Neurofilament light chain for classifying the aetiology of alteration of consciousness.

Neurofilament light chain has become a promising biomarker for neuroaxonal injury; however, its diagnostic utility is limited to chronic disorders or specific contexts. Alteration of consciousness is a common clinical problem with diverse aetiologies, many of which require timely diagnoses. We evaluated the value of neurofilament light chain alone, as well as creating diagnostic models, in distinguishing causes of alteration of consciousness. Patients presenting with alteration of consciousness were enrolled. Initial clinical data of each participant were evaluated by a neurologist to give a provisional diagnosis. Each participant subsequently received advanced investigations and follow-up to conclude the final diagnosis. All diagnoses were classified into a structural or non-structural cause of alteration of consciousness. Plasma and cerebrospinal fluid levels of neurofilament light chain were measured. Cerebrospinal fluid neurofilament light chain and other clinical parameters were used to develop logistic regression models. The performance of cerebrospinal fluid neurofilament light chain, the neurologist's provisional diagnosis, and the model to predict the final diagnosis were compared. For the results, among 71 participants enrolled, 67.6% and 32.4% of their final diagnoses were classified as structural and non-structural, respectively. Cerebrospinal fluid neurofilament light chain demonstrated an area under the curve of 0.75 (95% confidence interval 0.63-0.88) which was not significantly different from a neurologist's provisional diagnosis 0.85 (95% confidence interval 0.75-0.94) (P = 0.14). The multivariable regression model using cerebrospinal fluid neurofilament light chain and other basic clinical data achieved an area under the curve of 0.90 (95% confidence interval 0.83-0.98). In conclusion, neurofilament light chain classified causes of alteration of consciousness with moderate accuracy. Nevertheless, including other basic clinical data to construct a model improved the performance to a level that was comparable to clinical neurologists.

Prospective evaluation of plasma phosphorylated tau in a real-life memory clinic in Thailand.

INTRODUCTION: Despite the substantial accuracy of plasma p-tau in diagnosing Alzheimer's disease (AD) in research cohorts, data on real-life memory clinic patients are lacking. METHODS: Memory clinic patients at their early symptomatic stages were prospectively enrolled to undergo routine clinical assessment, plasma p-tau181 quantification (Simoa), amyloid and tau-positron emission tomography (PET). The diagnostic performance of plasma p-tau181, neurocognitive specialists, and regional tau-PET were compared head-to-head using amyloid-PET as the reference standard. RESULTS: Plasma p-tau181 has the area under the curve (AUC), sensitivity, specificity, and accuracy of 0.84 (95% confidence interval [CI] 0.73-0.94), 0.80 (95% CI 0.64-0.90), 0.75 (95% CI 0.51-0.90), and 0.78 (95% CI 0.65-0.88) for detecting amyloid-PET positivity in early symptomatic patients, respectively. The AUC of clinical diagnosis and tau-PET were 0.70 (95% CI 0.56-0.85) and 0.88 (95% CI 0.79-0.97), respectively. DISCUSSION: Plasma p-tau181 also performed well in real-life memory clinic settings and its role in clinical practice is supported.

IP-10 and complement activation as friend or foe in COVID-19.

INTRODUCTION: The Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs. METHODS: Plasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort. RESULTS: IP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D <0.001) and in groups B and D when compared between nadir and recovery phases (p <0.001). RANTES levels were elevated in all groups across all phases with no significant differences. SC5b-9 levels increased significantly as compared to healthy controls [pre-nadir- group A versus healthy, p =0.122; group B-D versus healthy, p =0.021); nadir-group A versus healthy, p =0.003; group B-D versus healthy, p <0.001; recovery phase (p <0.001)] but not between groups A and B-D at pre-nadir (p=0.606). CONCLUSION: The absence of significant pro-inflammatory responses and early elevation of IP-10 levels and complement activation may be favorable and necessary for viral elimination in COVID-19 patients. Expression of distinct cyto-chemokines during each clinical phase may be useful for guiding proper therapeutic interventions on alleviating thrombo-inflammation responses to COVID-19 infection.

Evaluating the efficiency of specimen pooling for PCR-based detection of COVID-19.

In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.