD had nearly four times the odds of 30-day mortality (odds ratio, 3.86; 95% confidence interval [CI], 1.55-9.64; P = .004) and men with PAD had almost three times the odds of 30-day mortality (odds ratio, 2.77; 95% CI, 1.42-5.40; P = .003). Five-year survival was 87.8% in men without PAD, 77.8% in men with PAD, 85% in women without PAD, and 76.2% in women with PAD (P < .001). After risk adjustment, only men with PAD had an increased hazard of death at 5 years (hazard ratio, 1.52; 95% CI, 1.07-2.17; P = .019) compared with men without PAD. CONCLUSIONS: PAD is a potent risk factor for increased perioperative mortality in both men and women following OAR. In women, this equates to nearly four times the odds of perioperative mortality compared with men without PAD. Future study evaluating risk/benefit is needed to determine if women with PAD reflect a high-risk cohort that may benefit from a more conservative OAR threshold for treatment.

Characterization and management of type II and complex endoleaks after fenestrated/branched endovascular aneurysm repair.

INTRODUCTION: Endoleaks are more common after fenestrated/branched endovascular aneurysm repair (F/B-EVAR) than infrarenal EVAR secondary to the length of aortic coverage and number of component junctions. Although reports have focused on type I and III endoleaks, less is known regarding type II endoleaks after F/B-EVAR. We hypothesized that type II endoleaks would be common and often complex (associated with additional endoleak types), given the potential for multiple inflow and outflow sources. We sought to describe the incidence and complexity of type II endoleaks after F/B-EVAR. METHODS: F/B-EVAR data prospectively collected at a single institution in an investigational device exemption clinical trial (G130210) were retrospectively analyzed (2014-2021). Endoleaks were characterized by type, time to detection, and management. Primary endoleaks were defined as those present on completion imaging or at first postoperative imaging, and secondary were those on subsequent imaging. Recurrent endoleaks were those that developed after a successfully resolved endoleak. Reinterventions were considered for type I or III endoleaks or any endoleak associated with sac growth >5 mm. Technical success defined as the absence of flow in the aneurysm sac at procedure conclusion and methods of intervention were captured. RESULTS: Among 335 consecutive F/B-EVARs (mean ± standard deviation follow-up: 2.5 ± 1.5 years), 125 patients (37%) experienced 166 endoleaks (81 primary, 72 secondary, and 13 recurrent). Of these 125 patients, 50 (40% of patients) underwent 71 interventions for 60 endoleaks. Type II endoleaks were the most frequent (n = 100, 60%), with 20 identified during the index procedure, 12 (60%) of which resolved before 30-day follow-up. Of the 100 type II endoleaks, 20 (20%; 12 primary, 5 secondary, and 3 recurrent) were associated with sac growth; 15 (75%) of those with associated sac growth underwent intervention. At intervention, 6 (40%) were reclassified as complex, with a concomitant type I or type III endoleak. Initial technical success for endoleak treatment was 96% (68 of 71). There were 13 recurrences, all of which were associated with complex endoleaks. CONCLUSIONS: Nearly half of the patients who underwent F/B-EVAR experienced an endoleak. The majority were classified as type II, with nearly a fifth associated with sac expansion. Interventions for a type II endoleak frequently led to reclassification as complex, with a concomitant type I or III endoleak not appreciated on computed tomography angiography and/or duplex. Further study is needed to determine if the primary treatment goal for complex aneurysm repair is sac stability or sac regression, as this would inform both the importance of properly classifying endoleaks noninvasively and the intervention threshold for managing type II endoleaks.

The association between diabetes mellitus and its management with outcomes following endovascular repair for descending thoracic aortic aneurysm.

OBJECTIVE: Prior literature is conflicted regarding the effect of diabetes mellitus (DM) on outcomes after endovascular repair of aortic aneurysms. In this study, we aimed to examine the association between DM and outcomes after thoracic endovascular aneurysm repair (TEVAR) for thoracic aortic aneurysm (TAA). METHODS: We identified patients who underwent TEVAR for TAA of the descending thoracic aorta in the Vascular Quality Initiative between 2014 and 2022. We created two cohorts, DM and nonDM, based on the patient's preoperative DM status, and secondarily substratified patients with DM by management strategy: dietary management, noninsulin medications, and insulin therapy cohorts. Outcomes included perioperative and 5-year mortality, in-hospital complications, indications for repair, and 1-year sac dynamics, which were analyzed with multivariable cox regression, multivariable logistic regression, and χ2 tests, respectively. RESULTS: We identified 2637 patients, of which 473 (18%) had DM preoperatively. Among patients with DM, 25% were diet controlled, 54% noninsulin medications, and 21% insulin therapy. Within patients who underwent TEVAR for TAA, the proportions of ruptured presentation were higher in the dietary-managed (11.1%) and insulin-managed (14.3%) cohorts relative to noninsulin therapy (6.6%) and those without DM (6.9%). After multivariable regression analysis, we found that DM was associated with similar perioperative mortality (odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.81) and 5-year mortality compared with patients without DM (hazard ratio, 1.15; 95% CI, 0.91-1.48). Furthermore, all in-hospital complications were comparable between patients with DM and patients without DM. Compared with patients without DM, dietary management of DM was significantly associated with higher adjusted perioperative mortality (OR, 2.16; 95% CI, 1.03-4.19) and higher 5-year mortality (hazad ratio, 1.50; 95% CI, 1.03-2.20), although this was not the case for other DM subgroups. All cohorts displayed similar 1-year sac dynamics, with sac regression occurring in 47% of patients without DM vs 46% of patients with DM (P = .27). CONCLUSIONS: Preoperatively, patients with DM who underwent TEVAR had a higher proportion of ruptured presentation when treated with diet or insulin medications than when treated with noninsulin medications. After TEVAR for descending TAA, DM was associated with a similar risk of perioperative and 5-year mortality as nonDM. In contrast, dietary therapy for DM was associated with significantly higher perioperative mortality and 5-year mortality.

The impact of completion and follow-up endoleaks on survival, reintervention, and rupture.

OBJECTIVE: Endoleaks may be seen at case completion of endovascular abdominal aortic aneurysm repair (EVAR), and the presence of an endoleak may impact outcomes. However, the clinical implications of various endoleaks seen during follow-up is not well-described. Therefore, we studied the impact of endoleaks at completion and at follow-up on mid-term outcomes. METHODS: We reviewed patients who underwent EVAR from 2003 to 2016 within the Vascular Quality Initiative-Medicare database and identified patients with endoleak at procedure completion and during follow-up, excluding those presenting with rupture. We stratified cohorts by presence of completion and follow-up endoleak subtypes. The primary outcome was 5-year survival, and secondary outcomes included 5-year freedom from reintervention and freedom from rupture. We used Kaplan-Meier estimates and log-rank tests to analyze differences in time-to-event endpoints. RESULTS: Of 21,745 patients with completion endoleak data, 5085 (23%) had an endoleak. Compared with those without endoleak, those with type I endoleaks had lower 5-year survival (69% vs 75%; P < .001), type II endoleaks had higher survival (79%; P < .001), and types III, IV, and indeterminate were not statistically different (73%, 73%, and 75%, respectively). Freedom from reintervention for types I and III endoleaks were significantly lower than no endoleak cohort (I: 76%; P < .001; III: 72%; P < .001 vs 83%), but freedom from rupture was higher for those with type II and III endoleak (95% and 97% vs 94%; P < .001). Of 14,479 patients with detailed follow-up endoleak data, 2290 (16%) had an endoleak. Compared with those without endoleak, types I and III had significantly lower 5-year survival (I: 80%; P = .002; III: 66%; P < .001 vs 84%), but there were no differences for types II (82%) and indeterminate (77%). Those with any type of follow-up endoleak had lower 5-year freedom from reintervention (I: 70%; P < .001; II: 76%; P = .006; III: 36%; P < .001; indeterminate: 60%; P = .007 vs 84%), and lower freedom from rupture (I: 92%; P < .001; II: 91%; P = .16; III: 88%; P = .01; indeterminate: 90%; P = .11 vs 94%). CONCLUSIONS: Compared with patients with no endoleak, those with type I completion endoleaks have lower 5-year survival and freedom from reintervention. Patients with types I and III follow-up endoleaks also have lower survival, and any endoleak at follow-up is associated with lower freedom from reintervention and freedom from rupture. These data highlight the importance of careful patient selection and close postoperative follow-up after EVAR, as the presence of endoleaks, specifically type I and III, over time portends worse outcomes.

Are frog calls relatively difficult to locate by mammalian predators?

Frogs call in acoustically dense choruses to attract conspecific females. Their calls can potentially reveal their location to predators, many of which are mammals. However, frogs and mammals have very different acoustic receivers and mechanisms for determining sound source direction. We argue that frog calls may have been selected so that they are harder to locate with the direction-finding mechanisms of mammals. We focus on interaural time delay (ITD) estimation using delay-line coincidence detection (place code), and a binaural excitatory/inhibitory (E/I) ITD mechanism found in mammals with small heads (population code). We identify four "strategies" which frogs may employ to exploit the weaknesses of either mechanism. The first two strategies used by the frog confound delay estimation to increase direction ambiguity using highly periodic calls or narrowband calls. The third strategy relies on using short pulses. The E/I mechanism is susceptible to noise with sounds being pulled to the medial plane when signal-to-noise ratio is low. Together, these three strategies compromise both ongoing and onset determination of location using either mechanism. Finally, frogs call in dense choruses using various means for controlling synchrony, maintaining chorus tenure, and abruptly switching off calling, all of which serve to confound location finding. Of these strategies, only chorusing adversely impacts the localization performance of frogs' acoustic receivers. We illustrate these strategies with an analysis of calls from three different frog species.