Cathelicidin preserves intestinal barrier function in polymicrobial sepsis.

ObjectivesThe intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.DesignTo examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp+/+) and knockout (Cnlp-/-) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model.ResultsThe ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.ConclusionsEndogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis

Glass–water interphase reactivity with calcium rich solutions

International audienc

The cost-effectiveness of an outpatient anesthesia consultation clinic before surgery: a matched Hong Kong cohort study

<p>Abstract</p> <p>Background</p> <p>Outpatient anesthesia clinics are well established in North America, Europe and Australia, but few economic evaluations have been published. The Perioperative Systems in Hong Kong are best described as a hybrid model of the new and old systems of surgical care. In this matched cohort study, we compared the costs and effects of an outpatient anesthesia clinic (OPAC) with the conventional system of admitting patients to the ward a day before surgery for their pre-anesthesia consultation. A second objective of the study was to determine the patient’s median Willingness To Pay (WTP) value for an OPAC.</p> <p>Methods</p> <p>A total of 352 patients were matched (1:1) on their elective surgical procedure to either the clinic group or to the conventional group. The primary outcome was quality of recovery score and overall perioperative treatment cost (US$). To detect a difference in the joint cost-effect relationship between groups, a cost-effectiveness acceptability curve (CEAC) was drawn. A modified Poisson regression model was used to examine the factors associated with patients willing to pay more than the median WTP value for an OPAC.</p> <p>Results</p> <p>The quality of recovery scores on the first day after surgery between the clinic and conventional groups were similar (mean difference, -0.1; 95$463, 95% CI, -$648 to -$278 per patient; <it>P</it> <0.001), the total perioperative cost was similar between groups (mean difference, -$172; 95$684 to $340 per patient; <it>P</it> = 0.51). The CEAC showed that we could not be 95$13) for a clinic consultation (RR 3.27, 95% CI, 2.32 to 4.64; <it>P</it> <0.001).</p> <p>Conclusions</p> <p>There is uncertainty about the cost-effectiveness of an OPAC in the Hong Kong setting. Most clinic patients were willing to pay a small amount for an anesthesia clinic consultation.</p

Perioperative systems as a quality model of perioperative medicine and surgical care

Objectives: There has been a recent widespread international ‘paradigm shift’ to new Perioperative Systems for surgical patient care. These new systems are based on a multidisciplinary team providing an integrated process of care from the time a decision is made that a patient should have an operation until the patient has recovered from surgery. The objectives of this review were to outline the rationale for new Perioperative Systems, synthesize the evidence supporting these new systems and consider the current state of Perioperative Systems and its future development. Methods: A systematic review of studies that focus on preoperative management practices to improve patient preparation for surgery and anaesthesia, with restriction to study designs with the highest levels of evidence for the synthesis of evidence. Results: Perioperative Systems are regarded as the standard model of care in Australia, New Zealand, North America and increasingly in Europe. The benefits of Perioperative Systems include: increased surgical volume and flow (20–35%), shorter preoperative length of stay (−0.2 to −1.3 days), fewer cancellations of surgery (absolute reduction 1–8%), relative reduction in the number (23–55%) and cost (40–59%) of preoperative investigations and a lower risk of wound infection (relative risk 0.30, 95% CI 0.12–0.78) compared to the traditional system. The mean reduction in the total cost per patient associated with a Perioperative System was 8–18%. Future developments include offering health promotion activities in the weeks before surgery to improve long term patient outcomes after surgery. Conclusion: There is evidence of quality benefits for patients, clinicians and health administrators associated with new Perioperative Systems. Despite this, these systems are yet to be fully developed in many jurisdictions

Publication bias affected the estimate of postoperative nausea in an acupoint stimulation systematic review

Background and Objective: To assess the effect of publication bias and country effect on the results and conclusion of a systematic review of wrist P6 acupoint stimulation for the prevention of postoperative nausea and vomiting. Methods: Reanalysis of a systematic review of 26 randomized trials comparing P6 acupoint stimulation with sham published in the Cochrane Database of Systematic Reviews using the Copas' sensitivity approach. Results: If it is assumed that all studies that have ever been carried out are included, or that those selected for review are truly representative of all such studies, then the estimated relative risk (RR) for nausea was 0.71 (95% Cl: 0.58 to 0.88, P <.01) and for vomiting was 0.70 (95% Cl: 0.56 to 0.88, P <.01) after adjusting for country effect. For nausea, adjustment for publication bias suggests that the risk has been overestimated. If around 33% of studies have been unpublished, the RR of nausea (0.92, 95% Cl: 0.80 to 1.06, P =.25) is no longer significant. For vomiting, however, there is no strong evidence of publication bias. The number of unpublished studies required to substantially overturn the above significant result is implausibly large. Conclusion: Publication bias affects the published estimate of postoperative nausea, not vomiting. (c) 2006 Elsevier Inc. All rights reserved