The CXC-Chemokine CXCL4 Interacts with Integrins Implicated in Angiogenesis

The human CXC-chemokine CXCL4 is a potent inhibitor of tumor-induced angiogenesis. Considering that CXCL4 is sequestered in platelet α-granules and released following platelet activation in the vicinity of vessel wall injury, we tested the hypothesis that CXCL4 might function as a ligand for integrins. Integrins are a family of adhesion receptors that play a crucial role in angiogenesis by regulating early angiogenic processes, such as endothelial cell adhesion and migration. Here, we show that CXCL4 interacts with αvβ3 on the surface of αvβ3-CHO. More importantly, human umbilical vein endothelial cells adhere to immobilized CXCL4 through αvβ3 integrin, and also through other integrins, such as αvβ5 and α5β1. We further demonstrate that CXCL4-integrin interaction is of functional significance in vitro, since immobilized CXCL4 supported endothelial cell spreading and migration in an integrin-dependent manner. Soluble CXCL4, in turn, inhibits integrin-dependent endothelial cell adhesion and migration. As a whole, our study identifies integrins as novel receptors for CXCL4 that may contribute to its antiangiogenic effect

Predicting Patients at Risk for 3-Day Postdischarge Readmissions, ED Visits, and Deaths

Background: Transitional care interventions can be utilized to reduce post-hospital discharge adverse events (AEs). However, no methodology exists to effectively identify high-risk patients of any disease across multiple hospital sites and patient populations for short-term postdischarge AEs. Objectives: To develop and validate a 3-day (72 h) AEs prediction model using electronic health records data available at the time of an indexed discharge. Research Design: Retrospective cohort study of admissions between June 2012 and June 2014. Subjects: All adult inpatient admissions (excluding in-hospital deaths) from a large multicenter hospital system. Measures: All-cause 3-day unplanned readmissions, emergency department (ED) visits, and deaths (REDD). The REDD model was developed using clinical, administrative, and socioeconomic data, with data preprocessing steps and stacked classification. Patients were divided randomly into training (66.7%), and testing (33.3%) cohorts to avoid overfitting. Results: The derivation cohort comprised of 64,252 admissions, of which 2782 (4.3%) admissions resulted in 3-day AEs and 13,372 (20.8%) in 30-day AEs. The c-statistic (also known as area under the receiver operating characteristic curve) of 3-day REDD model was 0.671 and 0.664 for the derivation and validation cohort, respectively. The c-statistic of 30-day REDD model was 0.713 and 0.711 for the derivation and validation cohort, respectively. Conclusions: The 3-day REDD model predicts high-risk patients with fair discriminative power. The discriminative power of the 30-day REDD model is also better than the previously reported models under similar settings. The 3-day REDD model has been implemented and is being used to identify patients at risk for AEs

Tissue diagnostics using laser-induced fluorescence

We have performed extensive investigations of laser-induced fluorescence in animal and human tissue aimed at instant tissue characterization. Autofluorescence, as well as specific fluorescence from HPD/DHE and other photosensitizers, has been utilized. The studies have been focused on the demarcation of malignant tumours and atheroscleortic plaques. A nitrogen laser or an excimer-pumped dye laser was used to induce fluorescence, which was analysed with an intensified optical multichannel system. A fibre-optic sensor system was developed for the clinical work. Multi-colour fluorescence imaging has also been demonstrated along a line and equipment for two-dimensional imaging is being constructed. Dimensionless spectroscopic functions, which are not affected by factors that are clinically uncontrollable have been employed for optimum tissue discrimination. The investigations have so far been performed in a time-integrated mode, but time-resolved studies are now being initiated to fully exploit the diagnostic power of tissue laser-induced fluorescence. In addition to a presentation of our own work a brief review of tissue fluorescence studies performed by other groups is also given