Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction – a randomised placebo-controlled trial (KARE): study protocol

Abstract Background Acute lung injury is a common, devastating clinical syndrome associated with substantial mortality and morbidity with currently no proven therapeutic interventional strategy to improve patient outcomes. The objectives of this study are to test the potential therapeutic effects of keratinocyte growth factor for patients with acute lung injury on oxygenation and biological indicators of acute inflammation, lung epithelial and endothelial function, protease:antiprotease balance, and lung extracellular matrix degradation and turnover. Methods/design This will be a prospective, randomised, double-blind, allocation-concealed, placebo-controlled, phase 2, multicentre trial. Randomisation will be stratified by presence of severe sepsis requiring vasopressors. Patients in an ICU fulfilling the American–European Consensus Conference Definition of acute lung injury will be randomised in a 1:1 ratio to receive an intravenous bolus of either keratinocyte growth factor (palifermin, 60 μg/kg) or placebo (0.9% sodium chloride solution) daily for a maximum of 6 days. The primary endpoint of this clinical study is to evaluate the efficacy of palifermin to improve the oxygenation index at day 7 or the last available oxygenation index prior to patient discontinuation from the study.A formal statistical analysis plan has been constructed. Analyses will be carried out on an intention-to-treat basis. A single analysis is planned at the end of the trial. P = 0.05 will be considered statistically significant and all tests will be two-sided. For continuously distributed outcomes, differences between groups will be tested using independent-sample t tests, analysis of variance and analysis of covariance with transformation of variables to normality or nonparametric equivalents. The trial will be reported in line with the Consolidated Standards of Reporting Trials (Consort 2010 guidelines). Trial registration http://ISRCTN9569067

Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe?

Osteoarthritis of the hip is a significant source of morbidity in the elderly. Treatment guidelines are available for the management of hip osteoarthritis, but these do not address the application of intraarticular corticosteroid injection. The intraarticular injection of corticosteroid is used in the management of other large joint osteoarthritic diseases and is well studied in the knee, however, this data cannot be used to make sound clinical decisions regarding its use for hip osteoarthritis. There are also concerns regarding the safety of this modality. Review of the published literature reveals that there are eight trials examining the efficacy of intraarticular corticosteroid injection for hip osteoarthritis and of these only four are randomized controlled trials. In general, the available literature demonstrates a short-term reduction of pain with corticosteroid injection and is indicated for patients refractory to non-pharmacologic or analgesic and NSAID therapy. The use of radiologic-guidance is recommended and, with proper sterile technique, the risk of adverse outcomes is very low. Future randomized controlled trials are needed to further examine the efficacy and safety of intraarticular corticosteroid injection for hip osteoarthritis

The role of ATP and adenosine in the brain under normoxic and ischemic conditions

By taking advantage of some recently synthesized compounds that are able to block ecto-ATPase activity, we demonstrated that adenosine triphosphate (ATP) in the hippocampus exerts an inhibitory action independent of its degradation to adenosine. In addition, tonic activation of P2 receptors contributes to the normally recorded excitatory neurotransmission. The role of P2 receptors becomes critical during ischemia when extracellular ATP concentrations increase. Under such conditions, P2 antagonism is protective. Although ATP exerts a detrimental role under ischemia, it also exerts a trophic role in terms of cell division and differentiation. We recently reported that ATP is spontaneously released from human mesenchymal stem cells (hMSCs) in culture. Moreover, it decreases hMSC proliferation rate at early stages of culture. Increased hMSC differentiation could account for an ATP-induced decrease in cell proliferation. ATP as a homeostatic regulator might exert a different effect on cell trophism according to the rate of its efflux and receptor expression during the cell life cycle. During ischemia, adenosine formed by intracellular ATP escapes from cells through the equilibrative transporter. The protective role of adenosine A1 receptors during ischemia is well accepted. However, the use of selective A1 agonists is hampered by unwanted peripheral effects, thus attention has been focused on A2A and A3 receptors. The protective effects of A2A antagonists in brain ischemia may be largely due to reduced glutamate outflow from neurones and glial cells. Reduced activation of p38 mitogen-activated protein kinases that are involved in neuronal death through transcriptional mechanisms may also contribute to protection by A2A antagonism. Evidence that A3 receptor antagonism may be protective after ischemia is also reported

Intra-articular Corticosteroid Injection for the Treatment of Idiopathic Adhesive Capsulitis of the Shoulder

Treatment for idiopathic adhesive capsulitis or frozen shoulder of the shoulder is controversial. The hypothesis of the study is that intra-articular corticosteroid injection in the early stages of idiopathic adhesive capsulitis will lead to a razpid resolution of stiffness and symptoms. This is a retrospective cohort study of only patients with stage 1 or stage 2 adhesive capsulitis. The diagnosis was made by history and physical examination and only when other causes of pain and motion loss were eliminated. Stage 1 adhesive capsulitis was defined as significant improvement in pain and normalization of motion following intra-articular injection. Stage 2 included patients who had significant improvement in pain and partial improvement in motion following injection. Seven patients with stage 1 and 53 patients with stage 2 comprised the baseline cohort. The mean age was 52 years (range: 30 to 78); 46 patients were female and nine patients had diabetes mellitus. Patients completed a physical examination as well as a shoulder rating questionnaire for symptoms and disability. Criteria for resolution were defined as forward flexion and external rotation to within 15° of the contralateral side and internal rotation to within three spinal levels of the contralateral side. Forty-four of the patients out of 60 met the criteria for recovery at a mean of 6.7 months. The mode and median time to recovery was 3 months. The mean score at final follow-up for 41 patients using the shoulder-rating questionnaire of L’Insalata was 90 (range 52–100). The mean time to recovery for the stage 1 patients was 6 weeks (range: 2 weeks to 3 months), and it was 7 months for stage 2 patients (range: 2 weeks to 2 years). Glenohumeral corticosteroid injection for early adhesive capsulitis may have allowed patients to recover motion at a median time of 3 months. In many cases, the patients had improvement prior to the 3-month mark; however, that was the routine time for follow-up. Patients with stage 1 disease tended to resolve more rapidly than stage 2 patients. Prompt recognition of stage 1 and stage 2 idiopathic adhesive capsulitis and early injection of corticosteroid with local anesthesia may be both diagnostic and therapeutic