Pneumococcal Polysaccharide Vaccine Ameliorates Murine Lupus

Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (TFH) and T follicular regulatory cells (TFR), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with fewer TFH and increased TFR. Together, the data support use of Prevnar vaccination in individuals with SLE

Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach

Objectives Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by\ua0physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. Design and Setting A systematic review of literature followed by web-based voting on findings of a consensus conference. Participants A total of 555 clinicians from 61 countries. Interventions The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents\u2019 agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians\u2019 approach to interventions also were investigated. Measurements and Main Results According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians\u2019 agreement. Conclusions Physicians\u2019 clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians\u2019 opinions and routine practices to understand the clinicians\u2019 response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement 6567% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to \u201cdo you agree\u201d and \u201cdo you use\u201d) showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality

Objective: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. Design: A systematic review of the literature followed by a consensus-based voting process. Setting: A web-based international consensus conference. Participants: Two hundred fifty-one physicians from 46 countries. Interventions: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. Measurements and Main Results: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. Conclusion: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale

Effect of Volatile Anesthetics on Myocardial Infarction After Coronary Artery Surgery: A Post Hoc Analysis of a Randomized Trial

Objective: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). Design: A post hoc analysis of a randomized trial. Setting: Cardiac surgical operating rooms. Participants: Patients undergoing elective, isolated CABG. Interventions: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. Measurements and Main Results: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). Conclusions: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality