Mechanical stimulation of the pro-angiogenic capacity of human fracture haematoma: involvement of VEGF mechano-regulation.

Compromised angiogenesis appears to be a major limitation in various suboptimal bone healing situations. Appropriate mechanical stimuli support blood vessel formation in vivo and improve healing outcomes. However, the mechanisms responsible for this association are unclear. To address this question, the paracrine angiogenic potential of early human fracture haematoma and its responsiveness to mechanical loading, as well as angiogenic growth factors involved, were investigated in vitro. Human haematomas were collected from healthy patients undergoing surgery within 72 h after bone fracture. The haematomas were embedded in a fibrin matrix, and cultured in a bioreactor resembling the in vivo conditions of the early phase of bone healing (20% compression, 1 Hz) over 3 days. Conditioned medium (CM) from the bioreactor was then analyzed. The matrices were also incubated in fresh medium for a further 24 h to evaluate the persistence of the effects. Growth factor (GF) concentrations were measured in the CM by ELISAs. In vitro tube formation assays were conducted on Matrigel with the HMEC-1 cell line, with or without inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Cell numbers were quantified using an MTS test. In vitro endothelial tube formation was enhanced by CM from haematomas, compared to fibrin controls. The angiogenesis regulators, vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1), were released into the haematoma CM, but not angiopoietins 1 or 2 (Ang1, 2), basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF). Mechanical stimulation of haematomas, but not fibrin controls, further increased the induction of tube formation by their CM. The mechanically stimulated haematoma matrices retained their elevated pro-angiogenic capacity for 24 h. The pro-angiogenic effect was cancelled by inhibition of VEGFR2 signalling. VEGF concentrations in CM tended to be elevated by mechanical stimulation; this was significant in haematomas from younger, but not from older patients. Other GFs were not mechanically regulated. In conclusion, the paracrine pro-angiogenic capacity of early human haematomas is enhanced by mechanical stimulation. This effect lasts even after removing the mechanical stimulus and appears to be VEGFR2-dependent

Predicting excess cost for older inpatients with clinical complexity: A retrospective cohort study examining cognition, comorbidities and complications

Hospital-acquired complications increase length of stay and contribute to poorer patient outcomes. Older adults are known to be at risk for four key hospital-acquired complications (pressure injuries, pneumonia, urinary tract infections and delirium). These complications have been identified as sensitive to nursing characteristics such as staffing levels and level of education. The cost of these complications compared to the cost of admission severity, dementia, other comorbidities or age has not been established.To investigate costs associated with nurse-sensitive hospital-acquired complications in an older patient population 157,178 overnight public hospital episodes for all patients over age 50 from one Australian state, 2006/07 were examined. A retrospective cohort study design with linear regression analysis provided modelling of length-of-stay costs. Explanatory variables included patient age, sex, comorbidities, admission severity, dementia status, surgical status and four complications. Extra costs were based on above-average length-of-stay for each patient's Diagnosis Related Group from hospital discharge data.For adults over 50 who have length of stay longer than average for their diagnostic condition, comorbid dementia predicts an extra cost of A$874, (US$1,247); any one of four key complications predicts A$812 (US$1,159); each increase in admission severity score predicts A$295 ($US421); each additional comorbidity predicts A$259 (US$370), and for each year of age above 50 predicts A$20 (US$29) (all estimates significant at p<0.0001).Hospital-acquired complications and dementia cost more than other kinds of inpatient complexity, but admission severity is a better predictor of excess cost. Because complications are potentially preventable and dementia care in hospitals can be improved, risk-reduction strategies for common complications, particularly for patients with dementia could be cost effective.Complications and dementia were found to cost more than other kinds of inpatient complexity