Mechanical Fractionation of Adipose Tissue-A Scoping Review of Procedures to Obtain Stromal Vascular Fraction.

Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile.

Stronger pinch strength at long-term follow-up after pyrocarbon disc interposition arthroplasty compared to trapeziectomy with ligament reconstruction and tendon interposition for CMC-1 osteoarthritis.

BACKGROUND/INTRODUCTION: In this study, we wanted to compare the pyrocarbon disc interposition arthroplasty (PDI) with trapeziectomy plus ligament reconstruction tendon interposition (LRTI). Primarily, we tested whether PDI resulted in a higher pinch strength. Secondarily, we compared the grip strength, range of motion (ROM), patient reported outcomes, satisfaction and complications. METHODS: Due to scarcity of preoperative hand measurements, we performed a descriptional cross-sectional cohort study of patients operated between 2006 and 2014, with a minimum of 5 years of follow-up. Patients were treated with PDI or LRTI. We determined key pinch strength as primary outcome, followed by tip- and tripod pinch, grip strength, palmar abduction and opposition; the Michigan Hand Outcome Questionnaire (MHQ), Patient Reported hand and Wrist evaluation (PRWHE), satisfaction and complications. Propensity score matching was used to match both study groups on demographic variables. A ratio of 2:1 was used resulting in inclusion of 62 (of 154) PDI and 31 (of 31) LRTI thumbs. RESULTS: The PDI-group patients showed stronger key and tip pinch strength than the LRTI group (p=0.027 and p=0.036 respectively). Tripod pinch, grip strength and ROM were equal for both groups. MHQ and PRWHE were comparable, with higher satisfaction for the PDI group. Eight PDI patients were converted to LRTI due to pain. CONCLUSION/DISCUSSION: This study confirmed our hypothesis that key and tip pinch strength is stronger after PDI compared to LRTI for CMC-1 joint osteoarthritis. Both techniques have comparable outcomes considering patient reported outcome (MHQ and PRWHE), ROM and complications.

Carotid tortuosity is associated with extracranial carotid artery aneurysms.

Background: Tortuous arteries may be associated with carotid dissection. The intima disruption caused by a carotid dissection is a possible cause of extracranial carotid artery aneurysms (ECAAs). The aim was to investigate if carotid tortuosity is also associated with ECAA in patients without presence or history of a carotid artery dissection. Methods: A retrospective case-control study was performed including 35 unilateral ECAA patients (cases) and 105 age- and sex-matched controls. Tortuosity was expressed as tortuosity-index (TI), curvature, and torsion measured on computed tomography angiography (CTA) data in 3Mensio Vascular and MATLAB by two independent investigators. Primary comparison was tortuosity in ipsi- versus contralateral carotid artery within the cohort of ECAA patients. Secondary comparison was tortuosity with ipsilateral carotid arteries in control patients. All observations were assessed on inter- and intra-operator reproducibility. Results: Carotid tortuosity was comparable within the cohort of ECAA patients (Spearman correlation 0.76, P<0.001), yet distinctively higher in comparison with unilateral controls. After adjustment for patient characteristics, presence of ECAA was associated with TI (ß 0.146, 95% CI: 0.100-0.192). All tortuosity observations showed excellent inter- and intra-operator reproducibility. Conclusions: Carotid tortuosity seems to be a risk factor for development of ECAA. Surveillance of individuals with increased carotid tortuosity therefore potentially ensures prompt diagnosis and treatment of ECAA. However, future research should investigate if persons with an increased tortuosity do indeed develop ECAA.

Delayed Development of Aneurysmal Dilatations in Patients with Extracranial Carotid Artery Dissections.

OBJECTIVE: Dissection of the carotid artery (CaAD) may result in aneurysm formation. The present study was undertaken to evaluate the time of onset of post-dissection extracranial carotid artery aneurysms (ECAA) following CaAD, and to analyse independent risk factors for the development of these aneurysms. METHODS: From four European stroke centres, 360 patients with extracranial CaAD were included. The time between the estimated dissection onset and aneurysm formation was analysed, and the clinical risk factors increasing the probability of aneurysm were assessed. RESULTS: The median duration of follow up was 5.2 months (range 0 - 24 months). A total of 75 post-dissection ECAAs were identified in 70 patients (19.4%, 95% confidence interval [CI] 15.7 - 23.8). In 52 of 70 (74%) patients, the ECAA was diagnosed at the initial clinical work up of CaAD diagnosis, with the median estimated time of dissection onset to ECAA diagnosis being six days (interquartile range [IQR] 0 - 25). In the remaining 18 (26%) patients who had normal carotid arteries at the initial imaging, the aneurysm diagnosis was made a median of 6.2 months (189 days) from the original imaging (IQR 128 - 198). A Cox proportional hazards model showed that both multiple artery dissections (hazard ratio [HR] 2.58, 95% CI 1.54 - 4.33) and arterial tortuosity (HR 1.79, 95% CI 1.08 - 2.95) were associated with presence of ipsilateral ECAA. CONCLUSION: This post hoc cohort analysis showed substantially delayed development of ipsilateral ECAA in patients with CaAD, months after baseline. Multiple dissections and arterial tortuosity are associated with the presence of ECAA and can be used in future prediction models of ECAA development in patients with CaAD.

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.

Cerebral Small Vessel Disease in Standard Pre-operative Imaging Reports Is Independently Associated with Increased Risk of Cardiovascular Death Following Carotid Endarterectomy.

OBJECTIVE: Cerebral white matter lesions (WMLs) and lacunar infarcts are surrogates of cerebral small vessel disease (SVD). WML severity as determined by trained radiologists predicts post-operative stroke or death in patients undergoing carotid endarterectomy (CEA). It is unknown whether routine pre-operative brain imaging reports as part of standard clinical practice also predict short and long term risk of stroke and death after CEA. METHODS: Consecutive patients from the Athero-Express biobank study that underwent CEA for symptomatic high degree stenosis between March 2002 and November 2014 were included. Pre-operative brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) reports were reviewed for reporting of SVD, defined as WMLs or any lacunar infarcts. The primary outcome was defined as any stroke or any cardiovascular death over three year follow up. The secondary outcome was defined as the 30 day peri-operative risk of stroke or cardiovascular death. RESULTS: A total of 1038 patients were included (34% women), of whom 659 (63.5%) had CT images and 379 (36.5%) MRI images available. Of all patients, 697 (67%) had SVD reported by radiologists. Patients with SVD had a higher three year risk of cardiovascular death than those without (6.5% vs. 2.1%, adjusted HR 2.52 [95% CI 1.12-5.67]; p = .026) but no association was observed for the three year risk of stroke (9.0% vs. 6.7%, for patients with SVD vs. those without, adjusted HR 1.24 [95% CI 0.76-2.02]; p = .395). No differences in 30 day peri-operative risk were observed for stroke (4.4% vs. 2.9%, for patients with vs. those without SVD; adjusted HR 1.49 [95% CI 0.73-3.05]; p = .28), and for the combined stroke/cardiovascular death risk (4.4% vs. 3.5%, adjusted HR 1.20 [95% CI 0.61-2.35]; p = .59). CONCLUSION: Presence of SVD in pre-operative brain imaging reports can serve as a predictor for the three year risk of cardiovascular death in symptomatic patients undergoing CEA but does not predict peri-operative or long term risk of stroke.

Co-prevalence of extracranial carotid aneurysms differs between European intracranial aneurysm cohorts.

BACKGROUND AND PURPOSE: Previously, we showed that co-prevalence of extracranial carotid artery aneurysms (ECAAs) in patients with intracranial aneurysms (IAs) was 2% in a Dutch cohort. In order to obtain more precise estimates and discover potential predictors of ECAA co-prevalence in the European population, we retrospectively compared differences and similarities of our Dutch cohort with a Finnish cohort using protocolled imaging of the cerebrovascular tree. METHODS: IA patients within the prospective database of the Kuopio University Hospital were eligible for this study (n = 1,118). Image analysis and hospital chart review were conducted. RESULTS: In total, 458 patients with complete carotid imaging conform protocol were analyzed. Twenty-four ECAAs in 21 patients were identified (4.6%, 95% CI 2.9-6.9), a higher co-prevalence than in the Dutch cohort (1.9%; 95% CI 1.0-3.3), prevalence odds ratio (POR) 2.45 (95% CI 1.19-5.03). In the Finnish cohort, 25% of all ECAAs were located around the carotid bifurcation, others in the internal carotid artery distally from the bifurcation. Independent predictors for ECAA co-prevalence were origin of country (POR 2.41, 95% CI 1.15-5.06) and male gender (POR 2.25, 95% CI 1.09-4.64). CONCLUSION: The co-prevalence of ECAA in IA patients was twice as high in the Finnish compared to the Dutch IA cohort, with origin of country and male gender as independent predictors. Twenty-five percent of ECAAs would be missed, if the carotid bifurcation was not imaged. Therefore, we propose to always include imaging of the carotid bifurcation as the gold standard technique to identify ECAA in IA patients.

Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort.

Recent genome-wide association studies (GWAS) have discovered ten genetic risk variants for abdominal aortic aneurysms (AAA). To what extent these genetic variants contribute to the pathology of aneurysms is yet unknown. The present study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and aneurysm related-symptoms in aortic and peripheral aneurysm patients. Aneurysm tissue of 415 patients included in the Aneurysm-Express biobank was used. A best-fit polygenic risk score (PRS) based on previous GWAS effect estimates was modeled for each clinical phenotype. The best-fit PRS (including 272 variants at PT = 0.01015) showed a significant correlation with aneurysm diameter (R2 = 0.019, p = 0.001). No polygenic association was found with clinical symptoms or artery type. In addition, the ten genome-wide significant risk variants for AAA were tested individually, but no associations were observed with any of the clinical phenotypes. All models were corrected for confounders and data was normalized. In conclusion, a weighted PRS of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in diameter in aneurysm patients. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of susceptibility variants on aneurysmal disease initiation and progression.

The Effect of Metabolic Syndrome on the Occurrence of Restenosis After Carotid Endarterectomy.

OBJECTIVES: The metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. The effect of MetS on clinical outcome in patients with cerebrovascular disease remains largely unknown because conflicting results have been published. This study aimed to determine the influence of MetS on the occurrence of restenosis after carotid endarterectomy (CEA). METHODS: All patients who underwent CEA between June 2003 and December 2014 in two tertiary academic referral centres in The Netherlands were included. MetS was defined if three or more of the following criteria were present: hypertension, obesity, high fasting serum blood glucose, high serum triglycerides, or low serum high density lipoprotein cholesterol. The primary outcome measure was the occurrence of ipsilateral restenosis after index surgery. The secondary outcome measure was (all cause) mortality during follow up. For the primary analysis, missing data were multiply imputed using multivariable imputation by chained equations. A Cox proportional hazards model was used to perform an adjusted analysis on the multiply imputed data sets. RESULTS: A total of 1668 CEA procedures (in 1577 patients) were performed. The presence or absence of MetS could not be determined in 263 patients because of missing data. There was no significant difference in freedom from restenosis in the MetS group vs. the no-MetS group (hazard ratio [HR], 1.10; 95% confidence interval [CI] 0.98-1.23; p = .10) or in all cause mortality (HR 1.20; 95% CI 0.94-1.54; p = .14). CONCLUSION: This study shows that MetS does not predict restenosis after CEA. Also, the presence of MetS did not influence patient survival negatively.

Comparability of semiautomatic tortuosity measurements in the carotid artery.

PURPOSE: Increased arterial tortuosity has been suggested as a predisposing factor for carotid artery dissection, which is an important risk factor for development of extracranial carotid artery aneurysms (ECAA). Prior to comparison with non-ECAA controls, the optimal measurement technique should be defined. This study describes the difference between software packages in terms of reproducibility and absolute outcome of arterial tortuosity measurements in ECAA patients. METHODS: CT-angiography analysis was performed on 12 ECAA patients selected from our registry, using four software packages: 3mensio Vascular, TeraRecon, Vital Images, and Aycan OsiriX PRO. The tortuosity index (TI) was calculated from the skull base until the carotid bifurcation and aortic arch, and was defined as the centerline's true length divided by the straight line distance. Intraclass correlation coefficients (ICC) with 95% confidence intervals were calculated to quantify inter- and intra-observer variability within one software package, and differences in measured TI between packages. RESULTS: Inter-observer agreement was nearly perfect for 3mensio, excellent for Vital Images and OsiriX, and substantial for TeraRecon, with ICC 0.99 (0.96-1.0), 0.90 (0.69-0.97), 0.84 (0.53-0.95), and 0.72 (0.28-0.91), respectively. Intra-observer agreement ranged from ICC 1.0 for 3mensio to 0.91 for TeraRecon. Agreements in TI ranged from ICC 0.99 (0.98-1.0) for 3mensio vs. OsiriX, to 0.95 (0.82-0.98) for 3mensio vs. TeraRecon. Median time needed to complete one round of measurements was highest for OsiriX (p = 0.013). CONCLUSIONS: Carotid artery tortuosity measurements are reproducible and comparable between current commercially available software packages, with high intra-observer agreement. Although the reproducibility differed per software packages, all packages scored an acceptable inter-observer agreement.