Varied Practice in Laparoscopy Training: Beneficial Learning Stimulation or Cognitive Overload?

Vascular Surger

IL-6: A Janus-like factor in abdominal aortic aneurysm disease

AbstractBackground and aimsAn abdominal aortic aneurysm (AAA) is part of the atherosclerotic spectrum of diseases. The disease is hallmarked by a comprehensive localized inflammatory response with striking IL-6 hyperexpression. IL-6 is a multifaceted cytokine that, depending on the context, acts as a pro- or anti-inflammatory factor. In this study, we explore a putative role for IL-6 in AAA disease.MethodsELISA’s, Western blot analysis, real time PCR and array analysis were used to investigate IL-6 expression and signaling in aneurysm wall samples from patients undergoing elective AAA repair. A role for IL-6 in AAA disease was tested through IL-6 neutralization experiments (neutralizing antibody) in the elastase model of AAA disease.ResultsWe confirmed an extreme disparity in aortic wall IL-6 content between AAA and atherosclerotic disease (median [5th–95th percentile] aortic wall IL-6 content: 281.6 [0.0–1820.8] (AAA) vs. 1.9 [0.0–37.8] μg/g protein (atherosclerotic aorta), (p < 0.001). Array analysis followed by pathway analysis showed that IL-6 hyper-expression is followed by increased IL-6 signaling (p < 0.000039), an observation confirmed by higher aneurysm wall pSTAT3 levels, and SOCS1 and SOCS3 mRNA expression, (p < 0.018).Remarkably, preventive IL-6 neutralization i.e. treatment started one day prior to the elastase-induction resulted in >40% 7-day mortality due to aortic rupture. In contrast, delayed IL-6 neutralization (i.e. neutralization started at day 4 after elastase induction) did not result in ruptures, and quenched AAA growth (p < 0.021).ConclusionsAAA disease is characterized by increased IL-6 signaling. In the context of the elastase model of AAA disease, IL-6 appears a multi-faceted factor, protective upon acute injury, but negatively involved in the perpetuation of the disease process

Toward Optimizing Risk Adjustment in the Dutch Surgical Aneurysm Audit

Background: To compare hospital outcomes of aortic aneurysm surgery, casemix correction for preoperative variables is essential. Most of these variables can be deduced from mortality risk prediction models. Our aim was to identify the optimal set of preoperative variables associated with mortality to establish a relevant and efficient casemix model.Methods: All patients prospectively registered between 2013 and 2016 in the Dutch Surgical Aneurysm Audit (DSAA) were included for the analysis. After multiple imputation for missing variables, predictors for mortality following univariable logistic regression were analyzed in a manual backward multivariable logistic regression model and compared with three standard mortality risk prediction models: Glasgow Aneurysm Score (GAS, mainly clinical parameters), Vascular Biochemical and Haematological Outcome Model (VBHOM, mainly laboratory parameters), and Dutch Aneurysm Score (DAS, both clinical and laboratory parameters). Discrimination and calibration were tested and considered good with a C-statistic &gt; 0.8 and Hosmer-Lemeshow (H-L) P &gt; 0.05. Results: There were 12,401 patients: 9,537 (76.9%) elective patients (EAAA), 913 (7.4%) acute symptomatic patients (SAAA), and 1,951 (15.7%) patients with acute rupture (RAAA). Overall postoperative mortality was 6.5%; 1.8% after EAAA surgery, 6.6% after SAAA, and 29.6% after RAAA surgery. The optimal set of independent variables associated with mortality was a mix of clinical and laboratory parameters: gender, age, pulmonary comorbidity, operative setting, creatinine, aneurysm size, hemoglobin, Glasgow coma scale, electrocardiography, and systolic blood pressure (C-statistic 0.871). External validation overall of VBHOM, DAS, and GAS revealed C-statistics of 0.836, 0.782, and 0.761, with an H-L of 0.028, 0.00, and 0.128, respectively.Conclusions: The optimal set of variables for casemix correction in the DSAA comprises both clinical and laboratory parameters, which can be collected easily from electronic patient files and will lead to an efficient casemix model.</p

Identifying Women at High Risk of 90 Day Death after Elective Open Abdominal Aortic Aneurysm Repair:A Multicentre Case Control Study

Objective: The aim of this study was to identify risk factors for 90 day death after elective open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in women.Methods: This was a multicentre case control study. The nationwide Dutch Surgical Aneurysm Audit registry (2013–2019) was solely used to identify women who underwent elective OSR as eligible patients. Data for this study were subsequently collected from the patients’ medical files. Women with AAA were included and those who died (cases) were compared with those who survived (controls) 90 days after surgery. Inflammatory, mycotic, or symptomatic or ruptured AAA were excluded. The association between pre- and peri-operative risk factors and death was assessed by logistic regression analysis in the whole sample and after matching cases to controls of the same age at the time of repair. Mesenteric artery patency was also assessed on pre-operative computed tomography and used in the analysis.Results: In total, 266 patients (30 cases and 236 controls) from 21 hospitals were included. Cases were older (median [interquartile range; IQR] 75 years [71, 78.3] vs. 71 years [66, 77]; p =.002) and more often had symptomatic peripheral arterial disease (PAD) (14/29 [48%] vs. 49/227 [22%]; p =.002). Intra-operative blood loss (median [IQR] 1.6 L [1.1, 3.0] vs. 1.2 L [0.7, 1.8]), acute myocardial infarction (AMI) (10/30 [33%] vs. 8/236 [3%]), renal failure (17/30 [57%] vs. 33/236 [14%]), and bowel ischaemia (BI) (17/29 [59%] vs. 12/236 [5%]) were more prevalent among cases. Older age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.03–1.19) and PAD (OR 3.91, 95% CI 1.57–9.74) were associated with death. Multivariable analysis demonstrated that, after adjustment for age, AMI (OR 9.34, 95% CI 1.66–52.4) and BI (OR 35.6, 95% CI 3.41–370) were associated with death. Superior mesenteric artery stenosis of &gt;70% had a clinically relevant association with BI (OR 5.23, 95% CI 1.43–19.13; p =.012).Conclusion: Age, symptomatic PAD, AMI, and BI were risk factors for death after elective OSR in women. The association between a &gt;70% SMA stenosis and BI may call for action in selected cases.</p

The effect of injectable biocompatible elastomer (PDMS) on the strength of the proximal fixation of endovascular aneurysm repair grafts: An in vitro study

PurposeOne of the major concerns in the long-term success of endovascular aneurysm repair (EVAR) is stent graft migration, which can cause type I endoleak and even aneurysm rupture. Fixation depends on the mechanical forces between the graft and both the aortic neck and the blood flow. Therefore, there are anatomical restrictions for EVAR, such as short and angulated necks. To improve the fixation of EVAR grafts, elastomer (PDMS) can be injected in the aneurysm sac. The support given by the elastomer might prevent dislocation and migration of the graft. The aim of this study was to measure the influence of an injectable biocompatible elastomer on the fixation strength of different EVAR grafts in an in vitro model.MethodsThe proximal part of three different stent grafts was inserted in a bovine artery with an attached latex aneurysm. The graft was connected to a tensile testing machine, applying force to the proximal fixation, while the artery with the aneurysm was fixated to the setup. The force to obtain graft dislodgement (DF) from the aorta was recorded in Newtons (N). Three different proximal seal lengths (5, 10, and 15 mm) were evaluated. The experiments were repeated after the space between the graft and the latex aneurysm was filled with the elastomer. Independent sample ttests were used for the comparison between the DF before and after elastomer treatment for each seal length.ResultsThe mean DF (mean ± SD) of all grafts without elastomer sac filling for a proximal seal length of 5, 10, and 15 mm were respectively, 4.4 ± 3.1 N, 12.2 ± 10.6 N, and 15.1 ± 6.9 N. After elastomer sac filling, the dislodgement forces increased significantly (P < .001) to 20.9 ± 3.8 N, 31.8 ± 9.8 N, and 36.0 ± 14.1 N, respectively.ConclusionsThe present study shows that aneurysm sac filling may have a role as an adjuvant procedure to the present EVAR technique. The strength of the proximal fixation of three different stent grafts increases significantly in this in vitro setting. Further in vivo research must be done to see if this could facilitate the treatment of aneurysms with short infrarenal necks.Clinical RelevanceStent graft migration and endoleak due to suboptimal fixation are major drawbacks of currently available stent grafts. Optimizing the proximal fixation by peri-graft elastomer aneurysm sac filling may lead to lower incidence of graft migration and endoleak. It might make endovascular aneurysm repair available to larger group of patients with an abdominal aortic aneurysm

Treatment Outcome Trends for Non-Ruptured Abdominal Aortic Aneurysms:A Nationwide Prospective Cohort Study

Objective: The Dutch Surgical Aneurysm Audit (DSAA) initiative was established in 2013 to monitor and improve nationwide outcomes of aortic aneurysm surgery. The objective of this study was to examine whether outcomes of surgery for intact abdominal aortic aneurysms (iAAA) have improved over time.Methods: Patients who underwent primary repair of an iAAA by standard endovascular (EVAR) or open surgical repair (OSR) between 2014 and 2019 were selected from the DSAA for inclusion. The primary outcome was peri-operative mortality trend per year, stratified by OSR and EVAR. Secondary outcomes were trends per year in major complications, textbook outcome (TbO), and characteristics of treated patients. The trends per year were evaluated and reported in odds ratios per year.Results: In this study, 11 624 patients (74.8%) underwent EVAR and 3 908 patients (25.2%) underwent OSR. For EVAR, after adjustment for confounding factors, there was no improvement in peri-operative mortality (aOR [adjusted odds ratio] 1.06, 95% CI 0.94 – 1.20), while major complications decreased (2014: 10.1%, 2019: 7.0%; aOR 0.91, 95% CI 0.88 – 0.95) and the TbO rate increased (2014: 68.1%, 2019: 80.9%; aOR 1.13, 95% CI 1.10 – 1.16). For OSR, the peri-operative mortality decreased (2014: 6.1%, 2019: 4.6%; aOR 0.89, 95% CI 0.82 – 0.98), as well as major complications (2014: 28.6%, 2019: 23.3%; aOR 0.95, 95% CI 0.91 – 0.99). Furthermore, the proportion of TbO increased (2014: 49.1%, 2019: 58.3%; aOR 1.05, 95% CI 1.01 – 1.10). In both the EVAR and OSR group, the proportion of patients with cardiac comorbidity increased.Conclusion: Since the establishment of this nationwide quality improvement initiative (DSAA), all outcomes of iAAA repair following EVAR and OSR have improved, except for peri-operative mortality following EVAR which remained unchanged.</p

Excess Mortality for Abdominal Aortic Aneurysms and the Potential of Strict Implementation of Cardiovascular Risk Management: A Multifaceted Study Integrating Meta-Analysis, National Registry, and PHAST and TEDY Trial Data

Objective: Previous studies imply a profound residual mortality risk following successful abdominal aorta aneurysm (AAA) repair. This excess mortality is generally attributed to increased cardiovascular risk. The aim of this study was (1) to quantify the excess residual mortality for patients with AAA, (2) to evaluate the cross sectional level of cardiovascular risk management, and (3) to estimate the potential of optimised cardiovascular risk management to reduce the excess mortality in these patients. Methods: Excess mortality was estimated through a systematic review and meta-analysis, and through data from the Swedish National Health Registry. Cardiovascular risk profiles were individually assessed during eligibility screening of patients with AAA for two multicentre pharmaceutical AAA stabilisation trials. The potential of full implementation of cardiovascular risk management was estimated through the validated Second Manifestations of ARTerial disease (SMART) risk scores algorithm. Results: The meta-analysis showed a similarly impaired survival for patients who received early repair (small AAA) or regular repair (≥ 55 mm), and a further impaired survival for patients under surveillance for a small AAA. Excess mortality was further quantified using Swedish population data. The data revealed a more than quadrupled and doubled five year mortality rate for women and men who had their AAA repaired, respectively. Evaluation of the level of risk management of 358 patients under surveillance in 16 Dutch hospitals showed that the majority of patients with AAA did not meet therapeutic targets set for risk management in high risk populations, and indicated a more pronounced prevention gap in women. Application of the SMART risk score algorithm predicted that optimal implementation of risk management guidelines would reduce the 10 year risk of major adverse cardiovascular events from 43% to 14%. Conclusion: Independent of the rupture risk, AAA is associated with a worryingly compromised life expectancy with a particularly poor prognosis for women. Optimal implementation of cardiovascular risk prevention guidelines is predicted to profoundly reduce cardiovascular risk

Preparation of microscaner data and core photos for joint analysis and linking

Vascular Surger

Standard Outpatient Re-Evaluation for Patients Not Admitted to the Hospital After Emergency Department Evaluation for Acute Abdominal Pain

The aim of the present study was to investigate the efficacy and safety of standard outpatient re-evaluation for patients who are not admitted to the hospital after emergency department surgical consultation for acute abdominal pain. All patients seen at the emergency department between June 2005 and July 2006 for acute abdominal pain were included in a prospective study using a structured diagnosis and management flowchart. Patients not admitted to the hospital were given appointments for re-evaluation at the outpatient clinic within 24 h. All clinical parameters, radiological results, diagnostic considerations, and management proposals were scored prospectively. Five-hundred patients were included in this analysis. For 148 patients (30%), the final diagnosis was different from the diagnosis after initial evaluation. Eighty-five patients (17%) had a change in management after re-evaluation, and 20 of them (4%) were admitted to the hospital for an operation. Only 6 patients (1.2%) had a delay in diagnosis and treatment, which did not cause extra morbidity. Standard outpatient re-evaluation is a safe and effective means of improving diagnostic accuracy and helps to adapt management for patients that are not admitted to the hospital after surgical consultation for acute abdominal pain at the emergency department.Vascular Surger

Activator protein-1 (AP-1) signalling in human atherosclerosis: results of a systematic evaluation and intervention study

Animal studies implicate the AP-1 (activator protein-1) pro-inflammatory pathway as a promising target in the treatment of atherosclerotic disease. It is, however, unclear whether these observations apply to human atherosclerosis. Therefore we evaluated the profile of AP-1 activation through histological analysis and tested the potential benefit of AP-1 inhibition in a clinical trial. AP-1 activation was quantified by phospho-c-Jun nuclear translocation (immunohistochemistry) on a biobank of aortic wall samples from organ donors. The effect of AP-1 inhibition on vascular parameters was tested through a double blind placebo-controlled cross-over study of 28 days doxycycline or placebo in patients with symptomatic peripheral artery disease. Vascular function was assessed by brachial dilation as well as by plasma samples analysed for hs-CRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6), IL-8, ICAM-1 (intercellular adhesion molecule-1), vWF (von Willebrand factor), MCP-1 (monocyte chemoattractant protein-1), PAI-1 (plasminogen activator inhibitor-1) and fibrinogen. Histological evaluation of human atherosclerosis showed minimal AP-1 activation in non-diseased arterial wall (i.e. vessel wall without any signs of atherosclerotic disease). A gradual increase of AP-1 activation was found in non-progressive and progressive phases of atherosclerosis respectively (P<0.044). No significant difference was found between progressive and vulnerable lesions. The expression of phospho-c-Jun diminished as the lesion stabilized (P<0.016) and does not significantly differ from the normal aortic wall (P<0.33). Evaluation of the doxycycline intervention only revealed a borderline-significant reduction of circulating hs-CRP levels (−0.51 μg/ml, P=0.05) and did not affect any of the other markers of systemic inflammation and vascular function. Our studies do not characterize AP-1 as a therapeutic target for progressive human atherosclerotic disease