Actus Santé

Post-Disease Divergence in SARS-CoV-2 RNA Detection between Nasopharyngeal, Anterior Nares and Saliva/Oral Fluid Specimens - Significant Implications for Policy & Public Health

Background - Patients have been shown to shed SARS-CoV-2 viral RNA in nasopharyngeal (NP) specimens for over 100 days after resolution of clinical disease (1, 2). How this relates to anterior nares and oral fluid specimens has not previously been investigated. Methods - We prospectively collected oral fluid, anterior nares, NP swab and serum specimens from 1,326 individuals at 2 'drive-through' testing locations. The Curative SARS-CoV-2 Assay (Curative Assay)(3) on oral fluid and anterior nares specimens was compared to the EURORealTime SARS-CoV-2 Assay (EuroRT Assay)(4) on anterior nares and NP specimens. Viral culture and IgG serology were used to assess infectious potential and stage of disease. Additionally we investigated differences in viral RNA detection between specimen types, both early (< 21 days) and late (> 21 days) in SARS-CoV-2 infection, by using an employee surveillance program with daily SARS-CoV-2 testing to precisely determine infection date, even without symptoms. We prospectively collected oral fluid, anterior nares and NP swab specimens from 165 subjects with early infections and 22 subjects with late infections. Specimens were tested using the Curative Assay with the 'high-sensitivity' Hologic Aptima SARS-CoV-2 Assay (Hologic Assay)(5) on an NP swab used as the comparator. Late infection specimens were also tested with EuroRT and Zymo Quick SARS-CoV-2 rRT-PCR Kit (Zymo) (6) Assays. Results - The 'drive-through' study showed similar sensitivities of oral fluid and anterior nares specimens on the Curative Assay to anterior nares specimens tested with the EuroRT Assay. However NP specimens tested with the same EuroRT assay produced 20-30% more positives. Incorporating viral culture and serology data to exclude NP RT-PCR positives that are not infectious or late in the course of disease showed a Positive Percent Agreement (PPA) for of 98.2% and 96.2% and Negative Percent Agreement (NPA) of 97.6% and 98.1% for anterior nares and oral fluid specimens, respectively. Within 21 days of infection, the Curative Assay showed a PPA and NPA of 100% and 100%, respectively for oral fluid; of 100% and 99% respectively for anterior nares; and of 98.2% and 99.0%, respectively in nasopharyngeal specimens compared to an NP specimen on the Hologic Assay. 29 positives were asymptomatic and showed 100% PPA and 100% NPA for all specimen types. After 21 days from infection onset, significant divergence between NP and other specimen types occurred on all 4 assays. Out of 22 paired sample sets, 18, 13, 8 and 4 NP specimens were positive on the Curative, Zymo, Hologic and EuroRT assays, respectively, compared to only 3, 2, 0 and 1 positive anterior nares specimens. Only one oral fluid sample was positive in both the Curative and Zymo assays. Conclusions - We used a unique population to show significant divergence between NP specimens and anterior nares or oral fluid specimens >21 days from SARS-CoV-2 infection, which appears to be biological variation and is independent of assay used. This has significant public health implications for the use of NP specimens in community testing programs and policy implications for evaluation of novel specimen types and tests where the use of NP swabs as a comparator may say more about the study population than the assay or specimen type to be evaluated and may unnecessarily limit access to testing.
Catégories: Actus Santé

Deep Learning for Predicting Cognitive Gap as a Reliable Biomarker of Dementia

Neuroimaging data may reflect the mental status of both cognitively preserved individuals and patients with neurodegenerative diseases. To find the relationship between cognitive performance and the difference between predicted and observed functional test results, we developed a Convolutional Neural Network (CNN) based regression model to estimate the level of cognitive decline from preprocessed T1-weighted MRI images. In this study, we considered the Predicted Cognitive Gap (PCG) as the biomarker to accurately classify Healthy Control (HC) subjects versus Alzheimer disease (AD) subjects. The proposed model was tested on a dataset that includes 422 HC and 377 AD cases. The performance of the proposed solution was measured using Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) and achieved 0.987 (ADAS-cog), 0.978 (MMSE), 0.898 (RAVLT), 0.848 (TMT), 0.829 (DSST) for averaged brain images; and 0.985 (ADAS-cog), 0.987 (MMSE), 0.901 (RAVLT), 0.8474 (TMT), 0.796 (DSST) for middle slice skull stripped brain images. The results achieved indicate that PCG can accurately separate healthy subjects from demented ones and thus, the structure of the brain contributes to the level of human cognition and their functional abilities. Therefore, PCG could be used as a biomarker for dementia.
Catégories: Actus Santé

Opportunistic Assessment of Ischemic Heart Disease Risk Using Abdominopelvic Computed Tomography and Medical Record Data: a Multimodal Explainable Artificial Intelligence Approach

Current risk scores for predicting ischemic heart disease (IHD) risk - the leading cause of global mortality - have limited efficacy. While body composition (BC) imaging biomarkers derived from abdominopelvic computed tomography (CT) correlate with IHD risk, they are impractical to measure manually. Here, in a retrospective cohort of 8,197 contrast-enhanced abdominopelvic CT examinations undergoing up to 5 years of follow-up, we developed improved multimodal opportunistic risk assessment models for IHD by automatically extracting BC features from abdominal CT images and integrating these with features from each patient's electronic medical record (EMR). Our predictive methods match and, in some cases, outperform clinical risk scores currently used in IHD risk assessment. We provide clinical interpretability of our model using a new method of determining tissue-level contributions from CT along with weightings of EMR features contributing to IHD risk. We conclude that such a multimodal approach, which automatically integrates BC biomarkers and EMR data, can enhance IHD risk assessment and aid primary prevention efforts for IHD.
Catégories: Actus Santé

PREVALENCE OF ABDOMINAL OBESITY AND ITS ASSOCIATION WITH CARDIOVASCULAR RISK AMONG THE ADULT POPULATION IN BURKINA FASO

ABSTRACT Objective: The objective of this study is to determine the prevalence of abdominal obesity and its associated factors in Burkina Faso. We hypothesize that there is a high burden of abdominal obesity and it is significantly associated with sociodemographic and cardiovascular risk factors. Design: We performed secondary analysis of the survey conducted in Burkina Faso using the World Health Organization (WHO) STEPwise approach. Setting: The study was conducted in Burkina Faso with all 13 regions of the country included. Participants: Our study involved 4308 adults of both sexes aged 25 to 64 years. Main outcome: Our primary outcome was the abdominal obesity which was could defined using a cut-off point of waist circumference (WC) of [≥]94 cm for men and [≥]80 cm for women. Results: The overall age-standardized prevalence of abdominal obesity was 22.5% (95% CI: 21.3- 23.7). This age-standardized prevalence was 35.9% (95% CI: 33.9- 37.9) among women and 5.2% (95% CI: 4.3- 6.2) among men (p < 0.001). In urban areas, the age-standardized prevalence of abdominal obesity was 42.8% (95% CI: 39.9- 45.7) and 17.0% (95%CI: 15.7- 18.2) in rural areas (p < 0.001). The overall age-standardized prevalence of very high WC (WC [≥]102 cm for men and [≥]88 cm for women) was 10.2% (95%CI: 9.3- 11.1). According to the National Institute for Health and Clinical Excellence (NICE) BMI- WC matrix, which combines the body mass index (BMI) and WC to define different levels of cardiovascular health risk, 14.6% of adult had an increased cardiovascular health risk. Conclusion: Our study shows a high prevalence of abdominal obesity among the adult population in Burkina Faso. These findings suggest that the measurement of WC should be systematically incorporated in Burkina Faso primary healthcare centers for the early detection of high cardiovascular risk in order to reduce levels of premature death. Keywords: abdominal obesity, associated factors, prevalence, Burkina Faso, cardiovascular health risk
Catégories: Actus Santé

Molecular epidemiology of SARS-CoV-2 - a regional to global perspective

Background: After a year of the global SARS-CoV-2 pandemic, a highly dynamic genetic diversity is surfacing. Among nearly 1000 reported virus lineages, dominant lineages such as B.1.1.7 or B.1.351 attract media attention with questions regarding vaccine efficiency and transmission potential. In response to the pandemic, the Jena University Hospital began sequencing SARS-CoV-2 samples in Thuringia in early 2020. Methods: Viral RNA was sequenced in tiled amplicons using Nanopore sequencing. Subsequently, bioinformatic workflows were used to process the generated data. As a genomic background, 9,642 representative SARS-CoV-2 genomes (1,917 of German origin) were extracted from more than 300.000 genomes. Results: In a comprehensive bioinformatics analysis, we have set Thuringian isolates in the German, European and global context. In Thuringia, a largely rural German region without an international airport and a population density below the German average, we discovered many of the common "EU lineages". German samples are scattered across eight major clades, and Thuringian samples occupy four of them. Conclusion: The rapid emergence and spread of novel variants are of great concern as these lineages could transmit more efficiently, evade current vaccine efforts or undermine diagnostic test accuracy. To anticipate and mitigate these threats, a continuous molecular surveillance is essential.
Catégories: Actus Santé

Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19?

Abstract Background: Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause Torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods: This was a retrospective cohort study. 172 patients with COVID-19 included, hospitalized at hospitals of Babol University of Medical Sciences between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results: 83.1% of patients received hydroxychloroquine plus azithromycin vs 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 {+/-} 15.4. The mean of post-treatment QTc interval in the monotherapy group was shorter than the mean of post-treatment QTc interval in the combination therapy group but it had no significant statistical difference (462.5 {+/-} 43.1 milliseconds vs 464.3 {+/-} 59.1 milliseconds; P = 0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc [≥] 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, 14 patients did not continue therapy after 4 days. Conclusion: Hospitalized patients treated with hydroxychloroquine with or without azithromycin, had no significant difference in prolongation of QT interval and outcome. But the number of patients with prolonged QT intervals in this study emphasizes careful cardiac monitoring during therapy; especially in high-risk patients.
Catégories: Actus Santé

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

ABSTRACT Rationale Macrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. Objective To investigate the outcome of personalized immunotherapy in critical COVID-19. Methods In this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score [≥]2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin [≤]4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints. Measurements and Main Results The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment. Conclusions Biomarkers may guide favourable anakinra responses in critically ill patients with COVID-19. Trial Registration: ClinicalTrials.gov, NCT04339712 Key-words: anakinra; tocilizumab; acute respiratory distress syndrome; COVID-19; interleukin-6; ferritin; HLA-DR; macrophage activation; monocytes Abstract Word count: 250
Catégories: Actus Santé

Identification of COVID-19 Subtypes Based on Immunogenomic Profiling

Although previous studies have shown that the host immune response is crucial in determining clinical outcomes in COVID-19 patients, the association between host immune signatures and COVID-19 patient outcomes remains unclear. Based on the enrichment levels of 11 immune signatures (eight immune-inciting and three immune-inhibiting signatures) in leukocytes of 100 COVID-19 patients, we identified three COVID-19 subtypes: Im-C1, Im-C2, and Im-C3, by clustering analysis. Im-C1 had the lowest immune-inciting signatures and high immune-inhibiting signatures. Im-C2 had medium immune-inciting signatures and high immune-inhibiting signatures. Im-C3 had the highest immune-inciting signatures while the lowest immune-inhibiting signatures. Im-C3 and Im-C1 displayed the best and worst clinical outcomes, respectively, suggesting that antiviral immune responses alleviated the severity of COVID-19 patients. We further demonstrated that the adaptive immune response had a stronger impact on COVID-19 outcomes than the innate immune response. The patients in Im-C3 were younger than those in Im-C1, indicating that younger persons have stronger antiviral immune responses than older persons. Nevertheless, we did not observe a significant association between sex and immune responses in COVID-19 patients. In addition, we found that the type II IFN response signature was an adverse prognostic factor for COVID-19. Our identification of COVID-19 immune subtypes has potential clinical implications for the management of COVID-19 patients.
Catégories: Actus Santé

Non-Congruent SARS-CoV-2 Waves in England

Examination of the chronology, location and size of waves of SARS-CoV-2 infection across England could shed light on the inter-play between the 1st and the 2nd Waves. From mid-October onwards such an analysis becomes increasingly difficult due to the emergence of a new strain (VOC-202012/01) and in light of the differential implementation of lockdown measures and tiers. Therefore, we sought to examine trends and correlations in virus prevalence and covid-related deaths spanning the start of the UK pandemic in March 2020 through to early November 2020, i.e., including the first growth period of the 2nd Wave. We found striking regional relationships between the 1st and the 2nd Wave that are difficult to explain other than by involving some role for changing levels of immunity in the population affecting the progression of the pandemic.
Catégories: Actus Santé

A Mathematical Model of Platelet Antiparasitic Action in Erythrocytes and Merozoites During Malaria Infection

Platelets have been seen traditionally as fragments of blood mediating coagulation. However, evidence during malaria infection suggests that platelets also act against merozoites, an infectious form of malaria in the bloodstream, and megakaryocytes can release giant platelets with a larger volume than normal platelets. We propose a mathematical model to study the interaction between red blood cells, merozoites, and platelets during malaria infection. We analyzed two cases of the interaction of platelets with malaria infection. In the first one, we considered the isolated action of normal platelets and, in the second one, the joint antiparasitic action of both normal and giant platelets. Numerical simulations were performed to evaluate the stability of the equilibrium points of the system of equations. The model showed that the isolated antiparasitic action of normal platelets corroborates malaria infection control. However, the system can converge to a presence-merozoite equilibrium point, or an oscillatory behavior may appear. The joint antiparasitic action of both normal and giant platelets eliminated the oscillatory behavior and drove the dynamics to converge to lower parasitic concentration than the case of isolated action of normal platelets. Moreover, the joint antiparasitic action of platelets proved more easily capable of eliminating the infection.
Catégories: Actus Santé

Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis

Background. Several studies have reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect endothelial cells, and endothelial dysfunction is often found in severe cases of coronavirus disease 2019 (COVID-19). To better understand the pathological mechanisms underlying endothelial dysfunction in COVID-19-associated coagulopathy, we conducted a systematic review and meta-analysis to assess biomarkers of endothelial cells in patients with COVID-19. Methods. A literature search was conducted on online databases for observational studies evaluating biomarkers of endothelial dysfunction and composite poor outcomes in COVID-19 patients. Results. A total of 1187 patients from 17 studies were included in this analysis. The estimated pooled means for von Willebrand Factor (VWF) antigen levels in COVID-19 patients was higher compared to healthy control (306.42 [95% confidence interval (CI) 291.37-321.48], p<0.001; I2:86%), with the highest VWF antigen levels was found in deceased COVID-19 patients (448.57 [95% CI 407.20-489.93], p<0.001; I2:0%). Meta-analysis showed that higher plasma levels of VWF antigen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 antigen (PAI-1) antigen, and soluble thrombomodulin (sTM) were associated with composite poor outcome in COVID-19 patients ([standardized mean difference (SMD) 0.74 [0.33-1.16], p<0.001; I2:80.4%], [SMD 0.55 [0.19-0.92], p=0.003; I2:6.4%], [SMD 0.33 [0.04-0.62], p=0.025; I2:7.9%], and [SMD 0.55 [0.10-0.99], p=0.015; I2:23.6%], respectively). Conclusion. The estimated pooled means shows increased levels of VWF antigen in COVID-19 patients. Several biomarkers of endothelial dysfunction, including VFW antigen, t-PA, PAI-1, and sTM, are significantly associated with increased composite poor outcome in patients with COVID-19. Keywords: Endothelial dysfunction, von Willebrand Factor, tissue-type plasminogen activator, plasminogen activator inhibitor-1, thrombomodulin, COVID-19 PROSPERO registration number: CRD42021228821
Catégories: Actus Santé

Escape of SARS-CoV-2 501Y.V2 variants from neutralization by convalescent plasma

New SARS-CoV-2 variants with mutations in the spike glycoprotein have arisen independently at multiple locations and may have functional significance. The combination of mutations in the 501Y.V2 variant first detected in South Africa include the N501Y, K417N, and E484K mutations in the receptor binding domain (RBD) as well as mutations in the N-terminal domain (NTD). Here we address whether the 501Y.V2 variant could escape the neutralizing antibody response elicited by natural infection with earlier variants. We were the first to outgrow two variants of 501Y.V2 from South Africa, designated 501Y.V2.HV001dF and 501Y.V2.HV002. We examined the neutralizing effect of convalescent plasma collected from six adults hospitalized with COVID-19 using a microneutralization assay with live (authentic) virus. Whole genome sequencing of the infecting virus of the plasma donors confirmed the absence of the spike mutations which characterize 501Y.V2. We infected with 501Y.V2.HV001dF and 501Y.V2.HV002 and compared plasma neutralization to first wave virus which contained the D614G mutation but no RBD or NTD mutations. We observed that neutralization of the 501Y.V2 variants was strongly attenuated, with IC50 6 to 200-fold higher relative to first wave virus. The degree of attenuation varied between participants and included a knockout of neutralization activity. This observation indicates that 501Y.V2 may escape the neutralizing antibody response elicited by prior natural infection. It raises a concern of potential reduced protection against re-infection and by vaccines designed to target the spike protein of earlier SARS-CoV-2 variants.
Catégories: Actus Santé

A Hybrid Machine Learning Framework for Enhancing the Prediction Power in Large Scale Population Studies: TheATHLOS Project

The ATHLOS cohort is composed of several harmonized datasets of international cohorts related to health and aging. The healthy aging scale has been constructed based on a selection of particular variables from 16 individual studies. In this paper, we consider a selection of additional variables found in ATHLOS and investigate their utilization for predicting the healthy aging. For this purpose motivated by the dataset's volume and diversity, we focus our attention upon the clustering for prediction scheme, where unsupervised learning is utilized to enhance prediction power, showing the predictive utility of exploiting structure in the data by clustering. We show that imposed computation bottlenecks can be surpassed when using appropriate hierarchical clustering within a clustering for ensemble classification scheme while retaining prediction benefits. We propose a complete methodology which is evaluated against baseline methods and the original concept. The results are very encouraging suggesting further developments in this direction along with applications in tasks with similar characteristics. A strait-forward open source implementation is provided for the R project.
Catégories: Actus Santé

Novel COVID-19 phenotype definitions reveal phenotypically distinct patterns of genetic association and protective effects

Multiple large COVID-19 genome-wide association studies (GWAS) have identified reproducible genetic associations indicating that some infection susceptibility and severity risk is heritable. Most of these studies ascertained COVID-19 cases in medical clinics and hospitals, which can lead to an overrepresentation of cases with severe outcomes, such as hospitalization, intensive care unit admission, or ventilation. Here, we demonstrate the utility and validity of deep phenotyping with self-reported outcomes in a population with a large proportion of mild and subclinical cases. Using these data, we defined eight different phenotypes related to COVID-19 outcomes: four that align with previously studied COVID-19 definitions and four novel definitions that focus on susceptibility given exposure, mild clinical manifestations, and an aggregate score of symptom severity. We assessed replication of 13 previously identified COVID-19 genetic associations with all eight phenotypes and found distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. We then performed a discovery GWAS, which suggested some novel phenotypes may better capture protective associations and also identified a novel association in chr11/GALNT18 that reproduced in two fully independent populations.
Catégories: Actus Santé

Impulse dispersion of aerosols during playing wind instruments

Musical activities especially singing and playing wind instruments have been singled out as potentially high-risk activities for transmission of SARS CoV-2, because of a higher rate of aerosol production and emission. Playing wind instruments can produce condensation water, droplets of saliva, and aerosol particles, which hover and convectional spread in the environmental air and can be potentially infectious. The aim of this study is to investigate the primary impulse dispersion of aerosols during playing different wind instruments in comparison to breathing and speaking. Nine professional musicians (3 trumpeters, 3 cross flutists and 3 clarinetists) of the Bavarian Symphony Orchestra performed the main theme of Ludwig van Beethoven' 9th symphony, 4th movement in different pitches and loudness. Thereby, the inhaled air volume was marked with small aerosol particles produced with a commercial e-cigarette. The expelled aerosol cloud was recorded by cameras from different perspectives. Afterwards, the dimensions and dynamics of the aerosol cloud was measured by segmenting the video footage at every time point. Overall, the flutes produced the largest dispersion at the end of task of up to maximum distances of 1.88 m in front direction. Thereby it was observed an expulsion of aerosol in different directions: upwards and downwards at the mouthpiece, at the end of the instrument and along the flute at the key plane. In comparison, the maximum impulse dispersion generated by the trumpets and clarinets were lower in frontal and lateral direction (1.2 m and 1.0 m in front- direction). The expulsion to the sides was also lower. Consequently, a distance of 3 m to the front and to the sides of 2 m for the flutes in an orchestral formation is proposed, for trumpets and clarinets a safety distance of 2 m to the front and 1.5 m between instrumentalists are recommendable.
Catégories: Actus Santé

Contamination of air and surfaces in workplaces with SARS-CoV-2 virus: a systematic review

Objectives This systematic review aimed to evaluate the evidence for air and surface contamination of workplace environments with SARS-CoV-2 RNA and the quality of the methods used to identify actions necessary to improve the quality of the data. Methods We searched Web of Science and Google Scholar until 24th December 2020 for relevant articles and extracted data on methodology and results. Results The vast majority of data come from healthcare settings, with typically around 6 % of samples having detectable concentrations of SARS-CoV-2 RNA and almost none of the samples collected had viable virus. There were a wide variety of methods used to measure airborne virus, although surface sampling was generally undertaken using nylon flocked swabs. Overall, the quality of the measurements was poor. Only a small number of studies reported the airborne concentration of SARS-CoV-2 virus RNA, mostly just reporting the detectable concentration values without reference to the detection limit. Imputing the geometric mean air concentration assuming the limit of detection was the lowest reported value, suggests typical concentrations in health care settings may be around 0.01 SARS-CoV-2 virus RNA copies/m3. Data on surface virus loading per unit area were mostly unavailable. Conclusion The reliability of the reported data is uncertain. The methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments should be standardised to facilitate more consistent interpretation of contamination and to help reliably estimate worker exposure.
Catégories: Actus Santé

Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth

Preterm births are prevalent and a leading cause of neonatal death in the United States. Despite the availability of effective interventions, to date there is not a robust and widely applicable test to identify pregnancies at high risk for spontaneous preterm birth (sPTB). Previously, a sPTB predictor based on the ratio of two proteins, IBP4/SHBG, was validated as an accurate predictor of sPTB in the observational study Proteomic Assessment of Preterm Risk (PAPR). Here it is demonstrated that the same predictor threshold associated with 2-fold increased risk of sPTB, namely -1.4, is also statistically significant for predicting elevated risk of sPTB in the observational study Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TreeToP).
Catégories: Actus Santé

The Forgotten Tract of Vision in Multiple Sclerosis: Vertical Occipital Fasciculus, Its Integrity, and Visuospatial Memory

Background: Visual disturbances are a common disease manifestation and a major patient complaint in Multiple Sclerosis (MS) due to lesions damaging white matter tracts involved in vision. Vertical Occipital Fasciculus (VOF) connects ventral and dorsal visual streams and was neglected for more than a century. It has recently become under focus in brain-related disorders. Thus, its role in the visual dysfunction in MS needs to be clarified. Objective: Evaluate the integrity of bilateral VOFs in MS and its association with clinical and visual evaluations. Methods: 56 relapsing-remitting MS (RRMS) and 25 healthy controls (HC) were recruited. We acquired MS Functional Composite, Expanded Disability Status Scale (EDSS), and Brief Visuospatial Memory Test-Revised (BVMT-R), and structural and diffusion MRI scans. After VOF tractography, its integrity markers were statistically tested for between-group differences and clinical and visual tests associations. Results: RRMS patients had lower fiber integrity in bilateral VOFs compared to HC. Lower integrity of bilateral VOFs was associated with poor clinical outcomes, higher visual score in EDSS, and lower total immediate and delayed recall in BVMT-R. Conclusion: VOF damage is seen in RRMS and is associated with visual symptoms and visuospatial learning impairments.
Catégories: Actus Santé

Effects of stricter management guidelines on return-to-play timeframes following concussion in professional Australian Rules football

Background Management of concussion remains a serious issue for professional sports, particularly with the growing knowledge on the consequences of repetitive concussion. One primary concern is the subjective assessment of recovery that dictates the time until a concussed athlete is returned to competition. In response to this concern, the Australian Football League (AFL) changed its policy in 2020 such that clearance for return-to-play was extended from one day, to a minimum of five days, prior to the next scheduled match. Objective We sought to examine the impact of the AFL policy change by asking whether the time to return-to-play after concussion was increased in the 2020 season relative to previous years. Methods Retrospective data on injury and return-to-play were sourced from publicly available tables published on the AFL website. We compared the number of matches missed and the number of days missed in concussed players across 2017 to 2020 inclusive. Results Analysis of data from 166 concussed players revealed no increase in the number of matches missed in 2020 relative to previous years as would have been expected from an extend recovery protocol. Considering the number of days missed in 2020 relative to 2017-19 we found, paradoxically, that there was an overall reduction in the average time to return-to-play in 2020 (11.2 vs 16.2 days). Conclusion This study demonstrates that any policy change around concussion management requires ongoing auditing to ensure clearance meets policy objectives and highlights the need for objective measures for return-to-play after concussion.
Catégories: Actus Santé

Patients with Asthma and Chronic Obstructive Pulmonary Disease (COPD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19

Background: Respiratory diseases such as chronic obstructive pulmonary disease (COPD) have been associated with increased risk of severe SARS-CoV-2 infection, but the mechanisms and putative immune pathways are unclear. Besides, increased levels of several immune mediators in patients with severe coronavirus disease 19 (COVID-19) have been reported. Objective: To perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma and COPD and to evaluate their relationship with biomarkers of severe COVID-19. Methods: 92 protein biomarkers were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic. Results: Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 and CCL3 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). Functional annotation revealed their enrichment in chemokine signaling pathways related with response to viral infections. Some of these proteins were found up-regulated upon SARS-Cov-2 infection of Calu-3 cells. Also, HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE have been found increased in patients with severe COVID-19. HGF, the most significant protein in this study as well as its correlated proteins could be associated with the increased risk of severe COVID-19 in COPD patients. Conclusions: Asthma and COPD patients have altered plasma levels of proteins that have been found associated with increased risk of severe COVID-19. The reasons for sharing these profiles with this infection are unknown, but our study suggest that adult patients with asthma and COPD have a systemic dysregulation in chemokine networks that could make them more susceptible to severe COVID-19.
Catégories: Actus Santé

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