Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

The role of tumour necrosis factor (TNF)-alpha in the mobilization and migration of human epidermal Langerhans cells (LC) has been investigated. Intradermal injection of normal human volunteers with homologous recombinant TNF-alpha was found to cause a dose-dependent reduction in the frequency of LC within epidermal sheets 2 h later. Equivalent results were obtained when epidermal LC were identified on the basis of either CD1a or HLA-DR expression. At the dose of TNF-alpha used routinely (500 U), treatment resulted in an average reduction in LC density of approximately 24%. Treatment with TNF-alpha was associated with a perivascular polymorphonuclear infiltration at 2 h, but the epidermis appeared normal with neither fibrinoid necrosis nor vasculitis, and LC morphology was not affected significantly. These results demonstrate that TNF-alpha provides an important signal for LC migration in humans and is likely therefore to play a crucial part in the induction of cutaneous immune responses.

These data demonstrate that LF is able to influence cutaneous immune and inflammatory responses, possibly because of an impaired production of local proinflammatory cytokines.