The Effect of CytoSorb on Inflammatory Markers in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The effectiveness of CytoSorb at removing inflammatory mediators in critically ill patients is controversial. DATA SOURCES: Electronic databases were searched from inception to May 2023. STUDY SELECTION: Randomized controlled trials reporting the effects of CytoSorb therapy on inflammatory parameters in critically ill patients with hyperinflammatory conditions were included. DATA EXTRACTION: Two authors screened articles for eligibility, extracted data, and assessed the risk of bias, conflicts of interest, and certainty of evidence (CoE). The primary outcome was interleukin (IL)-6 at 1 day after initiation of the therapy. Secondary outcomes included various inflammatory markers at 1, 2, 3, and 5 days and mortality. Data were pooled if at least three trials reported the outcome of interest. We conducted meta-analyses of the data using a random-effects model. DATA SYNTHESIS: Seventeen trials ( n = 855) were included. Fourteen trials were judged to have notable concern about conflicts of interest. Seven trials were performed in medical ICU patients with hyperinflammatory conditions and 10 in complex cardiovascular surgery under cardiopulmonary bypass. Hemoadsorption with CytoSorb was not associated with lower IL-6 at 1 day (mean difference -5.98 [95% CI, -30.44 to 18.48] pg/mL), 2 days, 3 days, or 5 days after initiation of the treatment, as well as the concentration of procalcitionin. The levels of C-reactive protein were not lower with CytoSorb at 1, 2, and 3 days. The use of CytoSorb was associated with higher mortality at latest follow-up (relative risk = 1.22 [95% CI, 1.02-1.45]) and at 30 days. CoE ranged from low to very low. CONCLUSIONS: The use of CytoSorb hemoadsorption in a mixed population of critically ill patients with hyperinflammatory conditions does not exhibit a consistent decrease in IL-6 and other inflammatory parameters within the first 5 days of treatment. The significant uncertainty surrounding these findings highlights the need for further investigations.

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial. METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized-controlled trials to assess the mortality and safety of CytoSorb® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow-up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI). RESULTS: Fourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb® was associated with higher mortality at latest follow-up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04-1.49], p = .02, [TSA-adjusted CI, 0.92-1.68]) and at 30-days or in-hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06-1.88], p = .02, [TSA-adjusted CI, 0.44-4.62]). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb®. Certainty of evidence ranged from low to very low. CONCLUSION: Low certainty of evidence showed that the use of CytoSorb® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high-quality randomized trials to clarify mortality and adverse events related to CytoSorb®. EDITORIAL COMMENT: Hemoadsorption with CytoSorb® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient-important benefits. The findings from this systematic review and meta-analysis suggests an increased risk of adverse events including mortality. With no apparent benefits and at the same time risk of harm, use of hemoadsorption with CytoSorb® in daily clinical practice cannot be recommended at this time.

Rectal gonorrhoea and chlamydia among men who have sex with men in coastal Kenya.

Background: Men who have sex with men (MSM) have a higher prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections compared to the rest of the population, often remaining undiagnosed. In Kenya, prevalence of rectal CT and NG infection and NG antimicrobial sensitivity are poorly described. Methods: MSM who reported receptive anal intercourse (RAI) were recruited from an ongoing human immunodeficiency virus acquisition and treatment study in coastal Kenya in 2016-2017. Rectal swabs were collected at two time points 6 months apart to estimate prevalence and incidence of CT/NG infection using a molecular point-of-care assay. Participants positive for CT or NG were treated according to national guidelines. NG culture and antimicrobial susceptibility testing was performed. Participant and risk behaviour characteristics were collected and association with baseline CT/NG prevalence assessed by multivariable regression analysis. Results: Prevalence of CT/NG in 104 MSM was 21.2% (CT 13.5%, NG 9.6%, dual infection 1.9%) at baseline and 25.9% in 81 MSM at follow-up (CT 14.8%, NG 14.8%, dual infection 3.7%). CT/NG incidence was estimated at 53.0 (95% CI, 34.5-81.3) per 100 person-years. Most CT/NG positive participants were asymptomatic: 95.5% at baseline and 100% at follow-up. CT/NG infection was associated with being paid for sex [adjusted odds ratio (aOR)=6.2, 95% CI (1.7-22.9)] and being in formal employment [aOR=7.5, 95% CI (1.1-49.2)]. Six NG isolates were obtained at follow-up; all were susceptible to ceftriaxone and cefixime and all were resistant to penicillin, tetracycline and ciprofloxacin. Conclusions: There is a high prevalence and incidence of asymptomatic rectal CT and NG in MSM reporting RAI in coastal Kenya. MSM who were paid for sex or had formal employment were more likely to be infected with CT/NG suggesting increased risk behaviour during transactional sex. Antimicrobial susceptibility results suggest that current antibiotic choices in Kenya are appropriate for NG treatment.