The optimal operative protocol to accomplish CO2-EVAR resulting from a prospective interventional multicenter study.

OBJECTIVES: Carbon dioxide (CO2) angiography for endovascular aortic repair (CO2-EVAR) is used to treat abdominal aortic aneurysms (AAAs), especially in patients with chronic kidney disease or allergy to iodinated contrast medium (ICM). However, some technical issues regarding the visualization of the lowest renal artery (LoRA) and the best quality image through angiographies performed from pigtail or introducer sheath are still unsolved. The aim of this study was to analyze different steps of CO2-EVAR to create an operative standardized protocol. METHODS: Patients undergoing CO2-EVAR were prospectively enrolled in five European centers from 2019 to 2021. CO2-EVAR was performed using an automated injector (pressure, 600 mmHg; volume, 100 cc); a small amount of ICM was injected in case of difficulty in LoRA visualization. LoRA visualization and image quality (1 = low, 2 = sufficient, 3 = good, 4 = excellent) were analyzed at different procedure steps: preoperative CO2 angiography from pigtail and femoral introducer sheath (first step), angiographies from pigtail at 0%, 50%, and 100% of proximal main body deployment (second step), contralateral hypogastric artery (CHA) visualization with CO2 injection from femoral introducer sheath (third step), and completion angiogram from pigtail and femoral introducer sheath (fourth step). Intraoperative and postoperative CO2-related adverse events were also evaluated. χ2 and Wilcoxon tests were used for statistical analysis. RESULTS: In the considered period, 65 patients undergoing CO2-EVAR were enrolled (55/65 [84.5%] male; median age, 75 years [interquartile range (IQR), 11.5 years]). The median ICM injected was 17 cc (IQR, 51 cc); 19 (29.2%) of 65 procedures were performed with 0 cc ICM. Fifty-five (84.2%) of 65 patients underwent general anesthesia. In the first step, median image quality was significantly higher with CO2 injected from femoral introducer (pigtail, 2 [IQR, 3] vs introducer, 3 [IQR, 3]; P = .008). In the second step, LoRA was more frequently detected at 50% (93% vs 73.2%; P = .002) and 100% (94.1% vs 78.4%; P = .01) of proximal main body deployment compared with first angiography from pigtail; similarly, image quality was significantly higher at 50% (3 [IQR, 3] vs 2 [IQR, 3]; P ≤ .001) and 100% (4 [IQR, 3] vs 2 [IQR, 3]; P = .001) of proximal main body deployment. CHA was detected in 93% cases (third step). The mean image quality was significantly higher when final angiogram (fourth step) was performed from introducer (pigtail, 2.6 ± 1.1 vs introducer, 3.1 ± 0.9; P ≤ .001). The intraoperative (7.7%) and postoperative (12.5%) adverse events (pain, vomiting, diarrhea) were all transient and clinically mild. CONCLUSIONS: Preimplant CO2 angiography should be performed from femoral introducer sheath. Gas flow impediment created by proximal main body deployment can improve image quality and LoRA visualization with CO2. CHA can be satisfactorily visualized with CO2 alone. Completion CO2 angiogram should be performed from femoral introducer sheath. This operative protocol allows performance of CO2-EVAR with 0 cc or minimal ICM, with a low rate of mild temporary complications.

Vascular education through e-Learning.

Background: The COVID-19 pandemic has changed everyday life and work in many ways. As travelling to meetings and conferences was almost completely suppressed for most of healthcare professionals, e-Learning became increasingly prominent. The overall utility of e-Learning during the COVID-19 pandemic as well as its shortcomings in the international community of vascular surgery were assessed through the EL-COVID study. Regional variability was observed amongst participating nations, which is currently being addressed through several ongoing subgroup analyses. Our study completes the aforementioned efforts and aims to investigate the adherence and adoption of vascular e-Learning in Germany. Methods and participants: Using an online survey, EL-COVID gathered answers from 856 vascular surgeons, of whom 70 were located in Germany. We analyzed the answers of 62 German responders that attended at least one e-Learning activity and compared them with the remaining worldwide data. Results: Out of all European countries, Germany was best represented and ranked second worldwide after Mainland China (n=109). 30.6 percent of the German responders were female (vs. 20% worldwide; p=0.048) and 56.4% were vascular surgeons with >5 years of practice (vs. 56.3; p=0.975). The international cohort generally engaged in more e-Learning. Most German participants attended less than 4 online activities, while only 24.2% took part in more than 4 such events (vs. 56.3; p<0.0001). While the overall impression of e-Learning activities during the COVID-19 pandemic was positive, German employers were less supportive of participation during working hours (30.6% vs. 44%; p=0.042). The main reason for not attending was lack of time due to increased workload (56.5% vs. 50%; p=0.328). National and international societies played a lesser role in promoting such activities in Germany (22.6% vs. 39.2%; p=0.010), the same accounts for social media (16.1 vs. 30.3; p=0.017). Conclusions: E-Learning complements the classical training methods and has been embraced as a relevant alternative in the time of the COVID-19 pandemic. The results of this survey appeal to German employers and national societies to improve support and dissemination of e-Learning activities in the vascular medicine community.

The Association of Spondylitis and Aortic Aneurysm Disease.

OBJECTIVES: The aim of this study is to assess any relation between spondylitis and aortic aneurysmal disease by reviewing the current literature. METHODS: A systematic search was undertaken using MEDLINE, EMBASE and CENTRAL databases till May 2019, for articles reporting on patients suffering from spondylitis and aortic aneurysm. RESULTS: The most involved aortic segment was infrarenal aorta (56.9%). The lumbar vertebrae were more frequently affected (79.7%). Commonest symptoms were back pain (79.1%), fever (33.7%) and lower limb pain (29.1%). 55.8% of cases were diagnosed using computed tomography. The pathology was attributed to infectious causes in 25.1% of cases. 53.4% of patients were treated only for the aneurysm, 27.9% for both pathologies, while two patients solely for the vertebral disease. Endovascular aneurysm repair was chosen in 12.8% of cases. The 30-day mortality was 8.1% (7/86); mostly from vascular complications. CONCLUSIONS: A synchronous spondylitis and aortic aneurysm may share common etiopathology, when an infectious or inflammatory cause is presented. The lumbar vertebrae are more frequently affected. Low quality data do not allow safe conclusion to suggest the best treatment option.

Vascular e-Learning During the COVID-19 Pandemic: The EL-COVID Survey.

BACKGROUND: The corona virus disease (COVID-19) pandemic has radically changed the possibilities for vascular surgeons and trainees to exchange knowledge and experience. The aim of the present survey is to inventorize the e-learning needs of vascular surgeons and trainees as well as the strengths and weaknesses of vascular e-Learning. METHODS: An online survey consisting of 18 questions was created in English, with a separate bilingual English-Mandarin version. The survey was dispersed to vascular surgeons and trainees worldwide through social media and via direct messaging from June 15, 2020 to October 15, 2020. RESULTS: Eight hundred and fifty-six records from 84 different countries could be included. Most participants attended several online activities (>4: n = 461, 54%; 2-4: n = 300, 35%; 1: n = 95, 11%) and evaluated online activities as positive or very positive (84.7%). In deciding upon participation, the topic of the activity was most important (n = 440, 51.4%), followed by the reputation of the presenter or the panel (n = 178, 20.8%), but not necessarily receiving accreditation or certification (n = 52, 6.1%). The survey identified several shortcomings in vascular e-Learning during the pandemic: limited possibility to attend due to lack of time and increased workload (n = 432, 50.5%), no protected/allocated time (n = 488, 57%) and no accreditation or certification, while technical shortcomings were only a minor problem (n = 25, 2.9%). CONCLUSIONS: During the COVID-19 pandemic vascular e-Learning has been used frequently and was appreciated by vascular professionals from around the globe. The survey identified strengths and weaknesses in current e-Learning that can be used to further improve online learning in vascular surgery.

Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans.

Circulating or tissue-related biomarkers are of clinical value for risk stratification in patients with abdominal aortic aneurysms. Relaxin-2 (RL2) has been linked to the presence and size of arterial aneurysms, and to the extent of atherosclerosis in human subjects. Here, we assessed the expression levels of RL2 in aneurysmal (AA, n = 16) and atherosclerotic (ATH, n = 22) arteries, and established the correlation between RL2 levels and the presence/size of AA and the clinical severity of atherosclerosis. The expression levels of metalloproteinases (MMPs) and endothelial nitric oxide synthetase (eNOS) were also detected for correlations with different phenotypes of atherosclerosis and AA. Temporal artery biopsy specimens (n = 6) and abdominal aortic tissues harvested from accident victims during autopsy (n = 10) were used as controls. Quantitative tissue biomarker analysis revealed that tissue-specific RL2 was increased in patients with larger or symptomatic AA compared to subjects with atherosclerotic disease and healthy controls. In situ RL2 levels were proportional to the size and the severity of aneurysmatic disease, and were substantially elevated in patients with symptomatic aneurysm of any diameter or asymptomatic aneurysm of a diameter >350% of that of the normal artery. In contrast, tissue RL2 was inversely associated with the clinical severity of atherosclerotic lesions. Correlation between RL2 and MMP2 was different between ATH1 and ATH2, depending on atherosclerosis grade. Overall, tissue RL2 is differentially associated with discrete phenotypes of arterial disease and might exert multipotent biological effects on vascular wall integrity and remodeling in human subjects.

Associations between serum relaxin 2, aneurysm formation/size and severity of atherosclerosis: a preliminary prospective analysis.

Serum relaxin 2 (RL2) is a pleiotropic hormone that acts on various organs and systems, particularly the cardiovascular system. Although RL2 seems to upregulate the synthesis of nitric monoxide (NO) and matrix metalloproteinase (MMP)-2 and -9, current literature on its role in atherosclerosis and aneurysm formation is scarce. The aim of this study was to investigate the levels of serum RL2 in patients with an arterial aneurysm as well as in atherosclerotic patients, and correlate them with the severity of their related vascular disease. A total of 53 subjects were enrolled in this study: 37 patients were scheduled to undergo surgery: 21 patients for different forms of atherosclerotic disease (ATH), 16 patients for an arterial aneurysm (AA), 6 patients for undergoing temporal artery biopsy (TAB), and 10 healthy blood donors (HBD) served as the control groups. RL2 was measured using enzymelinked immunosorbent assay. RL2 was significantly higher in AA patients compared to ATH (P<0.01), TAB (P<0.001) and HBD (P<0.01). No significant difference was found between the ATH and TAB groups (P>0.05). In addition, ATH and AA patients were further subdivided based on the severity of their disease. Serum RL2 was progressively increased in patients with arterial aneurysms, showing a positive relationship with the size of the aneurysmatic dilatation. By contrast, the RL2 level was inversely related to the severity of the atherosclerotic disease. Studies with a larger cohort incorporating a consistent study population are warranted to verify our results and shed light on the mechanistic background of these processes.

Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.

Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. The aim of this study was to elucidate the predictive value of Apo J in internal carotid artery (ICA) restenosis following CEA. This retrospective study examined all prospectively collected data for patients who underwent CEA at our surgical department over a 2-year period. The serum ApoJ levels of 100 patients were examined; 56 patients who underwent CEA comprised the vascular group (VG), and 44 patients who underwent minor surgery comprised the control group (CG). ApoJ samples were obtained preoperatively, 24 h after the surgical procedure and at 1, 6 and 12 months thereafter during the follow-up. The preoperative difference in ApoJ levels between the CG and VG was statistically signifcant; the mean values were 39.11±14.16 and 83.03±35.35 µg/mL, respectively. In the VG, the serum ApoJ levels were 112.09±54.40, 71.20±23.70, 69.92±25.76 and 62.25±19.17 µg/mL at postoperative day 1 and at 1, 6 and 12 months post-operatively, respectively, while the ApoJ concentrations of patients in the CG remained unchanged. Further subdivision of the VG into patients with or without restenosis revealed that restenosis patients presented signifcantly higher mean ApoJ values than non-restenosis VG patients. In summary, ApoJ seems to be an important predictor for carotid restenosis at 6 and 12 months postoperatively.

Cytokines as biomarkers of inflammatory response after open versus endovascular repair of abdominal aortic aneurysms: a systematic review.

The repair of an abdominal aortic aneurysm (AAA) is a high-risk surgical procedure related to hormonal and metabolic stress-related response with an ensuing activation of the inflammatory cascade. In contrast to open repair (OR), endovascular aortic aneurysm repair (EVAR) seems to decrease the postoperative stress by offering less extensive incisions, dissection, and tissue manipulation. However, these beneficial effects may be offset by the release of cytokines and arachidonic acid metabolites during intra-luminal manipulation of the thrombus using catheters in endovascular repair, resulting in systemic inflammatory response (SIR), which is clinically called post-implantation syndrome. In this systematic review we compared OR with EVAR in terms of the post-interventional inflammatory response resulting from alterations in the circulating cytokine levels. We sought to summarize all the latest evidence regarding post-implantation syndrome after EVAR. We searched Medline (PubMed), ClinicalTrials.gov and the Cochrane library for clinical studies reporting on the release of cytokines as part of the inflammatory response after both open/conventional and endovascular repair of the AAA. We identified 17 studies examining the cytokine levels after OR versus EVAR. OR seemed to be associated with a greater SIR than EVAR, as evidenced by the increased cytokine levels, particularly IL-6 and IL-8, whereas IL-1ß, IL-10 and TNF-α showed conflicting results or no difference between the two groups. Polyester endografts appear to be positively correlated with the incidence of post-implantation syndrome after EVAR. Future large prospective studies are warranted to delineate the underlying mechanisms of the cytokine interaction in the post-surgical inflammatory response setting.

Stenting of Subclavian Artery True and False Aneurysms: A Systematic Review.

BACKGROUND: Aneurysms of the subclavian artery are usually the result of trauma, atherosclerosis, or thoracic outlet syndrome. Until the 90s, open surgical repair was considered the only therapeutic choice, exhibiting high complication rates. Since the first report of endovascular repair of subclavian aneurysms in 1991, promising results have been published. The aim of this review was to summarize all available data on subclavian artery (SA) true and false aneurysm stenting to reach conclusions regarding morbidity, mortality, and other procedure-related characteristics. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Eligible studies were sought in the Medline (PubMed), ClinicalTrials.gov, and Cochrane library-Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 2017 using the following MeSH terms: "endovascular", "hybrid", "aneurysm", "pseudo-aneurysm", "pseudo-aneurysm", "false aneurysm", "arterial injury", "subclavian artery", "axillo-subclavian," and "axillosubclavian artery". The reference lists of eligible articles and pertinent reviews were screened for potential relevant studies. RESULTS: Seventy-three studies encompassing data on 142 patients who underwent endovascular or hybrid SA aneurysm repair were deemed eligible. One hundred forty-seven stents and stent grafts were used. Median age of all patients was 56 years, and males comprised 46% of the study sample. Trauma was the most common mechanism of injury. Pulsatile mass or hematoma was the most frequent presenting sign. Pseudoaneurysms were the most frequent type of aneurysms, followed by true aneurysms. Most authors used self-expanding polytetrafluoroethylene-covered stents. Access was obtained by either brachial, femoral, or both arteries. Through-and-through technique was also used in angulated vessels. All-cause mortality was 10.6%, slightly higher to that already reported in literature and lower to the respective rate of the open repair. Reintervention rate was 8.5% despite the high 15.5% complication rate. CONCLUSIONS: Endovascular SA aneurysm repair is a technically feasible technique, useful in both elective and emergency cases. Although preliminary results quote its safety and efficacy, larger cohort studies are warranted to elucidate its benefit in treating SA aneurysms.

Histone deacetylase inhibitors as a new anticancer option: How far can we go with expectations? delivery systems.

Histone modification that occurs through the process of acetylation plays a key role in the epigenetic regulation of gene expression. The balance between histone deacetylases (HDACs) and histone acetyltransferases controls this process. Histone deacetylase inhibitors (HDACIs) can induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Therefore, HDAIs represent a group of enzymes that can be used for the development of pharmaceutical agents against a variety of malignant diseases. The mechanisms of their anticancer effect depend on many factors. HDACIs vorinostat, romidepsin and belinostat have been approved for some T-cell lymphomas and panobinostat for multiple myeloma. Other HDACIs are tested in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed.

Neoaortoiliac System Procedure to Treat Infected Aortic Grafts.

BACKGROUND: The aim of this case series is to report the results of our center in the surgical treatment of infected abdominal aortic grafts using the neoaortoiliac system (NAIS) procedure. METHODS: Four male and 2 female patients underwent an NAIS repair after endovascular (n = 3), open (n = 2), or combined surgery (n = 1) in our center. Mean age was 73 ± 5.2 years. Graft infection was diagnosed by computed tomography angiography (CTA), and only in 2 cases further imaging was necessary. The diagnosis was set at average 6.2 years after the initial procedure. RESULTS: Four patients underwent a standard pantaloon NAIS procedure, 1 patient with a small aortic diameter received 1 femoral vein as aortoaortic interposition graft, and 1 patient received a unilateral aortoiliac bypass; all patients received autologous femoral veins grafts. Thirty-day mortality was zero, with in-hospital mortality of 1 patient (16.7%). Mean hospital stay was 27 ± 4.9 days, with mean intensive care unit stay of 2.2 days (range: 1-3). During follow-up (mean: 6.17 months, range: 1-24 months), 2 patients presented with thigh wound complications, one of which required surgical revision. One patient was readmitted due to upper gastrointestinal (GI) bleeding as a side effect of anticoagulation, without the presence of ulcer or other GI pathology. CONCLUSIONS: In our early experience, NAIS showed to be a demanding procedure for both the patient and the surgical team. It avoids however the disadvantages of extra-anatomic bypass and other methods used to treat aortic graft infection. Larger study groups are necessary to support these findings.

Management of concomitant abdominal aortic aneurysm and colorectal cancer.

OBJECTIVE: To conduct a systematic review of the literature and perform an analysis of outcomes of treatment of concomitant colorectal cancer (CRC) and abdominal aortic aneurysm (AAA) with a focus on the different treatment options and the related therapeutic outcomes. METHODS: A review of the English-language medical literature from 1980 to 2015 was undertaken using the PubMed and EMBASE databases to identify studies reporting surgical treatment of patients with concomitant CRC and AAA. The search identified 24 articles encompassing 254 patients (81% male; mean age 73.5 ± 6.1 years). RESULTS: In 96 patients (37.9%) cancer resection was performed first, followed by AAA repair at a later stage (open aortic repair [OAR], 79.2%; endovascular abdominal aortic repair [EVAR], 20.8%). Eighty-two patients (32.3%) underwent AAA repair (OAR, 47.5%; EVAR, 52.5%) before CRC resection. Seventy-one patients (27.9%) underwent combined OAR and CRC resection, and just five (1.9%) were treated with EVAR and cancer surgery in a single stage. There were eight of 96 interval AAA ruptures (8.3%), mostly in the early postoperative period concerning aneurysms >6 cm in diameter. The mean interval between the two procedures was much shorter in patients treated with EVAR than OAR (11.5 ± 1.8 days vs 103.9 ± 42.3 days). The overall 30-day mortality rate was 10.9%. Data from observational studies showed no significant differences in 30-day mortality between patients treated in one or two stages (P = .89). No mortality was recorded in any of the EVAR-treated patients. There was only one graft infection recorded (0.4%). CONCLUSIONS: Among different approaches, no significant differences in 30-day outcomes among patients treated in either two or one stage were evident. EVAR showed the lowest mortality and also diminished the delay between the two procedures in <2 weeks for a two-stage approach, although it has been associated with a significant risk for thrombotic events. The coexistence of AAA and CRC seems to favor the use of EVAR in treating those patients.

Hybrid Treatment of Large Brachial Artery Pseudoaneurysms.

BACKGROUND: Conventional surgical treatment of brachial artery pseudoaneurysms (BAPs) includes aneurysm excision/opening and subsequent arterial reconstruction with different options depending on the extent of the arterial deficit. Endovascular repair of BAPs with stent grafting has also been reported but published experience remains limited. In this report, we present our experience with a novel hybrid approach consisting of primary endovascular aneurysm exclusion with a stent graft and subsequent open surgical evacuation of pseudoaneurysm content for decompression of adjacent structures. METHODS: This study included all patients who underwent hybrid repair of a BAP within the period 2005-2014 in our institution. Data were collected retrospectively. RESULTS: During the study period a total of 5 patients with iatrogenic BAPs were treated. Mean BAP diameter was 58 ± 4.9 mm. Technical success was 100%. Thirty-day mortality was null. No major perioperative complications were noted. Hand ischemia and neurological symptoms were reversed in all patients after the procedure. During follow-up (median 24 months, range 6-60 months) all stent grafts remained patent and no aneurysm relapse was noticed. No signs of stent-graft infection were noticed in any of the patients and no reintervention was needed. CONCLUSIONS: Primary endovascular exclusion of BAPs with a stent graft followed by surgical evacuation of pseudoaneurysm sac content is associated with good early and mid-term results in this limited experience. Larger patient cohorts are required for further evaluation of this technique.

Meta-analysis of the Effect of Stent Design on 30-Day Outcome After Carotid Artery Stenting.

PURPOSE: To review the contemporary literature and analyze whether stent cell design plays a role in 30-day outcomes after carotid artery stenting (CAS). METHODS: A systematic review of the literature was undertaken that identified 9 studies comparing the effect of different cell design on 30-day outcome in patients undergoing CAS. Random-effects models were applied to calculate pooled outcome data for mortality and cerebrovascular morbidity. Results are reported as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: The 9 studies included 8018 patients who underwent 8028 CAS procedures (4018 open-cell stents, 4010 closed-cell stents). Six studies were retrospective in design, one was a registry, and only two studies prospectively compared the effect of different cell designs. Nearly half of the patients (3452, 43.1%) were symptomatic, with no significant difference between the closed- and open-cell stent groups (p=0.93). During the first month after the procedure, there were no significant differences in mortality (OR 0.69, 95% CI 0.39 to 1.24, p=0.21), transient ischemic attacks (OR 0.95, 95% CI 0.69 to 1.30, p=0.74), or strokes (OR 1.17, 95% CI 0.83 to 1.66, p=0.37). CONCLUSION: This meta-analysis showed that 30-day cerebrovascular complications after CAS were not significantly different for the open-cell group in comparison to the closed-cell group. Future prospective clinical trials comparing different free cell areas and other stent design properties are still needed to further investigate whether stent design plays a significant role in the results of carotid stenting.

An Update on the Inflammatory Response after Endovascular Repair for Abdominal Aortic Aneurysm.

Postimplantation syndrome (PIS) is the clinical and biochemical expression of an inflammatory response following endovascular repair of an aortic aneurysm (EVAR). The goal of this review is to provide an update on the inflammatory response after endovascular repair of abdominal aortic aneurysm, discussing its causes and effects on the clinical outcome of the patient. PIS concerns nearly one-third of patients after EVAR. It is generally a benign condition, although in some patients it may negatively affect outcome. The different definitions and conclusions drawn from several studies reveal that PIS needs to be redefined with standardized diagnostic criteria. The type of the endograft's material seems to play a role in the inflammatory response. Future studies should focus on a better understanding of the underlying pathophysiology, predictors, and risk factors as well as determining whether effective preventive strategies are necessary.