Autoimmune glial fibrillary acidic protein astrocytopathy masquerading as tuberculosis of the central nervous system: a case series.

We describe the case history of three patients with meningoencephalitis who were initially treated for presumed tuberculous meningoencephalitis before being diagnosed with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. We highlight the overlapping clinical features between autoimmune GFAP astrocytopathy and tuberculous meningoencephalitis and the challenges in early diagnosis, as both entities respond to an initial course of steroids accompanying antituberculous medications. Early evaluation of GFAP-immunoglobulin G in the cerebrospinal fluid of patients who present with aseptic meningoencephalitis could reveal autoimmune GFAP astrocytopathy, which responds favorably to immunotherapy.

Estimating transmission dynamics of SARS-CoV-2 at different intraspatial levels in an institutional outbreak.

INTRODUCTION: Large, localised outbreaks of COVID-19 have been repeatedly reported in high-density residential institutions. Understanding the transmission dynamics will inform outbreak response and the design of living environments that are more resilient to future outbreaks. METHODS: We developed an individual-based, multilevel transmission dynamics model using case, serology and symptom data from a 60-day cluster randomised trial of prophylaxes in a densely populated foreign worker dormitory in Singapore. Using Bayesian data augmentation, we estimated the basic reproduction number and the contribution that within-room, between-level and across-block transmission made to it, and the prevalence of infection over the study period across different spatial levels. We then simulated the impact of changing the building layouts in terms of floors and blocks on outbreak size. RESULTS: We found that the basic reproduction number was 2.76 averaged over the different putative prophylaxes, with substantial contributions due to transmission beyond the residents' rooms. By the end of ~60 days of follow up, prevalence was 64.4 % (95 % credible interval 64.2-64.6 %). Future outbreak sizes could feasibly be halved by reducing the density to include additional housing blocks, or taller buildings, while retaining the overall number of men in the complex. DISCUSSION: The methods discussed can potentially be utilised to estimate transmission dynamics at any high-density accommodation site with the availability of case and serology data. The restructuring of infrastructure to reduce the number of residents per room can dramatically slow down epidemics, and therefore should be considered by policymakers as a long-term intervention.

Long-term outcomes of ischaemic stroke patients with diabetes in a multi-ethnic cohort in Singapore.

INTRODUCTION: Diabetes increases the risk of ischaemic stroke especially among Asians. This study aims to investigate contemporaneous long-term cardiovascular outcomes of ischaemic stroke patients with diabetes in a multi-ethnic Asian cohort. METHODS: Consecutive patients with ischaemic stroke were recruited from the National University Hospital, Singapore. Data on age, gender, ethnicity, risk factors (including diabetes status and body mass index [BMI]), stroke severity and mechanisms were collected. These patients were followed up until the day of the first cardiovascular event or July 2016, whichever was earlier. The primary endpoint was the time from enrolment to the first occurrence of a composite of cerebrovascular and coronary artery events. RESULTS: Between July 2011 and December 2013, 720 patients (mean age 60.6 years, 71% men, 43% with diabetes, median National Institute Health Stroke Severity scale 2) were enrolled and followed up. A total of 175 cardiovascular events occurred during a median follow-up of 3.25 years (6.90 events per 1,000 person-month), comprising 133 cerebrovascular and 42 coronary artery events. The adjusted hazard ratio of diabetes was 1.50 (95% CI 1.08-2.10). In a multivariable Cox proportional hazards model, Malay and Indian ethnicities, BMI <23kg/m2 and a prior diagnosis of diabetes were identified as independent predictors of recurrent cardiovascular events. CONCLUSION: Our study provides quantitative data on the event rates of ischaemic stroke patients with diabetes. These findings provide insights on stroke predictors in a multi-ethnic Asian population, which may have implications in the design of future interventional studies.

Products of 5-lipoxygenase and myeloperoxidase activities are increased in young male cigarette smokers.

The significance of 5-lipoxygenase and myeloperoxidase activities has not been extensively studied among young male smokers. Leukotriene B(4), 20-hydroxy-leukotriene B(4), 20-carboxy-leukotriene B(4) and 3-chlorotyrosine were measured in plasma and urinary samples of young male smokers at 8 hours following cigarette abstinence and an hour after cigarette smoking. Leukotriene B(4) and 3-chlorotyrosine were determined in neutrophils isolated from these individuals. The levels of these markers were compared with those of age-matched controls. In vitro studies were performed to evaluate the production of leukotriene B(4) and 3-chlorotyrosine from human neutrophils following exposure to nicotine and cotinine. Thirty male smokers (mean age, 27.4 years) and 28 male non-smokers (mean age, 28.7 years) were studied. Plasma levels of leukotriene B(4), 20-carboxy-leukotriene B(4) and 3-chlorotyrosine were higher in smokers than in non-smokers; leukotriene B(4) and 20-carboxy-leukotriene B(4) levels increased further an hour after cigarette smoking. Peripheral neutrophils isolated from smokers showed greater expressions of myeloperoxidase and 5-lipoxygenase activities compared with non-smokers, while plasma leukotriene B(4) and 3-chlorotyrosine were correlated significantly with high-sensitivity C-reactive protein and plasma nicotine concentrations. Exposure of human neutrophils to nicotine and cotinine resulted in a higher production of leukotriene B(4) and 3-chlorotyrosine. To conclude, leukotriene B(4) and 3-chlorotyrosine levels are increased in young male cigarette smokers. These results suggest that cigarette smoking aggravates neutrophil-mediated inflammation by modulating the activities of myeloperoxidase and 5-lipoxygenase pathways.