Spatial mapping of mitochondrial networks and bioenergetics in lung cancer.

Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells1. The mitochondria form highly organized networks, in which their outer and inner membrane structures define their bioenergetic capacity2,3. However, in vivo studies delineating the relationship between the structural organization of mitochondrial networks and their bioenergetic activity have been limited. Here we present an in vivo structural and functional analysis of mitochondrial networks and bioenergetic phenotypes in non-small cell lung cancer (NSCLC) using an integrated platform consisting of positron emission tomography imaging, respirometry and three-dimensional scanning block-face electron microscopy. The diverse bioenergetic phenotypes and metabolic dependencies we identified in NSCLC tumours align with distinct structural organization of mitochondrial networks present. Further, we discovered that mitochondrial networks are organized into distinct compartments within tumour cells. In tumours with high rates of oxidative phosphorylation (OXPHOSHI) and fatty acid oxidation, we identified peri-droplet mitochondrial networks wherein mitochondria contact and surround lipid droplets. By contrast, we discovered that in tumours with low rates of OXPHOS (OXPHOSLO), high glucose flux regulated perinuclear localization of mitochondria, structural remodelling of cristae and mitochondrial respiratory capacity. Our findings suggest that in NSCLC, mitochondrial networks are compartmentalized into distinct subpopulations that govern the bioenergetic capacity of tumours.

Publisher Correction: In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

Preoperative proteinuria is independently associated with mortality after fenestrated endovascular aneurysm repair.

OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) has become a mainstay in treating complex aortic aneurysms, though baseline patient factors predicting long-term outcomes remain poorly understood. Proteinuria is an early marker for chronic kidney disease and associated with adverse cardiovascular outcomes, but its utility in patients with aortic aneurysms is unknown. We aimed to determine whether preoperative proteinuria impacts long-term survival after FEVAR. METHODS: A single-institution, retrospective review of all elective FEVAR was performed. Preoperative proteinuria was assessed by urinalysis: negative (0-29 mg/dL), 1+ (30-100 mg/dL), 2+ (101-299 mg/dL), and 3+ (≥300 mg/dL). The cohort was stratified by patients with proteinuria (≥30 mg/dL) vs those without (<30 mg/dL). Baseline, perioperative, and long-term outcomes were compared. The primary outcome, all-cause mortality, was evaluated by Kaplan-Meier analysis and independent predictors with Cox proportional hazards modeling. RESULTS: Among 181 patients who underwent standard FEVAR from 2012 to 2022 (mean follow-up 33 months), any proteinuria was noted in 30 patients (16.6%). Patients with proteinuria were more likely to be Black (10.0% vs 1.3%) with a lower estimated glomerular filtration rate (eGFR) (52.7 ± 24.7 vs 67.7 ± 20.5 mL/min/1.73 m2), higher Society for Vascular Surgery comorbidity score (10.9 ± 4.3 vs 8.2 ± 4.7) and calcium channel blocker therapy (50.0% vs 29.1%), and larger maximal aneurysm diameter (67.2 ± 16.9 vs 59.8 ± 9.8 mm) (all P < .05). Thirty-day mortality was higher in the proteinuria group (10.0% vs 1.3%; P = .03). Overall survival at 1 and 5 years was significantly lower for those with proteinuria (71.5% vs 92.3% and 29.5% vs 68.1%; log-rank P < .001). On multivariable analysis, preoperative proteinuria was independently associated with over threefold higher hazard of mortality (hazard ratio [HR]: 3.21, 95% confidence interval [CI]: 1.66-6.20; P < .001), whereas preoperative eGFR was not predictive (HR: 0.99, 95% CI: 0.98-1.01; P = .28). Additional significant predictors included chronic obstructive pulmonary disease (HR: 2.04), older age (HR: 1.05), and larger maximal aneurysm diameter (HR: 1.03; all P < .05). CONCLUSIONS: In our 10-year experience with FEVAR, preoperative proteinuria was observed in 17% of patients and was significantly associated with worse survival. In this cohort, proteinuria was independently associated with all-cause mortality, whereas eGFR was not, suggesting that urinalysis may provide an additional simple metric for risk-stratifying patients before FEVAR.

Results of the North American Complex Abdominal Aortic Debranching (NACAAD) Registry.

BACKGROUND: Hybrid debranching repair of pararenal and thoracoabdominal aortic aneurysms was initially designed as a better alternative to standard open repair, addressing the limitations of endovascular repair involving the visceral aorta. We reviewed the collective outcomes of hybrid debranching repairs using extra-anatomic, open surgical debranching of the renal-mesenteric arteries, followed by endovascular aortic stenting. METHODS: Data from patients who underwent hybrid repair in 14 North American institutions during 10 years were retrospectively reviewed. Society of Vascular Surgery scores were used to assess comorbidity risk. Early and late outcomes, including mortality, morbidity, reintervention, and patency were analyzed. RESULTS: A total of 208 patients (118 male; mean age, 71±8 years old) were treated by hybrid repair with extraanatomic reconstruction of 657 renal and mesenteric arteries (mean 3.2 vessels/patient). Mean aneurysm diameter was 6.6±1.3 cm. Thoracoabdominal aortic aneurysms were identified in 163 (78%) patients and pararenal aneurysms in 45 (22%). A single-stage repair was performed in 92 (44%) patients. The iliac arteries were the most common source of inflow (n=132; 63%), and most (n=150; 72%) had 3 or more bypasses. There were 30 (14%) early deaths, ranging widely across sites (0%-21%). A Society of Vascular Surgery comorbidity score >15 was the primary predictor of early mortality (P<0.01), whereas mortality was 3% in a score ≤9. Early complications occurred in 140 (73%) patients and included respiratory complications in 45 patients (22%) and spinal cord ischemia in 22 (11%), of whom 10 (45%) fully recovered. At 5 years, survival was 61±5%, primary graft patency was 90±2%, and secondary patency was 93±2%. The most significant predictor of late mortality was renal insufficiency (P<0.0001). CONCLUSIONS: Mortality after hybrid repair and visceral debranching is highly variable by center, but strongly affected by preoperative comorbidities and the centers' experience with the technique. With excellent graft patency at 5 years, the outcomes of hybrid repair done at centers of excellence and in carefully selected patients may be comparable (or better) than traditional open or even totally endovascular approaches. However, in patients already considered as high-risk for surgery, it may not offer better outcomes.

Impact of gut microbiota on liver transplantation.

The gut microbiota has been gaining attention due to its interactions with the human body and its role in pathophysiological processes. One of the main interactions is the "gut-liver axis," in which disruption of the gut mucosal barrier seen in portal hypertension and liver disease can influence liver allograft function over time. For example, in patients who are undergoing liver transplantation, preexisting dysbiosis, perioperative antibiotic use, surgical stress, and immunosuppressive use have each been associated with alterations in gut microbiota, potentially impacting overall morbidity and mortality. In this review, studies exploring gut microbiota changes in patients undergoing liver transplantation are reviewed, including both human and experimental animal studies. Common themes include an increase in Enterobacteriaceae and Enterococcaceae species and a decrease in Faecalibacterium prausnitzii and Bacteriodes, while a decrease in the overall diversity of gut microbiota after liver transplantation.

Five-year outcomes from a prospective, multicenter study of endovascular repair of iliac artery aneurysms using an iliac branch device.

OBJECTIVE: We have reported the 5-year results of a pivotal prospective, multicenter study conducted in the United States of a specifically designed iliac branch endoprosthesis (IBE; W.L. Gore & Associates, Flagstaff, AZ) for endovascular repair of aortoiliac aneurysms and common iliac artery aneurysms. METHODS: A total of 63 patients (98.4% male; mean age, 70 years) with aortoiliac or common iliac artery aneurysms had undergone implantation of a single IBE device and a bifurcated aortoiliac stent graft. Patients with bilateral common iliac artery aneurysms (n = 22; 34.9%) had undergone either staged occlusion or surgical revascularization of the contralateral internal iliac artery before study enrollment. At 5 years, 36 of the 63 patients had completed the final study follow-up examinations, including clinical examinations (n = 35) and computed tomography (n = 32), with the results evaluated by an independent core laboratory and adverse events adjudicated by a clinical events committee. RESULTS: At 5 years, freedom from all-cause mortality was 85.7% and freedom from aneurysm-related mortality was 100%. The nine deaths that had occurred (range, 132-1898 days) were adjudicated as unrelated to the aneurysm or procedure. Primary patency of the internal and external iliac artery IBE limbs was 95.1% and 100%, respectively. No patients had experienced new-onset buttock claudication on the IBE side or self-reported new-onset erectile dysfunction. The common iliac artery diameter on the IBE side was either unchanged or had decreased by ≥5 mm in 30 of the 31 patients (96.8%) with a baseline (1 month) and 5-year (range, 1641-2006 days) computed tomography scan available. Of the 31 evaluable patients, 9 (29.0%) had had an increase of ≥5 mm in the aortic diameter, 5 of whom had had a concurrent type II endoleak. No type I or type III endoleaks or device migration were identified by the core laboratory. Six patients had undergone eight secondary interventions, including five interventions for a type II endoleak. The freedom from secondary intervention was 90.5%. CONCLUSIONS: The 5-year results of our prospective, multicenter study have confirmed the safety, efficacy, and durability of the IBE device for the treatment of aortoiliac and iliac artery aneurysms. The device effectively prevented common iliac artery aneurysm rupture, maintained the patency of the internal iliac artery, and avoided the complications associated with internal iliac artery sacrifice. Although common iliac artery aneurysm enlargement was rare, abdominal aortic enlargement was more common, suggesting that the outcomes of endovascular aneurysm repair might be different for patients with or without associated common iliac artery aneurysms.

Utilizing remote access for electronic medical records reduces overall electronic medical record time for vascular surgery residents.

OBJECTIVE: Survey data suggests that surgical residents spend 20% to 30% of training time using the electronic medical record (EMR), raising concerns about burnout and insufficient operative experience. We characterize trainee EMR activity in the vascular surgery service of a quaternary care center to identify modifiable factors associated with high EMR use. METHODS: Resident activity while on the vascular surgery service was queried from the EMR. Weekends and holidays were excluded to focus on typical staffing periods. Variables including daily time spent, post-graduate year (PGY), remote access via mobile device or personal laptop, and patient census including operative caseload were extracted. Univariate analysis was performed with t tests and χ2 tests where appropriate. We then fit a linear mixed-effects model with normalized daily EMR time as the outcome variable, random slopes for resident and patient census, and fixed effects of PGY level, academic year, and fractional time spent using remote access. RESULTS: EMR activity for 53 residents from July 2015 to June 2019 was included. The mean daily EMR usage was 1.6 hours, ranging from 3.6 hours per day in PGY1 residents to 1.1 hours in PGY4 to 5 residents. Across all PGYs, the most time-consuming EMR activities were chart review (43.0%-46.6%) and notes review (22.4%-27.0%). In the linear mixed-effects model, increased patient census was associated with increased daily EMR usage (Coefficient = 0.61, P-value < .001). Resident seniority (Coefficient = -1.2, P-value < .001) and increased remote access (Coefficient = -0.44, P-value < .001) were associated with reduced daily EMR usage. Over the study period, total EMR usage decreased significantly from the 2015/2016 academic year to the 2018/2019 academic year (mean difference, 2.4 hours vs 1.78; P-value < .001). CONCLUSIONS: In an audit of EMR activity logs on a vascular surgery service, mean EMR time was 1.6 hours a day, which is lower than survey estimates. Resident seniority and remote access utilization were associated with reduced time spent on the EMR, independent of patient census. Although increasing EMR accessibility via mobile devices and personal computers have been hypothesized to contribute to poor work-life balance, our study suggests a possible time-saving effect by enabling expedient access for data review, which constitutes the majority of resident EMR activity. Further research in other institutions and specialties is needed for external validation and exploring implications for resident wellness initiatives.

Most privately insured patients do not receive federally recommended abdominal aortic aneurysm screening.

OBJECTIVE: Since 2005, the United States Preventative Services Task Force has recommended abdominal aortic aneurysm (AAA) ultrasound screening for 65- to 75-year-old male ever-smokers. Integrated health systems such as Kaiser Permanente and the Veterans Affairs (VA) health care system report 74% to 79% adherence, but compliance rates in the private sector are unknown. METHODS: The IBM Marketscan Commercial and Medicare Supplemental databases (2006-2017) were queried for male ever-smokers continuously enrolled from age 65 to 75 years. Exclusion criteria were previous history of AAA, connective tissue disorder, and aortic surgery. Patients with abdominal computed tomographic or magnetic resonance imaging from ages 65 to 75 years were also excluded. Screening was defined as a complete abdominal, retroperitoneal, or aortic ultrasound. A logistic mixed-effects model utilizing state as a random intercept was used to identify patient characteristics associated with screening. RESULTS: Of 35,154 eligible patients, 13,612 (38.7%) underwent screening. Compliance varied by state, ranging from 24.4% in Minnesota to 51.6% in Montana (P < .05). Screening activity increased yearly, with 0.7% of screening activity occurring in 2008 vs 22.2% in 2016 (P <.05). In a logistic mixed-effects model adjusting for state as a random intercept, history of hypertension (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.13), coronary artery disease (OR, 1.17; 95% CI, 1.10-1.22), congestive heart failure (OR, 1.14; 95% CI, 1.01-1.22), diabetes (OR, 1.1; 95% CI, 1.06-1.16), and chronic kidney disease (OR, 1.4; 95% CI, 1.24-1.53) were associated with screening. Living outside of a census-designated metropolitan area was negatively associated with screening (OR, 0.92; 95% CI, 0.87-0.97). CONCLUSIONS: In a private claims database representing 250 million claimants, 38.7% of eligible patients received United States Preventative Services Task Force-recommended AAA screening. Compliance was nearly one-half that of integrated health systems and was significantly lower for patients living outside of metropolitan areas. Efforts to improve early detection of AAA should include targeting non-metropolitan areas and modifying Medicare reimbursement and incentivization strategies to improve guideline adherence.

Female sex is independently associated with reduced inpatient mortality after endovascular repair of blunt thoracic aortic injury.

BACKGROUND: Female sex has been associated with decreased mortality after blunt trauma, but whether sex influences the outcomes of thoracic endovascular aortic repair (TEVAR) for traumatic blunt thoracic aortic injury (BTAI) is unknown. METHODS: In this retrospective study of a prospectively maintained database, the Vascular Quality Initiative registry was queried from 2013 to 2020 for patients undergoing TEVAR for BTAI. Univariate Student's t-tests and χ2 tests were performed, followed by multivariate logistic regression for variables associated with inpatient mortality. RESULTS: Of 806 eligible patients, 211 (26.2%) were female. Female patients were older (47.9 vs 41.8 years, P < .0001) and less likely to smoke (38.3% vs 48.2%, P = .044). Most patients presented with grade III BTAI (54.5% female, 53.6% male), followed by grade IV (19.0% female, 19.5% male). Mean Injury Severity Scores (30.9 + 20.3 female, 30.5 + 18.8 male) and regional Abbreviated Injury Score did not vary by sex. Postoperatively, female patients were less likely to die as inpatients (3.8% vs 7.9%, P = .042) and to be discharged home (41.4% vs 52.2%, P = .008). On multivariate logistic regression, female sex (odds ratio [OR]: 0.05, P = .002) was associated with reduced inpatient mortality. Advanced age (OR: 1.06, P < .001), postoperative transfusion (OR: 1.05, P = .043), increased Injury Severity Score (OR: 1.03, P = .039), postoperative stroke (OR: 9.09, P = .016), postoperative myocardial infarction (OR: 9.9, P = .017), and left subclavian coverage (OR: 2.7, P = .029) were associated with inpatient death. CONCLUSIONS: Female sex is associated with lower odds of inpatient mortality after TEVAR for BTAI, independent of age, injury severity, BTAI grade, and postoperative complications. Further study of the influence of sex on postdischarge outcomes is needed.

Reverse Cheese-Wire Septotomy to Create a Distal Landing Zone for Thoracic Endovascular Aortic Repair.

PURPOSE: The objective of this study is to describe a novel method for creating a distal landing zone for thoracic endovascular aortic repair (TEVAR) in chronic aortic dissection. The technique is described in a patient with prior total arch and descending aortic replacement, with false lumen expansion. TECHNIQUE: A cheese-wire endovascular septotomy was desired to create a single lumen above the celiac axis. To avoid dividing the septum caudally across the visceral segment, we performed a modified septotomy in a cephalad direction. Stiff wires were passed into the prior surgical graft, through true lumen on the right and false lumen on the left. An additional wire was passed across an existing fenestration at the level of the celiac axis, and snared and externalized. 7F Ansel sheaths were advanced and positioned tip-to-tip at the fenestration. Using the stiff wires as tracks, the through-wire was pushed cephalad to endovascularly cut the septum. Angiogram demonstrated successful septotomy, and TEVAR was performed to just above the celiac with successful aneurysm exclusion and no endoleak or retrograde false lumen perfusion. Follow-up computed tomography angiogram (CTA) showed continued exclusion without false lumen perfusion. CONCLUSIONS: This novel modification in a reverse direction provides an alternative method for endovascular septotomy, when traditional septotomy may threaten the visceral vessels.

Cardiac Pulsatile Helical Deformation of the Thoracic Aorta Before and After Thoracic Endovascular Aortic Repair of Type B Dissections.

PURPOSE: Type B aortic dissections propagate with either achiral (nonspiraling) or right-handed chiral (spiraling) morphology, have mobile dissection flaps, and are often treated with thoracic endovascular aortic repair (TEVAR). We aim to quantify cardiac-induced helical deformation of the true lumen of type B aortic dissections before and after TEVAR. MATERIAL AND METHODS: Retrospective cardiac-gated computed tomography (CT) images before and after TEVAR of type B aortic dissections were used to construct systolic and diastolic 3-dimensional (3D) surface models, including true lumen, whole lumen (true+false lumens), and branch vessels. This was followed by extraction of true lumen helicity (helical angle, twist, and radius) and cross-sectional (area, circumference, and minor/major diameter ratio) metrics. Deformations between systole and diastole were quantified, and deformations between pre- and post-TEVAR were compared. RESULTS: Eleven TEVAR patients (59.9±4.6 years) were included in this study. Pre-TEVAR, there were no significant cardiac-induced deformations of helical metrics; however, post-TEVAR, significant deformation was observed for the true lumen proximal angular position. Pre-TEVAR, cardiac-induced deformations of all cross-sectional metrics were significant; however, only area and circumference deformations remained significant post-TEVAR. There were no significant differences of pulsatile deformation from pre- to post-TEVAR. Variance of proximal angular position and cross-sectional circumference deformation decreased after TEVAR. CONCLUSION: Pre-TEVAR, type B aortic dissections did not exhibit significant helical cardiac-induced deformation, indicating that the true and false lumens move in unison (do not move with respect to each other). Post-TEVAR, true lumens exhibited significant cardiac-induced deformation of proximal angular position, suggesting that exclusion of the false lumen leads to greater rotational deformations of the true lumen and lack of true lumen major/minor deformation post-TEVAR means that the endograft promotes static circularity. Population variance of deformations is muted after TEVAR, and dissection acuity influences pulsatile deformation while pre-TEVAR chirality does not. CLINICAL IMPACT: Description of thoracic aortic dissection helical morphology and dynamics, and understanding the impact of thoracic endovascular aortic repair (TEVAR) on dissection helicity, are important for improving endovascular treatment. These findings provide nuance to the complex shape and motion of the true and false lumens, enabling clinicians to better stratify dissection disease. The impact of TEVAR on dissection helicity provides a description of how treatment alters morphology and motion, and may provide clues for treatment durability. Finally, the helical component to endograft deformation is important to form comprehensive boundary conditions for testing and developing new endovascular devices.

Review of pediatric combined heart-liver transplantation: A roadmap to success.

BACKGROUND: Combined heart-liver transplantation (CHLT) is a promising technique to address end stage organ failure in patients with concomitant heart failure and chronic liver disease. While most experience with CHLT has involved adult patients, the expanding population of children born with univentricular congenital heart disease who underwent the Fontan procedure and develop Fontan-associated liver disease (FALD) has emerged as a growing indication for pediatric CHLT. METHODS: Currently, CHLT is performed at a select subset of experienced transplant centers, especially in the pediatric population. RESULTS: While technically demanding, CHLT may offer survival benefit when compared to heart transplant alone with decreased rejection of both synchronous allografts and equivalent outcomes with respect to waitlist time and post-operative complications. Limitations in the technique can be attributed to need for an appropriate multidisciplinary care center, challenges with donor organ availability and allocation, and the complexity associated with patient selection and peri-operative management. CONCLUSION: In this review, we summarize the history of CHLT, discuss patient selection, and highlight key facets of peri-operative care in the pediatric population.

Endovascular aortic arch repair with chimney technique for pseudoaneurysm.

BACKGROUND: Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones. METHODS: A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter. RESULTS: The median age of 32 patients was 68.0 years (range, 28-81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred. CONCLUSION: For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.

Precocious Rupture of Abdominal Aortic Aneurysms Below Size Criteria for Repair: Risk Factors and Outcomes.

BACKGROUND: Practice guidelines recommend elective repair for abdominal aortic aneurysms (AAAs) ≥ 5.5 cm in men and ≥ 5 cm in women to prevent rupture; however, some rupture at smaller diameters. We identify risk factors for rupture AAA (rAAA) below this threshold and compare outcomes following rAAA repair above/below size criteria. METHODS: The Vascular Quality Initiative (2013-2019) was queried for patients undergoing repair for rAAA and stratified based on diameter into small and large cohorts [Small: < 5.5 cm (men), < 5.0 cm (women)]. Univariate analysis was performed, and Kaplan-Meier analysis compared overall survival, aneurysm-related mortality, and reintervention at 12 months. RESULTS: Five thousand one hundred sixty two rAAA were identified. Small rAAA patients [n = 588] were more likely to have hypertension (81.3% vs. 77.0%, P < 0.02), diabetes (18.2% vs. 14.9%, P < 0.04), and end-stage renal disease (2.9% vs. 0.9%, P < 0.01) and be on optimal medical therapy (32.1% vs. 26.8%, P < 0.01). Women were more likely to rupture at smaller diameters compared to men (P < 0.01). Small rAAA patients were more likely to undergo endovascular aortic repair (EVAR) (70.2% vs. 56.0%, P < 0.01) and had lower in-hospital mortality (17.7% vs. 27.7%, P < 0.01) and fewer perioperative complications across all categories. At 12 months, small rAAA patients had better overall survival, freedom from aneurysm-related mortality, and freedom from reintervention, largely driven by EVAR approach. CONCLUSIONS: More than 11% of patients presenting with ruptured AAA were below the recommended size threshold for repair, and they tended to be younger, non-White, and have hypertension, diabetes, and/or renal failure. Patients with small rAAA experienced lower in-hospital morbidity and mortality and improved 1-year survival, and EVAR was associated with better outcomes than open repair. However, women more frequently rupture at smaller diameters compared to men. Given contemporary elective outcomes for women, a randomized controlled trial for EVAR versus surveillance at a sex-specific size threshold is needed.

Association of Baseline Chronic Kidney Disease Stage With Short- and Long-Term Outcomes After Fenestrated Endovascular Aneurysm Repair.

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) is a well-established treatment approach for juxtarenal and short-neck infrarenal aortic aneurysms. Recommendations and clinical outcomes are lacking for offering FEVAR in patients with chronic kidney disease (CKD). We aimed to compare short- and long-term outcomes for patients with none-to-mild versus moderate-to-severe CKD undergoing FEVAR. METHODS: We retrospectively reviewed consecutive patients undergoing standard FEVAR with Cook devices at a single institution. The cohort was stratified by preoperative CKD stage none-to-mild or moderate-to-severe (CKD 1-2 and CKD 3-5, respectively). The primary outcome was postoperative acute kidney injury (AKI). Secondary outcomes included 30-day perioperative complications, 1- and 5-year rates of overall survival, dialysis, renal target artery patency, endoleak, and reintervention assessed by the Kaplan-Meier method. Aneurysm sac regression, number of surveillance computed tomography (CT) scans, and CKD stage progression were assessed at latest follow-up. Multivariate Cox proportional hazards modeling was used to evaluate the association of CKD stage 3 and stage 4-5 with all-cause mortality, controlling for differences in baseline characteristics. RESULTS: From 2012- to 2022, 184 patients (of which 82% were male) underwent FEVAR with the Cook ZFEN device (mean follow-up 34.3 months). Group CKD 3-5 comprised 77 patients (42%), was older (75.2 vs. 73.0 years, P = 0.04), had increased preoperative creatinine (1.6 vs. 0.9 mg/dL, P < 0.01), and demonstrated increased renal artery ostial calcification (37.7% vs. 21.5%, P = 0.02) compared with Group CKD 1-2. Perioperatively, CKD 3-5 sustained higher estimated blood loss (342 vs. 228 ml, P = 0.01), longer operative times (186 vs. 162 min, P = 0.04), and longer length of stay (3 vs. 2 days, P < 0.01). Kaplan-Meier 1- and 5-year survival estimates were lower for CKD 3-5 (82.3% vs. 95.1%, P < 0.01 and 55.4% vs. 70.8%, P = 0.02). Fewer CKD 3-5 patients remained free from chronic dialysis at 1 year (94.4% vs. 100%, P = 0.015) and 5 years (84.7% vs. 100%, P < 0.01). There were no significant differences in postoperative AKI rate (CKD 1-2 6.5% vs. CKD 3-5 14.3%, P = 0.13), long-term renal artery patency, reinterventions, type I or III endoleak, mean sac regression, or total follow-up CT scans between groups. CKD stage progression occurred in 47 patients (31%) at latest follow-up but did not differ between stratified groups (P = 0.17). On multivariable modeling, age (hazard ratio 1.05, 95% confidence interval 1.01-1.09, P = 0.02) and CKD stage 4-5 (hazard ratio 6.39, 95% confidence interval 2.26-18.05, P < 0.01) were independently associated with mortality. CONCLUSIONS: Preoperative CKD status did not negatively impact the durability or technical success related to aneurysm outcomes after FEVAR. Worsening CKD stage was associated with lower 1- and 5-year overall survival and freedom from dialysis after FEVAR with no statistically significant differences in 30-day or long-term technical aneurysm outcomes.

Impact of renal chimney intra-aortic stent length on branch and end-stent angle in chimney endovascular aneurysm repair and endovascular aneurysm sealing configurations.

OBJECTIVE: Practice patterns and durability of parallel stent graft techniques in complex endovascular aneurysm repair (EVAR) remain poorly defined. We aimed to quantify and compare the impact of renal chimney intra-aortic stent length (IASL) on geometric deformations of renal arteries in complex EVAR. METHODS: Thirty-eight nonconsecutive patients underwent EVAR utilizing parallel stent graft techniques (chimney EVAR [chEVAR], n = 28; chimney endovascular aneurysm sealing [chEVAS], n = 10) between 2010 and 2016. A total of 59 renal chimney stent grafts were used. Geometric quantification was derived from three-dimensional model-based centerline extraction. Renal chimney intra-aortic stent length (IASL) was defined as the length of chimney stent that extended from the proximal edge of the chimney stent to the ostium of the corresponding renal artery. RESULTS: Mean IASL for both left and right renal arteries in the cohort was 35.7 mm. Renal arteries containing chimney IASL <30 mm trended toward a greater branch angle (135.4 vs. 127.8°, p = .06). Left renal arteries showed significantly greater branch angle among those with IASL <40 mm (135.5 vs. 121.7°, p = .045). Mean IASL for renal arteries in chEVAR was significantly longer compared to chEVAS (39.2 vs. 26.3 mm, p = .003). No difference was noted in overall branch angle or end-stent angle based on procedure type. ChEVAR with IASL <30 mm had significantly greater end-stent angle (48.2 vs. 33.5°, p = .03). In contrast, chEVAS patients showed no difference in end-stent angle based on IASL thresholds, but did have significantly greater branch angle among those with IASL <30 mm when grouped by both all renal arteries (133.5 vs. 113.5°, p = .004) and right renal arteries (134.3 vs. 111.6°, p = .02). CONCLUSIONS: Renal chimney stents with longer IASL appear to exhibit less renal artery deformation, suggesting a more gradual and perpendicular transition of the chimney stent across the renal ostium.

Neurogenic Thoracic Outlet Syndrome in Division 1 Collegiate Athletes: Presentation, Diagnosis, and Treatment.

OBJECTIVE: Athletes who engage in repetitive upper-extremity exercise are susceptible to neurogenic thoracic outlet syndrome (nTOS). We sought to identify typical presenting symptoms and common findings on diagnostic workup, in addition to evaluating rates of return to play following various treatment interventions. DESIGN: Retrospective chart review. SETTING: Single institution. PARTICIPANTS: Medical records of Division 1 athletes containing the diagnosis of nTOS between the years 2000 and 2020 were identified. Athletes with arterial or venous thoracic outlet syndrome were excluded. INDEPENDENT VARIABLES: Demographics, sport, participation status, clinical presentation, physical examination findings, diagnostic workup, and treatments provided. MAIN OUTCOME MEASURES: Rate of return to play (RTP) to collegiate athletics. RESULTS: Twenty-three female and 13 male athletes were diagnosed and treated for nTOS. Digit plethysmography showed diminished or obliterated waveforms with provocative maneuvers in 23 of 25 athletes. Forty-two percent were able to continue competing despite symptoms. Of the athletes who were initially unable to compete, 12% returned to full competition after physical therapy alone, 42% of those remaining were able to RTP after botulinum toxin injection, and an additional 42% of the remaining athletes RTP after thoracic outlet decompression surgery. CONCLUSIONS: Many athletes diagnosed with nTOS will be able to continue competing despite symptoms. Digit plethysmography is a sensitive diagnostic tool for nTOS to document anatomical compression at the thoracic inlet. Botulinum toxin injection had a significant positive effect on symptoms and a high rate of RTP (42%), allowing numerous athletes to avoid surgery and its prolonged recovery and associated risks. CLINICAL RELEVANCE: This study demonstrates that botulinum toxin injection had a high rate of return to full competition in elite athletes without the risks and recovery needed for surgical intervention, suggesting that this may be a good intervention especially among elite athletes who only experience symptoms with sport-related activities.

Impact of Scalene Muscle Botulinum Toxin Injection With and Without Surgery in Neurogenic Thoracic Outlet Syndrome.

OBJECTIVE: Scalene blocks are part of both the diagnostic and treatment algorithm for patients presenting with symptoms of neurogenic thoracic outlet syndrome (nTOS). However, there is a paucity of data on the utility of scalene botulinum toxin injection (BTI) before surgical decompression. We sought to determine the impact of BTI with and without surgery at a multidisciplinary referral center. DESIGN: Retrospective cohort study. SETTING: Single institution tertiary academic center, 2011 to 2020. PATIENTS: Seventy-seven consecutive patients. INTERVENTIONS: Scalene muscle BTI for nTOS with or without surgical decompression. MAIN OUTCOME MEASURES: Pain relief and Quick Disability of the Arm, Shoulder and Hand (QDASH) score. RESULTS: Seventy-seven patients, with a mean age of 31.4 years, had BTI for symptoms of nTOS. All patients underwent pretreatment physical therapy through the Edgelow protocol for a mean duration of 3.4 months. However, 72.7% had dynamic vascular compression on duplex ultrasound with provocative maneuvers and 85.7% had a positive physical examination finding. After BTI, 77.9% reported subjective relief, confirmed by an improved QDASH disability score. Thirty-one patients (40.3%) then went on to have further persistent symptoms and proceeded with first rib resection. After BTI + Surgery, 96.8% reported symptomatic relief and had a median QDASH score improvement of 21 (range: 10-40), with all reaching minimal clinically important differences in the QDASH score after combination therapy. CONCLUSIONS: In this reported series of chemodenervation in patients with nTOS, BTI is helpful in alleviating symptoms before definitive surgical decompression. BTI followed by first rib resection provides additional symptom improvement over BTI alone.

Predictors of sac regression after fenestrated endovascular aneurysm repair.

OBJECTIVE: Aneurysm sac regression after standard endovascular aortic repair is associated with improved outcomes, but similar data are limited after fenestrated endovascular aortic repair (FEVAR). We sought to evaluate sac regression after FEVAR, and identify any predictors of this favorable outcome. METHODS: Patients undergoing elective FEVAR using the commercially available Zenith Fenestrated device (ZFEN; Cook Medical, Bloomington, IN) from 2012 to 2018 at a single institution were reviewed retrospectively. The maximal aortic diameter was compared between the preoperative scan and those obtained in follow-up. Patients with of 5 mm or more sac regression were included in the regression (REG) group, with all others in the nonregression (NONREG) group. Outcomes were compared between groups using univariate analysis, and logistic regression analysis was performed to identify any predictive factors for sac regression. RESULTS: We included 132 patients undergoing FEVAR in the analysis. At a mean follow-up of 33.1 months, 65 patients (49.2%) had sac regression of 5 mm or more and comprised the REG group (n = 65 [49.2%]). The REG group had smaller diameter devices, and were less likely to have had concomitant chimney grafts placed (P < .05). The NONREG group had a higher incidence of type II endoleak (35.8% vs 12.3%; P = .002). Sac regression was associated with a significant mortality benefit on Kaplan-Meier analysis (log rank P = .02). Multivariate analysis identified adjunctive parallel grafting (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.03-0.36; P < .01), persistent type II endoleak (OR, 0.13; 95% CI, 0.02-0.74; P < .01), and a greater number of target vessels (OR, 0.25; 95% CI, 0.10-0.62; P = .002) as independent predictors of failure to regress. CONCLUSIONS: Sac regression after FEVAR occurred in nearly one-half of patients, but seems to be less common in patients with persistent type II endoleaks and those undergoing concomitant parallel grafting. Sac regression was associated with a significant survival advantage, and can be used as a clinical marker for success after FEVAR.