This study aimed to analyze the role of endothelial progenitor cell (EPC)-derived angiogenic factors and chemokines in the multistep process driving angiogenesis with a focus on the recently discovered macrophage migration inhibitory factor (MIF)/chemokine receptor axis. Primary murine and murine embryonic EPCs (eEPCs) were analyzed for the expression of angiogenic/chemokines and components of the MIF/CXC chemokine receptor axis, focusing on the influence of hypoxic versus normoxic stimulation. Hypoxia induced an upregulation of CXCR2 and CXCR4 but not CD74 on EPCs and triggered the secretion of CXCL12, CXCL1, MIF, and vascular endothelial growth factor (VEGF). These factors stimulated the transmigration activity and adhesive capacity of EPCs, with MIF and VEGF exhibiting the strongest effects under hypoxia. MIF-, VEGF-, CXCL12-, and CXCL1-stimulated EPCs enhanced tube formation, with MIF and VEGF exhibiting again the strongest effect following hypoxia. Tube formation following in vivo implantation utilizing angiogenic factor-loaded Matrigel plugs was only promoted by VEGF. Coloading of plugs with eEPCs led to enhanced tube formation only by CXCL12, whereas MIF was the only factor which induced differentiation towards an endothelial and smooth muscle cell (SMC) phenotype, indicating an angiogenic and differentiation capacity in vivo. Surprisingly, CXCL12, a chemoattractant for smooth muscle progenitor cells, inhibited SMC differentiation. We have identified a role for EPC-derived proangiogenic MIF, VEGF and MIF receptors in EPC recruitment following hypoxia, EPC differentiation and subsequent tube and vessel formation, whereas CXCL12, a mediator of early EPC recruitment, does not contribute to the remodeling process. By discerning the contributions of key angiogenic chemokines and EPCs, these findings offer valuable mechanistic insight into mouse models of angiogenesis and help to define the intricate interplay between EPC-derived angiogenic cargo factors, EPCs, and the angiogenic target tissue.

BackgroundThe increased use of laparoscopy has resulted in certain complications specifically associated with the laparoscopic approach, such as port-site incisional hernia (PIH). Until today, it is not finally clarified if port-site closure should be performed by fascia suture or not. Furthermore, the optimal treatment strategy in PIH (suture vs. mesh) is still widely unclear. The aim of this study was to present our experience with PIH in two independent departments and to derive possible treatment strategies from these results.MethodsBetween 2003 and 2013, 54 patients were operated due to port-site incisional hernia in two surgical centres. Their data were collected and retrospectively analyzed depending on surgical technique of port-site hernia repair (Mesh repair group, n = 13 vs. Suture only group, n = 41).ResultsPort site incisional hernia occurred in 96% (52 patients) after the use of trocars with 10 mm or larger diameter. Patients treated with mesh repair had significantly higher body mass index (BMI) (32 ± 9 vs. 27 ± 4; p = 0.023) and significantly higher rates of cardiac diseases (77% vs. 39%; p = 0.026) than patients in the suture only group. Mean fascial defect size was significantly larger in the Mesh repair group than in the Suture only group (31 ± 24 mm vs. 24 ± 32 mm; p = 0.007) and mean time of operation was significantly longer in patients operated with mesh repair (83 ± 47 min vs. 40 ± 28 min; p < 0.001). There were no significant differences in mean hospital stay (3 ± 4 days; p = 0.057) and hernia recurrence rates (9%; p = 0.653) between study groups. Mean time of follow up was 32 ± 35 months.ConclusionsIn Port sites of 10 mm and larger diameter fascia should be closed by suture, whereas the risk of hernia development in 5 mm trocar placements seems to be a rare complication. Port-site incisional hernia should be treated by suture or mesh repair depending on fascial defect size and the patients' risk factors regarding preexisting deseases and body mass index.

Objectives Here we aimed to clarify the role of CXCR2 in the macrophage migration inhibitory factor (MIF)-mediated effects after myocardial ischemia and reperfusion (I/R). As a pleiotropic chemokine-like cytokine, MIF has been identified to activate multiple receptors including CD74 and CXCR2. In models of myocardial infarction (MI), MIF exerts both pro-inflammatory effects and protective effects in cardiomyocytes. Likewise, CXCR2 displays opposing effects in resident versus circulating cells. Approach and results Using bone marrow (BM) transplantation, we generated chimeric mice with CXCR2−/− BM-derived inflammatory cells and wild-type resident cells (wt/CXCR2−/−), with CXCR2−/− cardiomyocytes and wild-type BM-derived cells (CXCR2−/−/wt) and wild-type controls reconstituted with wild-type BM (wt/wt). All groups were treated with anti-MIF or isotype control antibody before they underwent myocardial I/R. Blocking MIF increased infarction size and impaired cardiac function in wt/wt and wt/CXCR2−/− mice but ameliorated functional parameters in CXCR2−/−/wt mice, as analyzed by echocardiography and Langendorff perfusion. Neutrophil infiltration and angiogenesis were unaltered by MIF blockade or CXCR2 deficiency. Monocyte infiltration was blunted in wt/CXCR2−/− mice and reduced by MIF blockade in wt/wt and CXCR2−/−/wt mice. Moreover, MIF blockade attenuated collagen content in all groups in a CXCR2-independent manner. Conclusions The compartmentalized and opposing effects of MIF after myocardial I/R are largely mediated by CXCR2. Whereas MIF confers protective effects improving myocardial healing and function through CXCR2 in resident cells, complementing paracrine effects through CD74/AMPK, it exerts detrimental effects on CXCR2-bearing inflammatory cells, increasing monocyte infiltration and impairing heart function. These dichotomous findings should be considered, when developing novel therapeutic strategies to treat MI.

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Based on our findings, surgical delay in the case of appendicitis and operation at night did not increase the risk for postoperative complications. However, the mean waiting time was less than 12 h and patients aged 70 years or older were at a higher risk for postoperative complications. Furthermore, for the subgroup of patients with complicated appendicitis, the time interval to surgery had a significant influence on the occurrence of postoperative complications. Therefore, the contemporary operation depending on the clinical symptoms and patient age remains our recommendation.

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Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1α (SDF-1α) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1α-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1α in infarcted myocardium. In addition, a significant increased density of CD31+ vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.

Background: Non-alcoholic fatty liver disease (NAFLD) is a frequent condition in obese patients and regularly progresses to non-alcoholic steatohepatitis (NASH) and subsequent cirrhosis. Histologic evaluation is the gold standard for grading and staging, but invasive biopsies are associated with obvious risks. The aim of this study was to evaluate different non-invasive tools for screening of NAFLD and fibrosis in obese patients. Methods: In a prospective cohort study liver specimens of 141 patients were taken during bariatric surgery. Serological parameters and clinical data were collected and the following scores calculated: NASH clinical scoring system (NCS), aspartate aminotransferase to platelet ratio index (APRI), FIB-4 as well as NAFLD fibrosis score (NFS). Liver function capacity was measured preoperatively by LiMAx test (enzymatic capacity of cytochrome P450 1A2). Intraoperative liver biopsies were classified using NAFLD activity score (NAS) and steatosis, activity and fibrosis (SAF) score. Results: APRI was able to differentiate between not NASH and definite NASH with a sensitivity of 74% and specificity of 67% (AUROC 0.76). LiMAx and NCS also showed significant differences between not NASH and definite NASH. No significant differences were found for NFS and Fib-4. APRI had a high sensitivity (83%) and specificity (76%) in distinguishing fibrosis from no fibrosis (AUROC = 0.81). NCS and Fib-4 also revealed high AUROCs (0.85 and 0.67), whereas LiMAx and NFS did not show statistically significant differences between fibrosis stages. Out of the patients with borderline NASH in the histologic NAS score, 48% were classified as NASH by SAF score. Conclusions: APRI allows screening of NAFLD as well as fibrosis in obese patients. This score is easy to calculate and affordable, while conveniently only using routine clinical parameters. Using the NAS histologic scoring system bears the risk of underdiagnosing NASH in comparison to SAF score.