Macrophage migration inhibitory factor, infection, the brain, and corticosteroids

Bacterial meningitis is a complex disorder in which injury is caused, in part, by the causative organism and, in part, by the host's own inflammatory response. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and a neuro-endocrine mediator that might play a role in pneumococcal meningitis. Here, we discuss the role of MIF in infection, the brain, and corticosteroids and conclude that experimental meningitis studies have to determine whether MIF is a potential target for adjunctive therapy in pneumococcal meningitis

Community-Acquired Bacterial Meningitis in Alcoholic Patients

BACKGROUND: Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. METHODS/PRINCIPAL FINDINGS: This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). CONCLUSIONS/SIGNIFICANCE: Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patient

Delayed life-threatening subdural hematoma after minor head injury in a patient with severe coagulopathy: a case report

Minor head injury is a frequent cause for neurologic consultation and imaging. Most patients with minor head injury will make an uneventful recovery, but in a very small proportion of these patients life threatening intracranial complications occur. We describe a patient on oral anticoagulation therapy, and severely impaired coagulation, with normal head computed tomography on admission, who developed a subdural hematoma requiring surgery 12 hours later. Current guidelines and literature for the management of minor head injury are discussed

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study

BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm(3 )(interquartile range 531–6983 per mm(3)) and 104 patients (33%) had a CSF WBC <1000/mm(3). Patients with a CSF WBC <1000/mm(3 )were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1–4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm(3 )more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02–1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17–5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm(3 )increments 0.67, 95% CI 0.47–0.97) were associated with a CSF WBC <1000/mm(3). CONCLUSION: A low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis

Perfusion CT to evaluate the effect of transluminal angioplasty on cerebral perfusion in the treatment of vasospasm after subarachnoid hemorrhage

INTRODUCTION: Delayed ischemic neurologic deficits secondary to vasospasm are a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Treatment of vasospasm after SAH is associated with complications, and reliable techniques for evaluating effects of treatment of vasospasm in such patients are warranted. We present the use of perfusion computed tomography (PTC) to evaluate the effect of transluminal percutaneous angioplasty in a with SAH and vasospasm-induced ischemia. METHODS: Dynamic PCT with deconvolution produced maps of time-to-peak, mean transit time, regional cerebral blood flow, and regional cerebral blood volume, with a computerized automated map of the infarct and penumbra. CT scanners with quadruple detector array were used before and after angioplasty. RESULTS: Before angioplasty and intraarterial papaverine, PCT showed normal to decreased cerebral blood flow and increased cerebral blood volume and mean transit time in the middle cerebral artery territory of the left hemisphere. After angioplasty and intraarterial papaverine, PCT showed normalization of perfusion parameters. CONCLUSION: PCT can be a useful technique in monitoring angioplasty treatment effects in patients with vasospasm after SA

Genetic Variation in the β2-Adrenocepter Gene Is Associated with Susceptibility to Bacterial Meningitis in Adults

Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04–1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12–2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60–3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88–4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts

Українська культура як чинник української державності: історичний аспект

У статті подано особливості формування української національної культури кінця XIX - XX століть. Охарактеризовано розвиток культури за умови становлення української державності. Автор намагався простежити вплив національного суспільства на розвиток культури в конкретний історичний період.The article introduces the features of formation of the Ukrainian national culture of the 19th-20th centuries. Characterized by the development of culture during becoming of Ukrainian statehood. The author tried to trace the influence of the national society for the development of culture in a specific historical period

Temporal profile of pneumonia after stroke

The occurrence of pneumonia after stroke is associated with a higher risk of poor outcome or death. We assessed the temporal profile of pneumonia after stroke and its association with poor outcome at several time points to identify the most optimal period for testing pneumonia prevention strategies. METHODS: We analyzed individual patient data stored in the VISTA (Virtual International Stroke Trials Archive) from randomized acute stroke trials with an inclusion window up to 24 hours after stroke onset and assessed the occurrence of pneumonia in the first 90 days after stroke. Adjusted odds ratios and hazard ratios were calculated for the association between pneumonia and poor outcome and death by means of logistic and Cox proportional hazard regression, respectively, at different times of follow-up. RESULTS: Of 10 821 patients, 1017 (9.4%) had a total of 1076 pneumonias. Six hundred eighty-nine (64.0%) pneumonias occurred in the first week after stroke. The peak incidence was on the third day and the median time of onset was 4.0 days after stroke (interquartile range, 2–12). The presence of a pneumonia was associated with an increased risk of poor outcome (adjusted odds ratio, 4.8 [95% CI, 3.8–6.1]) or death (adjusted hazard ratio, 4.1 [95% CI, 3.7–4.6]). These associations were present throughout the 90 days of follow-up. CONCLUSIONS: Two out of 3 pneumonias in the first 3 months after stroke occur in the first week, with a peak incidence on the third day. The most optimal period to assess pneumonia prevention strategies is the first 4 days after stroke. However, pneumonia occurring later was also associated with poor functional outcome or death

Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion

Group B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants