Low Progesterone and Low Estradiol Levels Associate with Abdominal Aortic Aneurysms in Men

Context Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.ObjectiveTo describe the associations between serum sex steroids and early, screening-detected AAA in men.MethodsWe validated a high-sensitivity liquid chromatography-tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men.Outcomes includedAssociations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence.ResultsDehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI 1.18-2.22]) and estradiol (1.40 [95% CI 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI 2.25-7.31]).​​​​​​​ConclusionMeasured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independently of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.</p

Tissue remodelling proteases as prognostic factors in colon and rectal cancer

Background: Colorectal cancer is the third most common cancer in Sweden and the main treatment is surgery. The TNM classification is the principal staging tool, although insufficient in identifying all patients with poor survival. The identification of molecular prognostic markers would be important in order to further aid in the identification of these patients. Components participating in the remodellation of extracellular matrix were analysed for their association with tumour progression and survival. Methods: Patients with colorectal cancer were included in the studies during 1999-2004. Protein expression was evaluated by ELISA technique and immunohistochemistry, and related to tumour classifications. The association with cancer specific survival (CSS) was analysed by Cox proportional hazard analysis and differences between survival curves (Kaplan-Meier method) were evaluated by the Log Rank test. Results: The expression of all measured markers were significantly higher in tumour tissue compared to tumour free mucosa. Matrix metalloproteinase-1 (MMP-1) protein expression in tumour tissue and MMP-2 expression in plasma was associated with increasing tumour stage (T-status) and lymph node metastasis in patients without distant metastatic disease. When survival data were analysed, MMP-2 in tumour tissue and MMP-1 and -9 expression in adjacent tumour free mucosa were associated with CSS in colon cancer. The association with CSS was maintained for MMP-1 in multivariate analysis also in patients without distant metastatic disease. High levels of urokinase Plasminogen Activator (uPA) expression in tumour free mucosa were associated with improved survival, but only in patients with rectal cancer. uPA expression below the chosen cut-off value identified M0 patients with increased risk of poor survival. TGF-beta1 and PAI-1 protein expression was associated with metastatic disease and the survival analysis confirmed these results. Discussion: Results indicate that the association of systemically measured factors with survival is due to their strong correlation with metastatic disease. These findings might reflect a generalised response to the metastatic disease. The differential association of MMP-1, MMP-9 and uPA expression with cancer specific survival in adjacent tumour free mucosa in colon and rectal cancer was unexpected. This also means that prognostic information could be available already in the preoperative setting, which could open up the opportunity to offer neo-adjuvant therapy to high-risk patients. The results suggest that the macroscopically normal mucosa in the tumour-bearing segment reflects local tumour progression, and it seems evident that important changes in the microenvironment, even remote from the tumour, are present

Arterial Blood Flow and Effects on Limb Tissue Perfusion During Endoshunting of the Common Iliac Artery in an Experimental Porcine Model

Objective: Temporary arterial shunting is an established method to prevent tissue ischaemia. Although less well established, shunting might also be achieved through endovascular and hybrid techniques, known as endoshunting. Endoshunting offers advantages, for example, enabling minimally invasive access and avoiding complete occlusion of the donor artery. In an ex vivo bench test, volume flow in various interconnected endoshunt systems has been tested previously. This study aimed to investigate the capacity of the best performing endoshunt system in vivo. Methods: Six anaesthetised pigs had their common iliac arteries (CIAs) explored, with the left CIA serving as the experimental and the right CIA as the control. Mean arterial pressure, regional blood flow, endoshunt flow, and regional oxygen extraction and lactate production were recorded. Distal muscle perfusion was monitored using near infrared spectroscopy (NIRS). Each experiment involved baseline registration, cross clamping of the left CIA, a 120 minute endoshunt session, and restoration of native flow. Results: During cross clamping, NIRS values on the experimental side reached the lowest measurable value. Following endoshunt activation, there were no NIRS value differences between the experimental and control extremities whereas the average arterial flow decreased in both the experimental (270–140 mL/min, p = .028) and control extremities (245–190 mL/min, p = .25), with a greater drop on the endoshunted side (48% vs. 22%, respectively). Lactate levels temporarily increased by 42% in the endoshunted limb on endoshunt activation but were normalised within an hour. Oxygen extraction remained constant at 55% on the control side but increased to 70% on the endoshunted side (p = .068). Conclusion: In this animal model, a flow optimised endoshunt system appeared to provide sufficient blood flow and restored stable tissue perfusion. Although arterial flow was slightly lower and oxygen extraction slightly higher on the endoshunted side, the endoshunt seemed to deliver adequate perfusion to prevent significant ischaemia

Routine open abdomen treatment compared with on-demand open abdomen or direct closure following open repair of ruptured abdominal aortic aneurysms: A propensity score–matched study

Objective: To investigate whether a strategy of treatment with a primarily open abdomen improves outcome in terms of mortality and major complications in patients treated with open repair for a ruptured abdominal aortic aneurysm compared to a strategy of primary closure of the abdomen. Design: Retrospective cohort study. Methods: Patients treated with a primarily open abdomen at a centre where this strategy was routine in most ruptured abdominal aortic aneurysm patients were compared to a propensity score–matched control group of patients who had the abdomen closed at the end of the primary operation in a majority of the cases. Results: In total, 79 patients treated with a primarily open abdomen after open repair for ruptured abdominal aortic aneurysm at Sahlgrenska University Hospital were compared to a propensity score–matched control group of 148 patients. The abdomen was closed at the end of the procedure in 108 (73%) of the control patients. There was no difference in 30-day mortality between patients treated with a primarily open abdomen at Sahlgrenska University Hospital and the controls, 21 (26.6%) versus 49 (33.1%), p = 0.37. The adjusted odds ratio for mortality at 30 days was 0.66 (95% confidence interval: 0.35–1.25) in patients treated with a primarily open abdomen at Sahlgrenska University Hospital compared to the controls. No difference was observed between the groups regarding 90-day mortality, postoperative renal failure requiring renal replacement therapy, postoperative intestinal ischaemia necessitating bowel resection or postoperative bleeding requiring reoperation. Conclusions: The study did not show any survival advantage or difference in major complications between patients treated with a primarily open abdomen after open repair for ruptured abdominal aortic aneurysm and propensity-matched controls where the abdomen was primarily closed in a majority of the cases

Optimisation of Volume Flow Rates when Using Endovascular Shunting Techniques: An Experimental Study in Different Bench Flow Circuits

Objective: Acute tissue ischaemia may arise due to arterial emergencies or during more complex vascular procedures and may be mitigated by temporary shunting techniques. Endovascular shunting (ES) techniques enable percutaneous access and shunting from the donor artery without the need to completely interrupt the arterial flow in the donor artery. An endoshunt system may also cover longer distances than most conventional shunts. The aim was to investigate and optimise the flow rates in different endovascular shunt systems. Methods: Step 1: The flow capacity of different ES configurations was compared with the flow capacity of a 9 Fr Pruitt–Inahara shunt (PIS). An intravenous bag with 0.9% NaCl, pressurised to 90 mmHg, was connected simultaneously to a PIS and to one of the tested ES configurations. The two shunt systems were then opened at the same time. The delivered fluid volumes from the shunt systems were collected and measured. The volume flow rate was subsequently calculated. Steps 2 and 3: Within a heart lung machine circuit, pressure–flow charts were constructed for the individual ES components and for the fully connected optimised endoshunt systems. The flow rate was increased in steps of 40–50 mL/min while monitoring the driving pressure, enabling the creation and comparison of the pressure–flow charts for the individually tested components. In total, seven individual inflow and outflow potential ES components were investigated with inflow and outflow diameters ranging from 6 to 15 Fr. Results: ES systems based on standard donor introducers led to substantially lower volume flow than the corresponding PIS volume flow, whereas ES systems based on dedicated 6 or 8 Fr dialysis access introducers (Prelude Short Sheet, Merit Medical) matched PIS flow rates. The introduction of 30 cm long ¼′′ perfusion tubing within the ES system did not affect volume flow for any of the tested ES configurations. Conclusion: Endoshunting techniques can match PIS volume flow rates over short and long distances. The achieved ES flow rate is highly dependent on the components used within the ES system

Consequences of screening in abdominal aortic aneurysm: development and dimensionality of a questionnaire

Abstract Background In interview studies, men under surveillance for screening-detected abdominal aortic aneurysms have reported ambivalence towards this diagnosis: the knowledge was welcomed together with worries, feelings of anxiety and existential thoughts about life’s fragility and mortality due to the diagnosis. Previous surveys about health-related quality of life aspects among men under surveillance for screening-detected aneurysm have all used generic patient-reported outcomes. Therefore, the aim of this study was to extend the core-questionnaire Consequences of Screening for use in abdominal aortic aneurysm screening by testing for comprehension, content coverage, dimensionality, and reliability. Methods In interviews, the suitability, content coverage, and relevance of the core-questionnaire Consequences of Screening were tested on men under surveillance for a screeningdetected abdominal aortic aneurysm. The results were thematically analysed to identify the key consequences of abnormal screening results. Item Response Theory and Classical Test Theory were used to analyse data. Dimensionality, differential item functioning, local response dependency and reliability were established by item analysis, examining the fit between item responses and Rasch models. Results The core-questionnaire Consequences of Screening was found to be relevant for men offered regular follow-up of an asymptomatic screening-detected abdominal aortic aneurysm. Fourteen themes especially relevant for men diagnosed with a screening-detected abdominal aortic aneurysm were extracted from the interviews: ‘Uncertainty about the result of the ultra sound examination’, ‘Change in body perception’, ‘Guilt’, ‘Fear and powerlessness’, ‘Negative experiences from the examination’, ‘Emotional reactions’, ‘Change in lifestyle’, ‘Better not knowing’, ‘Fear of rupture’, ‘Sexuality’, ‘Information’, ‘Stigmatised’, ‘Self-blame for smoking’, ‘Still regretful smoking’. Altogether, 55 new items were generated: 3 were single items and 13 were only relevant for former or current smokers. 51 of the 52 items belonging to a theme were confirmed to fit Rasch models measuring fourteen different constructs. No differential item functioning and only minor local dependency was revealed between some of the 51 items. Conclusions The reliability and the dimensionality of a condition-specific measure with high content validity for men under surveillance for a screening-detected abdominal aortic aneurysm have been demonstrated. This new questionnaire called COS-AAA covers in two parts the psychosocial experience in abdominal aortic aneurysm screening

Corrigendum to “Optimization of Volume Flow Rates when Using Endovascular Shunting Techniques – An Experimental Study in Different Bench Flow Circuits. [EJVES Vascular Forum Volume 58, 2023, Pages 5–10]”

Objective: Acute tissue ischaemia may arise due to arterial emergencies or during more complex vascular procedures and may be mitigated by temporary shunting techniques. Endovascular shunting (ES) techniques enable percutaneous access and shunting from the donor artery without the need to completely interrupt the arterial flow in the donor artery. An endoshunt system may also cover longer distances than most conventional shunts. The aim was to investigate and optimise the flow rates in different endovascular shunt systems. Methods: Step 1: The flow capacity of different ES configurations was compared with the flow capacity of a 9 Fr Pruitt–Inahara shunt (PIS). An intravenous bag with 0.9% NaCl, pressurised to 90 mmHg, was connected simultaneously to a PIS and to one of the tested ES configurations. The two shunt systems were then opened at the same time. The delivered fluid volumes from the shunt systems were collected and measured. The volume flow rate was subsequently calculated. Steps 2 and 3: Within a heart lung machine circuit, pressure–flow charts were constructed for the individual ES components and for the fully connected optimised endoshunt systems. The flow rate was increased in steps of 40–50 mL/min while monitoring the driving pressure, enabling the creation and comparison of the pressure–flow charts for the individually tested components. In total, seven individual inflow and outflow potential ES components were investigated with inflow and outflow diameters ranging from 6 to 15 Fr. Results: ES systems based on standard donor introducers led to substantially lower volume flow than the corresponding PIS volume flow, whereas ES systems based on dedicated 6 or 8 Fr dialysis access introducers (Prelude Short Sheath, Merit Medical) matched PIS flow rates. The introduction of 30 cm long ¼′′ perfusion tubing within the ES system did not affect volume flow for any of the tested ES configurations. Conclusion: Endoshunting techniques can match PIS volume flow rates over short and long distances. The achieved ES flow rate is highly dependent on the components used within the ES system