Outcomes of lower extremity arterial bypass using the Human Acellular Vessel in patients with chronic limb-threatening ischemia.

OBJECTIVE: Patients with chronic limb-threatening ischemia (CLTI) and no great saphenous vein to use as a conduit for arterial bypass have a high risk for amputation despite advances in medical and endovascular therapies. This report presents findings from a U.S. Food and Drug Administration (FDA) supported study of the Human Acellular Vessel (HAV) (Humacyte Inc.) used as a conduit for arterial bypass in patients with CLTI and inadequate or absent autologous conduit. METHODS: The HAV is a 6-mm, 40-cm vessel created from human vascular smooth muscle cells seeded onto a polyglycolic acid scaffold pulsed in a bioreactor for 8 weeks as cells proliferate and the scaffold dissolves. The resultant vessel is decellularized, creating a nonimmunogenic conduit composed of collagen, elastin, and extracellular matrix. The FDA issued an Investigational New Drug for an intermediate-sized, single-center study of the HAV under the agency's Expanded Access Program in patients with advanced CLTI and inadequate or absent autologous conduit. Technical results and clinical outcomes were analyzed and reported. RESULTS: Between March 2021 and July 2023, 29 patients (20 males; mean age, 71 ± 11 years) underwent limb salvage operation using the HAV as a bypass conduit. Most patients had advanced CLTI (Rutherford class 5/6 in 72%; wound, ischemia, and foot infection stage 3/4 in 83%), and 97% had previously failed revascularization(s) of the extremity. Two HAVs were sewn together to attain the needed bypass length in 24 patients (83%). Bypasses were to tibial arteries in 23 patients (79%) and to the popliteal artery in 6 (21%). Technical success was 100%, and the 30-day mortality rate was 7% (2 patients). With 100% follow-up (median, 9.3 months), the limb salvage rate was 86% (25/29 patients). There were 16 reinterventions to restore secondary patency, of which 15 (94%) were successful. Primary and secondary patency of the HAV at 9 months were 59% and 71%, respectively. CONCLUSIONS: The HAV has demonstrated short- to intermediate-term safety and efficacy as an arterial bypass conduit in a complex cohort of patients with limb-threatening ischemia and no autologous options. This experience using the FDA's Expanded Access Program provides real-world data to inform regulatory deliberations and future trials of the HAV, including the study of the vessel as a first-line bypass conduit in less severe cases of chronic limb ischemia.

Comparative outcomes of arterial bypass using the human acellular vessel and great saphenous vein in patients with chronic limb ischemia.

OBJECTIVE: The Human Acellular Vessel (HAV) is a novel, off-the-shelf biologic conduit being evaluated for arterial reconstructions. Regulatory studies in peripheral arterial disease (PAD) to date have consisted of single-arm cohorts with no comparator groups to contrast performance against established standards. This study aimed to compare outcomes of the HAV with autologous great saphenous vein (GSV) in patients with advanced PAD undergoing infrageniculate bypass. METHODS: Patients with advanced PAD and no autologous conduit who underwent bypass with the 6-mm diameter HAV (Group 1; n = 34) (March 2021-February 2024) were compared with a multicenter historical cohort who had bypass with single-segment GSV (group 2; n = 88) (January 2017-December 2022). The HAV was used under an Investigational New Drug protocol issued by the Food and Drug Administration (FDA) under the agency's Expanded Access Program. RESULTS: Demographics were comparable between groups (mean age 69 ± 10 years; 71% male). Group 1 had higher rates of tobacco use (37 pack-years vs 28 pack-years; P = .059), coronary artery disease (71% vs 43%; P = .007), and prior coronary artery bypass grafting (38% vs 14%; P = .003). Group 1 had more patients classified as wound, ischemia, and foot infection clinical stage 4 (56% vs 33%; P = .018) and with previous index leg revascularizations (97% vs 53%; P < .001). Both groups had a similar number of patients with chronic limb-threatening ischemia (Rutherford class 4-6) (88% vs 86%; P = .693) and Global Anatomic Staging System stage III (91% vs 96%; P = .346). Group 1 required a composite conduit (two HAV sewn together) in 85% of bypasses. The tibial vessels were the target in 79% of group 1 and 100% of group 2 (P < .001). Group 1 had a lower mean operative time (364 minutes vs 464 minutes; P < .001). At a median of 12 months, major amputation-free survival (73% vs 81%; P = .55) and overall survival (84% vs 88%; P = .20) were comparable. Group 1 had lower rates of primary patency (36% vs 50%; P = .044), primary-assisted patency (45% vs 72%; P = .002), and secondary patency (64% vs 72%; P = .003) compared with group 2. CONCLUSIONS: Implanted under Food and Drug Administration Expanded Access provisions, the HAV was more likely to be used in redo operations and cases with more advanced limb ischemia than GSV. Despite modest primary patency, the HAV demonstrated resilience in a complex cohort with no autologous conduit options, achieving good secondary patency and providing major amputation-free survival comparable with GSV at 12 months.

Comprehensive Genomic Characterization in Ovarian Low-Grade and Chemosensitive and Chemoresistant High-Grade Serous Carcinomas.

INTRODUCTION: Genomic characterization of serous ovarian carcinoma (SOC), which includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), remains necessary to improve efficacy of platinum-based chemotherapy. The aim of this study was to investigate the genomic variations in these SOC groups, also in relation to chemoresponse. METHODS: Forty-five samples of SOC were retrospectively analyzed by next-generation sequencing on DNA/RNA extracts from formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained at diagnosis. HGSCs were classified as platinum-resistant and platinum-sensitive. RESULTS: In the LGSC group, 44% of the carcinomas had mutually exclusive variants in the RAS/RAF pathway, while additional likely oncogenic variants in the CDKN2A, SMARCA4, and YAP1 genes were observed in the remaining LGSCs. Tumor mutation burden (TMB) was significantly lower in the intrinsically chemoresistant LGSC group than in the HGSC group. In the HGSC cohort, TP53 variants were found in 90% and homologous recombination repair (HRR) pathway variants in 41% of the neoplasms. HGSCs of the chemoresistant group without classic mutations in the HRR pathway were characterized by additional variants in FGFR2 and with an FGFR3::TACC3 fusion. In addition, HGSCs showed MYC, CCNE1, and AKT2 gains that were almost exclusively observed in the chemosensitive HGSC group. CONCLUSION: These results suggest that very low TMB and MYC, CCNE1, and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy strategies.

Ocular Ischemic Syndrome and the Role of Carotid Artery Revascularization.

BACKGROUND: Ocular ischemic syndrome (OIS) is a rare presentation of atherosclerotic carotid artery stenosis that can result in permanent visual loss. This severely disabling syndrome remains under diagnosed and undertreated due to lack of awareness; especially since it requires expedited multidisciplinary care. The relevance of early diagnosis and treatment is increasing due to an increasing prevalence of cerebrovascular disease. METHODS: The long-term visual and cerebrovascular outcomes following intervention for nonarteritic OIS, remain poorly described and were the objective of this concise review. We conducted a PubMed search to include all English language publications (cohort studies and case reports) between 2002 and 2023. RESULTS: A total of 33 studies (479 patients) report the outcomes of treatment of OIS with carotid endarterectomy (CEA, 304 patients, 19 studies), and carotid artery stenting (CAS, 175 patients, 14 studies). Visual outcomes were improved or did not worsen in 447 patients (93.3%). No periprocedural stroke was reported. Worsening visual symptoms were rare (35 patients, 7.3%); they occurred in the immediate postoperative period secondary to ocular hypoperfusion (3 patients) and in the late postoperative period due to progression of systemic atherosclerotic disease. Symptomatic recurrence due to recurrent stenosis after CEA was reported in 1 patient (0.21%); this was managed successfully with CAS. None of these studies report the results of transcarotid artery revascularization, the long-term operative outcome or stroke rate. CONCLUSIONS: OIS remains to be an underdiagnosed condition. Early diagnosis and prompt treatment are crucial in reversal or stabilization of OIS symptoms. An expedited multidisciplinary approach between vascular surgery and ophthalmology services is necessary to facilitate timely treatment and optimize outcome. If diagnosed early, both CEA and CAS have been associated with visual improvement and prevention of progressive visual loss.

Clinical presentation, operative management, and long-term outcomes of rupture after previous abdominal aortic aneurysm repair.

OBJECTIVE: The aim of the present study was to evaluate the presentation trends, intervention, and survival of patients who had been treated for late abdominal aortic aneurysm rupture (LAR) after open repair (OR) or endovascular aortic aneurysm repair (EVAR). METHODS: We reviewed the clinical data from a single-center, retrospective database for patients treated for LAR from 2000 to 2020. The end points were the 30-day mortality, major postoperative complication, and survival. The outcomes between LAR managed with EVAR (group I) vs OR were compared (group II). RESULTS: Of 390 patients with infrarenal aortic rupture, 40 (10%) had experienced aortic rupture after prior aortic repair and comprised the LAR cohort (34 men; age 78 ± 8 years). LAR had occurred before EVAR in 30 and before OR in 10 patients. LAR was more common in the second half of the study with 32 patients after 2010. LAR after prior OR was secondary to ruptured para-anastomotic pseudoaneurysms. After initial EVAR, LAR had occurred despite reintervention in 17 patients (42%). The time to LAR was shorter after prior EVAR than after OR (6 ± 4 vs 12 ± 4 years, respectively; P = .003). Treatment for LAR was EVAR for 25 patients (63%; group I) and OR for 15 (37%, group II). LAR after initial OR was managed with endovascular salvage for 8 of 10 patients. Endovascular management was more frequent in the latter half of the study period. In group I, fenestrated repair had been used for seven patients (28%). Salvage for the remaining cases was feasible with EVAR, aortic cuffs, or limb extensions. The incidence of free rupture, time to treatment, 30-day mortality (8% vs 13%; P = .3), complications (32% vs 60%; P = .1), and disposition were similar between the two groups. Those in group I had had less blood loss (660 vs 3000 mL; P < .001) and less need for dialysis (0% vs 33%; P < .001) than those in group II. The median follow-up was 21 months (interquartile range, 6-45 months). The overall 1-, 3-, and 5-year survival was 76%, 52%, and 41%, respectively, and was similar between groups (28 vs 22 months; P = .48). Late mortality was not related to the aorta. CONCLUSIONS: LAR after abdominal aortic aneurysm repair has been encountered more frequently in clinical practice, likely driven by the frequency of EVAR. However, most LARs, including those after previous OR, can now be salvaged with endovascular techniques with lower morbidity and mortality.

Results of a Flexible Patient-Centered Approach to the Timing of Thoracic Outlet Decompression in Paget Schroetter Syndrome.

BACKGROUND: Treatment algorithms for subclavian vein (SCV) effort thrombosis (Paget-Schroetter syndrome- PSS) are multiple, ranging from thrombolysis (TL) with immediate or delayed thoracic outlet decompression (TOD) to conservative treatment with anticoagulation alone. We follow a regimen of TL/pharmacomechanical thrombectomy (PMT) followed by TOD with first rib resection, scalenectomy, venolysis, and selective venoplasty (open or endovascular) performed electively at a time convenient for the patient. Oral anticoagulants are prescribed for 3 months or longer based upon response. The aim of this study was to evaluate outcomes of this flexible protocol. METHODS: Clinical and procedural details of consecutive patients treated for PSS from January 2001 to August 2016 were retrospectively reviewed. Endpoints included success of TL and eventual clinical outcome. Patients were divided into 2 groups-Group I: TL/PMT + TOD; Group II: medical management/anticoagulation + TOD. RESULTS: PSS was diagnosed in 114 patients; 104 (62 female, mean age 31 years) who underwent TOD were included in the study. Group I: 53 patients underwent TOD after initial TL/PMT (23 at our institution and 30 elsewhere) with success (acute thrombus resolution) in 80% (n = 20) and 72% (n = 24) respectively. Adjunctive balloon-catheter venoplasty was performed in 67%. TL failed to recanalize the occluded SCV in 11% (n = 6). Complete thrombus resolution was seen in 9% (n = 5). Residual chronic thrombus in 79% (n = 42) resulted in median SCV stenosis of 50% (range 10% to 80%). With continued anticoagulation, further thrombus retraction was noted with median 40% improvement in stenosis including in veins with unsuccessful TL. TOD was performed at a median of 1.5 months (range 2-8 months). Rethrombosis of the SCV occurred in 3 patients 1-3 days postoperatively and was managed with MT/SCV stenting/balloon angioplasty and anticoagulation. Symptomatic relief was achieved in 49/53 (92%) patients at a median follow-up of 14 months. Group II: 51 patients underwent TOD following medical treatment elsewhere with anticoagulation alone for an average 6 months (range 2-18 months) with recurrent SCV thrombosis in 5 (11%). Thirty-nine patients (76%) had persistent symptoms; the remaining had asymptomatic compression of the SCV with maneuvers. SCV occlusion persisted in 4 patients (7%); the indication for TOD being residual symptoms from compression of collateral veins, the median residual stenosis was 70% (range 30-90%). TOD was performed at a median of 6 months after diagnosis of PSS. Open venous reconstruction with endovenectomy and patch was performed in 4 patients and stenting in 2. Symptomatic relief was achieved in 46/51 (90%) at a median follow-up of 24 months. CONCLUSIONS: For Paget Schroetter syndrome a management protocol encompassing elective thoracic outlet decompression at a convenient time following thrombolysis is safe and effective, with low risk of rethrombosis. Continued anticoagulation in the interim results in further recanalization of the subclavian vein and may reduce the need for open venous reconstruction.

Thirty-year single-center experience with arterial thoracic outlet syndrome.

OBJECTIVE: Arterial thoracic outlet syndrome (ATOS) is rare. We present our 30-year experience with the management of ATOS at a high-volume referral center. METHODS: A retrospective review of all patients who had undergone primary operative treatment for ATOS from 1988 to 2018 was performed. ATOS was defined as subclavian artery pathology caused by extrinsic compression from a bony abnormality within the thoracic outlet. RESULTS: A total of 41 patients (45 limbs) underwent surgery for ATOS at a median age of 46 years (interquartile range [IQR], 34-58 years). Chronic symptoms (>6 weeks) were present in 31 limbs (69%). Of the 45 limbs, 13 (29%) presented with acute limb ischemia (ALI), requiring urgent brachial artery thromboembolectomy (BAT) in 9 and catheter-directed thrombolysis and thrombectomy (CDT) in 4. All patients underwent thoracic outlet decompression. 31 limbs (69%) required subclavian artery reconstruction. No perioperative deaths and only one major adverse limb event occurred. Patients with ALI underwent staged thoracic outlet decompression after initial BAT or CDT at a median of 23 days (IQR, 11-140 days). Of the 13 limbs with an initial presentation of ALI, 8 (62%) had recurrent thromboembolic events before thoracic outlet decompression subsequently requiring 10 additional BATs and 1 CDT. The cumulative probability of recurrent embolization at 14, 30, and 90 days was 8.33% (95% confidence interval [CI], 1.28%-54.42%), 16.67% (95% CI, 4.70%-59.06%), and 33.33% (95% CI, 14.98-74.20%), respectively. The median follow-up for 32 patients (35 limbs) was 13 months (IQR, 5-36 months). Subclavian artery/graft primary and secondary patency was 87% and 90%, respectively, at 5 years by Kaplan-Meier analysis. Of the 35 limbs, 5 (14%) had chronic upper extremity pain and 5 (14%) had persistent weakness. Preoperative forearm or hand pain and brachial artery occlusion were associated with chronic pain (P = .04 and P = .03) and weakness (P = .03 and P = .02). Of the 13 limbs that presented with ALI, 11 had a median follow-up after thoracic outlet decompression of 6 months (IQR, 5-14 months), including 9 (82%) with oral anticoagulation therapy. Anticoagulation therapy had no effect on subclavian artery patency (P = 1.0) or the presence of chronic symptoms (P = .93). CONCLUSIONS: The presentation of ATOS is diverse, and the diagnosis can be delayed. Preoperative upper extremity pain and brachial artery occlusion in the setting of ALI were associated with chronic pain and weakness after thoracic outlet decompression. Delayed thoracic outlet decompression was associated with an increased risk of recurrent thromboembolic events for patients who presented with ALI. An early and accurate diagnosis of ATOS is necessary to reduce morbidity and optimize outcomes.

Predictors of Long-Term Aortic Growth and Disease Progression in Patients with Aortic Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer.

BACKGROUND: We aimed to identify predictors of long-term aortic diameter change and disease progression in a population cohort of patients with newly diagnosed aortic dissection (AD), intramural hematoma (IMH), or penetrating aortic ulcer (PAU). METHODS: We used the Rochester Epidemiology Project record linkage system to identify all Olmsted County, MN-USA, residents diagnosed with AD, IMH, and PAU (1995-2015). The endpoints were aortic diameter change, freedom from clinical disease progression (any related intervention, aortic aneurysm, new aortic syndrome, rupture or death) and disease resolution (complete spontaneous radiological disappear). Linear regression was used to assess aortic growth rate; predictors of disease progression were identified with Cox proportional hazards. RESULTS: Of 133 incident cases, 46 ADs, 12 IMHs, and 28 PAUs with sufficient imaging data were included. Overall median follow-up was 8.1 years. Aortic diameter increase occurred in 40 ADs (87%, median 1.0 mm/year), 5 IMHs (42%, median 0.2 mm/year) and 14 PAUs (50%, median 0.4 mm/year). Symptomatic presentation (P = 0.045), connective tissue disorders (P = 0.005), and initial aortic diameter >42 mm (P = 0.013) were associated with AD growth rate. PAU depth >9 mm (P = 0.047) and female sex (P = 0.013) were associated with aortic growth rate in PAUs and IMHs. At 10 years, freedom from disease progression was 22% (95% CI 12-41) for ADs, 44% (95% CI 22-92) for IMHs, and 46% (95% CI 27-78) for PAUs. DeBakey I/IIIB AD (HR 3.09; P = 0.038), initial IMH aortic diameter (HR 1.4; P = 0.037) and PAU depth >10 mm (HR 3.92; P = 0.018) were associated with disease progression. No AD spontaneously resolved; resolution rate at 10 years was 22% (95% CI 0-45) for IMHs and 11% (95% CI 0-23) for PAUs. CONCLUSIONS: Aortic growth and clinical disease progression are observed in most patients with aortic syndromes, while spontaneous resolution is uncommon. Predictors of aortic growth and disease progression may be used to tailor appropriate follow-up and eventual early intervention.

Incidence and natural history of isolated abdominal aortic dissection: A population-based assessment from 1995 to 2015.

BACKGROUND: Isolated abdominal dissection (IAD) is an uncommon clinical problem that is less well-understood than thoracic aortic dissection (AD). We performed a population-based assessment of the incidence, natural history, and treatment outcomes of IAD to better characterize this disease. METHODS: We used the Rochester Epidemiology Project to identify all Olmsted County, MN residents with a diagnosis of AD, intramural hematoma or penetrating ulcer (1995-2015). Diagnostic imaging of all patients was reviewed to confirm the diagnosis of IAD for inclusion. Presentation, treatment, and outcomes were reviewed. Survival of IAD patients was compared to age- and sex-matched population controls 3:1. RESULTS: Of 133 residents with aortic syndrome (AD, intramural hematoma, or penetrating ulcer), 23 were initially diagnosed with IAD. Nine were reclassified as having a penetrating aortic ulcer and were excluded, leaving 14 patients for review (10 male [71%]; mean age, 71 years). Three patients (21%) were symptomatic (abdominal pain, back pain, hypertension) and none had malperfusion or rupture. Prior aortic dilatation was present in eight patients (57%) and Marfan syndrome in one (7%). Two patients (14%) had iatrogenic IAD. Initial management was medical in 13 and endovascular aneurysm repair in one (symptomatic subacute, infrarenal dissection with small aneurysm). The median clinical and imaging follow-up was 6.7 years (range, 0-17 years). An abdominal aortic aneurysm occurred in eight (six at the time of IAD diagnosis, one at 2.9 years, and one at 5.2 years after diagnosis). The average growth in the entire cohort was 0.9 ± 0.4 cm, which translated to an average growth rate of 0.09 cm/year. Subsequent intervention was performed in two patients; for severe aortic stenosis with claudication in one (infrarenal aortic stenting) and increasing aortic size in one (open repair). One patient required reintervention (thrombolysis and stenting for endovascular aneurysm repair limb thrombosis). Survival for IAD at 1, 3, and 5 years was 93%, 85%, and 76%, respectively, compared with population controls at 98%, 85%, and 71%, respectively (long rank P = .38). Mortality was due to cardiovascular causes in three patients (21%) and no deaths were aortic related. Major adverse cardiac events occurred in five patients (36%) owing to heart failure. CONCLUSIONS: IAD is rare. The initial management for asymptomatic patients is medical. The aortic growth rate is slow, with no aortic-related mortality and a low rate of aortic intervention. The overall mortality is similar to population controls. Heart failure and cardiac-related death are prevalent, suggesting that close cardiovascular care is needed in this patient population.

Effect of obesity on radiation exposure, quality of life scores, and outcomes of fenestrated-branched endovascular aortic repair of pararenal and thoracoabdominal aortic aneurysms.

BACKGROUND: The aim of the present study was to assess the effect of obesity on procedural metrics, radiation exposure, quality of life (QOL), and clinical outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms. METHODS: We reviewed the clinical data from 334 patients (236 men; mean age, 75 ± 8 years) enrolled in a prospective nonrandomized study to evaluate FB-EVAR from 2013 to 2019. The patients were classified using the body mass index (BMI) as obese (BMI ≥30 kg/m2) or nonobese (BMI <30 kg/m2). QOL questionnaires (short-form 36-item questionnaire) and imaging studies were obtained preoperatively and at 2 months and 6 months postoperatively, and annually thereafter. The procedures were performed using two different fixed imaging systems. The end points included procedural metrics (ie, total operative time, fluoroscopic time, contrast volume), radiation exposure, technical success, 30-day mortality, and major adverse events, QOL changes, freedom from target vessel instability, freedom from reintervention, and patient survival. RESULTS: The aneurysm extent was a pararenal aortic aneurysm in 117 patients (35%) and a thoracoabdominal aortic aneurysm in 217 patients (65%). Both groups had similar demographics, cardiovascular risk factors, and aneurysm extent, except for a greater incidence of hyperlipidemia and diabetes among the obese patients (P < .05). No significant differences were found in the procedural metrics or intraprocedural complications between the groups, except that the obese patients had greater radiation exposure than the nonobese patients (mean, 2.5 vs 1.6 Gy; P < .001), with the highest radiation exposure in those obese patients who had undergone the procedure using system 1 (fusion alone) instead of system 2 (fusion and digital zoom; mean, 4.1 vs 1.5 Gy; P < .001). Three patients had died within 30 days (0.8%), with no difference in mortality or major adverse events between the groups. The mental QOL scores had improved in the obese group at 2 and 12 months compared with the nonobese patients, with persistently higher scores up to 3 years. At 3 years, the obese and nonobese patients had a similar incidence of freedom from target vessel instability (74% ± 6% vs 80% ± 3%; P = .99, log-rank test), freedom from reintervention (66% ± 6% vs 73% ± 4%; P = .77, log-rank test), and patient survival (83% ± 5% vs 75% ± 4%; P = .16, log-rank test). CONCLUSIONS: FB-EVAR was performed with high technical success and low mortality and morbidity, with no significant differences between the obese and nonobese patients. The procedural metrics and outcomes were similar, with the exception of greater radiation exposure among obese patients, especially for the procedures performed using system 1 with fusion alone compared with system 2 (fusion and digital zoom). Obese patients had higher QOL mental scores at 2 and 12 months, with a similar reintervention rate, target vessel outcomes, and survival compared with nonobese patients.

Burden and causes of readmissions following initial discharge after aortic syndromes.

BACKGROUND: Aortic syndromes, including aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU), carry significant morbidity and mortality; few data exist regarding burden and causes of related rehospitalizations following initial discharge. METHODS: The study was conducted using the Rochester Epidemiology Project. All adult residents (age ≥18 years) with an incident diagnosis of AD, IMH, and PAU (1995-2015) were identified from the Rochester Epidemiology Project using the International Classification of Diseases, Ninth Revision and Tenth Revision codes and Hospital Adaptation of the International Classification of Diseases, second edition, codes. Assessment of any-cause (aortic and cardiovascular), aorta-related, or cardiovascular-related readmissions was determined following date of hospital discharge or diagnosis date (ie, the index event). RESULTS: A total of 117 patients of 130 cases of AD, IMH, and PAU included in the initial study population survived the index event and were evaluated. The median age of diagnosis was 74 years, and 70 (60%) were male. A total of 79 patients (68%) experienced at least one readmission. The median time to first any-cause, cardiovascular, and aortic readmission was 143, 861, and 171 days, respectively. The cumulative incidence of any-cause readmissions at 2, 4, and 10 years was 45%, 55%, and 69%, respectively. The cumulative incidence of cardiovascular readmissions at 2, 4, and 10 years was 15%, 20%, and 28%, respectively. The cumulative incidence of aortic readmissions at 2, 4, and 10 years was 38%, 46%, and 59%, respectively. Overall survival for the entire cohort at 2, 4, and 10 years was 84%, 75%, and 50%, respectively. CONCLUSIONS: Readmissions following initial discharge after diagnosis of aortic syndrome are common and not different across specific disease types. Whereas aorta-related rehospitalizations occur in more than half of patients but tend to be earlier, cardiovascular-related rehospitalizations tend to happen later in about one-third of patients. This may suggest the need for early follow-up focused on aortic complications, whereas later follow-up should address cardiovascular events.

Tumor-specific prognosis of mutation-positive patients with head and neck paragangliomas.

BACKGROUND: Genetic testing to identify succinate dehydrogenase (SDH) mutations in patients with head and neck paraganglioma (HNP) has been in clinical practice for more than a decade. However, the recurrence and metachronous tumor occurrence risks in surgically treated mutation-positive patients are not well studied. METHODS: Clinical and procedural details of consecutive patients who underwent excision for HNP from January 1996 to October 2016 were retrospectively reviewed. End points included recurrence, metachronous tumor detection, and mortality. Germline DNA was tested to identify mutations in SDHx genes. Patients were divided into three groups on the basis of genetic testing: group I, positive; group II, negative; and group III, unknown or offered but not tested. RESULTS: HNP was diagnosed in 268 patients, 214 (147 female; mean age, 47 years) included in this study. Directed genetic testing was performed in 68; mutations were detected in SDH in 47 (69%), a majority SDHD. In group I, 47 patients had 64 procedures for 81 tumors (52 carotid body tumors [CBTs]); 17 (36%) were bilateral, 7 (15%) multiple, 3 (6%) functional, and 7 (15%) malignant. Residual tumor in 10 was significant in 2, managed by radiation therapy and reoperation. Local recurrence was detected in 12 patients (25%) at a median of 8 years; 11 metachronous mediastinal and retroperitoneal paragangliomas were detected in 8 (17%) at a median of 13 years. Systemic metastases occurred in five (10%). Six patients (13%) had more than one recurrence. In group II, 21 patients had 22 procedures for 23 tumors, 17 CBTs. Two (9%) were bilateral and two (9%) malignant. Excision was complete in all with no recurrence or systemic metastasis at last follow-up. For group III, 146 patients underwent 153 procedures for 156 tumors, 95 CBTs; 7 (5%) were bilateral, 2 (1%) multiple, 8 (5%) functional, and 1 (0.6%) malignant. Local recurrence was detected in nine (6%) at a median of 9 years and metachronous HNP in three (2%) at a median of 5 years. Systemic metastases occurred in two (1%). Mortality was 4% in group I and 3% in group III, none procedure or tumor related. Group I (mutation positive) had 10-year overall, recurrence-free, and metachronous tumor-free survival rates of 93%, 69.4%, and 73%, respectively, lower than the other groups (P < .001). CONCLUSIONS: Bilateral, functional, malignant, recurrent, and metachronous tumors are more common in SDH mutation-positive patients with HNP. Overall survival in patients with HNP is high. Metachronous tumors or local recurrences occur late, and long-term follow-up is necessary.

Cerebrospinal fluid drainage complications during first stage and completion fenestrated-branched endovascular aortic repair.

OBJECTIVE: To determine the rates and risk factors of complications related to cerebrospinal fluid drainage (CSFD) during first stage and completion fenestrated-branched endovascular aortic repair (F-BEVAR) of pararenal and thoracoabdominal aortic aneurysms. METHODS: We reviewed the outcomes of 293 consecutive patients enrolled in a prospective, nonrandomized study to investigate outcomes of F-BEVAR between 2013 and 2018. Patients who received CSFD during first-stage thoracic endovascular aortic repair, index F-BEVAR, or completion of temporary aneurysm sac perfusion procedures were included in the analysis. CSFD complications were graded as severe or moderate if they were life threatening, escalated the level of care, or prolonged the hospital stay. Presence of substantial degenerative lumbar disease (DLD) was identified based on review of preoperative computed tomography. End points included technical difficulties during CSFD placement and CSFD-related complications. RESULTS: A total of 187 patients (mean age, 73 ± 8 years; 70% male) treated for 20 pararenal and 167 thoracoabdominal aortic aneurysms received CSFD in 240 procedures, including 51 first-stage thoracic endovascular aortic repairs, 184 index F-BEVARs, and 5 completion temporary aneurysm sac perfusion procedures. Nineteen patients (10%) had 22 CSFD-related complications after 21 aortic procedures (9%). Complications were graded as severe to moderate in 17 patients (9%). There were 12 patients (6%) with intracranial hypotension, including three (2%) who had intracranial hemorrhage and nine (5%) with post dural puncture headache requiring blood patches in six. Another six patients (3%) developed spinal hematomas resulting in paraplegia in two (1%) and transient paraparesis in two (1%). One patient had CSF leakage from the puncture site (no intervention required). Four patients had bleeding during attempted drain placement, which required postponement of F-BEVAR. Technical difficulties were experienced in 57 drain insertions (24%), more often in patients with DLD than in those without DLD (35/113 [31%] vs 22/121 [18%]; P = .03). Fluoroscopic guidance was used in 44 drain placements (18%) with a lower rate of technical difficulties compared with the blind approach (9% vs 28%; P = .01). There was a statistically nonsignificant trend toward more complications in patients with technical challenges (14% vs 7%; P = .10). Of 13 study patients who developed spinal cord injuries during aortic procedures, 4 (31%) were attributed to CSFD. CONCLUSIONS: Although CSFD is widely used to prevent ischemic spinal cord injury during complex aortic repair, the risk of major CSFD-related complications is not negligible and should be carefully weighed against its potential benefits. One-third of spinal cord injuries were caused by CSF drain placement. The use of fluoroscopic guidance may decrease the risk of CSFD-related complications.

Pre-operative Psoas Muscle Size Combined With Radiodensity Predicts Mid-Term Survival and Quality of Life After Fenestrated-Branched Endovascular Aortic Repair.

OBJECTIVE: To investigate the association between psoas muscle area (PMA) and density (PMD) with survival and quality of life (QoL) after fenestrated-branched endovascular aortic repair (F-BEVAR). METHODS: The study included 244 consecutive patients enrolled in a prospective study to investigate outcomes of F-BEVAR. Pre-operative computed tomography angiography was used to measure PMA (cm2) and PMD (Hounsfield unit [HU]) at the L3 level. Lean PMA (LPMA) was calculated (PMA × PMD). Patients were divided into two groups using the LPMA cut off point based on a Cox hazard model. Group A was defined as LPMA ≥350 (n = 79) and group B as LPMA < 350 cm2 × HU (n = 165). QoL was assessed at baseline and at 12 months using the Short Form-36. RESULTS: Patients in group A were younger (mean age 72 ± 8 vs. 76 ± 7 years; p < .001), more often male (95% vs. 59%; p < .001), and had higher body mass index (30 ± 6 vs. 27 ± 5 kg/m2; p = .001). There were no major differences in comorbidities, aneurysm extent, or procedural measures between the groups. Thirty day mortality (0% vs. 0.6%; p = 1.0) and major adverse event rates (15% vs. 24%; p = .18) were similar in groups A and B. At three years, patient survival was 94% ± 3% in group A and 75% ± 4% in group B (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.07-0.56; p = .002). The three-year survival difference was even more prominent in patients aged ≥75 years: 100% for group A and 72% ± 5% for group B (HR 0.12, 95% CI 0.02-0.86; p = .035). Patients in group A had significantly higher QoL scores at baseline and at 12 months. LPMA was the strongest independent predictor of survival during follow up in multivariable analysis (adjusted HR 0.59 per 1 standard deviation, 95% CI 0.40-0.87; p = .008). CONCLUSION: A high LPMA was independently and strongly associated with better mid term survival and QoL after F-BEVAR. LPMA may help to identify the best candidates for F-BEVAR among elderly patients.

Population-Based Assessment of Aortic-Related Outcomes in Aortic Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer.

BACKGROUND: The aim of the study was to analyze aortic-related outcomes after diagnosis of aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) from a population-based approach. METHODS: Retrospective review of an incident cohort of AD, IMH, and PAU patients in Olmsted County, Minnesota from 1995 to 2015. Primary end point was aortic death. Secondary end points were subsequent aortic events (aortic intervention, new dissection, or rupture not present at presentation) and first-time diagnosis of an aortic aneurysm. Outcomes were compared with randomly selected population referents matched for age and sex in a 3:1 ratio using Cox proportional hazards regression adjusting for comorbidities. RESULTS: Among 133 patients (77 AD, 21 IMH, and 35 PAU), 57% were males, and mean age was 71.8 years (standard deviation, 14). Median follow-up was 10 years. Of 73 deaths among AD/IMH/PAU patients, 23 (32%) were aortic-related. Estimated freedom from aortic death was 84%, 80%, and 77% at 5, 10, and 15 years. There were no aortic deaths among population referents (adjusted hazard ratio [HR] for aortic death in AD/IMH/PAU, 184.7; 95% confidence interval [95% CI], 10.3-3,299.2; P < 0.001). Fifty (38%) AD/IMH/PAU patients had a subsequent aortic event (aortic intervention, new dissection, or rupture), whereas there were 8 (2%) aortic events among population referents (all elective aneurysm repairs; adjusted HR for any aortic event and aortic intervention in AD/IMH/PAU patients, 33.3; 95% CI, 15.3-72.0; P < 0.001 and 31.5; 95% CI, 14.5-68.4; P < 0.001, respectively). After excluding aortic events/interventions ≤14 days of diagnosis, AD/IMH/PAU patients remained at increased risk of any aortic event (adjusted HR, 10.8; 95% CI, 3.9-29.8; P < 0.001) and aortic intervention (adjusted HR, 9.6; 95% CI, 3.4-26.8; P < 0.001). Among those subjects with available follow-up imaging, the risk of first-time diagnosis of aortic aneurysm was significantly increased for AD/IMH/PAU patients when compared with population referents (adjusted HR, 10.9; 95% CI, 5.4-21.7; P < 0.001 and 8.3; 95% CI, 4.1-16.7; P < 0.001 for thoracic and abdominal aneurysms, respectively) and remained increased when excluding aneurysms that formed within 14 days of AD/IMH/PAU (adjusted HR, 6.2; 95% CI, 1.8-21.1; P = 0.004 and 2.8; 95% CI, 1.0-7.6; P = 0.040 for thoracic and abdominal aneurysms, respectively). CONCLUSIONS: AD/IMH/PAU patients have a substantial risk of aortic death, any aortic event, aortic intervention, and first-time diagnosis of aortic aneurysm that persists even when the acute phase (≤14 days after diagnosis) is uncomplicated. Advances in postdiagnosis treatment are necessary to improve the prognosis in these patients.

Cardiovascular morbidity and mortality after aortic dissection, intramural hematoma, and penetrating aortic ulcer.

OBJECTIVE: The nonaortic cardiovascular morbidity and mortality of patients with aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) is unknown. We aimed to define the rates of cardiovascular (CV) events in a cohort of patients with newly diagnosed AD, IMH, and PAU. METHODS: We performed a retrospective review of all Olmsted County, Minnesota, residents diagnosed with AD, IMH, and PAU from 1995 to 2015. The primary outcome was nonaortic CV death. The secondary outcome was a first-time nonfatal CV event (myocardial infarction, heart failure [HF], or stroke). The outcomes were compared with age- and sex-matched population referents using Cox proportional hazards regression, with adjustment for comorbidities. RESULTS: A total of 133 patients (77 with AD, 21 with IMH, 35 with PAU; 57% male) with a mean age of 71.8 ± 14.1 years were identified. The median follow-up was 10 years. Compared with the population referents, the patients with AD/IMH/PAU had an increased risk of CV death (adjusted hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.4-4.2; P = .003) and an increased risk of any first-time nonfatal CV event (adjusted HR, 3.0; 95% CI, 1.9-4.8; P < .001), mainly resulting from an increased risk of first-time HF (adjusted HR, 2.7; 95% CI, 1.7-4.3; P < .001). When excluding events within 14 days of the diagnosis, the patients with AD/IMH/PAU remained at increased risk of CV death (adjusted HR, 2.6; 95% CI, 1.4-4.7; P = .002), any first-time nonfatal CV event (adjusted HR, 2.6; 95% CI, 1.5-4.4, P <.001), and first-time HF (adjusted HR 2.5, 95% CI 1.5-4.3; P < .001). CONCLUSIONS: Compared with the population referents, the patients with AD/IMH/PAU had a two- to threefold risk of nonaortic CV death, any first-time nonfatal CV event, and first-time HF. These data implicate the need for long-term cardiovascular management for patients with AD/IMH/PAU.

D-dimer levels in patients with thromboangiitis obliterans.

Background: Thromboangiitis obliterans (TAO) or Buerger disease is a recurring progressive segmental vasculopathy that presents with inflammation and thrombosis of small and medium arteries and veins of the hands and feet. The exact cause remains unknown, with tobacco use (primarily smoking but also smokeless tobacco) being highly associated with the disease. The diagnosis is clinical and the lack of a diagnostic gold standard is a deterrent to diagnosing it in patients with atypical presentations. Obliterative endarteritis occurs perhaps due to a mixture of thrombosis and inflammation. The diagnostic sensitivity and specificity of D-dimer as a biomarker for thrombosis is well reported from its use in other areas such as deep vein thrombosis. Identification of a biomarker linked to the causation yields a diagnostic adjunct with a role in therapeutic decision-making, aiding diagnosis in atypical presentation, monitoring disease activity and gauging response to therapy. Methods: Between April 2014 and May 2015, we studied serum D-dimer (a marker of thrombosis) in 62 patients with TAO and compared this to 330 normal age- and sex-matched controls. We included all patients with peripheral arterial disease clinically diagnosed to have TAO according to the Shionoya criteria. There was no history of thrombosis or arterial disease in the control group. The control group was matched for baseline characteristics such as age and sex. All patients underwent a standard diagnostic protocol including blood tests (haemoglobin and creatinine), electrocardiogram, chest X-ray and ankle brachial pressure index. Blood was collected using an evacuated tube system into a citrate anticoagulant tube for testing D-dimer. Results: All the 62 patients diagnosed to have TAO were men with an average age of 40 years (range 18-65 years). They all had a history of tobacco use and did not have other atherogenic risk factors (part of the diagnostic criteria). Medium-vessel involvement was present in 53 patients (85%) and the rest presented with additional involvement of the popliteal and femoral vessels. Upper limb involvement or superficial thrombophlebitis was present in 95% of patients. Laboratory and imaging studies were consistent with TAO. The groups were well matched for age (p = 0.3). The median and interquartile range for D-dimer values were 61 ng/ml and 41-88 ng/ml in controls (n = 330) and 247 ng/ml and 126478 ng/ml in patients (n = 62), respectively (p<0.001). Conclusions: D-dimer levels are considerably elevated in patients with TAO. This indicates an underlying thrombotic process and suggests its potential role as a diagnostic adjunct. It also leads us to hypothesize a potential therapeutic benefit of anticoagulants in this disease.

Lumbar sympathectomy versus prostanoids for critical limb ischaemia due to non-reconstructable peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a common circulatory problem that can lead to reduced blood flow to the limbs, which may result in critical limb ischaemia (CLI), a painful manifestation that occurs when a person is at rest. The mainstay of treatment for CLI is surgical or endovascular repair. However, when these means of treatment are not suitable, due to anatomical reasons or comorbidities, treatment for pain is limited. Lumbar sympathectomy and prostanoids have both been shown to reduce pain from CLI in people who suffer from non-reconstructable PAD, but there is currently insufficient evidence to determine if one treatment is superior. Due to the severity of the rest pain caused by CLI, and its impact on quality of life, it is important that people are receiving the best pain relief treatment available, therefore interest in this area of research is high. OBJECTIVES: To compare the efficacy of lumbar sympathectomy with prostanoid infusion in improving symptoms and function and avoiding amputation in people with critical limb ischaemia (CLI) due to non-reconstructable peripheral arterial disease (PAD). SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 29 March 2017) and CENTRAL (2017, Issue 2). The CIS also searched clinical trials databases for ongoing or unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), with parallel treatment groups, that compared lumbar sympathectomy (surgical or chemical) with prostanoids (any type and dosage) in people with CLI due to non-reconstructable PAD. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials, extracted data and assessed risk of bias. Any disagreements were resolved by discussion. We performed fixed-effect model meta-analyses, when there was no overt sign of heterogeneity, with risk ratios (RRs) and 95% confidence intervals (CIs). We graded the quality of evidence according to GRADE. MAIN RESULTS: We included a single study in this review comparing lumbar sympathectomy with prostanoids for the treatment of CLI in people with non-reconstructable PAD. The single study included 200 participants with Buerger's disease, a form of PAD, 100 in each treatment group, but only 162 were actually included in the analyses. The study compared an open surgical technique for lumbar sympathectomy with the prostanoid, iloprost, and followed participants for 24 weeks.Risk of bias was low for most evaluated domains. Due to the nature of the treatment, blinding of the participants and those providing the treatment would be impossible as a surgical procedure was compared with intravenous injections. It was not mentioned if blinded assessors evaluated the study outcomes, therefore, we judged subjective outcomes (i.e. pain reduction) to be at unclear risk of detection bias and objective outcomes (i.e. ulcer healing, amputation and mortality) at low risk of detection bias. We also rated the risk of attrition bias as unclear; 38 out of 200 (19%) participants were not included in the analysis without clear explanation (16 of 100 in the iloprost arm and 22 of 100 in the sympathectomy arm). The quality of evidence was low due to serious imprecision because the study numbers were low and there was only one study included.The single included study reported on the outcome of complete healing without pain or major amputation, which fell under three separate outcomes for our review: relief of rest pain, complete ulcer healing and avoidance of major amputation. We chose to keep the outcome as a singularly reported outcome in order to not introduce bias into the outcomes, which may have been the case if reported separately. The limited evidence suggests participants who received prostaglandins had improved complete ulcer healing without rest pain or major amputation when compared with those who received lumbar sympathectomy (RR 1.63, 95% CI 1.30 to 2.05), but as it was the only included study, we rated the data as low-quality and could not draw any overall conclusions. The study authors stated that more participants who received prostaglandins reported adverse effects, such as headache, flushing, nausea and abdominal discomfort, but only one participant experienced severe enough adverse effects to drop out. Five participants who underwent lumbar sympathectomy reported minor wound infection (low-quality evidence). There was no reported mortality in either of the treatment groups (low-quality evidence).The included study did not report on claudication distances, quality of life or functional status, ankle brachial pressure index (ABPI), tissue oxygenation or toe pressures, or progression to minor amputation, complications or provide any cost-effectiveness data. AUTHORS' CONCLUSIONS: Low-quality evidence from a single study in a select group of participants (people with Buerger's disease) suggests that prostaglandins are superior to open surgical lumbar sympathectomy for complete ulcer healing without rest pain or major amputation, but possibly incur more adverse effects. Further studies are needed to better understand if prostaglandins truly are more efficacious than open surgical lumbar sympathectomy and if there are any concerns with adverse effects. It would be of great importance for future studies to include other forms of PAD (as Buerger's disease is a select type of PAD), other methods of sympathectomy as well as data on quality of life, complications and cost-effectiveness.