Intraoperative Completion Studies and their Associations with Carotid Endarterectomy Outcomes.

OBJECTIVE: This study aimed at assessing outcomes after carotid endarterectomy (CEA) in dependence of center policy with respect to imaging intraoperative completion study (ICS i ) usage. SUMMARY BACKGROUND DATA: Although randomized controlled studies are missing, a beneficial effect was shown for ICS i techniques (i.e., angiography and intraoperative duplex ultrasound) after CEA. METHODS: This secondary data analysis is based on the German statutory quality assurance database. Research was funded by Germany's Federal Joint Committee Innovation Fund (G-BA Innovationsfonds, 01VSF19016 ISAR-IQ). According to their ICS i policy, hospitals were categorized as routine ICSi (>90%), selective ICSi (10-90%), or sporadic ICSi (<10%) centers . Primary study outcome was in-hospital stroke or death. Multivariable regression analyses were performed. RESULTS: Between 2012 and 2016, a total of 119,800 patients underwent CEA. In-hospital stroke or death rates were lower in routine ICSicenters (1.7%) compared to selective (2.1%) and sporadic ICSicenters (2.0%). The multivariable regression analysis showed, that in routine ICSicenters , ICS i use was associated with lower rates of stroke or death (aOR 0.64; 95% CI 0.44-0.93). In selective ICSicenters , ICS i was not associated with the occurrence of either of the assessed outcomes. In sporadic ICSicenters , ICS i was associated with higher rates of stroke or death (aOR 1.91; 95% CI 1.26-2.91). CONCLUSIONS: Lowest in-hospital stroke or death rates are achieved in r outine ICSicenters . While ICS i is associated with a lower perioperative risk in r outine ICSicenters , it might act as a surrogate marker for worse outcomes due to intraoperative irregularities in sporadic ICSicenters . Routine use of ICS i is advisable.

Aortic Vascular Graft and Endograft Infection-Patient Outcome Cannot Be Determined Based on Pre-Operative Characteristics.

Vascular graft/endograft infection (VGEI) is a serious complication after aortic surgery. This study investigates VGEI and patient characteristics, PET/CT quantification before surgical or conservative management of VGEI and post-intervention outcomes in order to identify patients who might benefit from such a procedure. PET standard uptake values (SUV) were quantitatively assessed and compared to a non-VGEI cohort. The primary endpoints were in-hospital mortality and aortic reintervention-free survival at six months. Ninety-three patients (75% male, 65 ± 10 years, 82% operated) were included. The initial operation was mainly for aneurysm (67.7%: 31% EVAR, 12% TEVAR, 57% open aortic repair). Thirty-two patients presented with fistulae. PET SUVTLR (target-to-liver ratio) showed 94% sensitivity and 89% specificity. Replacement included silver-coated Dacron (21.3%), pericardium (61.3%) and femoral vein (17.3%), yet the material did not influence the overall survival (p = 0.745). In-hospital mortality did not differ between operative and conservative treatment (19.7% vs. 17.6%, p = 0.84). At six months, 50% of the operated cohort survived without aortic reintervention. Short- and midterm morbidity and mortality remained high after aortic graft removal. Neither preoperative characteristics nor the material used for reconstruction influenced the overall survival, and, with limitations, both the in-hospital and midterm survival were similar between the surgically and conservatively managed patients.

A Modern Series of Secondary Aortoenteric Fistula - A 19-Year Experience.

OBJECTIVES: Secondary aortoenteric fistula is a rare and life-threatening condition. Clear evidence on the ideal therapeutic approach is largely missing. This study aims to analyze symptoms, etiology, risk factors, and outcomes based on procedural details. PATIENTS AND METHODS: All patients with secondary aortoenteric fistula admitted between 2003 and 2021 were included. Patient characteristics, surgical procedure details, and postoperative outcomes were analyzed. Outcomes were stratified and compared according to the urgency of operation and the procedure performed. Descriptive statistics were used. The primary endpoint was in-hospital mortality. RESULTS: A total of twentytwo patients (68% male, median age 70 years) were identified. Main symptoms were gastrointestinal bleeding, pain, and fever. From the twentytwo patients ten patients required emergency surgery and ten urgent surgery. Emergency patients were older on average (74 vs 63 years, P = .015) and had a higher risk of postoperative respiratory complications (80% vs 10%, P = .005). Primary open surgery with direct replacement of the aorta or an extra-anatomic bypass with an additional direct suture or resection of the involved bowel was performed in sixteen patients. In four patients underwent endovascular bridging treatment with the definitive approach as a second step. Other two patients died without operation (1x refusal; 1x palliative cancer history). In-hospital mortality was 27%, respectively. Compared to patients undergoing urgent surgery, those treated emergently showed significantly higher in-hospital (50% vs 0%, P = .0033) mortalities. CONCLUSION: Despite rapid diagnosis and treatment, secondary aortoenteric fistula remains a life-threatening condition with 27% in-hospital mortality, significantly increased upon emergency presentation.

Goal-directed Perioperative Albumin Substitution Versus Standard of Care to Reduce Postoperative Complications: A Randomized Clinical Trial (SuperAdd Trial).

OBJECTIVE: To investigate whether goal-directed albumin substitution during surgery and postanesthesia care to maintain a serum albumin concentration >30 g/L can reduce postoperative complications. BACKGROUND: Hypoalbuminemia is associated with numerous postoperative complications. Since albumin has important physiological functions, substitution of patients with hypoalbuminemia is worth considering. METHODS: We conducted a single-center, randomized, controlled, outcome assessor-blinded clinical trial in adult patients, American Society of Anesthesiologists physical status classification 3 to 4 or undergoing high-risk surgery. Patients, whose serum albumin concentration dropped <30 g/L were randomly assigned to goal-directed albumin substitution maintaining serum concentration >30 g/L or to standard care until discharge from the postanesthesia intermediate care unit. Standard of care allowed albumin substitution in hemodynamic instable patients with serum concentration <20 g/L, only. Primary outcome was the incidence of postoperative complications ≥2 according to the Clavien-Dindo Classification in at least 1 of 9 domains (pulmonary, infectious, cardiovascular, neurological, renal, gastrointestinal, wound, pain, and hematological) until postoperative day 15. RESULTS: Of 2509 included patients, 600 (23.9%) developed serum albumin concentrations <30 g/L. Human albumin 60 g (40-80 g) was substituted to 299 (99.7%) patients in the intervention group and to 54 (18.0%) in the standard care group. At least 1 postoperative complication classified as Clavien-Dindo Classification ≥2 occurred in 254 of 300 patients (84.7%) in the intervention group and in 262 of 300 (87.3%) in the standard treatment group (risk difference -2.7%, 95% CI, -8.3% to 2.9%). CONCLUSION: Maintaining serum albumin concentration of >30 g/L perioperatively cannot generally be recommended in high-risk noncardiac surgery patients.

Neurological event rates and associated risk factors in acute type B aortic dissections treated by thoracic aortic endovascular repair.

OBJECTIVES: Thoracic endovascular aortic repair is the method of choice in patients with complicated type B acute aortic dissection. However, thoracic endovascular aortic repair carries a risk of periprocedural neurological events including stroke and spinal cord ischemia. We aimed to look at procedure-related neurological complications within a large cohort of patients with type B acute aortic dissection treated by thoracic endovascular aortic repair. METHODS: Between 1996 and 2021, the International Registry of Acute Aortic Dissection collected data on 3783 patients with type B acute aortic dissection. For this analysis, 648 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair were included (69.4% male, mean age 62.7 ± 13.4 years). Patients were excluded who presented with a preexisting neurologic deficit or received adjunctive procedures. Demographics, clinical symptoms, and outcomes were analyzed. The primary end point was the periprocedural incidence of neurological events (defined as stroke, spinal cord ischemia, transient neurological deficit, or coma). Predictors for perioperative neurological events and follow-up outcomes were considered as secondary end points. RESULTS: Periprocedure neurological events were noted in 72 patients (11.1%) and included strokes (n = 29, 4.6%), spinal cord ischemias (n = 21, 3.3%), transient neurological deficits (n = 16, 2.6%), or coma (n = 6, 1.0%). The group with neurological events had a significantly higher in-hospital mortality (20.8% vs 4.3%, P < .001). Patients with neurological events were more likely to be female (40.3% vs 29.3%, P = .077), and aortic rupture was more often cited as an indication for thoracic endovascular aortic repair (38.8% vs 16.5%, P < .001). In patients with neurological events, more stent grafts were used (2 vs 1 stent graft, P = .002). Multivariable logistic regression analysis showed that aortic rupture (odds ratio, 3.12, 95% confidence interval, 1.44-6.78, P = .004) and female sex (odds ratio, 1.984, 95% confidence interval, 1.031-3.817, P = .040) were significantly associated with perioperative neurological events. CONCLUSIONS: In this highly selected group from dedicated aortic centers, more than 1 in 10 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair had neurological events, in particular women. Further research is needed to identify the causes and presentation of these events after thoracic endovascular aortic repair, especially among women.

Patients with Acute Limb Ischemia Might Benefit from Endovascular Therapy-A 17-Year Retrospective Single-Center Series of 985 Patients.

Acute lower limb ischemia (ALI) is a common vascular emergency, requiring urgent revascularization by open or endovascular means. The aim of this retrospective study was to evaluate patient demographics, treatment and periprocedural variables affecting the outcome in ALI patients in a consecutive cohort in a tertiary referral center. Primary outcome events (POE) were 30-day (safety) and 180-day (efficacy) combined mortality and major amputation rates, respectively. Secondary outcomes were perioperative medical and surgical leg-related complications and the 5-year combined mortality and major amputation rate. Statistical analysis used descriptive and uni- and multivariable Cox regression analysis. In 985 patients (71 ± 9 years, 56% men) from 2004 to 2020, the 30-day and 180-day combined mortality and major amputation rates were 15% and 27%. Upon multivariable analysis, older age (30 d: aHR 1.17; 180 d: 1.27) and advanced Rutherford ischemia stage significantly worsened the safety and efficacy POE (30 d: TASC IIa aHR 3.29, TASC IIb aHR 3.93, TASC III aHR 7.79; 180 d: TASC IIa aHR 1.97, TASC IIb aHR 2.43, TASC III aHR 4.2), while endovascular treatment was associated with significant improved POE after 30 days (aHR 0.35) and 180 days (aHR 0.39), respectively. Looking at five consecutive patient quintiles, a significant increase in endovascular procedures especially in the last quintile could be observed (17.5% to 39.5%, p < 0.001). Simultaneously, the re-occlusion rate as well as the number of patients with any previous revascularization increased. In conclusion, despite a slightly increasing early re-occlusion rate, endovascular treatment might, if possible, be favorable in ALI treatment.

ZILVERPASS Study: ZILVER PTX Stent versus Prosthetic Above-the-Knee Bypass Surgery in Femoropopliteal Lesions, 5-year Results.

PURPOSE: To report the 60-month safety and effectiveness results of a multicenter, prospective, randomized controlled trial comparing the ZILVER PTX paclitaxel-eluting stent to prosthetic above-the-knee bypass for the treatment of symptomatic TransAtlantic Inter-Society Consensus (TASC) C and D femoropopliteal lesions. MATERIALS AND METHODS: Patients were enrolled between October 2013 and July 2017. One of the secondary outcomes was primary patency at 60 months, defined as no evidence of binary restenosis or occlusion within the target lesion or bypass graft based on a duplex ultrasound peak systolic velocity ratio < 2.4 and no clinically-driven target lesion revascularization (TLR) in endovascular cases or reintervention to restore flow in the bypass at 60 months. Survival rates after 5 years were also analyzed. RESULTS: 220 patients (mean age 68.6 ± 10.5 years; 159 men) were included and randomized to ZILVER PTX (n = 113, 51.40%) or BYPASS group (n = 107, 48.60%). The 60-month primary patency rate was 49.3% for the ZILVER PTX group versus 40.7% for the bypass group (p = 0.6915). Freedom from TLR was 63.8% for the ZILVER PTX group versus 52.8% for the bypass group (p = 0.2637). At 5 years, no significant difference in survival rate could be seen between the ZILVER PTX and the bypass group (69.1% vs. 71% respectively, p = 0.5503). CONCLUSION: Even at 5 years, non-inferior safety and effectiveness results of the ZILVER PTX could be seen. These findings confirmed that the use of ZILVER PTX stents can be considered as a valid alternative for bypass surgery when treating long and complex femoropopliteal lesions.

Radiation therapy for cancer is potentially associated with reduced growth of concomitant abdominal aortic aneurysm.

PURPOSE: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency. METHODS: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort. RESULTS: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association. CONCLUSION: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

Editor's Choice - Temporal fluctuations of hospital incidence and mortality of ruptured abdominal aortic aneurysms in Germany: A secondary data analysis of German hospital episode statistics 2009 - 2018.

OBJECTIVE: Abdominal aortic aneurysm rupture (rAAA) is still associated with high mortality. Recent studies have shown higher incidences in autumn and winter, and worse outcomes after rAAA treatment on weekends in some countries. This study aimed to analyse seasonal, weekday, and daytime fluctuations of the hospital incidence, treatment modalities, and outcomes of rAAA, based on the most recent nationwide German real world data. METHODS: A secondary data analysis of diagnosis related group statistics (2009 - 2018), obtained from the German Federal Statistical Office, was conducted. Cases encoded by a diagnosis of rAAA in conjunction with procedural codes for endovascular aortic repair (EVAR) or open aortic repair were included. Patient and procedural characteristics, comorbidities, and outcomes were analysed for seasonal (spring, summer, autumn, and winter), weekday (Monday - Sunday) and daytime (0:00 - 8:00, 8:00 -16:00, 16:00 -20:00, and 20:00 - 24:00) fluctuations by descriptive statistics and multivariable regression analyses. RESULTS: Thirteen thousand and seventy patients (85% male, median age 75 years) were treated for rAAA. Endovascular aortic repair was associated with lower mortality (adjusted OR 0.40, 95% CI 0.37 - 0.44). While no significant seasonal fluctuations were found, on a weekday basis lower hospital incidences were found on Mondays (12%) and Sundays (11%) compared with other weekdays (15 - 16%). Similarly, EVAR rates were lower on Mondays and Sundays (25% and 24%, respectively) compared with other weekdays (30 - 33%). Multivariable analyses revealed higher mortality rates on Mondays and Sundays. On a daytime basis, lower EVAR rates and higher mortality rates were found during the 16:00 - 8:00 period. CONCLUSION: In German hospitals, incidences and EVAR rates to treat rAAA were lowest on Mondays and Sundays. The associated overall mortality rates were highest on the respective days. Further restructuring and centralisation of AAA treatment in Germany could potentially mitigate this weekday effect.

Completing the view - histologic insights from circular AAA specimen including 3D imaging : A methodologic approach towards histologic analysis of circumferential AAA samples.

Abdominal aortic aneurysm (AAA) is a pathologic enlargement of the infrarenal aorta with an associated risk of rupture. However, the responsible mechanisms are only partially understood. Based on murine and human samples, a heterogeneous distribution of characteristic pathologic features across the aneurysm circumference is expected. Yet, complete histologic workup of the aneurysm sac is scarcely reported. Here, samples from five AAAs covering the complete circumference partially as aortic rings are investigated by histologic means (HE, EvG, immunohistochemistry) and a new method embedding the complete ring. Additionally, two different methods of serial histologic section alignment are applied to create a 3D view. The typical histopathologic features of AAA, elastic fiber degradation, matrix remodeling with collagen deposition, calcification, inflammatory cell infiltration and thrombus coverage were distributed without recognizable pattern across the aneurysm sac in all five patients. Analysis of digitally scanned entire aortic rings facilitates the visualization of these observations. Immunohistochemistry is feasible in such specimen, however, tricky due to tissue disintegration. 3D image stacks were created using open-source and non-generic software correcting for non-rigid warping between consecutive sections. Secondly, 3D image viewers allowed visualization of in-depth changes of the investigated pathologic hallmarks. In conclusion, this exploratory descriptive study demonstrates a heterogeneous histomorphology around the AAA circumference. Warranting an increased sample size, these results might need to be considered in future mechanistic research, especially in reference to intraluminal thrombus coverage. 3D histology of such circular specimen could be a valuable visualization tool for further analysis.

ZILVERPASS Study: ZILVER PTX Stent vs. Bypass Surgery in Femoropopliteal Lesions, 3 year results and economic analysis.

BACKGROUND: To report the 3-year safety and effectiveness results of a multicenter, prospective, randomized controlled trial comparing the ZILVER PTX paclitaxel-eluting stent to surgical bypass and to conduct a health economic analysis up to 3-year follow-up of the two treatment modalities. METHODS: This is a study in symptomatic TransAtlantic Inter-Society Consensus (TASC) C and D femoropopliteal lesions comparing endovascular ZILVER PTX stenting vs. surgical bypass surgery using a prosthetic graft (ClinicalTrials.gov identifier NCT01952457). Between October 2013 and July 2017, 220 patients (mean age 68.6±10.5 years; 159 men) were enrolled and randomized to the ZILVER PTX treatment group (113, 51.40%) or the bypass treatment group (107, 48.60%). One of the secondary outcomes was primary patency at 3-year, defined as no evidence of binary restenosis or occlusion within the target lesion or bypass graft based on a duplex ultrasound peak systolic velocity ratio <2.4 and no clinically-driven target lesion revascularization (TLR) in endovascular cases or reintervention to restore flow in the bypass. An economic analysis was conducted to analyze the cost differences between ZILVER PTX and bypass, which shows the perspective of the public authority/organization that pays for healthcare in the two countries (payor), Germany and USA. RESULTS: The 3-year primary patency rate was 53.30% (95% CI 61.40% to 45.20%) for the ZILVER PTX group vs. 58.20% (95% CI 67.10% to 49.30%) for the bypass arm (P=0.9721). Freedom from TLR at 3-year was 62.80% (95% CI 72.60% to 53%) for the ZILVER PTX group vs. 65.30% (95% CI 75.40% to 55.20%) for the bypass group (P=0.635). There was also no significant difference (P=0.358) in survival rate at 3-year between the ZILVER PTX group 78.50%, (95% CI to 87.70% to 69.30%) and the bypass group 87.40% (95% CI 97.6% to 77.2%). None of the deaths was categorized as related to the procedure or device. The economic analysis, taking into account procedural-, hospitalization- and reintervention costs, showed a clear cost-benefit for Zilver PTX in both investigated countries up to 3-year follow-up: Germany (Bypass €9446 per patient versus ZILVER PTX €5755) and USA (Bypass $26,373 per patient versus ZILVER PTX $19,186). CONCLUSIONS: The non-inferior safety and effectiveness results of the ZILVER PTX stent were associated with lower costs for the payer and confirmed that ZILVER PTX stent treatment can be considered as a valid alternative for bypass surgery in long and complex femoropopliteal lesions.

Targeting long non-coding RNA NUDT6 enhances smooth muscle cell survival and limits vascular disease progression.

Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6) and its antisense target fibroblast growth factor 2 (FGF2) in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase of NUDT6, whereas FGF2 was downregulated. Targeting Nudt6 in vivo with antisense oligonucleotides in three murine and one porcine animal model of carotid artery disease and AAA limited disease progression. Restoration of FGF2 upon Nudt6 knockdown improved vessel wall morphology and fibrous cap stability. Overexpression of NUDT6 in vitro impaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another direct NUDT6 interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifies NUDT6 as a well-conserved antisense transcript of FGF2. NUDT6 silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.

CXCR4 - a possible serum marker for risk stratification of abdominal aortic aneurysms.

Background: Abdominal aortic aneurysm (AAA) rupture is still associated with a mortality rate of 80-90%. Imaging techniques or molecular fingerprinting for patient-specific risk stratification to identify pending rupture are still lacking. The chemokine (C-X-C motif) receptor (CXCR4) activation by CXCL12 ligand has been identified as a marker of inflammation and atherosclerosis, associated with AAA. Both are highly expressed in the aortic aneurysm wall. However, it is still unclear whether different expression levels of CXCR4 and CXCL12 can distinguish ruptured AAAs (rAAA) from intact AAAs (iAAA). Patients and methods: Abdominal aortic tissue samples (rAAA: n=29; iAAA: n=54) were excised during open aortic repair. Corresponding serum samples from these patients (n=9 from rAAAs; n=47 from iAAA) were drawn pre-surgery. Healthy aortic tissue samples (n=8) obtained from adult kidney donors during transplantation and serum samples from healthy adult volunteers were used as controls (n=5 each). Results: CXCR4 was mainly expressed in the media of the aneurysmatic tissue. Focal positive staining was also observed in areas of inflammatory infiltrates within the adventitia. In tissue lysates, no significant differences between iAAA, rAAA, and healthy controls were observed upon ELISA analysis. In serum samples, the level of CXCR4 was significantly increased in rAAA by 4-fold compared to healthy controls (p=0.011) and 3.0-fold for rAAA compared to iAAA (p<0.001). Furthermore a significant positive correlation between aortic diameter and serum CXCR4 concentration was found for both, iAAA and rAAA (p=0.042). Univariate logistic regression analysis showed that increased CXCR4 serum concentrations were associated with AAA rupture (OR: 4.28, 95% CI: 1.95-12.1, p=0.001). Conclusions: CXCR4 concentration was significantly increased in serum of rAAA patients and showed a significant correlation with an increased aortic diameter. The level of CXCR4 in serum was associated with a more than 4-fold risk increase for rAAA and thus could possibly serve as a biomarker in the future. However, further validation in larger studies is required.

Cancer, cancer treatment and aneurysmatic ascending aorta growth within a retrospective single center study.

Background: Multi-morbidity poses a substantial challenge for health care in an aging population. Recent studies did not provide evidence for general side effects of anti-cancer therapy regarding the growth rate of coincident abdominal aortic aneurysms, although it was suggested that specific therapeutic substances might accelerate growth. Aneurysm pathology, however, differs with respect to localization. Hence, we present the first ever analysis on the association of cancer and cancer therapy with growth alteration of aneurysms of the ascending aorta (AscAA). Patients and methods: A retrospective single-center identification of AscAA+cancer patients was performed in the institutional picture archiving and communication system (PACS). Included were all patients with ≥2 CT angiograms over ≥6 months and additional malignancy. Clinical data and aneurysm diameters were retrieved and analyzed for an association of cancer (stratified by tumor entity) or cancer therapy (stratified by several classes of chemotherapeutic agents and radiation therapy) with annual growth rate, respectively. Statistics included t-test, Wilcoxon test, and a linear regression model accounting for initial AscAA diameter and type of treatment. Results: From 2003 to 2021, 151 patients (median age 70 years; 85% male) with AscAA and coincident 163 malignancies were identified. Prostate (37%) and hematologic cancer (17%) were most frequent. One-hundred-eleven patients (74%) received chemotherapy and 75 patients (50%) had radiation. After exclusion of six patients with an initial AscAA diameter >55 mm, the average annual AscAA growth rate was 0.18±0.64 mm/year, with only 12 patients experiencing a growth rate >1mm/year. Neither tumor entity nor radiation or chemotherapy - alone or in combination - were significantly associated with an alteration of the annual AscAA growth rate. Likewise, a subanalysis for singular chemotherapeutic agents did not reveal a specific association with AscAA growth alteration. Conclusions: Growth rates of AscAA are low in this cohort with coincident malignancy. Cancer and/or chemotherapy or radiation are not associated with an alteration of the annual growth rate. Additional control examinations seem unnecessary.

Locoregional Anaesthesia and Intra-Operative Angiography in Carotid Endarterectomy: 16 Year Results of a Consecutive Single Centre Series.

OBJECTIVE: The benefit of local (LA) over general (GA) anaesthesia and the rationale of intra-operative imaging strategies during carotid endarterectomy (CEA) is debated. This study analysed the associations between patient characteristics, LA, and intra-operative imaging strategies and the in hospital stroke and death rates in elective CEA over a 16 year period. METHODS: All consecutive patients treated by elective CEA between January 2004 and December 2019 (n = 1 872; median age 71 years, 70% male, 37% symptomatic) were included. All patients were assessed neurologically before and within 48 hours after CEA. The primary outcome event was the combined rate of any in hospital stroke or death. Secondary outcome events were the combined rates of any in hospital major stroke (modified Rankin scale [mRS] 3 - 5) or death, stroke, minor stroke (mRS 0 - 2), major stroke, and death alone. To detect changes over time, four quartiles (2004 - 2007, 2008 - 2011, 2012 - 2015, and 2016 - 2019) of this cohort were analysed. Statistical analysis comprised trend tests, and uni- and multivariable logistic regression. RESULTS: Median patient age increased from 68 to 73 years (p < .001). Over time, LA (from 28% to 91%) and intra-operative imaging (angiography 2.8 - 98.1%, duplex ultrasound 0 - 78.2%) was applied more frequently. Surgical techniques did not change. The in hospital stroke or death and major stroke or death rates decreased from 3.7% to 1.5% (p = .041) and from 2.8% to 0.9% (p = .014), respectively, corresponding to a relative risk of decline of 7% and 12% annually. Multivariable analysis revealed that LA (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.1 - 0.62) and intra-operative angiography (OR 0.09, 95% CI 0.10 - 0.81) were associated with lower in hospital major stroke and death rates. CONCLUSION: These data demonstrate a decline in the combined rates of any in hospital major stroke or death after non-emergency CEA over time. Locoregional anaesthesia and intra-operative quality control were associated with these improvements and might be worthwhile in elective CEA.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

External Validity of Randomised Controlled Trials on Carotid Revascularisation: Trial Populations May Not Always Reflect Patients in Clinical Practice.

OBJECTIVE: The external validity of randomised controlled trials (RCTs) and their transferability to clinical practice is under investigated. This study aimed to analyse the exclusion criteria of recent carotid RCTs comparing carotid endarterectomy (CEA) and carotid artery stenting, and to assess the eligibility of consecutive clinical practice cohorts to those RCTs. METHODS: An analysis of the clinical and anatomical exclusion criteria of RCTs for asymptomatic (SPACE-2, ACST-2, CREST-1, and CREST-2) and symptomatic carotid stenosis (SPACE-1, CREST-1, ICSS, and EVA-3S) was performed. Two hundred consecutive asymptomatic and 200 consecutive symptomatic patients, treated by CEA, or transfemoral or transcarotid artery stenting at a tertiary referral university centre were assessed for their potential eligibility for each corresponding RCT. RCT patient data were pooled and differences from the clinical practice cohort analysed. Statistics were descriptive and comparative using Fisher's exact and t tests. RESULTS: The number of clinical and anatomical exclusion criteria differed widely between RCTs. Potential eligibility rates of the clinical practice cohort for RCTs with regard to asymptomatic carotid stenosis were 80.5% (ACST-2), 79.5% (SPACE-2), 47% (CREST-1), and 20% (CREST-2). For RCTs on symptomatic carotid stenosis the eligibility rates were 89% (ICSS), 86.5% (EVA-3S), 64% (SPACE-1), and 39% (CREST-1). Both clinical practice cohorts were older by about three years and patients were more often male vs. the RCTs. Furthermore, a history of smoking (asymptomatic patients), hypertension (symptomatic patients), and atrial fibrillation was diagnosed more often, whereas hypercholesterolaemia and coronary heart disease (asymptomatic patients) were less prevalent. More clinical practice patients were on antiplatelets, anticoagulants, and lipid lowering drugs. Symptomatic clinical practice patients presented more often with retinal ischaemia and less often with minor hemispheric strokes than patients in the RCTs. CONCLUSION: The external validity of contemporary carotid RCTs varies considerably. Patients in routine clinical practice differ from RCT populations with respect to age, comorbidities, and medication. These data are of interest for clinicians and guideline authors and may be relevant for the design of future comparative trials.