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Lutz J.T.,Intensive Care Medicine and Pain Therapy | Diener I.V.,Intensive Care Medicine and Pain Therapy | Freiberg K.,Intensive Care Medicine and Pain Therapy | Zillmann R.,Intensive Care Medicine and Pain Therapy | And 5 more authors.
Infection | Year: 2016

Purpose: Catheter-related bloodstream infections affect patients in surgical and intensive care settings worldwide, causing complications, aggravation of existing symptoms and increased length of stay. The trial aimed at comparing two registered skin antiseptics with respect to their residual and therefore infection-preventing effects. Methods: In a parallel, monocentric, prospective, triple-blind, randomized trial the difference in bacterial recolonization of catheter skin sites in central venous (CVC) and epidural catheters (EC) was investigated by comparing two alcoholic-based skin disinfectants. Patients receiving planned surgeries or intensive care were eligible for the trial. Those in the trial group received skin disinfection with the additive octenidine dihydrochloride (OCT) (n = 51), those in the control group were treated with benzalkonium chloride as additive (BAC) (n = 59) prior to catheter insertion. Randomization was carried out by assigning patients to groups week-wise. Endpoints of the investigation were skin colonization of the catheter site counted in colony forming units per swab at three time points: (1) prior to catheter insertion, on untreated skin; (2) directly after catheter insertion, prior to sterile coverage; (3) 48 h after catheter insertion. The hypothesis was tested by a Wilcoxon test with a two-sided alpha = 5 %. Results: From second to third swab, recolonization of the catheter-surrounding skin was significantly lower in the trial group for both sorts of catheters: delta 2–3 OCT group: 0.72 (95 % CI: 0.42; 1.02); delta 2–3 BAC group: 1.97 (95 % CI: 1.45; 2.50); p < 0.001. None of the patients enrolled developed a catheter-related blood stream infection (CRBSI) during follow-up. Conclusions: Previous studies have shown that skin colonization is strongly associated with the occurrence of CRBSI. This randomized controlled trial supports the observations made in previous trials that octenidine dihydrochloride in disinfectants is more effective than agents containing other additives with regard to skin recolonization surrounding CVC and EC insertion sites. Therefore, it is likely to also reduce the risk of CRBSI in these patient groups. The trial was approved by the North Rhine Medical Association in July 2014 (application-no.: 2014222). © 2016 The Author(s) Source

Jayasinghe C.,Johannes Gutenberg University Mainz | Jayasinghe C.,Laboratory Dr Wisplinghoff | Simiantonaki N.,Johannes Gutenberg University Mainz | Simiantonaki N.,Laboratory Dr Wisplinghoff | And 2 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2015

Background: For the successful therapeutic use of inhibitors of the vascular endothelial growth factor receptor (VEGFR) pathway detailed knowledge of the mechanisms leading to tumor progression is indispensable. The main goal of this study was to determine the relevance of the VEGFR-2 activating pathway for colon carcinoma (CC) metastasis. The initial event is ligand-induced receptor activation through tyrosine autophosphorylation. Methods: VEGFR-2, its ligands VEGF-C and VEGF-D and the phosphorylated (activated) receptor forms pVEGFR-2Tyr1175 and pVEGFR-2Tyr1214 were investigated immunohistochemically in different tumor compartments (intratumoral (zone 1) - invasive front (zone 2) - extratumoral soft tissue (zone 3)) and various cell types (tumor cells, inflammatory cells, macro- and microvasculature) in 84 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic CC. Results: VEGF-D produced by tumor cells has an autocrine affinity for its receptor VEGFR-2. In tumor budding regions VEGF-D-induced receptor activation by autophosphorylation at Tyr1214 seems to be a possible initial event of the VEGFR-2-mediated signaling pathway, but without effect on metastatic behaviour. In inflammatory cells of almost all CC VEGFR-2 phosphorylation at Tyr 1175 and Tyr 1214 was detectable without accompanying receptor expression, suggesting receptor activation without cell surface expression. Peritumoral inflammatory cells also expressed paracrine acting VEGF-C. The autocrine VEGF-D/VEGFR-2 signaling axis and receptor autophosphorylation at Tyr1214 appear to be main events for capillaries in all three tumor zones and for small vessels in zone 1 and 2. Independent of the metastatic status a large number of cases with capillary immunopositivity in the angiogenically active invasive front was documented, especially for VEGF-D, VEGFR-2 and pVEGFR-2Tyr1214. VEGFR-2 positive extratumoral capillaries were significantly more common in distant metastatic CC. In all tumor compartments the investigated biomolecules were also detected in different frequencies in the macrovasculature, which is responsible for sufficient tumor vascularization. In addition, vascular paracrine-acting VEGF-C production was widely detected, but without zone and vessel-type dependence. Conclusions: The VEGFR-2 activating pathway is closely involved in tumor cell-associated, vessel-mediated and immuno-inflammatory processes in colon carcinoma and appears to contribute to tumor survival and growth as well as maintenance of the infiltrative phenotype rather than to promote metastasis. © 2015 Jayasinghe et al.; licensee BioMed Central. Source

Jayasinghe C.,Johannes Gutenberg University Mainz | Jayasinghe C.,Laboratory Dr Wisplinghoff | Simiantonaki N.,Johannes Gutenberg University Mainz | Simiantonaki N.,Laboratory Dr Wisplinghoff | Kirkpatrick C.J.,Johannes Gutenberg University Mainz
BMC Cancer | Year: 2015

Background: Detailed knowledge of the essential pro-angiogenic biomolecules, the vascular endothelial growth factor (VEGF) family and its receptors, in the characteristically heterogeneous tumor tissue is a pre-requisite for an effective personalized target therapy. The effects of VEGF receptors after ligand binding are mediated through receptor tyrosine autophosphorylation. We determined the relevance of the VEGFR-1 activating pathway for colon cancer (CC) metastasis. Methods: The expression profiles of VEGFR-1, phosphorylated (activated) VEGFR-1 (pVEGFR-1Tyr1048, pVEGFR-1Tyr1213 and pVEGFR-1Tyr1333) and the VEGFR-1 ligands (VEGF, PlGF and VEGF-B) were investigated using immunohistochemistry in different tumor compartments (intratumoral - invasive front - extratumoral), cell types (tumor cells - macro- (large and small vessels) and the microvasculature (capillaries) - inflammatory cells) in human sporadic non-metastatic, lymphogenous metastatic and haematogenous metastatic CC. Results: VEGF and PlGF produced by tumor cells have an autocrine affinity for their receptor VEGFR-1. Subsequent PlGF-mediated receptor activation by autophosphorylation at Tyr1048 and Tyr1213 is a potential signaling pathway, which in turn seems to protect against distant metastasis and, in regions of tumor budding, additionally against lymph node metastasis. This autocrine link could be supported by possible formation of PlGF-VEGF heterodimers and PlGF-PlGF homodimers, which are known to have anti-metastatic properties. In contrast, in order to enhance their potential for distant metastasis tumor cells produce paracrine-acting VEGF-B. VEGFR-1 activation in tumor-associated macrovasculature but not capillaries appears to affect metastatic ability. Paracrine-mediated receptor autophosphorylation at Tyr1048 and Tyr1213 in small vessels located intratumorally and along the invasive front appears to be inversely correlated with metastasis, especially distant metastasis. Additionally, macrovessels are able to produce VEGFR-1 ligands, which influence the metastatic potential. Paracrine-acting VEGF-B production by intratumorally located small vessels and autocrine-acting PlGF production by extratumorally located small vessels seem to be associated with the non-metastatic phenotype. In contrast, VEGF-B-expressing extratumoral large and small vessels correlate with distant metastasis. Lymphocyte-associated VEGFR-1 expression in the invasive front without accompanying autophosphorylation could prevent against distant metastasis possibly by acting as a decoy and scavenger receptor. Conclusion: VEGFR-1 and its ligands participate in vascular, tumor cell-mediated and immuno-inflammatory processes in a complex biomolecule-dependent and tumor zone-specific manner and hence could influence metastatic behavior in CC. © Jayasinghe et al. Source

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