Browsing by Author "Brouwer, M"
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- Cerebrospinal Fluid Sex Steroid Hormones in Bacterial MeningitisPublication . Dias, S; Brouwer, M; Boelen, A; van de Beek, DUnfavorable outcome in bacterial meningitis is related to excessive inflammation and higher inflammatory markers have been reported in female than in male patients. Sex steroid hormones have immunomodulatory properties and can be found in the cerebrospinal fluid (CSF); however, their actions have not been studied in bacterial meningitis. We investigated the association between CSF sex steroid hormone levels and inflammatory parameters, disease severity, and outcome in pneumococcal meningitis. We identified adults with culture-proven pneumococcal meningitis in a prospective cohort study (2006-2014). We measured estradiol and testosterone in CSF using liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin (SHBG) using an enzyme-linked immunoassay. Hormone levels were compared according to outcome, which was graded using the Glasgow Outcome Scale (a score of 5 indicating favorable, 1-4 unfavorable outcome). Correlation analysis was used to measure the association between hormone levels and inflammatory cytokines, chemokines, and complement factors as well as severity of illness, as measured by the Glasgow Coma Scale and the Dutch Meningitis Risk Score. We included 60 patients: 20 men, 20 premenopausal (<50 years), and 20 postmenopausal (>50 years) women. Twenty-one (35%) patients had an unfavorable outcome and 11 (18%) died. Cases with an unfavorable outcome exhibited higher estradiol (median 14.0 vs 5.0 pmol/L, P = .04) and lower SHBG (0.40 vs 1.0 nmol/L, P = .03) levels compared with those with a favorable outcome. Estradiol was positively correlated with C-reactive protein (R = 0.42, P = .001), CSF protein (R = 0.33, P = .01), and proinflammatory cytokine levels. CSF concentrations of the sex steroid hormone estradiol were associated with outcome and CSF inflammation. Understanding the dose and time-dependent interaction between sex steroid hormones and the inflammatory response in bacterial meningitis represents an important and understudied topic.
- Sex-Based Differences in Adults with Community-Acquired Bacterial Meningitis: a Prospective Cohort StudyPublication . Dias, S; Brouwer, M; Bijlsma, M; Ende, A; Beek, DObjectives: To investigate sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis. Methods: From January 2006 to July 2014, we prospectively investigated sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis in a nationwide cohort study in the Netherlands. Sex was analysed along with known predictors of unfavourable outcome using logistic regression. Results: We evaluated 1412 episodes of meningitis, 707 (50%) in men. Men more often presented with a history of remote head injury (41/667 (6%) versus 14/658 (2%) women, p 0.0002) or alcoholism (61/652 (9%) versus 21/660 (3%) women, p <0.0001). Neck stiffness was less common in men (453/651 (70%) versus 524/671 (78%) women, p 0.0004). Despite greater illness severity, women were less likely to receive treatment in an intensive care unit (odds ratio (OR) 0.72, 95% CI 0.58-0.89, p 0.003) or mechanical ventilation (OR 0.67, 95% CI 0.54-0.85, p 0.001). Women exhibited higher serum inflammatory parameters than men (median C-reactive protein 211 versus 171, p 0.0001; median erythrocyte sedimentation rate 48 versus 33, p <0.0001). Corticosteroids improved prognosis in both sexes, but absolute risk reduction was higher in women (20% versus 15%, p 0.001), although we found no significant interaction between sex and dexamethasone (p 0.38). In the multivariable analysis, male sex was an independent predictor of unfavourable outcome (OR 1.34, 95% CI 1.03-1.75, p 0.03) and death (OR 1.47, 95% CI 1.04-2.07, p 0.03). Conclusions: Our findings show sex-based differences in adults with community-acquired bacterial meningitis. Male sex is an independent risk factor for adverse outcome. It is possible that sex-based differences in immune reaction could determine a distinct response to corticosteroids.
- Sex-Based Differences in Pneumococcal Serotype Distribution in Adults with Pneumococcal MeningitisPublication . Dias, S; Brouwer, M; Bijlsma, M; Ende, A; Beek, D
- Sex-Based Differences in the Response to Dexamethasone in Bacterial Meningitis: Analysis of the European Dexamethasone in Adulthood Bacterial Meningitis StudyPublication . Dias, S; Brouwer, M; Beek, DInflammatory markers have been found at higher concentrations in women than men with bacterial meningitis. To investigate sex-based differences in the response to dexamethasone, we performed a post hoc analysis of a double-blind, randomised multicentre trial of dexamethasone (10 mg, 4 times daily for 4 days) vs placebo in adults with bacterial meningitis. The primary outcome measure was the Glasgow outcome scale score at 8 weeks and interaction tests were used to examine subgroup differences. Between June 1993 and December 2001, 301 patients (56% male) were randomly assigned to a treatment group: 157 received dexamethasone and 144 placebo. Although dexamethasone reduced the risk of unfavourable outcome to a greater extent in women (relative risk [RR] 0.42, 95% confidence interval [CI] 0.21-0.86, P = .02) than men (RR 0.79, 95% CI 0.41-1.51, P = .55), on interaction testing (ratio of RR women:men 0.53, 95% CI 0.20-1.39, P = .19) patient sex was not a significant modifier of the effect of dexamethasone.