Comparative efficacy of antioxidant therapies for sepsis and septic shock in the intensive care unit: A frequentist network meta-analysis.

Background: Antioxidant therapy is gaining traction in managing sepsis and septic shock, owing to its perceived positive impact on patient outcomes. This study sought to compare the efficacy of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium, and N-acetylcysteine, both individually and in combination with other compounds such as vitamin B1, hydrocortisone, propolis, and glutamine) in treating sepsis or septic shock in the intensive care unit (ICU). Methods: The study involved randomized and multi-arm trials with sepsis or septic shock patients using melatonin, vitamin C, vitamin E, selenium, or N-acetylcysteine. Studies were sourced from PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO - Clinical Trials Registry Platform for the frequentist network meta-analysis on 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores. The risk of bias was assessed using the Physiotherapy Evidence Database scale. Therapies were compared directly and indirectly using R software. Results: The study of 56 trials involving 9,366 patients was included. Bias assessment revealed that 89.3 % of trials achieved excellent or good quality. Based on treatment ranking and pairwise comparisons, melatonin with propolis (SUCRA = 93.29 %) is effective in improving SOFA scores, statistically significant, with no publication bias (p= 0.73). High-dose vitamin C (SUCRA = 83.97 %), vitamin C with vitamin B1 (SUCRA = 78.72 %), and melatonin (SUCRA = 67.03 %) are potential therapies for organ dysfunction. Melatonin (SUCRA = 88.22 %) and high-dose vitamin C (SUCRA = 80.75 %) were the most effective in reducing 28-day mortality rates. However, analysis indicated that the results for 28-day mortality rates were not statistically significant. Also, these results contained publication bias (p= 0.02). Conclusion: The study offers fresh perspectives on antioxidant therapy treatments for sepsis or septic shock in ICU, emphasizing the combination of melatonin and propolis notably reduces SOFA scores for those patients.

Discovery and engineering of the antibody response against a prominent skin commensal.

The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8 + T cell response pre-emptively, in the absence of an infection 1 . However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain of S. epidermidis in which the parallel ß-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge. A similar strain of S. epidermidis expressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high titers of antibody under conditions of physiologic colonization, including a robust IgA response in the nasal mucosa. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a novel form of topical vaccination.