Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

Background Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcome. Methods A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Results 15 studies were included, reporting 699 patients. Most patients were male (71.7%) and the pooled mean age was 40.8 years. 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcome, one found them to predict better outcomes, and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Conclusion Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number CRD4202127120

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes:a systematic review and meta-analysis

Objective: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. Design: Systematic review and meta-analysis. Data sources: Major databases between December 2019 and January 2023. Study selection: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. Quality assessment, data extraction and analysis: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. Results: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). Conclusion: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO registration number: CRD42020178076