Passive leg raise (PLR) during cardiopulmonary (CPR) - a method article on a randomised study of survival in out-of-hospital cardiac arrest (OHCA).

BACKGROUND: It is estimated that about 275,000 inhabitants experience an out-of-hospital cardiac arrest (OHCA) every year in Europe. Survival in out-of-hospital cardiac arrest is relatively low, generally between five per cent and 10%. Being able to explore new methods to improve the relatively low survival rate is vital for people with these conditions. Passive leg raise (PLR) during cardiopulmonary resuscitation (CPR) has been found to improve cardiac preload and blood flow during chest compressions. The aim of our study is to evaluate whether early PLR during CPR also has an impact on one-month survival in sudden and unexpected out-of-hospital cardiac arrest (OHCA). METHOD/DESIGN: A prospective, randomized, controlled trial in which all patients (≥18 years) receiving out-of hospital CPR are randomized by envelope to be treated with either PLR or in the flat position. The ambulance crew use a special folding stool which allows the legs to be elevated about 20 degrees. Primary end-point: survival to one month. Secondary end-point: survival to hospital admission to one month and to one year with acceptable cerebral performance classification (CPC) 1-2. DISCUSSION: PLR is a simple and fast maneuver. We believe that the greatest benefit with PLR is when performed early in the process, during the first minutes of CPR and before the first defibrillation. To reach power this study need 3000 patients, we hope that this method article will encourage other sites to contact us and take part in our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01952197.

Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.

The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbours specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17-producing γδ T (γδT17) cells, the aberrant activation of which by IL-23 can provoke psoriasis-like inflammation. The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibres. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear. We exposed the skin of mice to imiquimod, which induces IL-23-dependent psoriasis-like inflammation. Here we show that a subset of sensory neurons expressing the ion channels TRPV1 and Nav1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors, DDCs failed to produce IL-23 in imiquimod-exposed skin. Consequently, the local production of IL-23-dependent inflammatory cytokines by dermal γδT17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response. These findings indicate that TRPV1(+)Nav1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses.