scholarly journals Systems medicine links microbial inflammatory response with glycoprotein-associated mortality risk

2015 ◽  
Author(s):  
Scott C Ritchie ◽  
Peter Würtz ◽  
Artika P Nath ◽  
Gad Abraham ◽  
Aki S Havulinna ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Complex Traits ◽  
Integrative Approach ◽  
Low Grade ◽  
Omics Data ◽  
Biological Processes ◽  
Systems Medicine ◽  
Standard Deviation Increase ◽  
Health Records ◽  
Increased Risk

Integrative analyses of high-throughput omics data have elucidated the aetiology and pathogenesis for complex traits and diseases, and the linking of omics information to electronic health records promises new insights into human health and disease. Recent nuclear magnetic resonance (NMR) spectroscopy biomarker profiling has implicated glycoprotein acetyls (GlycA) as a biomarker for cardiovascular risk and all-cause mortality. To elucidate biological processes contributing to GlycA- associated mortality risk, we leveraged human omics data from three population- based cohorts together with nation-wide Finnish hospital and mortality records. Elevated GlycA was associated with myriad infection-related inflammatory processes. Within individuals, elevated GlycA levels were stable over long time periods, up to a decade, and chronically elevated GlycA was also associated with modest elevation of numerous cytokines. Individuals with elevated GlycA also showed increased expression of a transcriptional sub-network, the Neutrophil Degranulation Module (NDM), suggesting an increased activity of microbe-driven immune response. Subsequent analysis of nation-wide hospitalisation and death records was consistent with a microbial basis for GlycA-associated mortality, with each standard deviation increase in GlycA raising an individual's future risk of hospitalization and death from non-localized infection by 40% and 136%, respectively. These results show that, beyond its established role in acute-phase response, elevated GlycA is more broadly a biomarker for low-grade chronic inflammation and increased neutrophil activity. Further, increased risk of susceptibility to severe microbial-infection events in healthy individuals suggests this inflammation is a contributor to mortality risk. Taken together, this study demonstrates the power of an integrative approach that combines omics data and health records to delineate the biological processes underlying a newly discovered biomarker, providing a model strategy for future systems medicine studies.

scholarly journals COVID-19 Post-acute Sequelae Among Adults: 12 Month Mortality Risk

2021 ◽  
Vol 8 ◽  
Author(s):  
Arch G. Mainous ◽  
Benjamin J. Rooks ◽  
Velyn Wu ◽  
Frank A. Orlando
Keyword(s):  
Mortality Risk ◽  
One Health ◽  
Comparison Group ◽  
Health Records ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Subgroup Analyses ◽  
All Cause Mortality ◽  
Initial Episode ◽  
The Relationship

Background: There are concerns regarding post-acute sequelae of COVID-19, but it is unclear whether COVID-19 poses a significant downstream mortality risk. The objective was to determine the relationship between COVID-19 infection and 12-month mortality after recovery from the initial episode of COVID-19 in adult patients.Methods: An analysis of electronic health records (EHR) was performed for a cohort of 13,638 patients, including COVID-19 positive and a comparison group of COVID-19 negative patients, who were followed for 12 months post COVID-19 episode at one health system. Both COVID-19 positive patients and COVID-19 negative patients were PCR validated. COVID-19 positive patients were classified as severe if they were hospitalized within the first 30 days of the date of their initial positive test. The 12-month risk of mortality was assessed in unadjusted Cox regressions and those adjusted for age, sex, race and comorbidities. Separate subgroup analyses were conducted for (a) patients aged 65 and older and (b) those <65 years.Results: Of the 13,638 patients included in this cohort, 178 had severe COVID-19, 246 had mild/moderate COVID-19, and 13,214 were COVID-19 negative. In the cohort, 2,686 died in the 12-month period. The 12-month adjusted all-cause mortality risk was significantly higher for patients with severe COVID-19 compared to both COVID-19 negative patients (HR 2.50; 95% CI 2.02, 3.09) and mild COVID-19 patients (HR 1.87; 95% CI 1.28, 2.74). The vast majority of deaths (79.5%) were for causes other than respiratory or cardiovascular conditions. Among patients aged <65 years, the pattern was similar but the mortality risk for patients with severe COVID-19 was increased compared to both COVID-19 negative patients (HR 3.33; 95% CI 2.35, 4.73) and mild COVID-19 patients (HR 2.83; 95% CI 1.59, 5.04). Patients aged 65 and older with severe COVID-19 were also at increased 12-month mortality risk compared to COVID-19 negative patients (HR 2.17; 95% CI 1.66, 2.84) but not mild COVID-19 patients (HR 1.41; 95% CI 0.84, 2.34).Discussion: Patients with a COVID-19 hospitalization were at significantly increased risk for future mortality. In a time when nearly all COVID-19 hospitalizations are preventable this study points to an important and under-investigated sequela of COVID-19 and the corresponding need for prevention.

scholarly journals Multi-omics Data Integration, Interpretation, and Its Application

2020 ◽  
Vol 14 ◽  
pp. 117793221989905 ◽  
Author(s):  
Indhupriya Subramanian ◽  
Srikant Verma ◽  
Shiva Kumar ◽  
Abhay Jere ◽  
Krishanpal Anamika
Keyword(s):  
Data Integration ◽  
High Throughput ◽  
Use Cases ◽  
Integrative Approach ◽  
Large Set ◽  
Omics Data ◽  
Biological Processes ◽  
Data Repositories ◽  
Tools And Methods ◽  
Omics Data Integration

To study complex biological processes holistically, it is imperative to take an integrative approach that combines multi-omics data to highlight the interrelationships of the involved biomolecules and their functions. With the advent of high-throughput techniques and availability of multi-omics data generated from a large set of samples, several promising tools and methods have been developed for data integration and interpretation. In this review, we collected the tools and methods that adopt integrative approach to analyze multiple omics data and summarized their ability to address applications such as disease subtyping, biomarker prediction, and deriving insights into the data. We provide the methodology, use-cases, and limitations of these tools; brief account of multi-omics data repositories and visualization portals; and challenges associated with multi-omics data integration.

scholarly journals In Silico Exploration of the Potential Role of Acetaminophen and Pesticides in the Etiology of Autism Spectrum Disorder

Toxics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 97
Author(s):  
Tristan Furnary ◽  
Rolando Garcia-Milian ◽  
Zeyan Liew ◽  
Shannon Whirledge ◽  
Vasilis Vasiliou
Keyword(s):  
Autism Spectrum Disorder ◽  
Prenatal Exposure ◽  
Pesticide Exposure ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Biomedical Literature ◽  
Spectrum Disorder ◽  
Biological Processes ◽  
Genetic Associations ◽  
Increased Risk

Recent epidemiological studies suggest that prenatal exposure to acetaminophen (APAP) is associated with increased risk of Autism Spectrum Disorder (ASD), a neurodevelopmental disorder affecting 1 in 59 children in the US. Maternal and prenatal exposure to pesticides from food and environmental sources have also been implicated to affect fetal neurodevelopment. However, the underlying mechanisms for ASD are so far unknown, likely with complex and multifactorial etiology. The aim of this study was to explore the potential effects of APAP and pesticide exposure on development with regards to the etiology of ASD by highlighting common genes and biological pathways. Genes associated with APAP, pesticides, and ASD through human research were retrieved from molecular and biomedical literature databases. The interaction network of overlapping genetic associations was subjected to network topology analysis and functional annotation of the resulting clusters. These genes were over-represented in pathways and biological processes (FDR p < 0.05) related to apoptosis, metabolism of reactive oxygen species (ROS), and carbohydrate metabolism. Since these three biological processes are frequently implicated in ASD, our findings support the hypothesis that cell death processes and specific metabolic pathways, both of which appear to be targeted by APAP and pesticide exposure, may be involved in the etiology of ASD. This novel exposures-gene-disease database mining might inspire future work on understanding the biological underpinnings of various ASD risk factors.

scholarly journals Integrative, multi-omics, analysis of blood samples improves model predictions: applications to cancer

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Erica Ponzi ◽  
Magne Thoresen ◽  
Therese Haugdahl Nøst ◽  
Kajsa Møllersen
Keyword(s):  
Lung Cancer ◽  
Biological Process ◽  
Case Control ◽  
Integrative Analysis ◽  
Data Sources ◽  
Omics Data ◽  
Biological Processes ◽  
Blood Samples ◽  
Model Predictions

Abstract Background Cancer genomic studies often include data collected from several omics platforms. Each omics data source contributes to the understanding of the underlying biological process via source specific (“individual”) patterns of variability. At the same time, statistical associations and potential interactions among the different data sources can reveal signals from common biological processes that might not be identified by single source analyses. These common patterns of variability are referred to as “shared” or “joint”. In this work, we show how the use of joint and individual components can lead to better predictive models, and to a deeper understanding of the biological process at hand. We identify joint and individual contributions of DNA methylation, miRNA and mRNA expression collected from blood samples in a lung cancer case–control study nested within the Norwegian Women and Cancer (NOWAC) cohort study, and we use such components to build prediction models for case–control and metastatic status. To assess the quality of predictions, we compare models based on simultaneous, integrative analysis of multi-source omics data to a standard non-integrative analysis of each single omics dataset, and to penalized regression models. Additionally, we apply the proposed approach to a breast cancer dataset from The Cancer Genome Atlas. Results Our results show how an integrative analysis that preserves both components of variation is more appropriate than standard multi-omics analyses that are not based on such a distinction. Both joint and individual components are shown to contribute to a better quality of model predictions, and facilitate the interpretation of the underlying biological processes in lung cancer development. Conclusions In the presence of multiple omics data sources, we recommend the use of data integration techniques that preserve the joint and individual components across the omics sources. We show how the inclusion of such components increases the quality of model predictions of clinical outcomes.

Lymphopenia and risk for long-term mortality among patients undergoing coronary angiography

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Zafrir ◽  
R Jaffe ◽  
H Sliman ◽  
O Barnett-Griness ◽  
W Saliba
Keyword(s):  
Coronary Angiography ◽  
Mortality Risk ◽  
Predictive Accuracy ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Cross Sectional ◽  
Distribution Width ◽  
Increased Risk ◽  
Long Term Mortality

Abstract Background Lymphopenia has been shown to be associated with adverse prognosis in chronic disease states that are related to immune dysregulation. Purpose We aimed to determine the association between lymphopenia and all-cause mortality in patients presenting to coronary angiography with or without acute coronary syndromes (ACS). We also investigated whether elevated red blood cell distribution width (RDW), an established cardiovascular prognostic marker, further refines risk stratification and improves predictive accuracy beyond lymphocytes count. Methods Retrospective cohort analysis of patients undergoing coronary angiography for evaluation or treatment of coronary artery disease between 2003 and 2018. Long-term mortality risk associated with relative (1000–1500 /μL) or severe (&lt;1000 /μL) lymphopenia was analyzed using Cox proportional hazards regression models, adjusting for comorbidities, ACS and RDW. Results Overall, 15179 patients underwent coronary angiography, at a mean age of 65±12 years. On cross-sectional analysis, lymphopenia was associated with kidney disease, cancer, heart failure and presentation with ACS, but lower rates of smoking and obesity. During a median follow-up of 7 (IQR 3.5–11.5) years, 4253 patients died. Compared to normal lymphocytes count (1500–5000 /μL), the multivariable adjusted hazard ratio (HR) (95% confidence interval) for mortality was 1.31 (1.21–1.41) and 1.97 (1.75–2.22) for relative and severe lymphopenia, respectively. The increase in mortality associated with severe lymphopenia was significant in patients presenting with non-ACS [HR 2.18 (1.74–2.73)], ST-segment elevation myocardial infarction (STEMI) [HR 1.59 (1.15–2.21)], or unstable angina/non-STEMI [HR 2.00 (1.70–2.34)]; p-for-interaction 0.626. The association of lymphopenia with mortality remained significant after additional adjustment to RDW. High RDW (&gt;14.5%) was associated with increased mortality risk in each of the lymphocytes count groups, and improved the predictive accuracy with AUC increase from 0.609 (0.601–0.616) to 0.646 (0.639–0.654) (p&lt;0.001). Conclusions Lymphopenia is associated with increased risk for long-term mortality in patients undergoing coronary angiography, regardless of coronary presentation. High RDW may enhance the predictive ability of lymphopenia. Lymphocyte count and mortality risk Funding Acknowledgement Type of funding source: None

scholarly journals Natural Bioactive Compounds Useful in Clinical Management of Metabolic Syndrome

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 630 ◽  
Author(s):  
Annalisa Noce ◽  
Manuela Di Lauro ◽  
Francesca Di Daniele ◽  
Anna Pietroboni Zaitseva ◽  
Giulia Marrone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Side Effects ◽  
Bioactive Compounds ◽  
Clinical Management ◽  
Endothelial Damage ◽  
Low Grade ◽  
Clinic Management ◽  
Pharmaceutical Therapy ◽  
Increased Risk

Metabolic syndrome (MetS) is a clinical manifestation characterized by a plethora of comorbidities, including hyperglycemia, abdominal obesity, arterial hypertension, and dyslipidemia. All MetS comorbidities participate to induce a low-grade inflammation state and oxidative stress, typical of this syndrome. MetS is related to an increased risk of cardiovascular diseases and early death, with an important impact on health-care costs. For its clinic management a poly-pharmaceutical therapy is often required, but this can cause side effects and reduce the patient’s compliance. For this reason, finding a valid and alternative therapeutic strategy, natural and free of side effects, could represent a useful tool in the fight the MetS. In this context, the use of functional foods, and the assumption of natural bioactive compounds (NBCs), could exert beneficial effects on body weight, blood pressure and glucose metabolism control, on endothelial damage, on the improvement of lipid profile, on the inflammatory state, and on oxidative stress. This review focuses on the possible beneficial role of NBCs in the prevention and in the clinical management of MetS and its comorbidities.

scholarly journals Uremic Sarcopenia and Its Possible Nutritional Approach

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 147
Author(s):  
Annalisa Noce ◽  
Giulia Marrone ◽  
Eleonora Ottaviani ◽  
Cristina Guerriero ◽  
Francesca Di Daniele ◽  
...  
Keyword(s):  
Physical Activity ◽  
Pathological Condition ◽  
Nutritional Therapy ◽  
Nutritional Supplement ◽  
Low Grade ◽  
Inflammatory Status ◽  
Protein Energy ◽  
Fiber Diet ◽  
Increased Risk ◽  
Intradialytic Parenteral Nutrition

Uremic sarcopenia is a frequent condition present in chronic kidney disease (CKD) patients and is characterized by reduced muscle mass, muscle strength and physical performance. Uremic sarcopenia is related to an increased risk of hospitalization and all-causes mortality. This pathological condition is caused not only by advanced age but also by others factors typical of CKD patients such as metabolic acidosis, hemodialysis therapy, low-grade inflammatory status and inadequate protein-energy intake. Currently, treatments available to ameliorate uremic sarcopenia include nutritional therapy (oral nutritional supplement, inter/intradialytic parenteral nutrition, enteral nutrition, high protein and fiber diet and percutaneous endoscopic gastrectomy) and a personalized program of physical activity. The aim of this review is to analyze the possible benefits induced by nutritional therapy alone or in combination with a personalized program of physical activity, on onset and/or progression of uremic sarcopenia.

scholarly journals 416 - Risk of Mortality Associated with Antipsychotics in Alzheimer's Disease

2020 ◽  
Vol 32 (S1) ◽  
pp. 132-132
Author(s):  
Liliana P. Ferreira ◽  
Núria Santos ◽  
Nuno Fernandes ◽  
Carla Ferreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Mortality Risk ◽  
Antipsychotic Treatment ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Mesh Terms ◽  
Risk Of Mortality ◽  
Increased Risk

Objectives: Alzheimer's disease (AD) is the most common cause of dementia and it is associated with increased mortality. The use of antipsychotics is common among the elderly, especially in those with dementia. Evidence suggests an increased risk of mortality associated with antipsychotic use. Despite the short-term benefit of antipsychotic treatment to reduce the behavioral and psychological symptoms of dementia, it increases the risk of mortality in patients with AD. Our aim is to discuss the findings from the literature about risk of mortality associated with the use of antipsychotics in AD.Methods: We searched Internet databases indexed at MEDLINE using following MeSH terms: "Antipsychotic Agents" AND "Alzheimer Disease" OR "Dementia" AND "Mortality" and selected articles published in the last 5 years.Results: Antipsychotics are widely used in the pharmacological treatment of agitation and aggression in elderly patients with AD, but their benefit is limited. Serious adverse events associated with antipsychotics include increased risk of death. The risk of mortality is associated with both typical and atypical antipsychotics. Antipsychotic polypharmacy is associated with a higher mortality risk than monotherapy and should be avoided. The mortality risk increases after the first few days of treatment, gradually reducing but continues to increase after two years of treatment. Haloperidol is associated with a higher mortality risk and quetiapine with a lower risk than risperidone.Conclusions: If the use of antipsychotics is considered necessary, the lowest effective dose should be chosen and the duration should be limited because the mortality risk remains high with long-term use. The risk / benefit should be considered when choosing the antipsychotic. Further studies on the efficacy and risk of adverse events with antipsychotics are needed for a better choice of treatment and adequate monitoring with risk reduction.

scholarly journals Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

2013 ◽  
Vol 20 (2) ◽  
pp. 251-262 ◽  
Author(s):  
Catherine M Olsen ◽  
Christina M Nagle ◽  
David C Whiteman ◽  
Roberta Ness ◽  
Celeste Leigh Pearce ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Menopausal Status ◽  
Low Grade ◽  
Ovarian Cancer Risk ◽  
Histological Subtypes ◽  
Increased Risk ◽  
Modifiable Factors ◽  
Menopausal Women ◽  
Increase Risk ◽  
Post Menopausal

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

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