Poor specificity of National Early Warning Score (NEWS) in spinal cord injuries (SCI) population: A retrospective cohort study

Study design. Retrospective chart audit. Objectives. The National Early Warning Score (NEWS) is based on seven physiological parameters which can be altered in some individuals with spinal cord injuries (SCI). The aim was to start the development of adapted NEWS suitable for SCI population. The objective was to determine the SBP NEWS specificity based on neurological level of injury (NLI) and completeness of injury. Setting. Tertiary centre in the UK. Methods. Adult patients admitted for the first time to the National Spinal Injuries Centre between 1 January 2015 and 31 December 2016 were included if they were >6 months post injury. Data were extracted retrospectively including the last ten consecutive BP and heart rate readings before discharge. Data were analysed based on different AIS grades, completeness of injury and NLI. Results. One hundred and ninety one patients were admitted in 2015 and 2016 and 142 patients were included in the primary analysis. The mean SBP ranged between 92 and 151 mmHg. Patients with the NLI of T6 and above (≥T6) motor complete lesions had a significantly lower SBP than motor incomplete lesions. The specificity of the SBP NEWS was 35.3% in ≥T6 motor complete individuals versus 80.3% in ≥T6 motor incomplete individuals. Conclusion. The baseline BP is significantly lower in the ≥T6 motor complete SCI individuals (>6 months post injury) resulting in a very low specificity of 35.3% to SBP NEWS, which could lead to mismatch between clinical deterioration and NEWS resulting in lack of timely clinical response

Mechanical Thrombectomy for Acute Ischemic Stroke in Metastatic Cancer Patients: A Nationwide Cross-Sectional Analysis

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the standard treatment for large vessel occlusion (LVO) acute ischemic stroke. Patients with active malignancy have an increased risk of stroke but were excluded from MT trials. METHODS: We searched the National Readmission Database for LVO patients treated with MT between 2016-2018 and compared the characteristics and outcomes of cancer-free patients to those with metastatic cancer (MC). Primary outcomes were all-cause in-hospital mortality and favorable outcome, defined as a routine discharge to home (regardless of whether home services were provided or not). Multivariate regression was used to adjust for confounders. RESULTS: Of 40,537 LVO patients treated with MT, 933 (2.3%) had MC diagnosis. Compared to cancer-free patients, MC patients were similar in age and stroke severity but had greater overall disease severity. Hospital complications that occurred more frequently in MC included pneumonia, sepsis, acute coronary syndrome, deep vein thrombosis, and pulmonary embolism (P\u3c0.001). Patients with MC had similar rates of intracerebral hemorrhage (20% vs. 21%) but were less likely to receive tissue plasminogen activator (13% vs. 23%, P\u3c0.001). In unadjusted analysis, MC patients as compared to cancer-free patients had a higher in-hospital mortality rate and were less likely to be discharged to home (36% vs. 42%, P=0.014). On multivariate regression adjusting for confounders, mortality was the only outcome that was significantly higher in the MC group than in the cancerfree group (P\u3c0.001). CONCLUSION: LVO patients with MC have higher mortality and more infectious and thrombotic complications than cancer-free patients. MT nonetheless can result in survival with good outcome in slightly over one-third of patients

A Novel Role for Wnt/Ca2+ Signaling in Actin Cytoskeleton Remodeling and Cell Motility in Prostate Cancer

Wnt signaling is a critical regulatory pathway in development and disease. Very little is known about the mechanisms of Wnt signaling in prostate cancer, a leading cause of death in men. A quantitative analysis of the expression of Wnt5A protein in human tissue arrays, containing 600 prostate tissue cores, showed >50% increase in malignant compared to benign cores (p<0.0001). In a matched pair of prostate cancer and normal cell line, expression of Wnt5A protein was also increased. Calcium waves were induced in prostate cells in response to Wnt5A with a 3 fold increase in Flou-4 intensity. The activity of Ca2+/calmodulin dependent protein kinase (CaMKII), a transducer of the non-canonical Wnt/Ca2+ signaling, increased by 8 fold in cancer cells; no change was observed in β-catenin expression, known to activate the canonical Wnt/β-catenin pathway. Mining of publicly available human prostate cancer oligoarray datasets revealed that the expression of numerous genes (e.g., CCND1, CD44) under the control of β-catenin transcription is down-regulated. Confocal and quantitative electron microscopy showed that specific inhibition of CaMKII in cancer cells causes remodeling of the actin cytoskeleton, irregular wound edges and loose intercellular architecture and a 6 and 8 fold increase in the frequency and length of filopodia, respectively. Conversely, untreated normal prostate cells showed an irregular wound edge and loose intercellular architecture; incubation of normal prostate cells with recombinant Wnt5A protein induced actin remodeling with a regular wound edge and increased wound healing capacity. Live cell imaging showed that a functional consequence of CaMKII inhibition was 80% decrease in wound healing capacity and reduced cell motility in cancer cells. We propose that non-canonical Wnt/Ca2+ signaling via CaMKII acts as a novel regulator of structural plasticity and cell motility in prostate cancer

Detection of equid herpesviruses among different Arabian horse populations in Egypt

Equid herpesviruses (EHVs) threaten equine health and can cause significant economic losses to the equine industry worldwide. Different equid herpesviruses, EHV‐1, EHV‐2, EHV‐4 and EHV5 are regularly detected among horse populations. In Egypt, monitoring is sporadic but EHV‐1 or EHV‐4 have been reported to circulate in the horse population. However, there is a lack of reports related to infection and health status of horses, likely due to the absence of regular diagnostic procedures. In the current study, the circulation of four infectious equid herpesviruses (EHV‐1, EHV‐2, EHV‐4 and EHV‐5) among different Arabian horse populations and donkeys residing the same farm was monitored. Different samples were collected and DNA was extracted and subjected to quantitative (q)‐PCR to detect the four equid herpesviruses using specific primers and probes. Antibody titres against EHV‐1 and EHV‐4 were tested using virus neutralization test and type‐specific ELISA. The results showed that EHV‐1, EHV‐2, EHV‐4 and EHV‐5 are endemic and can be a continuous threat for horses in the absence of vaccination programs and frequent virus reactivation. There is an urgent need for introduction of active regular surveillance measures to investigate the presence of different equid herpesviruses, and other equine viral pathogens, in various horse populations around Egypt and to establish a standardized cataloguing of equine health status

Thioredoxin Glutathione Reductase from Schistosoma mansoni: An Essential Parasite Enzyme and a Key Drug Target

Using both genetic and biochemical approaches, David Williams and colleagues show that the parasite thioredoxin glutathione reductase meets all the major criteria to be a key target for antischistosomal chemotherapy

The Conundrum of Low COVID-19 Mortality Burden in sub-Saharan Africa: Myth or Reality?

The burden of coronavirus disease (COVID-19) in sub-Saharan Africa (SSA) has been substantially lower compared to other regions of the world. Extensive morbidity and mortality were not observed among countries in SSA during the first wave of the COVID-19 pandemic. To explain this phenomenon, several hypotheses have been formulated, including the low median age of the population in most SSA countries, lack of long-term care facilities, cross-protection from other local coronaviruses, insufficient testing and reporting resulting in an undercounting of COVID-related deaths, genetic risk factors, or the benefit of early lockdowns that were extensive in many SSA countries. Early lockdowns in SSA have been some of the strictest and resulted in devastating economic and social consequences and increased mortality from other health-related problems including maternal deaths. We review the literature and rationale supporting the various hypotheses that have been put forward to account for relatively low hospitalization and death rates for COVID-19 in SSA. We conclude that the strongest evidence would support the demographic age structure with a very low median age as the primary factor in leading to the low mortality seen in the first wave of the pandemic. The impact of new variants of concern in SSA raises the risk of more severe waves. Nevertheless, furthering the understanding of the underlying explanations for the low morbidity and mortality seen across SSA countries may allow the adoption of unique strategies for limiting the spread of COVID-19 without the need for stringent lockdowns

Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies

BACKGROUND: Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories. METHODS: This expository paper provides an illustrative guide to summarising nonlinear growth trajectories for repeatedly measured continuous outcomes using (i) linear spline and (ii) natural cubic spline linear mixed-effects (LME) models, (iii) Super Imposition by Translation and Rotation (SITAR) nonlinear mixed effects models, and (iv) latent trajectory models. The underlying model for each approach, their similarities and differences, and their advantages and disadvantages are described. Their application and correct interpretation of their results is illustrated by analysing repeated bone mass measures to characterise bone growth patterns and their sex differences in three cohort studies from the UK, USA, and Canada comprising 8500 individuals and 37,000 measurements from ages 5-40 years. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts. RESULTS: Linear and natural cubic spline LME models and SITAR provided similar summary of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Growth velocity (in grams/year) peaked during adolescence, and peaked earlier in females than males e.g., mean age at peak bone mineral content accrual from multicohort SITAR models was 12.2 years in females and 13.9 years in males. Latent trajectory models (with trajectory shapes estimated using a natural cubic spline) identified up to four subgroups of individuals with distinct trajectories throughout adolescence. CONCLUSIONS: LME models with linear and natural cubic splines, SITAR, and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data. Scripts and synthetic datasets are provided for readers to replicate trajectory modelling and visualisation using the R statistical computing software