Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis

ABSTRACT: INTRODUCTION: Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. METHODS: Electronic searches in PubMed, Scopus, the MEDION database and Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. RESULTS: Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square p = 0.1009, I2 = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. CONCLUSIONS: To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers

Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) ‘resets’ these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices—which do not have the constraints of bioprinted scaffolds—the ‘reset’ vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call ‘Organ-On-VascularNet’. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting

Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity

Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease

Tree species diversity and utilities in a contracting lowland hillside rainforest fragment in Central Vietnam

Abstract Background Within the highly bio-diverse ‘Northern Vietnam Lowland Rain Forests Ecoregion’ only small, and mostly highly modified forestlands persist within vast exotic-species plantations. The aim of this study was to elucidate vegetation patterns of a secondary hillside rainforest remnant (elevation 120–330 m, 76 ha) as an outcome of natural processes, and anthropogenic processes linked to changing forest values. Methods In the rainforest remnant tree species and various bio-physical parameters (relating to soils and terrain) were surveyed on forty 20 m × 20 m sized plots. The forest's vegetation patterns and tree diversity were analysed using dendrograms, canonical correspondence analysis, and other statistical tools. Results Forest tree species richness was high (172 in the survey, 94 per hectare), including many endemic species (>16%; some recently described). Vegetation patterns and diversity were largely explained by topography, with colline/sub-montane species present mainly along hillside ridges, and lowland/humid-tropical species predominant on lower slopes. Scarcity of high-value timber species reflected past logging, whereas abundance of light-demanding species, and species valued for fruits, provided evidence of human-aided forest restoration and ‘enrichment’ in terms of useful trees. Exhaustion of sought-after forest products, and decreasing appreciation of non-wood products concurred with further encroachment of exotic plantations in between 2010 and 2015. Regeneration of rare tree species was reduced probably due to forest isolation. Conclusions Despite long-term anthropogenic influences, remnant forests in the lowlands of Vietnam can harbor high plant biodiversity, including many endangered species. Various successive future changes (vanishing species, generalist dominance, and associated forest structural-qualitative changes) are, however, expected to occur in small forest fragments. Lowland forest biodiversity can only be maintained if forest fragments maintain a certain size and/or are connected via corridors to larger forest networks. Preservation of the forests may be fostered using new economic incentive schemes

Bacterial risk factors for treatment failure and relapse among patients with isoniazid resistant tuberculosis

Background Drug resistant tuberculosis (TB) is increasing in prevalence worldwide. Treatment failure and relapse is known to be high for patients with isoniazid resistant TB treated with standard first line regimens. However, risk factors for unfavourable outcomes and the optimal treatment regimen for isoniazid resistant TB are unknown. This cohort study was conducted when Vietnam used the eight month first line treatment regimen and examined risk factors for failure/relapse among patients with isoniazid resistant TB. Methods Between December 2008 and June 2011 2090 consecutive HIV-negative adults (≥18 years of age) with new smear positive pulmonary TB presenting at participating district TB units in Ho Chi Minh City were recruited. Participants with isoniazid resistant TB identified by Microscopic Observation Drug Susceptibility (MODS) had extended follow-up for 2 years with mycobacterial culture to test for relapse. MGIT drug susceptibility testing confirmed 239 participants with isoniazid resistant, rifampicin susceptible TB. Bacterial and demographic factors were analysed for association with treatment failure and relapse. Results Using only routine programmatic sputum smear microscopy for assessment, (months 2, 5 and 8) 30/239 (12.6%) had an unfavourable outcome by WHO criteria. Thirty-nine patients were additionally detected with unfavourable outcomes during 2 year follow up, giving a total of 69/239 (28.9%) of isoniazid (INH) resistant cases with unfavourable outcome by 2 years of follow-up. Beijing lineage was the only factor significantly associated with unfavourable outcome among INH-resistant TB cases during 2 years of follow-up. (adjusted OR = 3.16 [1.54–6.47], P = 0.002). Conclusion One third of isoniazid resistant TB cases suffered failure/relapse within 2 years under the old eight month regimen. Over half of these cases were not identified by standard WHO recommended treatment monitoring. Intensified research on early identification and optimal regimens for isoniazid resistant TB is needed. Infection with Beijing genotype of TB is a significant risk factor for bacterial persistence on treatment resulting in failure/relapse within 2 years. The underlying mechanism of increased tolerance for standard drug regimens in Beijing genotype strains remains unknown