Lidocaine Infusion for the Management of Postoperative Pain and Delirium (LIMPP): protocol for a randomised control trial.

INTRODUCTION: Postoperative delirium is a frequent adverse event following elective non-cardiac surgery. The occurrence of delirium increases the risk of functional impairment, placement to facilities other than home after discharge, cognitive impairment at discharge, as well as in-hospital and possibly long-term mortality. Unfortunately, there is a dearth of effective strategies to minimise the risk from modifiable risk factors, including postoperative pain control and the analgesic regimen. Use of potent opioids, currently the backbone of postoperative pain control, alters cognition and has been associated with an increased risk of postoperative delirium. Literature supports the intraoperative use of lidocaine infusions to decrease postoperative opioid requirements, however, whether the use of postoperative lidocaine infusions is associated with lower opioid requirements and subsequently a reduction in postoperative delirium has not been investigated. METHODS AND ANALYSIS: The Lidocaine Infusion for the Management of Postoperative Pain and Delirium trial is a randomised, double-blinded study of a postoperative 48-hour infusion of lidocaine at 1.33 mg/kg/hour versus placebo in older patients undergoing major reconstructive spinal surgery at the University of California, San Francisco. Our primary outcome is incident delirium measured daily by the Confusion Assessment Method in the first three postoperative days. Secondary outcomes include delirium severity, changes in cognition, pain scores, opioid use, incidence of opioid related side effects and functional benefits including time to discharge and improved recovery from surgery. Lidocaine safety will be assessed with daily screening questionnaires and lidocaine plasma levels. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics board at the University of California, San Francisco. The results of this study will be published in a peer-review journal and presented at national conferences as poster or oral presentations. Participants wishing to know the results of this study will be contacted directly on data publication. TRIAL REGISTRATION NUMBER: NCT05010148.

Altered expression of lymphocyte homing chemokines in the pathogenesis of IgA nephropathy.

Defective adaptive humoral immune responses to mucosal immunogens, but intact systemic responses, are increasingly recognized in patients with IgA nephropathy (IgAN). Reduced expression of IgA+, J chain+ cells in the gut lamina propria, with collateral increases in these cells in the marrow, is also documented. Thus, there seems to be a derangement in a 'mucosa-marrow axis' in IgAN patients. Recent evidence indicates that chemokines regulate the localization of B cells and their progeny into respiratory and intestinal lamina propria, and into other lymphoid organs as well. Particularly, secretory epithelial cells express the chemokine CCL28, whereas small bowel cells uniquely express CCL25. Extramucosal sites preferentially express CXCL12, CXCL13 and/or CXCL16. Reciprocally, plasmablasts committed to IgA synthesis ubiquitously express the receptor (CCR10) for CCL28, and a subset also express the receptor (CCR9) for CCL25; neither of these is present on cells committed to IgG or IgM synthesis. Herein, the potential contributions of virally induced innate responses to defective mucosal immunity and overproduction of oligomeric IgA in the marrow and tonsils will be reviewed, particularly with respect to the influence that viral infection exerts upon the expression of selected chemokine and receptor pairs. The ramifications for pathogenesis of IgAN will be considered.