Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are subdivided by classic umbrella ...terms, such as "fibroblasts," "myofibroblasts," "smooth muscle cells," "fibrocytes," "mesangial cells," and "pericytes." However, a discriminative marker-based subclassification has to date not been established. Methods and Results As a first effort toward a classification scheme, a systematic literature search was performed to identify the most commonly used phenotypical and functional protein markers for characterizing and classifying vascular mesenchymal cell subpopulation(s). We next applied immunohistochemistry and immunofluorescence to inventory the expression pattern of identified markers on human aorta specimens representing early, intermediate, and end stages of human atherosclerotic disease. Included markers comprise markers for mesenchymal lineage (vimentin, FSP-1 fibroblast-specific protein-1/S100A4, cluster of differentiation (CD) 90/thymocyte differentiation antigen 1, and FAP fibroblast activation protein), contractile/non-contractile phenotype (α-smooth muscle actin, smooth muscle myosin heavy chain, and nonmuscle myosin heavy chain), and auxiliary contractile markers (h1-Calponin, h-Caldesmon, Desmin, SM22α smooth muscle protein 22α, non-muscle myosin heavy chain, smooth muscle myosin heavy chain, Smoothelin-B, α-Tropomyosin, and Telokin) or adhesion proteins (Paxillin and Vinculin). Vimentin classified as the most inclusive lineage marker. Subset markers did not separate along classic lines of smooth muscle cell, myofibroblast, or fibroblast, but showed clear temporal and spatial diversity. Strong indications were found for presence of stem cells/Endothelial-to-Mesenchymal cell Transition and fibrocytes in specific aspects of the human atherosclerotic process. Conclusions This systematic evaluation shows a highly diverse and dynamic landscape for the human vascular mesenchymal cell population that is not captured by the classic nomenclature. Our observations stress the need for a consensus multiparameter subclass designation along the lines of the cluster of differentiation classification for leucocytes.
Diabetes Mellitus (DM) is a common chronic disease, affecting 435 million people globally. Impaired vasculature in DM patients leads to complications like lower extremity arterial disease (LEAD) and ...foot ulcers, often resulting in amputations. DM causes additional peripheral neuropathy leading to multifactorial wound problems. Current diagnostics often deem unreliable, but Near-Infrared Fluorescence with Indocyanine Green (ICG NIR) can be used to assess the foot perfusion. Therefore, this study explores DM’s impact on foot perfusion using ICG NIR.
Baseline ICG NIR fluorescence imaging was performed in LEAD patients with and without DM. Ten perfusion parameters were extracted and analyzed to assess differences in perfusion patterns.
Among 109 patients (122 limbs) of the included patients, 32.8 % had DM. Six of ten perfusion parameters, mainly inflow-related, differed significantly between DM and non-DM patients (p-values 0.007–0.039). Fontaine stage 4 DM patients had the highest in- and outflow values, with seven parameters significantly higher (p-values 0.004–0.035).
DM is associated with increased in- and outflow parameters. Patients with- and without DM should not be compared directly due to different vascular pathophysiology and multifactorial wound problems in DM patients. Quantified ICG NIR fluorescence imaging offers additional insight into the effect of DM on foot perfusion.
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.
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.
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%.
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.
The processes driving human abdominal aortic aneurysm (AAA) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in ...preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in AAA progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and AAAs; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in AAA-related wall debilitation. A better understanding of the pathophysiologic processes driving AAA growth can contribute to pharmaceutical treatments in the future.
Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture.
Histologic evaluation of AAAs, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (AAA), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of AAAs (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in AAA tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of AAA adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured AAA (P < .0003) supports an association between the extent of fatty degeneration and rupture.
This translational study identifies extensive adventitial fatty degeneration as an ignored and distinctive feature of AAA disease. Enrichment of adipocyte genesis and adipocyte-related genes in ruptured AAA point to an association between the extent of fatty degeneration and rupture. This observation may (partly) explain the failure of medical therapy and could provide a lead for pharmaceutical alleviation of AAA progression.
Although it is assumed AAA progression is driven by a proteolytic imbalance and inflammation, clinical studies consistently fail to show a benefit of medical interventions targeting these pathways. In this context, we sought further, currently unidentified mechanisms involved in (terminal) AAA wall weakening. This translational study identifies extensive adventitial fatty degeneration as a distinctive feature of advanced AAA disease. Enrichment of adipocyte-related genes in ruptured AAA wall samples implies an association between the extent of fatty degeneration and rupture.
Purpose:
Post-EVAR (endovascular aneurysm repair) aneurysm sac growth can be seen as therapy failure as it is a risk factor for post-EVAR aneurysm rupture. This study sought to identify preoperative ...patient predictors for developing post-EVAR aneurysm sac growth.
Material and Methods:
A systematic review was conducted to select potential predictive preoperative factors for post-EVAR sac growth (including a total of 34.886 patients), which were evaluated by a retrospective single-center analysis of patients undergoing EVAR between 2009 and 2019 (N=247) with pre-EVAR computed tomography scans and at least 1 year follow-up. The primary study outcome was post-EVAR abdominal aortic aneurysm (AAA) sac enlargement (≥5 mm diameter increase). Multivariate Cox regression and Kaplan-Meier survival curves were constructed.
Results:
Potential correlative factors for post-EVAR sac growth included in the cohort analysis were age, sex, anticoagulants, antiplatelets, renal insufficiency, anemia, low thrombocyte count, pulmonary comorbidities, aneurysm diameter, neck diameter, neck angle, neck length, configuration of intraluminal thrombus, common iliac artery diameter, the number of patent lumbar arteries, and a patent inferior mesenteric artery. Multivariate analysis showed that infrarenal neck angulation (hazard ratio, 1.014; confidence interval (CI), 1.001–1.026; p=0.034) and the number of patent lumbar arteries (hazard ratio, 1.340; CI, 1.131–1.588; p<0.001) were associated with post-EVAR growth. Difference in estimated freedom from post-EVAR sac growth for patients with ≥4 patent lumbar arteries versus <4 patent lumbar arteries became clear after 2 years: 88.5% versus 100%, respectively (p<0.001). Of note, 31% of the patients (n=51) with ≥4 patent lumbar arteries (n=167) developed post-EVAR sac growth. In our cohort, the median maximum AAA diameter was 57 mm (interquartile range IQR = 54–62) and the median postoperative follow-up time was 54 months (IQR = 34–79). In all, 23% (n=57) of the patients suffered from post-EVAR growth. The median time for post-EVAR growth was 37 months (IQR = 24–63). In 46 of the 57 post-EVAR growth cases (81%), an endoleak was observed; 2.4% (n=6) of the patients suffered from post-EVAR rupture. The total mortality in the cohort was 24% (n=60); 4% (n=10) was AAA related.
Conclusions:
This study showed that having 4 or more patent lumbar arteries is an important predictive factor for postoperative sac growth in patients undergoing EVAR.
Clinical Impact
This study strongly suggests that having 4 or more patent lumbar arteries should be included in preoperative counseling for EVAR, in conjunction to the instructions for use (IFU).
The accurate prediction of foot ulcer healing remains a major challenge in clinical practice. To date, no reliable bedside tests are available. The primary aim of this study was to determine the ...prognostic performance of the maximal systolic acceleration (ACCmax) to predict ulcer healing. Secondary objectives comprised the investigation of the prognostic accuracy in patients prone to medial arterial calcification and to assess the potential risk of amputation.
A single-center retrospective cohort study was conducted. Patients aged ≥18 years who presented with a new-onset ulcer (i.e. Fontaine IV and neuropathic ulcers) on the foot and underwent an ACCmax measurement at the hallux were included. Ulcer healing was defined as an intact skin with epithelialization after 3 or 12 months of follow-up. Prognostic performance was calculated by using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).
In total, 136 patients with 143 wounds were included. Almost half of the patients were diagnosed with diabetes mellitus (47%), and wound infection was present in 42% of cases. After 3 months of follow-up, an NPV of 97.9%, PLR of 3.25, and NLR of 0.19 were found when applying an ACCmax threshold of 0.5 m/s2. When looking at 12 months, these numbers were 85.6%, 2.72, and 0.50, respectively. Subgroup analysis for patients with diabetes mellitus and chronic kidney disease showed comparable results. The risk of amputation increased significantly when a measurement below 1.0 m/s2 was present (odd ratio 5.3, P = 0.010).
ACCmax measurements at the hallux can have additional prognostic value in patients with foot ulcers. An ACCmax below 1.0 m/s2 is associated with nonhealing of an ulcer and a higher risk of amputation, while higher ACCmax values are associated with limb salvage. Therefore, ACCmax could be used for grading ischemia in a wound classification system.
OBJECTIVEIt remains unclear to what extent the morbidity and mortality conference (M&M) meets the objective of improving quality and safety of patient care. It has been suggested that M&M may be too ...focused on individual performance, hampering system-level improvement. The aim of this study was to assess focus and sustainability of lessons for patient care that were derived from M&M.
METHODSThis is an observational study of routinely collected data on evaluated complications and identified lessons at surgical M&M for 8 years, assessing type and recurrence of lessons and cases from which these were drawn. Semistructured interviews with clinicians were qualitatively analyzed to explore factors contributing to lesson focus and recurrence.
RESULTSThree hundred eighteen lessons were drawn from 10,883 evaluated complications, primarily for those that were more severe, related to surgical or other treatment, and occurring in nonemergent, lower risk cases (all P < 0.001). Most lessons targeted intraoperative (43%) rather than preoperative or postoperative care as well as specifically technical (87%) and individual-level issues (74%). There were 43 recurring lessons (14%), mostly about postoperative care (47%) and medication management (50%). Interviewed clinicians attributed the intraoperative, technical focus primarily to greater appeal and control but identified an array of factors contributing to lesson recurrence, such as typical staff turnover in teaching hospitals.
CONCLUSIONSThis study provided empirical evidence that learning at M&M has a tendency to focus on intraoperative, technical performance, with challenges to sustain lessons for more system-level issues. Morbidity and mortality conference formats need to anticipate these tendencies to ensure a wide focus for learning with lasting and wide impact.
Abstract Background There's a large clinical need for novel vascular grafts. Tissue engineered blood vessels (TEBVs) have great potential to improve the outcome of vascular grafting procedures. Here, ...we present a novel approach to generate autologous TEBV in vivo . Polymer rods were engineered and implanted, evoking an inflammatory response that culminates in encapsulation by a fibrocellular capsule. We hypothesized that, after extrusion of the rod, the fibrocellular capsule differentiates into an adequate vascular conduit once grafted into the vasculature. Methods and results Rods were implanted subcutaneously in pigs. After 4 weeks, rods with tissue capsules grown around it were harvested. Tissue capsules were grafted bilaterally as carotid artery interposition. One and 4-week patency were evaluated by angiography whereupon pigs were sacrificed. Tissue capsules before and after grafting were evaluated on tissue remodeling using immunohistochemistry, RNA profiling and mechanical testing. Rods were encapsulated by thick, well-vascularized tissue capsules, composed of circumferentially aligned fibroblasts, collagen and few leukocytes, with adequate mechanical strength. Patency was 100% after 1 week and 87.5% after 4 weeks. After grafting, tissue capsules remodeled towards a vascular phenotype. Gene profiles of TEBVs gained more similarity with carotid artery. Wall thickness and αSMA-positive area significantly increased. Interestingly, a substantial portion of (myo)fibroblasts present before grafting expressed smooth muscle cell markers. While leukocytes were hardly present anymore, the lumen was largely covered with endothelial cells. Burst pressure remained stable after grafting. Conclusions Autologous TEBVs were created in vivo with sufficient mechanical strength enabling vascular grafting. Grafts differentiated towards a vascular phenotype upon grafting.
(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary ...arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.
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