Soluble Glycoprotein VI Predicts Abdominal Aortic Aneurysm Growth Rate and is a Novel Therapeutic Target.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.

Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms.

BACKGROUND: Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention. METHODS: TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr-/-) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3-/-). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA. RESULTS: Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3-/- mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK. CONCLUSIONS: These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Incidence, diagnosis, management and outcome of acute mesenteric ischaemia: a prospective, multicentre observational study (AMESI Study).

BACKGROUND: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI). METHODS: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.2022 to 05.04.2023 were included. Participants who were subsequently shown not to have AMI or had localized intestinal gangrene due to strangulating bowel obstruction had only baseline and outcome data collected. RESULTS: AMI occurred in 0.038% of adult admissions in participating acute care hospitals worldwide. From a total of 705 included patients, 418 patients had confirmed AMI. In 69% AMI was the primary reason for admission, while in 31% AMI occurred after having been admitted with another diagnosis. Median time from onset of symptoms to hospital admission in patients admitted due to AMI was 24 h (interquartile range 9-48h) and time from admission to diagnosis was 6h (1-12 h). Occlusive arterial AMI was diagnosed in 231 (55.3%), venous in 73 (17.5%), non-occlusive (NOMI) in 55 (13.2%), other type in 11 (2.6%) and the subtype could not be classified in 48 (11.5%) patients. Surgery was the initial management in 242 (58%) patients, of which 59 (24.4%) underwent revascularization. Endovascular revascularization alone was carried out in 54 (13%), conservative treatment in 76 (18%) and palliative care in 46 (11%) patients. From patients with occlusive arterial AMI, revascularization was undertaken in 104 (45%), with 40 (38%) of them in one site admitting selected patients. Overall in-hospital and 90-day mortality of AMI was 49% and 53.3%, respectively, and among subtypes was lowest for venous AMI (13.7% and 16.4%) and highest for NOMI (72.7% and 74.5%). There was a high variability between participating sites for most variables studied. CONCLUSIONS: The overall incidence of AMI and AMI subtypes varies worldwide, and case ascertainment is challenging. Pre-hospital delay in presentation was greater than delays after arriving at hospital. Surgery without revascularization was the most common management approach. Nearly half of the patients with AMI died during their index hospitalization. Together, these findings suggest a need for greater awareness of AMI, and better guidance in diagnosis and management. TRIAL REGISTRATION: NCT05218863 (registered 19.01.2022).

Biomarkers In Prediction of Acute Mesenteric Ischaemia: a prospective multicentre study (BIPAMI study): a study protocol.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia. METHODS: This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student's t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio < 0.1 (< 0.2) indicate high (moderate) diagnostic accuracy, respectively. All biomarkers with at least moderate accuracy will be entered as binary covariates (using the best cutoffs) into the multivariable stepwise regression analysis to identify the best combination of biomarkers for all comparisons separately. The best models for each comparison will be used to construct a practical score to distinguish between no AMI, non-transmural AMI and transmural AMI. DISCUSSION: As a result of this study, we aim to propose a score including set of biomarkers that can be used for diagnosis and decision-making in patients with suspected AMI. TRIAL REGISTRATION: NCT06212921 (Registration Date 19-01-2024).

Tea consumption and the risk of abdominal aortic aneurysm.

BACKGROUND: Tea has the potential to lower the risk of abdominal aortic aneurysm (AAA) owing to its high antioxidant capacity. AAA risk factors including smoking, hypertension, and hypercholesterolaemia, may modify this association. METHODS: The study population included 45 047 men in the Cohort of Swedish Men (COSM) and 36 611 women in the Swedish Mammography Cohort (SMC), aged 45-83 years at baseline. The COSM was established in 1997 with all men who lived in two central Swedish counties (Västmanland and Örebro), and the SMC was established in 1987-1990 with women residing in Västmanland county. Tea consumption was assessed by means of food frequency questionnaires in 1997 and 2009. RESULTS: During 17.5 years of follow-up, 1781 AAA cases (1496 men, 285 women; 1497 non-ruptured, 284 ruptured) were ascertained via Swedish registers. Tea consumption was inversely associated with total AAA incidence in men and women. Women had a 23 (95 per cent c.i. 8 to 36) per cent lower risk of AAA per each cup per day increment, whereas men had a 9 (0 to 17) per cent lower risk (Pinteraction = 0.029). Tea consumption was associated with a lower risk of both non-ruptured (hazard ratio (HR) 0.93, 95 per cent c.i. 0.85 to 1.01) and ruptured (HR 0.84, 0.71 to 0.98) AAA. Smoking status modified the association (Pinteraction < 0.001), whereby tea consumption was associated with lower risk of AAA in ex-smokers (per cup per day, HR 0.89, 0.80 to 0.98) and in never smokers (HR 0.88, 0.77 to 1.00), but not in current smokers (HR 0.95, 0.84 to 1.06). Tea consumption was associated with a lower risk in participants with (HR 0.88, 0.80 to 0.98) and without (HR 0.93, 0.88 to 1.00) hypertension, and in those with (HR 0.82, 0.67 to 1.01) and without (HR 0.92, 0.86 to 0.98) hypercholesterolaemia. CONCLUSION: Tea consumption was associated with a reduced risk of AAA. The association was more pronounced for ruptured than non-ruptured AAA, and in patients with hypertension and hypercholesterolaemia than those without. The association was also observed in ex-smokers and never smokers, but not in current smokers.

Acute mesenteric ischaemia.

PURPOSE OF REVIEW: To summarize the recent evidence on acute mesenteric ischaemia (AMI). RECENT FINDINGS: The overall incidence of AMI is below 10/100 000 person years but increases exponentially with age. The overall mortality of AMI remains high, exceeding 50%, despite continuing progress and increasing availability of imaging and endovascular interventions. However, patients with (early) revascularization have significantly better outcomes. The majority of patients surviving the acute event are still alive at 1 year, but evidence on quality of life is scarce.Clinical suspicion of AMI is the key to timely diagnosis, with biphasic computed tomography-angiography the diagnostic method of choice. Currently, no biomarker has sufficient specificity to diagnose AMI. SUMMARY: Improved awareness and knowledge of AMI are needed to raise the suspicion of AMI in relevant patients and thereby to achieve better outcomes.

Carotid Endarterectomy After Intracranial Endovascular Thrombectomy for Acute Ischaemic Stroke in Patients with Carotid Artery Stenosis.

OBJECTIVE: Recent randomised controlled trials demonstrated the benefit of intracranial endovascular thrombectomy (EVT) in acute ischaemic stroke. There is no consensus, however, on how to treat concomitant extracranial carotid artery stenosis after EVT. The aim of this study was to evaluate the outcome in patients treated with carotid endarterectomy (CEA) after EVT, comparing complication rates among patients undergoing CEA for stroke without previous EVT. METHODS: This was a registry study of all patients (n = 3 780) treated with CEA after stroke in Sweden and the capital Helsinki region, Finland, from January 2011 to September 2020. Sixty three patients (1.7%; 0.5% 2011, 4.3% 2019) underwent EVT prior to CEA. The primary outcome was 30 day stroke and death rate. RESULTS: The EVT+CEA group had major stroke as the qualifying neurological event (QNE) in 79%, but just 5.9% had this in the CEA only group (p < .001). Intravenous thrombolysis was administered before EVT in 54% of patients in the EVT+CEA group, but in just 12% in those receiving CEA only (p < .001). The combined stroke and death rate at 30 days for EVT+CEA was 0.0% (95% confidence interval [CI] 0.0 - 5.7). One patient had a post-operative TIA, none had post-operative intracerebral or surgical site haemorrhage. CEA was performed within a median of seven days (interquartile range 4, 15) after QNE, and 75% had CEA ≤14 days from QNE. The main reason to postpone CEA was an infarct larger than one third of the middle cerebral artery territory. The stroke and death rate in patients treated with CEA only was 3.7% (95% CI 3.2 - 4.4), CEA was performed a median of eight days after QNE, and in 79.7% in ≤14 days. The three year survival after EVT+CEA was 93% (95% CI 85 - 100), compared with 87% (95% CI 86 - 88) after CEA only. Cox regression analysis adjusting for age showed no increased all cause mortality after EVT+CEA (HR 1.3, 95% CI 0.6 - 2.7, p = .52). CONCLUSION: These results indicate that CEA is safe to perform after previous successful EVT for acute ischaemic stroke. Results were comparable with those undergoing CEA only, despite the EVT+CEA patients having more severe stroke symptoms prior to surgery, and timing was similar.

Editor's Choice - Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial.

OBJECTIVE: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. METHODS: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. RESULTS: The median follow up was 19.4 years (interquartile range 16.9 - 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 - 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). CONCLUSION: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.

Editor's Choice - Update of the European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia in Light of the COVID-19 Pandemic, Based on a Scoping Review of the Literature.

OBJECTIVE: To perform a scoping review of how patients with COVID-19 are affected by acute limb ischaemia (ALI) and evaluate the recommendations of the 2020 ESVS ALI Guidelines for these patients. METHODS: Research questions were defined, and a systematic literature search was performed following the PRISMA guidelines. Abstracts and unpublished literature were not included. The definition of ALI in this review is in accordance with the ESVS guidelines. RESULTS: Most identified papers were case reports or case series, although population based data and data from randomised controlled trials were also identified. In total, 114 unique and relevant papers were retrieved. Data were conflicting concerning whether the incidence of ALI increased, or remained unchanged, during the pandemic. Case reports and series reported ALI in patients who were younger and healthier than usual, with a greater proportion affecting the upper limb. Whether or not this is coincidental remains uncertain. The proportion of men/women affected seems unchanged. Most reported cases were in hospitalised patients with severe COVID-19. Patients with ALI as their first manifestation of COVID-19 were reported. Patients with ALI have a worse outcome if they have a simultaneous COVID-19 infection. High levels of D-dimer may predict the occurrence of arterial thromboembolic events in patients with COVID-19. Heparin resistance was observed. Anticoagulation should be given to hospitalised COVID-19 patients in prophylactic dosage. Most of the treatment recommendations from the ESVS Guidelines remained relevant, but the following were modified regarding patients with COVID-19 and ALI: 1) CTA imaging before revascularisation should include the entire aorta and iliac arteries; 2) there should be a high index of suspicion, early testing for COVID-19 infection and protective measures are advised; and 3) there should be preferential use of local or locoregional anaesthesia during revascularisation. CONCLUSION: Although the epidemiology of ALI has changed during the pandemic, the recommendations of the ESVS ALI Guidelines remain valid. The above mentioned minor modifications should be considered in patients with COVID-19 and ALI.

Editor's Choice - European Society for Vascular Surgery Clinical Practice Guideline Development Scheme: An Overview of Evidence Quality Assessment Methods, Evidence to Decision Frameworks, and Reporting Standards in Guideline Development.

OBJECTIVE: A structured and transparent approach is instrumental in translating research evidence to health recommendations and evidence informed clinical decisions. The aim was to conduct an overview and analysis of principles and methodologies for health guideline development. METHODS: A literature review on methodologies, strategies, and fundamental steps in the process of guideline development was performed. The clinical practice guideline development process and methodology adopted by the European Society for Vascular Surgery are also presented. RESULTS: Sophisticated methodologies for health guideline development are being applied increasingly by national and international organisations. Their overarching principle is a systematic, structured, transparent, and iterative process that is aimed at making well informed healthcare choices. Critical steps in guideline development include the assessment of the certainty of the body of evidence; evidence to decision frameworks; and guideline reporting. The goal of strength of evidence assessments is to provide well reasoned judgements about the guideline developers' confidence in study findings, and several evidence hierarchy schemes and evidence rating systems have been described for this purpose. Evidence to decision frameworks help guideline developers and users conceptualise and interpret the construct of the quality of the body of evidence. The most widely used evidence to decision frameworks are those developed by the GRADE Working Group and the WHO-INTEGRATE, and are structured into three distinct components: background; assessment; and conclusions. Health guideline reporting tools are employed to ensure methodological rigour and transparency in guideline development. Such reporting instruments include the AGREE II and RIGHT, with the former being used for guideline development and appraisal, as well as reporting. CONCLUSION: This guide will help guideline developers/expert panels enhance their methodology, and patients/clinicians/policymakers interpret guideline recommendations and put them in context. This document may be a useful methodological summary for health guideline development by other societies and organisations.

Nationwide Study of Ruptured Abdominal Aortic Aneurysms During Twenty Years (1994-2013).

OBJECTIVE: To analyze the epidemiology of ruptured abdominal aortic aneurysms (RAAA) in Sweden over 20 years, and assess the effect of endovascular repair (EVAR) on surgical treatment rate and outcome. METHODS: All Swedish citizens >50 years with RAAA 1994 to 2013 were extracted from 3 national (Cause of Death, Patient, and Vascular Surgical) registries. Incidence, proportion repaired, surgical techniques, and 90-day mortality were assessed based on sex and age groups, with regression analysis. RESULTS: 18,726 individuals with RAAA were identified, 74.0% men. The incidence of RAAA decreased from 33.1/100,000: 1994 to 21.3/100,000: 2013 (relative change -35.6%, P < 0.001). The proportion of men with RAAA undergoing repair was 44.5%: 1994-1998, 49.7%: 2009-2013 (+11.7%, P < 0.001). In women, 22.3% were repaired in 1994-1998, versus 28.2%: 2009-2013 (+26.4%, P < 0.001). The proportion undergoing repair increased in octogenarians (men: +44.3%, P < 0.001; women +49.3%, P = 0.001). EVAR increased from 0% initially to 42.3% in men and 41.2% in women 2013. Overall, mortality rate among all individuals with RAAA decreased, men 75.8%: 1994-1998, 64.8%: 2009-2013 (-14.5%, P < 0.001); women 88.5%: 1994-1998, 82.2%: 2009-2013 (-7.1%, P < 0.001). Among those who underwent repair, mortality was 47.0% in men: 1994-1998, 31.8%: 2009-2013 (-32.3%, P < 0.001); women 51.8%: 1994-1998, 41.4%: 2009-2013 (-20.1%, P = 0.010). CONCLUSION: RAAA mortality among men decreased, mainly attributed to falling incidence of RAAA. The mortality was further reduced by more patients being offered repair, increasingly often with EVAR, and improved survival after repair. Incidence of rupture remained unchanged among women, who had higher RAAA mortality. Focused efforts to reduce RAAA mortality among women are warranted.

Surveillance to detect colonic ischemia with extraluminal pH measurement after open surgery for abdominal aortic aneurysm.

OBJECTIVE: Colonic ischemia (CI) is a life-threatening complication after aortic surgery. Postoperative surveillance of colonic perfusion might be warranted. The aim of the present study was to evaluate the safety and feasibility of postoperative extraluminal pH measurement (pHe) using colonic tonometry after open abdominal aortic aneurysm (AAA) repair. METHODS: Before closing the abdomen after open AAA repair, a tonometric catheter was placed transabdominally in contact with the sigmoid colon serosa, similar to a drainage catheter. Extraluminal partial pressure of carbon dioxide was measured postoperatively and combined with arterial blood gas analysis to calculate the pHe. The measurements were repeated every 4 hours with simultaneous intra-abdominal pressure measurements. The threshold for colonic malperfusion was set at pHe <7.2. RESULTS: A total of 27 patients were monitored, 12 had undergone surgery for ruptured AAAs and 15 for intact AAAs. Of the 27 patients, 4 developed clinically significant CI requiring surgery. All four cases were preceded by a prolonged (>5 hours) pHe <7.2 indicating malperfusion. A fifth patient, who, during monitoring, had had the lowest pHe of 7.21, developed mild CI with the onset after completion of monitoring, which was successfully managed conservatively. Seven patients who had had brief durations (<5 hours) of pHe <7.2 did not develop clinical signs of CI or any related adverse events. CONCLUSIONS: Measurements of pHe using colonic tonometry indicated malperfusion in all four patients who had developed clinically significant CI. A shorter duration of low pHe was well tolerated without any signs of CI. Measurement of pHe was safe and reliable for the surveillance of colonic perfusion after open aortic surgery, indicating a promising technique. However, larger studies are needed.

Chronic mesenteric ischemia: Clinical practice guidelines from the Society for Vascular Surgery.

BACKGROUND: Chronic mesenteric ischemia (CMI) results from the inability to achieve adequate postprandial intestinal blood flow, usually from atherosclerotic occlusive disease at the origins of the mesenteric vessels. Patients typically present with postprandial pain, food fear, and weight loss, although they can present with acute mesenteric ischemia and bowel infarction. The diagnosis requires a combination of the appropriate clinical symptoms and significant mesenteric artery occlusive disease, although it is often delayed given the spectrum of gastrointestinal disorders associated with abdominal pain and weight loss. The treatment goals include relieving the presenting symptoms, preventing progression to acute mesenteric ischemia, and improving overall quality of life. These practice guidelines were developed to provide the best possible evidence for the diagnosis and treatment of patients with CMI from atherosclerosis. METHODS: The Society for Vascular Surgery established a committee composed of vascular surgeons and individuals experienced with evidence-based reviews. The committee focused on six specific areas, including the diagnostic evaluation, indications for treatment, choice of treatment, perioperative evaluation, endovascular/open revascularization, and surveillance/remediation. A formal systematic review was performed by the evidence team to identify the optimal technique for revascularization. Specific practice recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation system based on review of literature, the strength of the data, and consensus. RESULTS: Patients with symptoms consistent with CMI should undergo an expedited workup, including a computed tomography arteriogram, to exclude other potential causes. The diagnosis is supported by significant arterial occlusive disease in the mesenteric vessels, particularly the superior mesenteric artery. Treatment requires revascularization with the primary target being the superior mesenteric artery. Endovascular revascularization with a balloon-expandable covered intraluminal stent is the recommended initial treatment with open repair reserved for select younger patients and those who are not endovascular candidates. Long-term follow-up and surveillance are recommended after revascularization and for asymptomatic patients with severe mesenteric occlusive disease. Patient with recurrent symptoms after revascularization owing to recurrent stenoses should be treated with an endovascular-first approach, similar to the de novo lesion. CONCLUSIONS: These practice guidelines were developed based on the best available evidence. They should help to optimize the care of patients with CMI. Multiple areas for future research were identified.

Incidence and Outcome of Popliteal Artery Injury Associated with Knee Dislocations, Ligamentous Injuries, and Close to Knee Fractures: A Nationwide Population Based Cohort Study.

OBJECTIVE: Arterial injury in knee trauma is rare but can be devastating if the diagnosis is delayed. The frequency of concomitant arterial injury resulting from knee dislocations remains unclear, and from knee fractures it remains unknown. The primary aim was to investigate the incidence of arterial injury in knee trauma requiring hospitalisation. Secondary aims were to identify risk factors and describe outcome. METHODS: Traumatic popliteal artery injury and knee trauma were identified by International Classification of Diseases (ICD)-10 codes from the Swedish National Inpatient registry (NPR), 1998-2014 and linked with data using the unique personal identification number with the National Registry for vascular surgery (Swedvasc). Risk factors for popliteal artery injury (PAI) such as cause of injury, comorbidities and injury severity were extracted from the NPR. Socio-economic status data and population count came from Statistics Sweden, and cause and date of death from the Swedish Cause of Death Registry. RESULTS: A total of 71 149 admissions due to all knee trauma were identified, and 359 with simultaneous PAIs. Some of those injuries were non-orthopaedic. The proportion of PAI after knee dislocation ranged between 3.4% (46/1370 dislocations or multiligamentous injuries) and 8.2% (46/564 dislocations), and 0.2% after fracture close to the knee (60/36 483). The most common causes of injury with PAI were falls causing knee dislocations and motor vehicle accidents (MVAs) causing fractures. The fact that all 46 injuries occurring after multiligamentous injuries were classified as knee dislocations is probably explained by the fact that the ICD codes are chosen retrospectively when the patient leaves the hospital. CONCLUSION: PAI after knee dislocation is not uncommon, and most frequently caused by a fall. PAI associated with knee fracture is rare and mostly caused by a MVA, while in low energy knee fractures PAI is practically non-existent.

Results After Open and Endovascular Repair of Popliteal Aneurysm: A Matched Comparison Within a Population Based Cohort.

OBJECTIVE: To identify factors affecting the outcome after open surgical (OSR) and endovascular (ER) repair of popliteal artery aneurysm (PA) in comparable cohorts. METHODS: A matched comparison in a national, population based cohort of 592 legs treated for PA (2008 - 2012), with long term follow up. Registry data from 899 PA patients treated in 2014 - 2018 were analysed for time trends. The 77 legs treated by ER were matched, by indication, with 154 legs treated with OSR. Medical records and imaging were collected. Analysed risk factors were anatomy, comorbidities, and medication. Elongation and angulations were examined in a core lab. The main outcome was occlusion. RESULTS: Patients in the ER group were older (73 vs. 68 years, p = .001), had more lung disease (p = .012), and were treated with dual antiplatelet therapy or anticoagulants more often (p < .001). The hazard ratio (HR with 95% confidence intervals) for occlusion was 2.69 (1.60 - 4.55, p < .001) for ER, but 3.03 (1.26 - 7.27, p = .013) for poor outflow. For permanent occlusion, the HR after ER was 2.47 (1.35 - 4.50, p = .003), but 4.68 (1.89 - 11.62, p < .001) for poor outflow. In the ER subgroup, occlusion was more common after acute ischaemia (HR 2.94 [1.45 - 5.97], p = .003; and poor outflow HR 14.39 [3.46 - 59.92], p < .001). Larger stent graft diameter reduced the risk (HR 0.71 [0.54 - 0.93], p = .014). In Cox regression analysis adjusted for indication and stent graft diameter, elongation increased the risk (HR 1.020 per degree [1.002 - 1.033], p = .030). PAs treated for acute ischaemia had a median stent graft diameter of 6.5 mm, with those for elective procedures being 8 mm (p < .001). Indications and outcomes were similar during both time periods (2008 - 2012 and 2014 - 2018). CONCLUSION: In comparable groups, ER had a 2.7 fold increased risk of any occlusion, and 2.4 fold increased risk of permanent occlusion, despite more aggressive medical therapy. Risk factors associated with occlusion in ER were poor outflow, smaller stent graft diameter, acute ischaemia, and angulation/elongation. An association between indication, acute ischaemia, and small stent graft diameter was identified.

Celiprolol Treatment in Patients with Vascular Ehlers-Danlos Syndrome.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare monogenetic disease caused by pathogenic variants in procollagen 3A1. Arterial rupture is the most serious clinical manifestation. A randomised controlled trial, the Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) trial, reported a significant protective effect of the beta blocker celiprolol. The aim was to study the outcome of celiprolol treatment in a cohort of Swedish patients with vEDS. METHODS: Uppsala is a national referral centre for patients with vEDS. They are assessed by vascular surgeons, angiologists, and clinical geneticists. Family history, previous and future clinical events, medication, and side effects are registered. Celiprolol was administered twice daily and titrated up to a maximum dose of 400 mg daily. Logistic regression was used to analyse predictors of vascular events. RESULTS: Forty patients with pathogenic sequence variants in COL3A1 were offered treatment with celiprolol in the period 2011-2019. The median follow up was 22 months (range 1-98 months); total follow up was 106 patient years. In two patients, uptitration of the dose is ongoing. Of the remaining 38, 26 (65%) patients reached the target dose of 400 mg daily. Dose uptitration was unsuccessful in six patients because of side effects; one died before reaching the maximum dose, and five terminated the treatment. Five major vascular events occurred; four were fatal (ruptured ascending aorta; aortic rupture after type B dissection; ruptured cerebral aneurysm; and ruptured pulmonary artery). One bled from a branch of the internal iliac artery, which was successfully coiled endovascularly. The annual risk of a major vascular event was 4.7% (n = 5/106), similar to the treatment arm of the BBEST trial (5%) and lower than in the control arm of the same trial (12%). No significant predictor of vascular events was identified. CONCLUSION: Treatment with celiprolol is tolerated in most patients with vEDS. Despite fatal vascular events, these observations suggest that celiprolol may have a protective effect in vEDS.

Mediterranean Diet is Associated with Reduced Risk of Abdominal Aortic Aneurysm in Smokers: Results of Two Prospective Cohort Studies.

OBJECTIVE: Smoking is a strong risk factor for the development of abdominal aortic aneurysm (AAA). It was hypothesised that a Mediterranean diet via its anti-oxidative properties would decrease the risk of AAA, particularly among smokers. METHODS: The study population included the Cohort of Swedish Men (45 072 men) and the Swedish Mammography Cohort (36 632 women), aged 45 - 83 years at baseline. A modified Mediterranean Diet (mMED) score, including eight food groups, was calculated based on a food frequency questionnaire. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During 17.5 years of follow up (1 427 841 person-years), 1 781 AAA cases (1 496 in men, 285 in women; 1 497 non-ruptured, 284 ruptured) were ascertained via Swedish registers. The mMED score was inversely associated with AAA incidence in men (per each one point increment in mMED score HR 0.96, 95% CI 0.93 - 1.00) and in women (HR 0.83, 95% CI 0.77 - 0.90), for non-ruptured (HR 0.95, 95% CI 0.92 - 0.99; in men with infrarenal aortic diameter ≥ 30 mm HR 0.90, 95% CI 0.81 - 1.00) and for ruptured AAA (HR 0.81, 95% CI 0.70 - 0.93). In current and ex-smokers with low (< 20) and moderate (20 - 39.9) pack-years of smoking, a statistically significant inverse association was observed. HRs for each one point increment in the mMED score in current smokers were 0.83 (95% CI 0.75 - 0.91) and 0.90 (95% CI 0.84 - 0.97), respectively; in ex-smokers 0.89 (95% CI 0.81 - 0.97) and 0.93 (95% CI 0.85 - 1.01), respectively. No association was observed among current or ex-smokers with ≥ 40 pack-years; HRs 1.02 (95% CI 0.91 - 1.13) and 0.95 (95% CI 0.83 - 1.10), respectively. CONCLUSION: Adherence to the Mediterranean diet was associated with a reduced AAA risk in current and ex-smokers with low pack-years of smoking.

Risk Factors for Abdominal Compartment Syndrome After Endovascular Repair for Ruptured Abdominal Aortic Aneurysm: A Case Control Study.

OBJECTIVE: Ruptured abdominal aortic aneurysms (rAAA) are treated by endovascular aneurysm repair (rEVAR) increasingly often. Despite rEVAR being a minimally invasive method, abdominal compartment syndrome (ACS) remains a significant post-operative threat. The aim of this study was to investigate risk factors for ACS after rEVAR, including aortic morphological features. METHODS: The Swedish vascular registry (Swedvasc) was assessed for ACS after rEVAR in the period 2008 - 2015. All patients identified were compared with controls (i.e., patients who did not develop ACS after rEVAR), matched by centre and repair date. Case records were reviewed, and radiology images analysed in a core laboratory. Comparisons were performed with respect to physiological and radiological risk factors. RESULTS: The study population consisted of 40 patients with ACS and 68 controls. Pre-operatively, patients with ACS had a lower blood pressure (BP) than controls (median 70 mmHg vs. 97 mmHg; p < .001). Intra-operatively, they had aortic balloon occlusion more often (55.0% vs. 10.3%; p < .001) and received more transfusions than controls (median nine units of packed red blood cells [pRBC] vs. two units; p < .001). Ninety-seven per cent of those who developed ACS had a pre-operative BP < 70 mmHg, aortic balloon occlusion, or received more than five pRBC unit transfusions. Treatment outside the instructions for use did not differ between patients and controls (57.5% vs. 54.4%; p = .84), and neither did the pre-operative patency of the inferior mesenteric artery (57.1% vs. 63.9%; p = .52) nor the number of visible lumbar arteries on pre-operative imaging (2 vs. 4; p = .014). In multivariable logistic regression, the number of intra-operative transfusions were predictive of ACS (p < .001), while pre-operative hypotension (p = .32) and aortic balloon occlusion (p = .018) were not. CONCLUSION: ACS after rEVAR is mainly associated with physiological factors and is unlikely to develop without the presence of a pre-operative BP < 70 mmHg, the need for an aortic occlusion balloon, or more than five intra-operative pRBC unit transfusions. Treatment outside the IFU or any other morphological factor were not associated with a risk of ACS.

Systematic Review of the Co-Prevalence of Arterial Aneurysms Within the Vasculature.

OBJECTIVE: Aneurysms are considered focal manifestations of a systemic vascular condition, and various studies report co-prevalence of aneurysms in different vascular beds. Insight into profiles of patients at risk of multiple aneurysms is lacking, and few clinical algorithms exist if additional screening is indicated. This systematic review assessed the co-prevalence of aneurysms in different vascular beds and analysed putative risk factors for multiple aneurysms. METHODS: Medline, Embase, and Cochrane libraries were searched up to February 2020 for studies reporting co-prevalence of aneurysms in different vascular beds using the keywords: "aneurysm", "co-prevalence", or synonyms. All studies were reviewed by two authors independently. Studies were excluded if they described concomitant treatment of multi-aneurysms, or if the aneurysm was reported solely bilateral, post-dissection, mycotic, traumatic, iatrogenic, or caused by a connective tissue disease. Radar plots were used to indicate studies that found an association between the investigated features and aneurysm co-prevalence against those that did not. RESULTS: Thirty-two studies met the inclusion criteria, describing in total 16 353 patients of whom 2 015 had at least one additional aneurysm. The weighted co-prevalence was 16.9% (95% confidence interval [CI] 11.8-22.6), I2 > 90%. At least 19 combinations of aneurysms were described, mostly derived from retrospective studies. Seventeen of 32 (53%) studies described concurrent aneurysms in patients with an abdominal aortic aneurysm. Predominantly positive associations were found for higher age, hypertension, stenotic disease, presence of multiple (at least three) aneurysms, and primary aneurysm size. CONCLUSION: Approximately one in six patients with a primary aneurysm harbours an additional aneurysm, increasing to one in four if the patient has a popliteal artery aneurysm. Higher age, hypertension, stenotic disease, presence of multiple (at least three) aneurysms, and primary aneurysm size were predictive of aneurysm co-prevalence. These clinical predictors may assist when deciding whether a patient with a primary aneurysm needs to be screened for additional aneurysms.