This prospective trial was designed to compare the performance characteristics of five different screening tests in parallel for the detection of advanced colonic neoplasia: CT colonography (CTC), ...colonoscopy (OC), flexible sigmoidoscopy (FS), faecal immunochemical stool testing (FIT) and faecal occult blood testing (FOBT).
Average risk adults provided stool specimens for FOBT and FIT, and underwent same-day low-dose 64-multidetector row CTC and OC using segmentally unblinded OC as the standard of reference. Sensitivities and specificities were calculated for each single test, and for combinations of FS and stool tests. CTC radiation exposure was measured, and patient comfort levels and preferences were assessed by questionnaire.
221 adenomas were detected in 307 subjects who completed CTC (mean radiation dose, 4.5 mSv) and OC; 269 patients provided stool samples for both FOBT and FIT. Sensitivities of OC, CTC, FS, FIT and FOBT for advanced colonic neoplasia were 100% (95% CI 88.4% to 100%), 96.7% (82.8% to 99.9%), 83.3% (95% CI 65.3% to 94.4%), 32% (95% CI 14.9% to 53.5) and 20% (95% CI 6.8% to 40.7%), respectively. Combination of FS with FOBT or FIT led to no relevant increase in sensitivity. 12 of 45 advanced adenomas were smaller than 10 mm. 46% of patients preferred CTC and 37% preferred OC (p<0.001).
High-resolution and low-dose CTC is feasible for colorectal cancer screening and reaches sensitivities comparable with OC for polyps >5 mm. For patients who refuse full bowel preparation and OC or CTC, FS should be preferred over stool tests. However, in cases where stool tests are performed, FIT should be recommended rather than FOBT.
Computer-aided detection (CAD) algorithms help to detect colonic polyps at CT colonography (CTC). The purpose of this study was to evaluate the accuracy of CAD versus an expert reader in CTC. One ...hundred forty individuals (67 men, 73 women; mean age, 59 years) underwent screening 64-MDCT colonography after full cathartic bowel cleansing without fecal tagging. One expert reader interpreted supine and prone scans using a 3D workstation with integrated CAD used as "second reader." The system's sensitivity for the detection of polyps, the number of false-positive findings, and its running time were evaluated. Polyps were classified as small (< or =5 mm), medium (6-9 mm), and large (> or =10 mm). A total of 118 polyps (small, 85; medium, 19; large, 14) were found in 56 patients. CAD detected 72 polyps (61%) with an average of 2.2 false-positives. Sensitivity was 51% (43/85) for small, 90% (17/19) for medium, and 86% (12/14) for large polyps. For all polyps, per-patient sensitivity was 89% (50/56) for the radiologist and 73% (41/56) for CAD. For large and medium polyps, per-patient sensitivity was 100% for the radiologist, and 96% for CAD. In conclusion, CAD shows high sensitivity in the detection of clinically significant polyps with acceptable false-positive rates.
Cathepsins have been described in the pathogenesis of abdominal aortic aneurysm (AAA), their exact role, especially in collagen degradation, is still unclear. The aim of the present study was ...therefore to analyse relevant cathepsins in human AAA tissue samples in relation to collagen I, III, and their degradation products.
Samples from 37 AAA patients obtained from elective open surgical repair and eight healthy non-aneurysmatic aortas from kidney donors were included. Expression of cathepsins B, D, K, L, S, cystatin C, collagen I and III, their degraded products C-Telopeptide of type 1 and 3 collagen (CTX-I, CTX-III), cellular markers for leukocytes (CD45), T cells (CD3), macrophage scavenger receptor-1 (MSR-1), synthetic, and contractile smooth muscle cells (SMCs) (smoothelin: SMTH, collagen I and III, myosin heavy chain: MHC, embryonic smooth muscle myosin heavy chain: SMemb) were determined at messenger RNA (mRNA) level, using SYBRGreen-based quantitative PCR and at protein level using enzyme-linked immunosorbent assay (ELISA).
Expression of cathepsins B, D, L, and S at mRNA level was significantly elevated in AAA compared to control aorta (1.7-fold, p = 0.025; 2.5-fold, p = 0.002; 2.6-fold, p = 0.034; and 7.0-fold, p = 0.003). Expression of cathepsin S correlated significantly with leukocytes and macrophages (ρ = 0.398, p = 0.033 and ρ = 0.422, p = 0.020), synthetic SMCs were significantly associated with cathepsins B, D, and L (ρ = 0.522, p = 0.003; ρ = 0.431, p = 0.015 and ρ = 0.467, p = 0.008). At protein level, cathepsins B and S were elevated in AAA compared to controls (5.4-fold, p = 0.001 and 7.3-fold, p < 0.001). Significant correlations were observed between collagen I, its degraded product, and cathepsin S (r = -0.350, p = 0.034 and r = +0.504, p < 0.001). Expression of cathepsin B was associated with SMCs, expression of cathepsin S with inflammatory cells.
Particularly cathepsin S was associated with the degradation product of collagen I and thus might be involved in the progression of AAA. Furthermore, cathepsin S correlated with inflammatory cells.
The concept of Distance Laboratory is presented. Based based on the widespread availability of personal computers and telecommunication networks as well as on utilising multimedia technology, this is ...an innovative approach for the automation of laboratory practicals as constituent of university teaching, and for both the spatial and temporal separation of students and experimental rigs and experimentation, respectively. An environment for the design of digital circuits was developed as the first realisation of the concept. A number of further experiments is in preparation.
The comprehensive coverage of sustainability issues in a supply chain incurs goal conflicts—i.e., sustainability tensions—and is often limited by market characteristics, such as the availability of ...sustainable materials and services. While the mainstream business is prioritizing economic goals, a number of entrepreneurs are trying to move forward to more sustainable business practices for their own company and their supply chain. Fairphone represents such a case in the electronics industry, which is openly communicating its sustainability efforts and shortcomings. This communication is content-analyzed in this study by applying the theoretical lenses of paradox sustainability tensions and sustainable supply chain management. Findings of this analysis reveal the limitation of sustainability efforts by supply side characteristics, while Fairphone is innovatively using the demand side of its supply chain to drive sustainability. The resulting tensions among both sides are addressed via pro-active and direct supplier and stakeholder engagement by Fairphone at their suppliers’ mines and factories. The systematic identification of tensions and practices by which they are addressed is adding to our understanding of sustainability practices and goal conflicts in supply chains.
Re-directing mesenchymal stromal cell (MSC) chondrogenesis towards a non-hypertrophic articular chondrocyte-(AC)-like phenotype is important for improving articular cartilage neogenesis to enhance ...clinical cartilage repair strategies. This study is the first to demonstrate that high levels of non-canonical WNT5A followed by WNT11 and
LEF1
discriminated MSC chondrogenesis from AC re-differentiation. Moreover, β-catenin seemed incompletely silenced in differentiating MSCs, which altogether suggested a role for WNT signaling in hypertrophic MSC differentiation. WNT inhibition with the small molecule IWP-2 supported MSC chondrogenesis according to elevated proteoglycan deposition and reduced the characteristic upregulation of
BMP4
,
BMP7
and their target
ID1
, as well as
IHH
and its target
GLI1
observed during endochondral differentiation. Along with the pro-hypertrophic transcription factor MEF2C, multiple hypertrophic downstream targets including
IBSP
and alkaline phosphatase activity were reduced by IWP-2, demonstrating that WNT activity drives BMP and hedgehog upregulation, and MSC hypertrophy. WNT inhibition almost matched the strong anti-hypertrophic capacity of pulsed parathyroid hormone-related protein application, and both outperformed suppression of BMP signaling with dorsomorphin, which also reduced cartilage matrix deposition. Yet, hypertrophic marker expression under IWP-2 remained above AC level, and in vivo mineralization and ectopic bone formation were reduced but not eliminated. Overall, the strong anti-hypertrophic effects of IWP-2 involved inhibition but not silencing of pro-hypertrophic BMP and IHH pathways, and more advanced silencing of WNT activity as well as combined application of IHH or BMP antagonists should next be considered to install articular cartilage neogenesis from human MSCs.
Objectives To compare biomechanical rupture risk parameters of asymptomatic, symptomatic and ruptured abdominal aortic aneurysms (AAA) using finite element analysis (FEA). Study design Retrospective ...biomechanical single center analysis of asymptomatic, symptomatic, and ruptured AAAs. Comparison of biomechanical parameters from FEA. Materials and methods From 2011 to 2013 computed tomography angiography (CTA) data from 30 asymptomatic, 15 symptomatic, and 15 ruptured AAAs were collected consecutively. FEA was performed according to the successive steps of AAA vessel reconstruction, segmentation and finite element computation. Biomechanical parameters Peak Wall Rupture Risk Index (PWRI), Peak Wall Stress (PWS), and Rupture Risk Equivalent Diameter (RRED) were compared among the three subgroups. Results PWRI differentiated between asymptomatic and symptomatic AAAs ( p < .0004) better than PWS ( p < .1453). PWRI-dependent RRED was higher in the symptomatic subgroup compared with the asymptomatic subgroup ( p < .0004). Maximum AAA external diameters were comparable between the two groups ( p < .1355). Ruptured AAAs showed the highest values for external diameter, total intraluminal thrombus volume, PWS, RRED, and PWRI compared with asymptomatic and symptomatic AAAs. In contrast with symptomatic and ruptured AAAs, none of the asymptomatic patients had a PWRI value >1.0. This threshold value might identify patients at imminent risk of rupture. Conclusions From different FEA derived parameters, PWRI distinguishes most precisely between asymptomatic and symptomatic AAAs. If elevated, this value may represent a negative prognostic factor for asymptomatic AAAs.
Objectives To analyze early and midterm complications after hybrid aortic arch repair (HAR). Methods Between January 1997 and November 2009 among 259 patients receiving thoracic endovascular aortic ...repair, HAR has been performed in 47 patients (median age, 64.5 years; range, 41-84). A retrospective analysis was performed. Complete supra-aortic debranching was performed in 15 patients (32%) and partial debranching in 23 patients (49%). Isolated left subclavian artery revascularization prior to thoracic endovascular aortic repair has been used in nine patients (19%). Emergency procedures were performed in 34% of all patients. Results The overall in-hospital mortality was 19% (9/47 patients), 27% after complete and 15.6% after partial debranching. Postoperative complications occurred in 32 patients (68%). Cardiocirculatory complications were observed in seven patients (15%). Pulmonary complications occurred in 12 patients (26%). A total of five patients (11%) experienced renal complications requiring hemodialysis. The stroke rate was 6.3%. Paraplegia was seen in three patients (6%). Proximal type I endoleaks were observed in seven patients. Retrograde aortic arch dissection was seen in three patients (6.3%). Cox proportional hazard regression showed the necessity for an emergency procedure as an independent predictor of death (hazard ratio, 2.9; 95% confidence interval, 1.1-7.5; P = .023). The reintervention rate was 27.6% with three patients requiring open conversion. Conclusions Hybrid aortic arch repair in high-risk patients is associated with a relevant morbidity, mortality, and reintervention rate. Patient selection is crucial and indication should be limited to patients not suitable for conventional aortic arch repair or emergency cases at present. Therefore, we recommend performing HAR only in high-volume centers with cardiovascular surgical cooperation.
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