Descending thoracic aortic mural ulceration is associated with postoperative spinal cord ischemia after branched endovascular aortic aneurysm repair.

OBJECTIVE: Paraplegia is one of the most feared complications after thoracoabdominal aortic aneurysm repair. The purpose of this study is to determine whether aortic thrombus characteristics are associated with spinal cord ischemia (SCI) after branched endovascular aneurysm repair (BEVAR). METHODS: From April 2011 to April 2020, 62 patients underwent elective BEVAR for thoracoabdominal aortic aneurysm and pararenal aortic aneurysms using a low-profile device and had a complete preoperative computed tomography angiography of the aorta from the sinotubular junction to the aortic bifurcation. Aortic thrombus was evaluated for thrombus thickness ≥5 mm, thrombus >2/3 of aortic circumference, and the presence of an ulcer-like thrombus. One point was assigned at each 5 mm axial image if all 3 criteria were met, resulting in a total "shaggy score" for the entire aorta. Data on demographics, procedural details, and outcomes were collected prospectively. All patients underwent a standard spinal cord protection protocol, including routine cerebrospinal fluid drainage. In July 2016, an insulin infusion protocol (IIP) was initiated to maintain postoperative blood glucose levels <120 mg/dL for 48 hours. The primary clinical end point was postoperative SCI. RESULTS: 10 (16%) patients developed postoperative SCI: 6 with transient paraparesis, 2 with persistent paraparesis, and 2 with persistent paraplegia. Patients with SCI were older, had higher shaggy scores, and were less likely to have been on an IIP. There were no significant differences in demographics, aneurysm type, or operative parameters. In a logistic multivariate regression model for SCI, age (odds ratio [OR]: 1.2 [1.1-1.4], P = .02) and shaggy score (OR: 1.2 [1.1-1.4], P = .02) were independently associated with increased risk of SCI, whereas treatment with the IIP was associated with lower risk of SCI (OR: 0.04 [0.006-0.50], P = .05). Of the individual components of the shaggy score, higher descending thoracic aortic ulcer scores were the most strongly associated with postoperative SCI (P = .009). CONCLUSIONS: Preoperative characterization of aortic wall thrombus is an important adjunctive tool for individualized clinical decision-making and patient counseling about the risk of SCI after BEVAR.

Predictors of amputation-free survival and wound healing after infrainguinal bypass with alternative conduits.

OBJECTIVE: Inadequate vein quality or prior harvest precludes use of autologous single segment greater saphenous vein (ssGSV) in many patients with chronic limb-threatening ischemia (CLTI). Predictors of patient outcome after infrainguinal bypass with alternative (non-ssGSV) conduits are not well-understood. We explored whether limb presentation, bypass target, and conduit type were associated with amputation-free survival (AFS) after infrainguinal bypass using alternative conduits. METHODS: A single-center retrospective study (2013-2020) was conducted of 139 infrainguinal bypasses performed for CLTI with cryopreserved ssGSV (cryovein) (n = 71), polytetrafluoroethylene (PTFE) (n = 23), or arm/spliced vein grafts (n = 45). Characteristics, Wound, Ischemia, and foot Infection (WIfI) stage, and outcomes were recorded. Multivariable Cox proportional hazards and classification and regression tree analysis modeled predictors of AFS. RESULTS: Within 139 cases, the mean age was 71 years, 59% of patients were male, and 51% of cases were nonelective. More patients undergoing bypass with cryovein were WIfI stage 4 (41%) compared with PTFE (13%) or arm/spliced vein (27%) (P = .04). Across groups, AFS at 2 years was 78% for spliced/arm, 79% for PTFE, and 53% for cryovein (adjusted hazard ratio for cryovein, 2.5; P = .02). Among cases using cryovein, classification and regression tree analysis showed that WIfI stage 3 or 4, age >70 years, and prior failed bypass were predictive of the lowest AFS at 2 years of 36% vs AFS of 58% to 76% among subgroups with less than two of these factors. Although secondary patency at 2 years was worse in the cryovein group (26% vs 68% and 89% in arm/spliced and PTFE groups; P < .01), in patients with tissue loss there was no statistically significant difference in wound healing in the cryovein group (72%) compared with other bypass types (72% vs 87%, respectively; P = .12). CONCLUSIONS: In patients with CLTI lacking suitable ssGSV, bypass with autogenous arm/spliced vein or PTFE has superior AFS compared with cryovein, although data were limited for PTFE conduits for distal targets. Despite poor patency with cryovein, wound healing is achieved in a majority of cases, although it should be used with caution in older patients with high WIfI stage and prior failed bypass, given the low rates of AFS.

Capturing the complexity of open abdominal aortic surgery in the endovascular era.

OBJECTIVE: Volume and quality benchmarks for open abdominal aortic surgery and particularly open aortic aneurysm repair (OAR) in the endovascular era are guided by the Society for Vascular Surgery guidelines, but the Vascular Quality Initiative (VQI) OAR module fails to capture the full spectrum of complex OAR. We hypothesized that VQI-ineligible complex OAR would be the dominant form of open repairs performed at a VQI-participating tertiary center. METHODS: All OAR cases performed at a single tertiary care center from 2007 to 2020 were reviewed. The VQI OAR criteria were applied with exclusions (non-VQI) defined as concomitant renal bypass, clamping above the superior mesenteric artery or celiac artery, repairs performed for trauma, anastomotic aneurysm, isolated iliac aneurysm, or infected aneurysms. Linear regression was used to assess temporal trends. RESULTS: Among a total of 481 open abdominal aortic operations, 355 (74%) were OAR. The average annual OAR volume remained stable over 14 years (25 ± 6; P = .46). Non-VQI OAR comprised 54% of all cases and persisted over time (R2 = 0.047, P = .46). Supraceliac clamping (35%) was often necessary. The proportion of endograft explantation cases significantly increased over time from 4% in 2007 to 20% in 2019 (P = .01). Infectious indications represented 20% (n = 70) of cases. Visceral branch grafts were performed in 16% of all cases. OAR for ruptured aneurysm constituted 10% of cases. Thirty-day mortality was significantly higher in non-VQI vs VQI-eligible OAR cases (10% vs 4%; P = .04). CONCLUSIONS: Complex OAR comprises a majority of OAR cases in a contemporary tertiary referral hospital, yet these cases are not accounted for in the VQI. Creation of a "complex OAR" VQI module would capture these cases in a quality-driven national registry and help to better inform benchmarks for volume and outcomes in aortic surgery.

Emotional Regulation in Surgery: Fostering Well-Being, Performance, and Leadership.

Emotional regulation is increasingly gaining acceptance as a means to improve well-being, performance, and leadership across high-stakes professions, representing innovation in thinking within the field of surgical education. As one part of a broader cognitive skill set that can be trained and honed, emotional regulation has a strong evidence base in high-stress, high-performance fields. Nevertheless, even as Program Directors and surgical educators have become increasingly aware of this data, with emerging evidence in the surgical education literature supporting efficacy, hurdles to sustainable implementation exist. In this white paper, we present evidence supporting the value of emotional regulation training in surgery and share case studies in order to illustrate practical steps for the development, adaptation, and implementation of emotional regulation curricula in three key developmental contexts: basic cognitive skills training, technical skills acquisition and performance, and preparation for independence. We focus on the practical aspects of each case to elucidate the challenges and opportunities of introducing and adopting a curricular innovation into surgical education. We propose an integrated curriculum consisting of all three applied contexts for emotional regulation skills and advocate for the dissemination of such a longitudinal curriculum on a national level.

Contemporary Experience with Paravisceral Aortic Aneurysm (PVAAA) Repair in a Tertiary Center.

OBJECTIVES: To describe contemporary outcomes from a single center capable of both complex open and endovascular aortic repair for paravisceral aortic aneurysms (PVAAA). METHODS: Data on all patients receiving open or endovascular (endo) treatment for aortic aneurysms with proximal extent at or above the renal arteries and distal to the inferior pulmonary ligament (IPL) were reviewed. Coarsened exact matching (CEM) on age, aneurysm type, gender, coronary artery disease (CAD), previous aortic surgery and symptomatic status created balanced cohorts for outcomes comparisons. RESULTS: Between October, 2006 and February, 2018, 194 patients were treated for juxtarenal (40%), pararenal (21%), paravisceral (6%) and Type 4 thoracoabdominal (34%) aortic aneurysms with open (81, 42%) or endo (113, 58%) at a single tertiary center. Endo repairs included renal coverage with a bifurcated graft (2%), unilateral (13%) or bilateral (4%) renal snorkels, Z-fen (15%), multi-branched graft (IDE protocol; 62%) and unique complex configurations (4%). On multivariable analysis, patients selected for open surgery were more likely to be symptomatic, whereas older patients, female patients and those with Type 4 TAAA extent were more often selected for endovascular treatment. Matching based on the significant independent covariates reduced the open and endovascular groups by one-third. Survival at 30 days was 97% for endo and 94% for open repair, 98% for both subgroups when excluding symptomatic cases, and was not different between the matched groups (98% vs 89%; P=0.23). Hospital and ICU stays were longer in open patients (8 vs. 10 days, 2 vs. 4, both P≤0.001). Post-op CVA, MI, lower extremity ischemia, surgical site infections and reoperation were not different between matched groups (all p>0.05), while pulmonary and intestinal complications, as well as grade 1/2 renal dysfunction by RIFLE criteria, were more common after open repair (all P<0.05). Spinal cord ischemia was significantly more frequent in the unmatched Endo group (11% vs. 1%, P=0.02), but this difference was not significant after matching. Composite major aortic complications was no different between treatment groups (unmatched P=0.91, matched P=0.87). Endo treatment resulted in patients more frequently discharged to home (84% vs. 66%, P=0.02). Reintervention after 30 days occurred more frequently in the endo group (P=0.002). Estimated survivals at 1 and 5 years for endo and open are 96% vs. 81% and 69% vs. 81% respectively (Log-rank P=0.57). CONCLUSIONS: Contemporary repair of PVAAA demonstrates safe outcomes with durable survival benefit when patients are well-selected for open or complex endovascular repair. We believe these data have implications for off-label device use in the treatment of PVAAA, and that open repair remains an essential option for younger, good risk patients in experienced centers.

Impact of the coronavirus disease 2019 pandemic on an academic vascular practice and a multidisciplinary limb preservation program.

With the aggressive resource conservation necessary to face the coronavirus disease 2019 pandemic, vascular surgeons have faced unique challenges in managing the health of their high-risk patients. An early analysis of patient outcomes after pandemic-related practice changes suggested that patients with chronic limb threatening ischemia have been presenting with more severe foot infections and are more likely to require major limb amputation compared with 6 months previously. As our society and health care system adapt to the new changes required in the post-coronavirus disease 2019 era, it is critical that we pay special attention to the most vulnerable subsets of patients with vascular disease, particularly those with chronic limb threatening ischemia and limited access to care.

Acute Insulin Resistance and Rapid Alterations in Neuronal Derived Blood Exosome Concentration After Branched Endovascular Aortic Aneurysm Repair.

OBJECTIVE: Hyperglycaemia following branched endovascular repair (BEVAR) of extensive aortic aneurysms is associated with post-operative lower extremity weakness (LEW). Insulin administration to maintain euglycaemia appears to decrease LEW rates. The purpose of this study was to examine changes in insulin receptor content of neuron derived blood exosomes (NDEs) after BEVAR. METHODS: Ten patients with a range of post-operative lower extremity neurological deficits after elective BEVAR were included in the study. Blood samples were collected pre-operatively, immediately after aneurysm repair, and on post-operative day 1. NDE insulin receptor substrate proteins were quantified by enzymevlinked immunosorbent assays. RESULTS: NDE levels of phosopho-serine312-type 1 insulin receptor substrate ([P-Ser312-IRS1], an inhibitor of insulin signalling) increased sevenfold in the immediate post-operative period (from 7.90 ± 0.89 to 58.54 ± 6.77 pg/mL; p < .001), whereas those of pan-tyrosine-phospho insulin receptor substrate ([P-panTyr-IRS1], which facilitates insulin signalling), rose only 50% (from 0.41 ± 0.07 to 0.63 ± 0.10 pg/mL; p = .03). As a result, the mean ratio of P-Ser312-IRS1 to P-panTyr-IRS1, which reflects the level of insulin resistance, increased fivefold immediately post-operatively (from 22.31 ± 3.28 to 106.33 ± 11.83; p < .001) and returned to normal levels by the next day (18.72 ± 1.87). CONCLUSION: BEVAR is associated with an acute state of insulin resistance within neuronal tissue. Further studies in a larger cohort of patients are needed to understand the potential interconnected processes of insulin resistance, hyperglycaemia, and spinal cord ischaemia after extensive endovascular aortic procedures.

Long-term durability of multibranched endovascular repair of thoracoabdominal and pararenal aortic aneurysms.

OBJECTIVE: The objective of this study was to assess the durability of multibranched endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms by examining the rates of late-occurring (beyond 30 days) complications. METHODS: There were 146 patients who underwent endovascular TAAA repair using a stent graft, with a total of 538 caudally oriented self-expanding branches. Four patients died in the perioperative period and were excluded, leaving 142 patients (mean age, 73 ± 8 years; 35 [24.7%] women). Follow-up included clinical examination and computed tomography angiography at 1 month, 6 months, and 12 months and yearly thereafter. RESULTS: Mean aneurysm diameter was 67 ± 9 mm. Sixty-seven TAAAs (47.2%) were Crawford type I, II, III, or V; 75 (52.8%) were type IV or pararenal. Three patients (2.1%) died >30 days after operation from perioperative complications. During a mean follow-up of 36 months (±28 months), there were four additional aneurysm-related deaths: one (0.7%) as a result of aneurysm rupture in the presence of untreatable type I endoleak, one (0.7%) after conversion to open repair for stent graft infection, one (0.7%) after occlusion of superior mesenteric artery and celiac branches, and one (0.7%) due to bilateral renal branch occlusion. There was one additional open conversion for stent graft infection (0.7%). Nineteen patients (13.3%) underwent 20 reinterventions for late-occurring complications, including 11 (7.7%) for renal branch occlusion or stenosis, 1 (0.7%) for mesenteric branch stenosis, 4 (2.8%) for graft limb occlusion, 1 (0.7%) for type IB endoleak (distal stent graft migration), and 1 (0.7%) for type III endoleak (fabric erosion); 2 (1.4%) open conversions were performed for stent graft infection. There were no late type IA endoleaks. By Kaplan-Meier analysis, freedom from aneurysm-related death was 91.1% and freedom from aneurysm-related death or reintervention was 76.8% at 5 years. The 5-year overall survival rate of 49.1% reflects the high rate of cardiopulmonary comorbidity. Although renal branch occlusion (23 occlusions of 256 renal branches [8.9%]) was the most common late complication, only five patients required permanent dialysis. CONCLUSIONS: Total endovascular repair of TAAAs and pararenal aortic aneurysms using axially oriented cuffs is safe, effective, and durable in the long term.

Multibranched endovascular aortic aneurysm repair in patients with and without chronic aortic dissections.

OBJECTIVE: The objective of this study was to compare multibranched endovascular aneurysm repair (MBEVAR) of postdissection thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs) with MBEVAR of degenerative TAAAs and PRAAs and to assess the role played by the preoperative correction of potential complicating factors, such as true lumen compression and false lumen origin of vital branches, using adjunctive maneuvers. METHODS: From July 2005 to July 2017, there were 162 patients who underwent elective MBEVAR of TAAAs and PRAAs. Data on demographics, procedural details, and outcomes were collected prospectively. RESULTS: The mean age was 73 ± 8 years, and 119 of 162 (74%) were men; 19 of 162 (12%) had prior aortic dissections. Patients with dissections were younger (65 ± 11 years vs 74 ± 7 years; P = .002) and were less likely to have smoked (13/19 [68%] vs 135/143 [94%]; P = .002) or to have peripheral artery disease (0/19 [0%] vs 35/143 [24%]; P = .01) compared with those without dissections. Patients with prior dissections were more likely to have Crawford type II (10/19 [53%] vs 22/143 [15%]; P = .001) and type III (6/19 [32%] vs 16/143 [11%]; P = .03) TAAAs and were more likely to require at least one pre-MBEVAR adjunctive procedure (14/19 [74%] vs 55/143 [38%]; P = .006) compared with those without dissection. There was no difference in perioperative death, stroke, or paraplegia rates between the two groups. Median follow-up was 2.4 years (interquartile range, 0.8-4.7) and did not differ significantly between the two groups. There were no significant differences in branch vessel occlusion, endoleak rate, or aneurysm-related death between the two groups. CONCLUSIONS: Patients with chronic type B aortic dissection are more likely to have extensive aneurysms and more likely to require adjunctive procedures to provide the appropriate anatomic substrate for MBEVAR, but this does not appear to affect the conduct of MBEVAR or its outcomes.

Late graft failure is rare after endovascular aneurysm repair using the Zenith stent graft in a cohort of high-risk patients.

OBJECTIVE: Device-specific data on the long-term efficacy of endovascular aneurysm repair (EVAR) are limited by the constant evolution of stent graft design. Whereas some modifications, such as barb-mediated fixation, probably enhance durability, others, such as thin-walled fabric, are of less certain benefit. The purpose of this study was to examine 15 years of a single-center experience of EVAR using the Zenith stent graft (Cook Medical, Bloomington, Ind). METHODS: Retrospective analysis was conducted of 325 high-risk patients who underwent elective EVAR with Zenith stent grafts between October 1998 and December 2005 under a physician-sponsored investigational device exemption. Patients' charts and death registries were reviewed to identify late stent graft failures and causes of death. Late stent graft failures were defined as type I or type III endoleaks; enlarging aneurysm sac requiring revision; and limb kinking or occlusion, stent graft infection, renal artery occlusion, or aneurysm rupture occurring >30 days after the index procedure. RESULTS: The mean age at treatment was 75.9 ± 7.4 years, and 300 of 325 (92%) were men. The mean aneurysm diameter was 60 ± 9 mm, and the median main body stent graft diameter was 28 mm (range, 22-32 mm). During a median follow-up time of 5.6 years (interquartile range, 2.6-8.7 years), there were six (2%) aneurysm-related deaths caused by the following: one stent graft infection, one infection of a femoral-femoral bypass graft placed after limb occlusion, one infection of a stent graft placed to treat a type IB endoleak, and three aneurysm ruptures. There were 19 (6%) late stent graft failures occurring at a median time of 4.0 years (range, 39 days-14.6 years) after the procedure. Patients with late stent graft failure were more likely to have had impaired renal function (creatinine concentration ≥2 mg/dL; 21% vs 6%; P = .03) and less likely to have had cardiac disease (42% vs 67%; P = .04) at the time of the index procedure. There was no significant association between late stent graft failure and age, sex, aneurysm size, stent graft diameter, diabetes, smoking, or lung disease. Kaplan-Meier estimated overall survival was 60% at 5 years, 29% at 10 years, and 12% at 15 years. Kaplan-Meier estimated freedom from aneurysm-related mortality was 98% at 5 years, 97% at 10 years, and 97% at 15 years. CONCLUSIONS: Late-occurring stent graft failures and aneurysm-related death are rare after EVAR using the Zenith stent graft, especially in high-risk patients whose comorbidities diminish life expectancy.

Strict Control of Blood Glucose With an Intravenous Insulin Infusion Decreases the Risk of Post-operative Lower Extremity Weakness After Complex Endovascular Aortic Aneurysm Repair.

OBJECTIVE/BACKGROUND: It has previously been shown that post-operative lower extremity weakness (LEW) is associated with elevated blood and cerebrospinal fluid (CSF) glucose levels after branched endovascular aneurysms repair (BEVAR) of extensive aortic aneurysms. The purpose of this study was to determine whether a post-operative insulin infusion protocol (IIP) to achieve tight blood glucose control decreases the rate of LEW. METHODS: From October 2013, blood and CSF samples were collected pre-operatively, immediately post-operatively, and on post-operative day one in asymptomatic patients undergoing BEVAR. In July 2016, an IIP was initiated to maintain post-operative blood glucose levels <120 mg/dL for 48 h. Data on demographics, operative repair, complications, and outcomes were collected prospectively. RESULTS: Between October 2013 and April 2018, 43 patients underwent BEVAR. Twenty-two (group A) underwent BEVAR before initiation of the IIP. Of these, seven (32%) developed LEW within 48 h of repair. This was temporary in five (23%) and permanent in two (9%) patients. Post-operative blood glucose levels were significantly higher in patients with LEW compared with those without LEW (140 ± 27 mg/dL vs. 117 ± 16 mg/dL; p = .02). Post-operative CSF glucose levels were significantly higher in patients with LEW compared with those without LEW (102 ± 15 mg/dL vs. 77 ± 15 mg/dL; p = .001). The subsequent 21 patients (group B) underwent BEVAR after initiation of the IIP. No patient in group B developed LEW while on the IIP, but one (5%) developed paraplegia on post-operative day four. The rate of early LEW (<48 h post-operatively) was significantly lower after initiation of the IIP (32% in group A vs. 0% in group B; p = .009). There was no difference in demographics, comorbidities, or operative time between the groups. CONCLUSION: An IIP to control blood glucose after BEVAR is associated with a decreased rate of post-operative LEW. Tight control of blood glucose should be considered after any extensive aortic reconstruction to minimise the risk of post-operative LEW.

The impact of prior aortic surgery on outcomes after multibranched endovascular aortic aneurysm repair.

OBJECTIVE: The purpose of this study was to evaluate the impact of prior aortic surgery on outcomes after multibranched endovascular aneurysm repair (MBEVAR) of thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs). METHODS: From July 2005 to October 2016, there were 153 patients who underwent elective endovascular repair of TAAA and PRAA using multibranched stent grafts. Data on demographics, procedural details, and outcomes were collected prospectively. RESULTS: The mean age was 73 ± 8 years, and 113 of 153 (74%) were men. Mean aneurysm diameter was 67 ± 9 mm. Before MBEVAR, 68 of 153 (44%) patients had undergone a prior aortic surgery; 49 of 68 (72%) had prior open aortic surgery, 15 of 68 (22%) had prior endovascular aortic surgery, and 4 of 68 (6%) had both. There were no significant differences in age, sex, preoperative aneurysm diameter, or medical comorbidities (coronary artery disease, lung disease, diabetes mellitus, or hypertension) in patients with previous aortic surgery compared with those without. Patients with previous aortic surgery had higher fluoroscopy times (131 ± 59 vs 118 ± 54 minutes; P = .18) and procedural times (370 ± 101 vs 345 ± 118 minutes; P = .27) during MBEVAR, but these differences did not reach statistical significance. Patients without previous aortic intervention had higher rates of postoperative paraplegia (9/85 [11%]) vs (0/68 [0%]; P = .005) compared with those with previous aortic surgery. Of 153 patients, 3 (2%) had a postoperative stroke, and this was not different between the two groups. Median follow-up time was 2.5 years (interquartile range, 1.0-4.5 years) and did not differ between those with and those without previous aortic surgery. Kaplan-Meier estimated 5-year freedom from aneurysm-related mortality and overall mortality was 90% and 48%, respectively, and did not differ between the two groups. There was also no difference in branch vessel occlusion between the two groups. CONCLUSIONS: A high proportion of patients undergoing MBEVAR for TAAA or PRAA have already undergone prior open or endovascular aortic procedures, but this does not appear to increase the complication rate or affect midterm clinical outcomes. Patients with prior aortic surgery who undergo MBEVAR have lower rates of paraplegia compared with those without prior surgery, which may be due to effective recruitment of collateral circulation.

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair.

OBJECTIVE: Hyperglycemia is associated with worsened clinical outcomes after central nervous system injury. The purpose of this study was to examine the association between lower extremity weakness (LEW) and the glucose levels of blood and cerebrospinal fluid (CSF) in patients undergoing multibranched endovascular aneurysm repair (MBEVAR) of thoracoabdominal and pararenal aortic aneurysms. METHODS: Blood and CSF samples were collected preoperatively, immediately after aneurysm repair, and on postoperative day 1 in 21 patients undergoing MBEVAR. Data on demographics, operative repair, complications, and outcomes were collected prospectively. RESULTS: There were 21 patients who underwent successful MBEVAR. Two patients had pre-existing paraplegia from prior open aortic surgery and were excluded from the current analysis. The mean age was 73 ± 8 years, and 15 of 19 (79%) were men. In the postoperative period, 7 of 19 (37%) patients developed LEW. This was temporary in 5 of 19 (26%) patients and permanent in 2 of 19 (11%) patients. The LEW group was older than the non-LEW group (77 ± 6 vs 70 ± 9 years, respectively; P = .10), had a lower preoperative glomerular filtration rate (58.6 ± 18.5 vs 71.4 ± 23.5 mL/min per 1.73 m2; P = .24), and was more likely to be taking a statin (100% vs 67%, respectively; P = .13), but these did not reach statistical significance. There was no significant difference in the prevalence of diabetes mellitus, hypertension, coronary artery disease, lung disease, or peripheral artery disease between the LEW and non-LEW groups. There was also no difference in operative time, blood loss, contrast material volume, or fluoroscopy times between the two groups. Preoperative blood and CSF glucose levels were similar in those with and without LEW. During the postoperative period, glucose values in the blood and CSF were significantly higher in those patients who developed LEW compared with those who did not develop LEW. In all patients with LEW, the elevation in the blood or CSF glucose level preceded the development of LEW. In a multivariable logistic regression model, CSF glucose concentration on postoperative day 1 was significantly and independently associated with the development of LEW (odds ratio, 2.30 [1.03-5.14] per 10 mg/dL increase in CSF glucose; P = .04). CONCLUSIONS: Elevated blood glucose and CSF glucose levels are associated with postoperative LEW in patients undergoing MBEVAR. The protective effect of euglycemia deserves further study in patients at risk for spinal cord ischemia.

Cryopreserved saphenous vein as a last-ditch conduit for limb salvage.

OBJECTIVE: In patients lacking autogenous vein suitable for infrainguinal bypass, cryopreserved saphenous vein (CSV) allograft (CryoLife, Inc, Kennesaw, Ga) may be an acceptable alternative. The purpose of this study was to examine outcomes of CSV conduit for infrainguinal revascularization. METHODS: Between February 2008 and August 2015, 70 patients underwent infrainguinal bypass grafts in 73 limbs using CSV. All patients lacked suitable arm or leg vein. Demographic data and patient outcomes were retrospectively collected using electronic medical records. RESULTS: The mean age of our cohort was 70 ± 14 years, and 36 (51%) were male; 47 (67%) were white, 39 (56%) had coronary artery disease, 27 (39%) had diabetes, 56 (80%) had hypertension, and 50 (71%) were former or current smokers. Median follow-up was 304 days (interquartile range, 130-991 days). Indications for the index operation included rest pain (27%), tissue loss (55%), and prosthetic graft infection (18%); 62 of 73 (85%) bypasses were performed for critical limb ischemia, and 45 of 73 (62%) were redo operations. Distal targets included superficial femoral artery or popliteal (38%), tibial (55%), and pedal (7%). All grafts had a minimum diameter of 3 mm. At 30 days, 55 of 64 grafts (86%) were patent; 9 were lost to early follow-up. The only significant risk factors associated with 30-day failure were ABO mismatch (43% vs 10%; P = .05) and donor blood type B or AB (40% vs 9%; P = .03). Estimated overall 1-year primary patency was 35%. In a multivariate analysis, nonblack race (P = .05), donor B or AB blood type (P = .01), and bypass to a tibial or pedal target (P = .05) were independently associated with loss of primary patency. There were 20 (27%) major amputations, and all grafts in these limbs had occluded at the time of amputation. Of the 33 limbs with ischemic tissue loss that had long-term follow-up, 17 of 33 (52%) went on to graft occlusion, 10 of 33 (30%) had a major amputation, and 24 of 33 (73%) had complete healing of the index wound. CONCLUSIONS: In the setting of a multidisciplinary team with aggressive wound care, CSV may be a reasonable choice for infrainguinal revascularization in patients with ischemic tissue loss who lack autogenous conduit. However, poor midterm to long-term patency suggests that optimal selection of patients is needed to derive meaningful clinical benefit.

A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency.

α1-Antitrypsin deficiency (ATD) is a common genetic disorder that can lead to end-stage liver and lung disease. Although liver transplantation remains the only therapy currently available, manipulation of the proteostasis network (PN) by small molecule therapeutics offers great promise. To accelerate the drug-discovery process for this disease, we first developed a semi-automated high-throughput/content-genome-wide RNAi screen to identify PN modifiers affecting the accumulation of the α1-antitrypsin Z mutant (ATZ) in a Caenorhabditis elegans model of ATD. We identified 104 PN modifiers, and these genes were used in a computational strategy to identify human ortholog-ligand pairs. Based on rigorous selection criteria, we identified four FDA-approved drugs directed against four different PN targets that decreased the accumulation of ATZ in C. elegans. We also tested one of the compounds in a mammalian cell line with similar results. This methodology also proved useful in confirming drug targets in vivo, and predicting the success of combination therapy. We propose that small animal models of genetic disorders combined with genome-wide RNAi screening and computational methods can be used to rapidly, economically and strategically prime the preclinical discovery pipeline for rare and neglected diseases with limited therapeutic options.

A C. elegans model of human α1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover.

The accumulation of serpin oligomers and polymers within the endoplasmic reticulum (ER) causes cellular injury in patients with the classical form α1-antitrypsin deficiency (ATD). To better understand the cellular and molecular genetic aspects of this disorder, we generated transgenic C. elegans strains expressing either the wild-type (ATM) or Z mutant form (ATZ) of the human serpin fused to GFP. Animals secreted ATM, but retained polymerized ATZ within dilated ER cisternae. These latter animals also showed slow growth, smaller brood sizes and decreased longevity; phenotypes observed in ATD patients or transgenic mouse lines expressing ATZ. Similar to mammalian models, ATZ was disposed of by autophagy and ER-associated degradation pathways. Mutant strains defective in insulin signaling (daf-2) also showed a marked decrease in ATZ accumulation. Enhanced ATZ turnover was associated with the activity of two proteins central to systemic/exogenous (exo)-RNAi pathway: the dsRNA importer, SID-1 and the argonaute, RDE-1. Animals with enhanced exo-RNAi activity (rrf-3 mutant) phenocopied the insulin signaling mutants and also showed increased ATZ turnover. Taken together, these studies allude to the existence of a novel proteostasis pathway that mechanistically links misfolded protein turnover to components of the systemic RNAi machinery.

Low-profile versus standard-profile multibranched thoracoabdominal aortic stent grafts.

OBJECTIVE: This study compared midterm results using low-profile stent grafts (LPSGs; 18F) and standard-profile stent grafts (SPSGs; 22F-24F) for endovascular pararenal and thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: From July 2005 to March 2015, 134 asymptomatic patients underwent endovascular repair of a pararenal or TAAA using multibranched aortic stent grafts. In March 2011, we started using a LPSG with nitinol stents and thin-walled polyester fabric. Prospectively collected data on operative repair, complications, and outcomes were compared between the two groups. RESULTS: LPSGs were used in 37 patients (8 women [21.6%]; mean ± standard deviation age, 72.5 ± 8 years) and SPSGs in 97 patients (25 [26%] women; mean age, 73 ± 8 years). Medical comorbidities, aneurysm size, and aneurysm extent were similar in the LPSG and SPSG groups. Mean follow-up time was longer in the SPSG group (3.1 ± 2 years) than in the LPSG group (1.3 ± 0.9 years; P < .001). Operative time, renal failure, stroke, myocardial infarction, and perioperative death were not significantly different between the two groups (P > .05). Aneurysm-related death, rupture, stent graft migration, type I or III endoleaks, aneurysm enlargement >5 mm, branch vessel occlusion, and reintervention rates were similar between the two groups (P > .05). However, the combined outcome of conduit use or access artery injury occurred at a lower rate in the LPSG group than in the SPSG group (16% vs 36%; P = .03). Women experienced significantly higher rates of conduit use and access artery injury than men after repair with SPSGs (64% vs 26%, respectively; P = .001) but similar rates after repair with the LPSG (25% vs 14%, respectively; P = .45). CONCLUSIONS: LPSGs had similar safety profile and midterm outcomes compared with the SPSGs for treatment of pararenal and TAAA. The substitution of LPSGs for SPSGs lowered the number of patients who required conduit insertion to avoid access artery injury, especially in women, thereby reducing an otherwise striking gender difference.

Standard off-the-shelf versus custom-made multibranched thoracoabdominal aortic stent grafts.

OBJECTIVE: The complex aortic branch anatomy in thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs) presents a challenge for endovascular repair. The multibranched endovascular device has durable midterm results with use of a custom branch stent graft (CSG) configuration. The midterm results with use of the standard branch stent graft (SSG) configuration are unknown, but it has the advantage of off-the-shelf technology. The goal of this study was to compare the midterm outcomes of CSG and SSG multibranched endovascular devices. METHODS: From July 2005 to September 2014, 133 patients underwent elective endovascular repair of TAAA and PRAA in a prospective trial. Beginning in December 2008, SSGs were used in those with suitable anatomy. RESULTS: Fifty patients (mean age, 71 ± 7 years; 11 women [22%]) were treated using SSGs, and 83 patients (mean age, 74 ± 9 years; 22 women [26.5%]) underwent repair using CSGs. The SSG and CSG groups were similar with regard to aneurysm size, aneurysm extent, and medical comorbidities, with the sole exception of lung disease, which was more common in the SSG group. All stent grafts were deployed as intended, with no conversions to open repair. Mean ± standard deviation follow-up (days) was 694 ± 525 for the SSG group and 942 ± 764 for the CSG group (P = .045). There were no significant differences in aneurysm-related death, renal failure requiring dialysis, stroke, endoleak, visceral or renal branch occlusion, lower extremity weakness, or reintervention (P > .05 for each). The volume of contrast material was significantly lower in those with SSGs compared with CSGs (P = .016), but there were no significant differences in operative or fluoroscopy times. Time to treatment (days from consent to surgery) was significantly lower in SSG patients compared with CSG patients (P = .01). CONCLUSIONS: For patients with suitable anatomy, the use of SSGs for TAAA and PRAA repair results in significantly shorter wait times to surgery and is as safe, effective, and durable in the midterm compared with CSGs.

Lower extremity weakness after endovascular aneurysm repair with multibranched thoracoabdominal stent grafts.

OBJECTIVE: We conducted our study to describe the incidence, presentation, management, risk factors, and outcomes of lower extremity weakness (LEW) after elective endovascular aneurysm repair with multibranched thoracoabdominal stent grafts. METHODS: Excluding symptomatic patients and those with aortic dissection, between July 2005 and October 2013, 116 patients with aortic aneurysms were treated in a prospective, single-center trial of multibranched endovascular aneurysm repair. LEW that resolved within 30 days of operation was classified as transient. Persistent LEW was defined as inability to walk or stand 30 days after surgery. Perioperative spinal cord protection measures included bypass as needed to maintain flow to the subclavian and internal iliac arteries, cerebrospinal fluid drainage, and permissive hypertension. RESULTS: Postoperative LEW occurred in 24 of 116 patients (20.6%). In 15 (12.9%), LEW was transient with full recovery. Nine patients (7.7%) had persistent LEW, three with paraparesis and six with paraplegia. Five of 24 patients (21%) awoke from anesthesia with LEW. Symptoms of LEW developed within 72 hours of operation in 14 of 24 (58%). Late-onset LEW (≥72 hours postoperatively) always occurred in the presence of a precipitating hypotensive event (5 of 24; 21%). Univariate analysis showed no association between LEW and Crawford type, staged repair, aneurysm extent, or postoperative endoleak. Baseline glomerular filtration rate <30 mL/min/1.73 m(2) (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2-14.6; P = .03), fluoroscopy time >190 minutes (OR, 3.6; 95% CI, 1.0-12.7; P = .04), and sustained hypotension (OR, 2.9; 95% CI, 1.1-7.7; P = .04) were identified as independent risk factors for LEW in multivariate analysis. CONCLUSIONS: Most episodes of LEW after multibranched endovascular aneurysm repair are transient and do not occur in the operating room. Adjunctive strategies to maintain spinal perfusion, including cerebrospinal fluid drainage and permissive hypertension, may help prevent permanent LEW.