Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis.

BACKGROUND AND AIMS: The distinct functions of immune cells in atherosclerosis have been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches. METHODS AND RESULTS: Single cell RNA-sequencing (scRNA-seq) was performed to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire demonstrated an unexpectedly high heterogeneity and was dominated by cells of the T-cell lineage, a finding confirmed by immunohistochemistry. Bioinformatical integration with 7 mouse scRNA-seq data sets from adventitial and atherosclerotic vascular tissue revealed a total of 51 identities of cell types and differentiation states, of which some were only poorly conserved between species and exclusively found in humans. Locations, frequencies, and transcriptional programs of immune cells in mouse models did not resemble the immune cell landscape in human carotid atherosclerosis. In contrast to standard mouse models of atherosclerosis, human plaque leukocytes were dominated by several T-cell phenotypes with transcriptional hallmarks of T-cell activation and memory formation, T-cell receptor-, and pro-inflammatory signaling. Only mice at the age of 22 months partially resembled the activated T-cell phenotype. In a validation cohort of 43 patients undergoing carotid endarterectomy, the abundance of activated immune cell subsets in the plaque defined by multi-color flow cytometry associated with the extend of clinical atherosclerosis. CONCLUSIONS: Integrative scRNA-seq reveals a substantial difference in the immune cell composition of murine and human carotid atherosclerosis - a finding that questions the translational value of standard mouse models for adaptive immune cell studies. Clinical associations suggest a specific role for T-cell driven (auto-) immunity in human plaque formation and -instability.

Editor's Choice - The VASCUNExplanT Project: An International Study Assessing Open Surgical Conversion of Failed Non-Infected Endovascular Aortic Aneurysm Repair.

OBJECTIVE: The need for open surgical conversion (OSC) after failed endovascular aortic aneurysm repair (EVAR) persists, despite expanding endovascular options for secondary intervention. The VASCUNExplanT project collected international data to identify risk factors for failed EVAR, as well as OSC outcomes. This retrospective cross sectional study analysed data after OSC for failed EVAR from the VASCUNET international collaboration. METHODS: VASCUNET queried registries from its 28 member countries, and 17 collaborated with data from patients who underwent OSC (2005 - 2020). Any OSC for infection was excluded. Data included demographics, EVAR, and OSC procedural details, as well as post-operative mortality and complication rates. RESULTS: There were 348 OSC patients from 17 centres, of whom 33 (9.4%) were women. There were 130 (37.4%) devices originally deployed outside of instructions for use. The most common indication for OSC was endoleak (n = 143, 41.1%); ruptures accounted for 17.2% of cases. The median time from EVAR to OSC was 48.6 months [IQR 29.7, 71.6]; median abdominal aortic aneurysm diameter at OSC was 70.5 mm [IQR 61, 82]. A total of 160 (45.6%) patients underwent one or more re-interventions prior to OSC, while 63 patients (18.1%) underwent more than one re-intervention (range 1 - 5). Overall, the 30 day mortality rate post-OSC was 11.8% (n = 41), 11.1% for men and 18.2% for women (p = .23). The 30 day mortality rate was 6.1% for elective cases, and 28.3% for ruptures (p < .0001). The predicted 90 day survival for the entire cohort was 88.3% (95% CI 84.3 - 91.3). Multivariable analysis revealed rupture (OR 4.23; 95% CI 2.05 - 8.75; p < .0001) and total graft explantation (OR 2.10; 95% CI 1.02 - 4.34; p = .04) as the only statistically significant predictive factors for 30 day death. CONCLUSION: This multicentre analysis of patients who underwent OSC shows that, despite varying case mix and operative techniques, OSC is feasible but associated with significant morbidity and mortality rates, particularly when performed for rupture.

Women with large intact abdominal aortic aneurysms remain untreated.

OBJECTIVE: A lower elective repair rate among women with abdominal aortic aneurysms (AAAs) has been a consistent finding. Reasons behind this gender gap have not been thoroughly outlined. METHODS: This was a retrospective multicenter cohort study (ClinicalTrials.gov: NCT05346289) at three European vascular centers in Sweden, Austria and Norway. Patients in surveillance with AAAs were consecutively identified starting from January 1, 2014, until reaching a total sample size of 200 women and 200 men. All individuals were followed for 7 years through medical records. Final treatment distributions and the proportion of "truly untreated" (surgically untreated despite reaching guideline-directed thresholds: 50 mm for women and 55 mm for men) were determined. In a complementary analysis, a universal 55-mm threshold was used. Gender-specific primary reasons behind untreated statuses were clarified. Eligibility for endovascular repair among the truly untreated was assessed in a structured computed tomography analysis. RESULTS: Women and men had similar median diameters at inclusion (46 mm; P = .54) and at treatment decisions (55 mm; P = .36). After 7 years, the repair rate was lower among women (47% vs 57%). More women were truly untreated (26% vs 8%; P < .001) despite similar mean ages as for male counterparts (79.3 years; P = .16). With the 55-mm threshold, 16% women still classified as truly untreated. Similar reasons for nonintervention were captured for women and men (50% due to comorbidities alone, 36% morphology and comorbidity). The endovascular repair imaging analysis revealed no gender differences. Among truly untreated women, ruptures were common (18%), and mortality was high (86%). CONCLUSIONS: Surgical AAA management differed between women and men. Women could be underserved in terms of elective repairs: one in every four women was untreated with over-the-threshold AAAs. The lack of obvious gender differences in eligibility analyses could imply unmeasured discrepancies (eg, in disease extent or patient frailty).

Effect of distance to the base of skull and tumor size characteristics on cranial nerve injuries in carotid body tumor resections.

OBJECTIVE: In the present study, we aimed to confirm the findings reported by Kim et al. They stated that the tumor's distance to the base of the skull was predictive of injury to the cranial nerves and their branches during carotid body tumor resection in an Austrian cohort. METHODS: In the present retrospective observational trial, we included all consecutive patients who had been discharged from our tertiary care teaching hospital with the diagnosis of a carotid body tumor (CBT) between January 2004 and December 2019. Tumor-specific parameters were measured from the preoperative contrast-enhanced computed tomography or magnetic resonance imaging studies. Patient-specific data were obtained from the patients' medical records. The effect of these parameters on the occurrence of cranial nerve injuries was calculated using univariate logistic regression analysis. Parameters significant on univariate analysis were included in a multivariate model. RESULTS: A total of 48 CBTs had been resected in 43 patients (29 women [67.4%] and 14 men [32.6%]), with a mean age of 55.6 years (95% confidence interval, 51.8-58.5). The mean distance to the base of the skull was 43.2 mm (95% confidence interval, 39.9-46.5). A total of 18 injuries to the cranial nerves and their branches in 10 CBTs were detected. The tumor-specific parameters that were significant on univariate analysis were the distance to the base of the skull (P = .009), craniocaudal tumor diameter (P = .027), and tumor volume (P = .036). Stepwise multivariate logistic regression analysis revealed that the distance to the base of the skull was the only parameter that remained statistically significant. CONCLUSIONS: We found that the distance to the base of the skull is a highly predictive parameter for injuries to the cranial nerves and their branches during CBT resection and should be included in the surgical risk assessment and patient information.

Contemporary management and outcomes of peripheral venous aneurysms: A multi-institutional study.

OBJECTIVE: Extremity venous aneurysms result in the risk of pulmonary embolism (PE) and chronic venous insufficiency. At present, owing to the rarity of these aneurysms, no consensus for their treatment has been established. The purpose of the present study was to review the presentation, natural history, and contemporary management of extremity venous aneurysms. METHODS: We performed a retrospective, multi-institutional review of all patients with extremity venous aneurysms treated from 2008 to 2018. A venous aneurysm was defined as saccular or fusiform with an aneurysm/vein ratio of >1.5. RESULTS: A total of 66 extremity aneurysms from 11 institutions were analyzed, 40 of which were in a popliteal location, 14 iliofemoral, and 12 in an upper extremity or a jugular location. The median follow-up was 27 months (range, 0-120 months). Of the 40 popliteal venous aneurysms, 8 (20%) had presented with deep vein thrombosis (DVT) or PE, 13 (33%) had presented with pain, and 19 had been discovered incidentally. The mean size of the popliteal venous aneurysms presenting with DVT or PE was larger than that of those presenting without thromboembolism (3.8 cm vs 2.5 cm; P = .003). Saccular aneurysm morphology in the lower extremity was associated with thromboembolism (30% vs 9%; P = .046) and fusiform aneurysm morphology with a thrombus burden >25% (45% vs 3%). Patients presenting with thromboembolism were more likely to have had a thrombus burden >25% in their lower extremity venous aneurysm compared with those who had presented without thromboembolism (70% vs 9%). Approximately half of all the patients underwent immediate intervention, and half were managed with observation or antithrombotic regimen. In the non-operative cohort, three patients subsequently developed a DVT. Eight patients in the medically managed cohort went on to require surgical intervention. Of the 12 upper extremity venous aneurysms, none had presented with DVT or PE, and only 2 (17%) had presented with pain. Of the 66 patients in the entire cohort, 41 underwent surgical intervention. The most common indication was the absolute aneurysm size. Nine patients had undergone surgery because of a DVT or PE, and 11 for pain or extremity swelling. The most common surgery was aneurysmorrhaphy in 21 patients (53%), followed by excision and ligation in 14 patients (35%). Five patients (12%) had undergone interposition bypass grafting. A postoperative hematoma requiring reintervention was the most common complication, occurring in three popliteal vein repairs and one iliofemoral vein repair. None of the patients, treated either surgically or medically, had reported post-thrombotic complications during the follow-up period. CONCLUSIONS: Large lower extremity venous aneurysms and saccular aneurysms with thrombus >25% of the lumen are more likely to present with thromboembolic complications. Surgical intervention for lower extremity venous aneurysms is indicated to reduce the risk of venous thromboembolism (VTE) and the need for continued anticoagulation. Popliteal aneurysms >2.5 cm and all iliofemoral aneurysms should be considered for repair. Upper extremity aneurysms do not have a significant risk of VTE and warrant treatment primarily for symptoms other than VTE.

The impact of activated protein C resistance on the patency of arteriovenous grafts for hemodialysis access.

INTRODUCTION: Vascular access is required for hemodialysis treatment. An effect of activated protein C resistance on access thrombosis rates has not yet been investigated. The aim of this study is to determine whether an activated protein C resistance is correlated with the patency of polytetrafluoroethylene arteriovenous grafts. METHODS: The primary endpoint was the impact of activated protein C resistance; secondary endpoints were the influence of Factor V Leiden thrombophilia, homocysteine, ß2-glycoprotein antibodies, and other laboratory values on the assisted primary patency. RESULTS: Forty-three grafts in 43 patients were included. The overall mean assisted primary patency was 18.4 months (±3.16 SE). Activated protein C resistance (p = 0.01) and ß2-glycoprotein antibodies (p = 0.018) had a significant influence on the assisted primary patency. The assisted primary patency for patients with low (<4) activated protein C resistance was 9.3 months compared to 24.8 of those with a high (≥4) activated protein C resistance. Patients with low (≤2.6) ß2-glycoprotein antibodies presented an assisted primary patency of 31.8 months whereas those with high (>2.6) ß2-glycoprotein antibodies showed 9.3 months. In all patients with a pathologic activated protein C resistance, a heterozygous or homozygous Factor V Leiden thrombophilia was detected. CONCLUSIONS: This study identified low activated protein C resistance and high ß2-glycoprotein antibodies as risk factors for thrombosis in polytetrafluoroethylene arteriovenous grafts. A prospective study is needed to clarify if oral anticoagulation should be administered to all patients with a pathologic activated protein C resistance blood value and/or factor V Leiden mutation.

Surgical resection and graft replacement for primary inferior vena cava leiomyosarcoma: A multicenter experience.

OBJECTIVE: Primary leiomyosarcoma of the inferior vena cava (IVC) is best managed with surgical resection when technically feasible. However, consensus is lacking regarding the best choice of conduit and reconstruction technique. The aim of the present multicenter study was to perform a comprehensive assessment through the VLFDC (Vascular Low Frequency Disease Consortium) to determine the most effective method for caval reconstruction after resection of primary leiomyosarcoma of the IVC. METHODS: A multicenter, standardized database review of patients who had undergone surgical resection and reconstruction of the IVC for primary leiomyosarcoma from 2007 to 2017 was performed. The demographics, periprocedural details, and postoperative outcomes were analyzed. RESULTS: A total of 92 patients (60 women and 32 men), with a mean age of 60.1 years (range, 30-88 years) were treated. Metastatic disease was present in 22%. The tumor location was below the renal veins in 49 (53%), between the renal and hepatic veins in 52 (57%), and above the hepatic veins in 13 patients (14%). The conduits used for reconstruction included ringed polytetrafluoroethylene (PTFE; n = 80), nonringed PTFE (n = 1), Dacron (n = 1), autogenous vein (n = 1), bovine pericardium (n = 4), and cryopreserved tissue (n = 5). Complete R0 resection was accomplished in 73 patients (79%). In-hospital mortality was 2%, with a median length of stay of 8 days. The primary patency of PTFE reconstructed IVCs was 97% and 92% at 1 and 5 years, respectively, compared with 73% at 1 and 5 years for the non-PTFE reconstructed IVCs. The overall 1-, 3-, and 5-year survival for the entire cohort were 94%, 86%, and 65%, respectively CONCLUSIONS: The findings from our multi-institutional study have demonstrated that complete en bloc resection of IVC leiomyosarcoma with vascular surgical reconstruction in selected patients results in low perioperative mortality and is associated with excellent long-term patency. A ringed PTFE graft was the most commonly used conduit for caval reconstruction, yielding excellent long-term primary patency.

Traumatic upper extremity injuries: Analysis of correlation of mangled extremity severity score and disabilities of the arm, shoulder and hand score.

BACKGROUND: The Mangled Extremity Severity Score is a decision-making tool for limb amputation after trauma. The Disabilities of the Arm, Shoulder and Hand questionnaire was developed to quantify posttraumatic functional deficits of the upper extremity. This study aims to determine the correlation between these two assessments. METHODS: In this study, a retrospective review of all patients with upper extremity injuries who had been treated with vascular reconstruction at two centres between 2005 and 2014 was performed. The respective Mangled Extremity Severity Score was calculated for each participant. Patients were recalled for follow-up examination and assessment of the Disabilities of the Arm, Shoulder and Hand Score. RESULTS: In this study, 14 patients met the inclusion criteria. The mean total Mangled Extremity Severity Score was 5.9 and the mean total Disabilities of the Arm, Shoulder and Hand Score was 30 points. There was no statistically significant correlation between these assessments (Spearman's rank correlation coefficient: 0.49, p=0.075). CONCLUSION: The Disabilities of the Arm, Shoulder and Hand Score did not correlate significantly with the Mangled Extremity Severity Score.

The Mangled Extremity Severity Score Fails to be a Good Predictor for Secondary Limb Amputation After Trauma with Vascular Injury in Central Europe.

BACKGROUND: The Mangled Extremity Severity Score (MESS) was constructed as an objective quantification criterion for limb trauma. A MESS of or greater than 7 was proposed as a cut-off point for primary limb amputation. Opinions concerning the predictive value of the MESS vary broadly in the literature. The aim of this study was to evaluate the applicability of the MESS in a contemporary civilian Central European cohort. METHODS: All patients treated for extremity injuries with arterial reconstruction at two centres between January 2005 and December 2014 were assessed. The MESS and the amputation rate were determined. RESULTS: Seventy-one patients met the inclusion criteria and could be evaluated for trauma mechanism and injury patterns. The mean MESS was 4.97 (CI 4.4-5.6). Seventy-three per cent of all patients (52/71) had a MESS < 7 and 27% (19/71) of ≥7. Eight patients (11%) underwent secondary amputation. Patients with a MESS ≥ 7 showed a higher, but statistically not significant secondary amputation rate (21.1%; 4/19) than those with a MESS < 7 (7.7%; 4/52; p = 0.20). The area under the ROC curve was 0.57 (95% CI 0.41; 0.73). CONCLUSIONS: Based on these results, the MESS appears to be an inappropriate predictor for amputation in civilian settings in Central Europe possibly due to therapeutic advances in the treatment of orthopaedic, vascular, neurologic and soft-tissue traumas.

Editor's Choice - Follow-up of Patients After Revascularisation for Peripheral Arterial Diseases: A Consensus Document From the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases and the European Society for Vascular Surgery.

Peripheral arterial diseases comprise different clinical presentations, from cerebrovascular disease down to lower extremity artery disease, from subclinical to disabling symptoms and events. According to clinical presentation, the patient's general condition, anatomical location and extension of lesions, revascularisation may be needed in addition to best medical treatment. The 2017 European Society of Cardiology guidelines in collaboration with the European Society for Vascular Surgery have addressed the indications for revascularisation. While most cases are amenable to either endovascular or surgical revascularisation, maintaining long-term patency is often challenging. Early and late procedural complications, but also local and remote recurrences frequently lead to revascularisation failure. The rationale for surveillance is to propose the accurate implementation of preventive strategies to avoid other cardiovascular events and disease progression and avoid recurrence of symptoms and the need for redo revascularisation. Combined with vascular history and physical examination, duplex ultrasound scanning is the pivotal imaging technique for identifying revascularisation failures. Other non-invasive examinations (ankle and toe brachial index, computed tomography scan, magnetic resonance imaging) at regular intervals can optimise surveillance in specific settings. Currently, optimal revascularisation surveillance programmes are not well defined and systematic reviews addressing long-term results after revascularisation are lacking. We have systematically reviewed the literature addressing follow-up after revascularisation and we propose this consensus document as a complement to the recent guidelines for optimal surveillance of revascularised patients beyond the perioperative period.

Follow-up of patients after revascularisation for peripheral arterial diseases: a consensus document from the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases and the European Society for Vascular Surgery.

Peripheral arterial diseases comprise different clinical presentations, from cerebrovascular disease down to lower extremity artery disease, from subclinical to disabling symptoms and events. According to clinical presentation, the patient's general condition, anatomical location and extension of lesions, revascularisation may be needed in addition to best medical treatment. The 2017 European Society of Cardiology guidelines in collaboration with the European Society for Vascular Surgery have addressed the indications for revascularisation. While most cases are amenable to either endovascular or surgical revascularisation, maintaining long-term patency is often challenging. Early and late procedural complications, but also local and remote recurrences frequently lead to revascularisation failure. The rationale for surveillance is to propose the accurate implementation of preventive strategies to avoid other cardiovascular events and disease progression and avoid recurrence of symptoms and the need for redo revascularisation. Combined with vascular history and physical examination, duplex ultrasound scanning is the pivotal imaging technique for identifying revascularisation failures. Other non-invasive examinations (ankle and toe brachial index, computed tomography scan, magnetic resonance imaging) at regular intervals can optimise surveillance in specific settings. Currently, optimal revascularisation surveillance programmes are not well defined and systematic reviews addressing long-term results after revascularisation are lacking. We have systematically reviewed the literature addressing follow-up after revascularisation and we propose this consensus document as a complement to the recent guidelines for optimal surveillance of revascularised patients beyond the perioperative period.

[Popliteal Artery Entrapment Syndrome: Three Unusual Cases with Different Courses to Diagnosis]. / Poplitealarterien-Entrapment-Syndrom: 3 untypische Fälle mit 3 verschiedenen Diagnosewegen.

INTRODUCTION: Popliteal artery entrapment syndrome (PAES) is a pathology characterised by anatomical anomalies of the relative position of the popliteal artery (PA) to the medial head of the gastrocnemius muscle (MHGM), resulting in mechanical compression causing damage to and occlusion of the artery. PATIENTS: From 2012 to 2018, we operated on 3 male patients aged 17 to 48 years, who presented with PAES in our department. The first and oldest patient had previously undergone femoro-popliteal bypass surgery in 2003 when aged 23, with the underlying diagnosis of "posttraumatic PAOD II b" followed by several reoperations. In 2012, during the preparation of the popliteal fossa for the interposition of the aneurysmatic bypass vein a strong tendinous strand of the MHGM was found intraoperatively to be constricting the vessels. This aberrant part of the MHGM was resected and the vein replaced. The second patient was referred to us in 2014 with the diagnosis "PAOD II b with thrombosed popliteal aneurysm" after having undergone intra-arterial lysis at age 33. Due to the remaining wall adherent thrombi and position of the aneurysm, interposition of the PA with a venous graft was planned. Intraoperatively a tendon was found proximal to the aneurysm, causing significant stenosis of the PA. This structure was resected and the interposition performed as planned. The third patient was a 17 year old adolescent, who presented with plantar and calf claudication in his right leg with paleness and pulselessness. Imaging showed occlusion of the popliteal artery in both legs. After initial intra-arterial lysis, HRMRI of the knee showed the atypical course of the PA undercrossing the MHGM from the medial side. Open surgical treatment was performed by myotomy, leading to refixation of the tendon of the MHGM in its physiological position. All patients received individual medical treatment for prophylaxis of rethrombosis. All three patients declined surgical treatment of the asymptomatic contralaterally diagnosed PAES. CONCLUSION: Popliteal artery entrapment syndrome is rare and usually associated with athletic, largely young male patients with pronounced calf muscles. Delayed diagnosis of PAES leads to severe vascular defects, unnecessary reintervention and prolonged illness as is shown in our first case. Therefore, calf and foot claudication in young patients should always bring to mind the differential diagnosis of popliteal entrapment syndrome.