The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies.

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

Near-Infrared Spectroscopy Monitoring in Cardiac and Noncardiac Surgery: Pairwise and Network Meta-Analyses.

Goal-directed therapy based on brain-oxygen saturation (bSo2) is controversial and hotly debated. While meta-analyses of aggregated data have shown no clinical benefit for brain near-infrared spectroscopy (NIRS)-based interventions after cardiac surgery, no network meta-analyses involving both major cardiac and noncardiac procedures have yet been undertaken. Randomized controlled trials involving NIRS monitoring in both major cardiac and noncardiac surgery were included. Aggregate-level data summary estimates of critical outcomes (postoperative cognitive decline (POCD)/postoperative delirium (POD), acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality) were obtained. NIRS was only associated with protection against POCD/POD in cardiac surgery patients (pooled odds ratio (OR)/95% confidence interval (CI)/I2/number of studies (n): 0.34/0.14-0.85/75%/7), although a favorable effect was observed in the analysis, including both cardiac and noncardiac procedures. However, the benefit of the use of NIRS monitoring was undetectable in Bayesian network meta-analysis, although maintaining bSo2 > 80% of the baseline appeared to have the most pronounced impact. Evidence was imprecise regarding acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality. There is evidence that brain NIRS-based algorithms are effective in preventing POCD/POD in cardiac surgery, but not in major noncardiac surgery. However, the specific target bSo2 threshold has yet to be determined.