Sex disparities in popliteal artery aneurysms.

OBJECTIVE: Only 5% of patients with popliteal artery aneurysms (PAAs) are female. Evidence on PAA treatment and outcomes in women is therefore scarce. The POPART Registry provides one of Europe's largest data collections regarding PAA treatment. Data on clinical presentation, aneurysm morphology, and perioperative outcomes after open surgical PAA repair in women will be presented. METHODS: POPART is a multicenter, noninterventional registry for open and endovascular PAA repair, with 42 participating centers in Germany and Luxembourg. All patients aged >18 years who have been treated for PAA since 2010 are eligible for study inclusion. Data collection is based on an online electronic case report form. RESULTS: Of the 1236 PAAs, 58 (4.8%) were in women. There were no significant differences in age or cardiopulmonary comorbidities. However, female patients had a lower prevalence of contralateral PAAs and abdominal aortic aneurysms (P < .05). PAAs in women were more likely to be symptomatic before surgery (65.5% vs 49.4%; P = .017), with 19% of women presenting with acute limb ischemia (vs 11%; P = .067). Women had smaller aneurysm diameters than men (22.5 mm vs 27 mm; P = .004) and became symptomatic at smaller diameters (20 mm vs 26 mm; P = .002). Only 8.6% of women and 11.6% of men underwent endovascular aneurysm repair (P > .05); therefore, the perioperative outcome analysis focused on open surgical repair. In total, 23.5% of women and 16.9% of men developed perioperative complications (P > .05). There were no differences in major cardiovascular events (P > .05), but women showed a higher incidence of impaired wound healing (15.7% vs 7.2%; P = .05) and major amputation (5.9% vs 1.1%; P = .027). Female sex was significantly associated with the need for nonvascular reinterventions within 30 days after surgery (odds ratio: 2.48, 95% confidence interval: 1.26-4.88), whereas no significant differences in the odds for vascular reinterventions were observed (odds ratio: 1.98, 95% confidence interval: 0.68-5.77). In the multiple logistic regression model, female sex, symptomatic PAAs, poor quality of outflow vessels, and graft material other than vein graft were independently associated with perioperative reinterventions. CONCLUSIONS: Women have smaller PAAs, are more likely to be symptomatic before treatment, and are more often affected by nonvascular reinterventions in the perioperative course. As our understanding of aneurysmatic diseases in women continues to expand, sex-specific treatment strategies and screening options for women in well-selected cohorts with modified screening protocols should be continuously re-evaluated.

Sex difference in early mortality after abdominal aortic aneurysm repair.

OBJECTIVE: Although female patients have a lower prevalence of abdominal aortic aneurysm (AAA), they seem to have a worse treatment outcome compared with male patients. Both maximum aneurysm diameter and aortic size index (ASI) are important indicators of the risk of AAA rupture, among which ASI has been shown capable of equalizing sex-related anatomical differences. Our study aimed to investigate whether sex is an independent risk factor for early postoperative mortality and how the diameter or ASI affects the association between sex and mortality. METHODS: We performed a retrospective analysis of patients who enrolled in the AAA registry of the German Society of Vascular Surgery from 2013 to 2019. The patients were treated by either open surgical repair (OSR) or endovascular aneurysm repair (EVAR). The association between sex and 30-day mortality was investigated using logistic regression analysis. The interaction and mediating effects of maximum aneurysm diameter and ASI were investigated to verify their roles in the effect of sex on mortality. The relationships between the diameter (or ASI) and the risk of 30-day mortality in different sexes were demonstrated by the restricted cubic spline. RESULTS: Overall, 23,275 cases were included in our analysis, with 20,130 male (86.5%) and 3139 female (13.5%) patients. Female patients had a smaller maximum aneurysm diameter (OSR, 55.23 ± 10.29 mm vs 58.05 ± 11.28 mm [P < .001]; EVAR, 54.06 ± 9.08 mm vs 56.11 ± 9.38 mm [P < .001]), but a higher ASI (OSR, 3.16 ± 0.71 vs 2.92 ± 0.69 [P < .001]; EVAR, 3.05 ± 0.66 vs 2.80 ± 0.59 [P < .001]) compared with male patients. The 30-day mortality rate was higher for female patients in both OSR (6.6% vs 4.2%; P = .002) and EVAR groups (1.8% vs 0.8%; P < .001). Logistic regression confirmed a significantly higher risk of 30-day mortality for female patients compared with male patients (odds ratio, 1.55; 95% confidence interval, 1.21-1.99; P = .001). No interaction was found between sex and diameter or ASI, but there were mediating effects for diameter and ASI in the effect of sex on 30-day mortality. For female patients, the risk of 30-day mortality linearly increased with the increase of diameter (PNonlinear = .089) or ASI (PNonlinear = .888), whereas the risk for male patients was U-shaped (for diameter, PNonlinear < .001; for ASI, PNonlinear = .020). CONCLUSIONS: Sex is an independent risk factor for 30-day mortality after AAA repair. Both diameter and ASI are mediating factors for the effect of sex on 30-day mortality. The relationship between diameter or ASI and the risk of 30-day mortality is different for male and female patients.

Characteristics of patients with multiple arterial aneurysms.

Background: The aim of this retrospective cross-sectional observational study was to determine differences of patients with multiple arterial aneurysms to patients with single arterial aneurysms. Patients and methods: Patients with the diagnosis of an arterial aneurysm from January 2006 to January 2016 in the department of vascular surgery Heidelberg were investigated. Excluded were patients with hereditary disorders of connective tissue or systemic inflammatory disease, as well as other arterial pathologies than true aneurysms. Patients with multiple aneurysms (defined by at least four aneurysms) were compared to patients with single aneurysms concerning age at initial diagnosis, sex and affected arterial site. To verify the findings, a replication of the study was performed at a comparable institution. Results: Of 3107 patients with arterial aneurysms, 918 were excluded. Of the resulting 2189 patients, 1238 (56.6%) patients had a single, 808 (36.9%) two or three, and 143 (6.5%) at least four aneurysms (group mult-AA). Nine hundred seventy-two patients (44.4%) had a single abdominal aortic aneurysm (group sing-AAA). Age at initial diagnosis differed between mult-AA (66.7±9.5 y) and sing-AAA (69.1±8.6 y) (p=0.0338). Within mult-AA, 138 patients (96.5%) were male, compared with 865 patients (89.0%) in sing-AAA (p=0.0041). The most frequent aneurysm localization shifted from the abdominal aorta and its branches in patients with a single aneurysm (n=1029; 83.1%) to pelvic and leg arteries in patients with at least four aneurysms (n=318; 63.2%). The replication of the study at the department of vascular surgery Frankfurt confirmed the younger age at initial diagnosis in mult-AA (67.3±12.5 y) compared to sing-AAA (70.9±9.6 y) (p=0.0259) and the distribution shift toward the arteries below the aortic bifurcation in mult-AA. Conclusions: Patients with multiple aneurysms are younger at initial diagnosis and differ concerning aneurysm localization compared to patients with a single aneurysm.

Systematic evaluation of imaging techniques and baseline characteristics in patients with suspected vasculitis.

Purpose: To assess the diagnostic value of different imaging modalities in distinguishing systemic vasculitis from other internal and immunological diseases. Methods: This retrospective study included 134 patients with suspected vasculitis who underwent ultrasound, magnetic resonance imaging (MRI), or 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between 01/2010 and 01/2019, finally consisting of 70 individuals with vasculitis. The main study parameter was the confirmation of the diagnosis using one of the three different imaging modalities, with the adjudicated clinical and histopathological diagnosis as the gold standard. A secondary parameter was the morphological appearance of the vessel affected by vasculitis. Results: Patients with systemic vasculitis had myriad clinical manifestations with joint pain as the most common symptom. We found significant correlations between different imaging findings suggestive of vasculitis and the final adjudicated clinical diagnosis. In this context, on MRI, vessel wall thickening, edema, and diameter differed significantly between vasculitis and non-vasculitis groups (p < 0.05). Ultrasound revealed different findings that may serve as red flags in identifying patients with vasculitis, such as vascular occlusion or halo sign (p = 0.02 vs. non-vasculitis group). Interestingly, comparing maximal standardized uptake values from PET/CT examinations with vessel wall thickening or vessel diameter did not result in significant differences (p > 0.05). Conclusions: We observed significant correlations between different imaging findings suggestive of vasculitis on ultrasound or MRI and the final adjudicated diagnosis. While ultrasound and MRI were considered suitable imaging methods for detecting and discriminating typical vascular changes, 18F-FDG PET/CT requires careful timing and patient selection given its moderate diagnostic accuracy.

Preoperative smoking cessation program in patients undergoing intermediate to high-risk surgery: a randomized, single-blinded, controlled, superiority trial.

BACKGROUND: At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery. METHODS: The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption. DISCUSSION: The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery. TRIAL REGISTRATION: BASEC #2021-02004; ClinicalTrials.gov: NCT05192837 . Registered on January 14, 2022.

[Care of vascular surgery patients during COVID-19: a Germany-wide survey]. / Versorgung gefäßchirurgischer Patienten während COVID-19: eine deutschlandweite Umfrage.

Background: COVID-19 resulted in postponement and cancellation of elective operations in all surgical disciplines worldwide, especially in the first weeks of the pandemic. The specific situation in vascular surgery clinics in Germany during this period has not yet been described. Objective: The purpose of the survey was to record the provision of vascular surgery services in the period from March 2020 to December 2020 as well as logistical and infrastructural changes that resulted from the pandemic situation. The focus of the survey was on mapping the supply situation as realistically as possible based on the assessment of the lead vascular surgeons. Material and methods: In cooperation with the German Society for Vascular Surgery and Vascular Medicine (DGG), the senior medical staff of all vascular centers in Germany were asked to take part in the survey. The questions were answered anonymously. Results: COVID-19 and corresponding measures resulted in relevant cancellations and postponements of operations, a loss of capacities and an increased workload. During the observational period there was a delay in the treatment of vascular surgical diseases and an increased occurrence of severe clinical stages compared to the corresponding period of the previous year. All levels of care were and continue to be affected. Discussion: In order to counteract the structural weakening and the restrictions in patient care, clinical processes, patient education and prioritization must be optimized. New concepts such as telemedicine and closer clinical control may make sense. A necessary infrastructure for emergency management (COVID) must not negatively affect the quality of care for (vascular) surgical patients in everyday life.

Real-world data of popliteal artery aneurysm treatment: Analysis of the POPART registry.

OBJECTIVE: Popliteal artery aneurysm (PAA) is a rare disease with a prevalence of 0.1% to 1%. Within previous years, endovascular repair (ER) of PAAs has been performed more frequently despite the lack of high-level evidence compared with open surgical repair (OSR). In 2014, the POPART registry was initiated to validate the current treatment options for PAA repair. METHODS: POPART is a multinational multicenter registry of the peri- and postoperative outcomes of ER and OSR for PAAs. Data sets were recorded using the online survey tool SurveyMonkey (available at: https://www.surveymonkey.com/). Regular monitoring and plausibility checks of the data sets are performed to ensure reliability. The aim of the present study was to report the findings from the POPART registry, which includes data from 41 centers. RESULTS: From June 2014 to August 2019, 794 cases had been recorded in the POPART registry. OSR had been performed in 662 patients and ER in 106 patients; 23 patients had been treated conservatively. Of the 106 patients in the primary ER group, 4 had required conversion to OSR. The ER patients were significantly older (ER, median, 71 years; OSR, median, 67 years; P < .05). No other significant differences were present in the demographic data, comorbidities, or aneurysm morphology between the two groups. Of the 662 patients in the OSR group, 50.3% were symptomatic compared with 29.2% of the 106 patients in the ER group (P < .05). Emergency treatment because of acute ischemia, critical ischemia, or rupture was necessary for 149 patients (22.5%) in the OSR group and 11 patients (10.3%) in the ER group. The most frequent postoperative complications were impaired wound healing (OSR, n = 47 [7.1%]; ER, n = 3 [2.8%]; P > .05) and major bleeding (OSR, n = 26 [3.9%]; ER, n = 3 [2.8%]; P > .05). The in-hospital length of stay was significantly longer for the OSR group than for the ER group (median, 10 days; range, 3-65 days; vs median, 7 days; range, 1-73 days). The overall patency for the OSR and ER groups after 12 and 24 months was 83.2% and 44.7% (P < .005) and 74.2% and 29.1% (P < .005), respectively. The outcomes with a prosthetic graft vs an autologous vein were significantly poorer in the OSR group (primary patency, 71.4% vs 88.1% at 12 months). CONCLUSIONS: To evaluate new treatment techniques such as ER for PAAs, real-world data are of essential importance. The present analysis of the first results for the POPART registry shows good perioperative results for endovascular treatment of PAA in asymptomatic patients with good outflow vessels. The perioperative complication rate is low and the postoperative hospital stay is shorter than after OSR. However, the patency rates after 12 and 24 months are low in the ER group compared to patients treated with open repair. More follow-up data is required for further interpretation; the completion of the data sets in the registry is ongoing.

IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation.

Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163-/CD68+) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals.

Emergency response to terrorist attacks: results of the federal-conducted evaluation process in Germany.

PURPOSE: Rescue missions during terrorist attacks are extremely challenging for all rescue forces (police as well as non-police forces) involved. To improve the quality and safety of the rescue missions during an active killing event, it is obligatory to adapt common rescue mission goals and strategies. METHODS: After the recent attacks in Europe, the Federal Office of Civil Protection and Disaster Assistance started an evaluation process on behalf of the Federal Ministry of the Interior and the Federal Ministry of Health. This was done to identify weaknesses, lessons learned and to formulate new adapted guidelines. RESULTS: The presented bullet point recommendations summarise the basic and most important results of the ongoing evaluation process for the Federal Republic of Germany. The safety of all the rescue forces and survival of the greatest possible number of casualties are the priority goals. Furthermore, the preservation and re-establishment of the socio-political integrity are the overarching goals of the management of active killing events. Strategic incident priorities are to stop the killing and to save as much lives as possible. The early identification and prioritised transportation of casualties with life-threatening non-controllable bleeding are major tasks and the shortest possible on-scene time is an important requirement with respect to safety issues. CONCLUSION: With respect to hazard prevention tactics within Germany, we attributed the highest priority impact to the bullet points. The focus of the process has now shifted to intense work about possible solutions for the identified deficits and implementation strategies of such solutions during mass killing incidents.

Shear Stress-Induced miR-143-3p in Collateral Arteries Contributes to Outward Vessel Growth by Targeting Collagen V-α2.

OBJECTIVE: Arteriogenesis, describing the process of collateral artery growth, is activated by fluid shear stress (FSS). Since this vascular mechanotransduction may involve microRNAs (miRNAs), we investigated the FSS-induced expression of vascular cell miRNAs and their functional impact on collateral artery growth during arteriogenesis. Approach and Results: To this end, rats underwent femoral artery ligation and arteriovenous anastomosis to increase collateral blood flow to maximize FSS and trigger collateral vessel remodeling. Five days after surgery, a miRNA expression profile was obtained from collateral tissue, and upregulation of 4 miRNAs (miR-24-3p, miR-143-3p, miR-146a-5p, and miR-195-5p) was verified by quantitative polymerase chain reaction. Knockdown of miRNAs at the same time of the surgery in an in vivo mouse ligation and recovery model demonstrated that inhibition of miR-143-3p only severely impaired blood flow recovery due to decreased arteriogenesis. In situ hybridization revealed distinct localization of miR-143-3p in the vessel wall of growing collateral arteries predominantly in smooth muscle cells. To investigate the mechanotransduction of FSS leading to the increased miR-143-3p expression, cultured endothelial cells were exposed to FSS. This provoked the expression and release of TGF-ß (transforming growth factor-ß), which increased the expression of miR-143-3p in smooth muscle cells in the presence of SRF (serum response factor) and myocardin. COL5A2 (collagen type V-α2)-a target gene of miR-143-3p predicted by in silico analysis-was found to be downregulated in growing collaterals. CONCLUSIONS: These results indicate that the increased miR-143-3p expression in response to FSS might contribute to the reorganization of the extracellular matrix, which is important for vascular remodeling processes, by inhibiting collagen V-α2 biosynthesis.

Exercise-Induced Vascular Adaptations under Artificially Versus Pathologically Reduced Blood Flow: A Focus Review with Special Emphasis on Arteriogenesis.

BACKGROUND: The vascular effects of training under blood flow restriction (BFR) in healthy persons can serve as a model for the exercise mechanism in lower extremity arterial disease (LEAD) patients. Both mechanisms are, inter alia, characterized by lower blood flow in the lower limbs. We aimed to describe and compare the underlying mechanism of exercise-induced effects of disease- and external application-BFR methods. METHODS: We completed a narrative focus review after systematic literature research. We included only studies on healthy participants or those with LEAD. Both male and female adults were considered eligible. The target intervention was exercise with a reduced blood flow due to disease or external application. RESULTS: We identified 416 publications. After the application of inclusion and exclusion criteria, 39 manuscripts were included in the vascular adaption part. Major mechanisms involving exercise-mediated benefits in treating LEAD included: inflammatory processes suppression, proinflammatory immune cells, improvement of endothelial function, remodeling of skeletal muscle, and additional vascularization (arteriogenesis). Mechanisms resulting from external BFR application included: increased release of anabolic growth factors, stimulated muscle protein synthesis, higher concentrations of heat shock proteins and nitric oxide synthase, lower levels in myostatin, and stimulation of S6K1. CONCLUSIONS: A main difference between the two comparators is the venous blood return, which is restricted in BFR but not in LEAD. Major similarities include the overall ischemic situation, the changes in microRNA (miRNA) expression, and the increased production of NOS with their associated arteriogenesis after training with BFR.

[Therapy of Peripheral Artery Aneurysms]. / Therapie primärer Aneurysmen der Extremitätenarterien.

Peripheral arterial aneurysms are rare vascular pathologies characterised by focal dilatation of at least 1.5-fold relative to the diameter of the native vessel. Primary arterial aneurysms can affect any segment of the arterial trunk. Diagnostic tests include duplex sonography, CT and MR angiography, and digital subtraction angiography. It is essential that the influx and efflux to the aneurysm should be mapped as precisely as possible. The most common type of peripheral arterial aneurysms are popliteal artery aneurysms, which frequently occur with aorta aneurysms. Peripheral arterial aneurysms are more common in patients with connective tissue disease or autoimmune disease (Ehlers-Danlos syndrome, Marfan syndrome, Behçet's disease). The current gold standard for therapy is surgery, although endovascular therapies have also been described. As the condition is rare, there is insufficient evidence to compare these approaches. Results from several register studies and single centre studies in patients with popliteal aneurysms indicate that endovascular therapy can give similar outcomes to open therapy if patients are carefully selected. Nevertheless, open surgery remains the gold standard. Therapy of aneurysms of the extremities must consider individual treatment criteria, such as the morphology of the aneurysm, its anatomical localisation - particularly with respect to mobilise segments, vascular efflux and the patient's general condition.

Arteriogenesis is modulated by bradykinin receptor signaling.

RATIONALE: Positive outward remodeling of pre-existing collateral arteries into functional conductance arteries, arteriogenesis, is a major endogenous rescue mechanism to prevent cardiovascular ischemia. Collateral arterial growth is accompanied by expression of kinin precursor. However, the role of kinin signaling via the kinin receptors (B1R and B2R) in arteriogenesis is unclear. OBJECTIVE: The purpose of this study was to elucidate the functional role and mechanism of bradykinin receptor signaling in arteriogenesis. METHODS AND RESULTS: Bradykinin receptors positively affected arteriogenesis, with the contribution of B1R being more pronounced than B2R. In mice, arteriogenesis upon femoral artery occlusion was significantly reduced in B1R mutant mice as evidenced by reduced microspheres and laser Doppler flow perfusion measurements. Transplantation of wild-type bone marrow cells into irradiated B1R mutant mice restored arteriogenesis, whereas bone marrow chimeric mice generated by reconstituting wild-type mice with B1R mutant bone marrow showed reduced arteriogenesis after femoral artery occlusion. In the rat brain 3-vessel occlusion arteriogenesis model, pharmacological blockade of B1R inhibited arteriogenesis and stimulation of B1R enhanced arteriogenesis. In the rat, femoral artery ligation combined with arterial venous shunt model resulted in flow-driven arteriogenesis, and treatment with B1R antagonist R715 decreased vascular remodeling and leukocyte invasion (monocytes) into the perivascular tissue. In monocyte migration assays, in vitro B1R agonists enhanced migration of monocytes. CONCLUSIONS: Kinin receptors act as positive modulators of arteriogenesis in mice and rats. B1R can be blocked or therapeutically stimulated by B1R antagonists or agonists, respectively, involving a contribution of peripheral immune cells (monocytes) linking hemodynamic conditions with inflammatory pathways.