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Objective: Intraplaque haemorrhage (IPH) has been independently associated with a higher risk of future ipsilateral stroke in patients with carotid artery stenosis. Evaluation of plaque characteristics may contribute to risk assessment of recurrent (silent) cerebrovascular events in order to prioritise patients for timing of treatment. It is unknown if patients showing histologically apparent IPH also have increased risk of silent ischaemic brain lesions in the waiting period between index event and revascularisation.Methods: A retrospective analysis was performed based on prospectively collected data of patients included simultaneously in the magnetic resonance imaging (MRI) substudy of the International Carotid Stenting Study and Athero-Express biobank. Patients randomised for carotid endarterectomy (CEA) underwent surgery between 2003 and 2008. Brain MRI was performed one to seven days prior to CEA. Plaques were histologically examined for presence of IPH. The primary outcome parameter was presence of silent ipsilateral brain ischaemia on magnetic resonance diffusion weighted imaging (MR-DWI) appearing hypo or isointense on apparent diffusion coefficient.Results: Fifty-three patients with symptomatic carotid stenosis meeting the study criteria were identified, of which 13 showed one or more recent ipsilateral DWI lesion on pre-operative scan. The median time between latest ipsilateral neurological event and revascularisation was 45 days (range 6e200) in DWI negative patients vs. 34 days (range 6e74, p = .16) in DWI positive patients. IPH was present in 24/40 (60.0%) DWI negative patients vs. 12/ 13 (92.3%) DWI positive patients (OR 8.00; 95% CI 0.95e67.7, p = .06). Multivariable logistic regression analysis correcting for age and type of index event revealed that IPH was independently associated with DWI lesions in the waiting period till surgery (OR 10.8; 95% CI 1.17e99.9, p = .04).Conclusion: Symptomatic patients with ipsilateral carotid stenosis and silent brain ischaemia on pre-operative MR-DWI, more often showed pathological evidence of IPH compared with those without ischaemic lesions. This identifies carotid IPH as a marker for patients at risk of silent brain ischaemia and possibly for future stroke and other arterial disease complications. Such patients may be more likely to benefit from CEA than those without evidence of ipsilateral carotid IPH.Objective: The aim was to compare peri-operative (30 day and/or in hospital) mortality between women and men in the Netherlands after elective repair of an asymptomatic abdominal aortic aneurysm (AAA).Methods: This was a retrospective study using data from the Dutch Surgical Aneurysm Audit (DSAA), a mandatory nationwide registry of patients undergoing AAA repair in the Netherlands. Patients who underwent elective open surgical (OSR) or endovascular aneurysm repair (EVAR) of an asymptomatic abdominal aortic aneurysm (AAA) between 2013 and 2018 were included. Absolute risk differences (ARDs) with 95% confidence intervals (CIs) in peri-operative mortality between...

Matrix metalloproteinases (MMPs) are involved in tissue remodelling, tumour invasion and metastasis. High levels of gelatinases MMP-2 and MMP-9 in various types of cancer tissue are associated with worse survival of the patients. Complexes of MMP-9 with neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2) were found in urine from breast cancer patients but were absent in healthy controls, suggesting a possible application as tumour marker. We analyzed the presence of MMP-9/NGAL complexes in tissue from gastric cancer patients and determined their possible clinical value. MMP-9, NGAL, and MMP-9/NGAL complexes were determined in 81 tissue homogenates from gastric cancer patients using quantitative zymography, ELISAs and a specific MMP-9 bioactivity assay. The tumour levels were examined for associations with established clinico-pathological parameters including classifications according to TNM, WHO, Laurén, and survival. Gastric carcinomas were found to have significantly increased MMP-9 (P<0.001), NGAL (P=0.002), and MMP-9/NGAL (P<0.001) levels compared to normal gastric mucosa. Immunohistochemistry revealed staining for MMP-9 mainly in neutrophils, occasionally in epithelial cells and endothelial cells, and incidentally in muscle cells, macrophages, and fibroblasts. NGAL was similarly distributed in neutrophils and epithelial cells, but was also present in groups of epithelial cells in which no MMP-9 was detected. Endothelial cells and fibroblasts showed little or no staining for NGAL. In the homogenates, NGAL was more abundantly present than MMP-9, in specific cases more than 100 times higher. Active MMP-9 levels correlated significantly with the total antigen level of MMP-9, but also with MMP-9/NGAL levels, confirming a possible protective role for NGAL-complex formation in MMP-9 (auto)activation. Although all gastric tumour subtypes showed higher MMP-9/NGAL levels than their corresponding normal tissue, only classification of the carcinomas according to Laurén and WHO showed significant differences between tumour subtypes. High levels of MMP-9/NGAL complexes in gastric tumours were significantly associated with worse survival in Cox's univariate (HR 2.087, P=0.006) and multivariate analysis (HR 2.095, P=0.025), whereas the levels of NGAL and MMP-9 alone were not indicative for survival. Conclusions: MMP-9/NGAL complexes are significantly enhanced in gastric carcinomas and are significantly associated with worse survival of the patients. The prognostic value of the complexes is in accordance with the presumed role of NGAL, i.e. the protection against autoproteolytic activity of MMP-9 after it has been released from the cells.

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