Incremental prognostic value of a novel metabolite-based biomarker score in congestive heart failure patients

Aims: The Cardiac Lipid Panel (CLP) is a newly discovered panel of metabolite-based biomarkers that has shown to improve the diagnostic value of N terminal pro B type natriuretic peptide (NT-proBNP). However, little is known about its usefulness in predicting outcomes. In this study, we developed a risk score for 4-year cardiovascular death in elderly chronic heart failure (CHF) patients using the CLP. Methods and results: From the Cardiac Insufficiency Bisoprolol Study in Elderly trial, we included 280 patients with CHF aged \u3e65 years. A targeted metabolomic analysis of the CLP biomarkers was performed on baseline serum samples. Cox regression was used to determine the association of the biomarkers with the outcome after accounting for established risk factors. A risk score ranging from 0 to 4 was calculated by counting the number of biomarkers above the cut-offs, using Youden index. During the mean (standard deviation) follow-up period of 50 (8) months, 35 (18%) subjects met the primary endpoint of cardiovascular death. The area under the receiver operating curve for the model based on clinical variables was 0.84, the second model with NT-proBNP was 0.86, and the final model with the CLP was 0.90. The categorical net reclassification index was 0.25 using three risk categories: 0-60% (low), 60-85% (intermediate), and \u3e85% (high). The continuous net reclassification index was 0.772, and the integrated discrimination index was 0.104. Conclusions: In patients with CHF, incorporating a panel of three metabolite-based biomarkers into a risk score improved the prognostic utility of NT-proBNP by predicting long-term cardiovascular death more precisely. This novel approach holds promise to improve clinical risk assessment in CHF patients. Keywords: Biomarkers; Congestive heart failure; Metabolite profiling; Metabolomics; Prognosi

Performance of a cardiac lipid panel compared to four prognostic scores in chronic heart failure

The cardiac lipid panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to four commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham risk score (FRS), Barcelona bio-HF (BCN Bio-HF) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, BCN Bio-HF 0.72, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients

Fusion within and between whorls of floral organs in Galipeinae (Rutaceae): structural features and evolutionary implications

Background and Aims Most genera of the neotropical Galipeinae (tribe Galipeeae, Rutoideae) exhibit several forms and degrees of fusion between the floral organs, including the union of petals into an apparently sympetalous corolla, the joining of the stamens among themselves and to the corolla, and the partial to complete connation of carpels. Though these and others floral traits are currently used in the circumscription of species in Galipeinae, few studies have shown in detail in which way (postgenital or congenital) and to what extent these fusions occur. To elucidate these anatomical conditions, a structural study of the flowers of the Galipeinae species was carried out. Methods Flowers of six species from three genera of Galipeinae were studied in their morphology, anatomy and development with stereomicroscopy, light microscopy and scanning electron microscopy (SEM). Key Results The floral tube is formed by synorganization of stamens with petals in all species, and exhibits three main patterns: (1) Conchocarpus heterophyllus and C. minutiflorus have a floral tube formed by marginal coherence/adherence of petals and filaments due to interwining trichomes (postgenital connection); (2) Erythrochiton brasiliensis has a tube formed by congenital fusion of petals and filaments; and (3) Galipea jasminiflora and Conchocarpus macrophyllus have a tube formed distally with the first pattern, and proximally with the second pattern. Although floral tubes seem to be homologous within Galipeinae, this is not true at the level of the family: the floral tube of Correa (from an only distantly related clade of the family) is formed by postgenital union of the petals representing a convergent structure. The gynoecium of the studied species of Galipeinae shows a great variability in the extent of fusion of carpel flanks. Even though different structures for the mature gynoecium were found in each genus, all genera show postgenitally fused carpel apices, which is related to the formation of a compitum, as described earlier for other members of Rutaceae. Conclusions The degree and diversity of fusions of floral organs in Galipeinae is unique within the order Sapindales. A study of the amount of diversification of Galipeinae in South America and comparison with other clades of Rutaceae would be of interes

Stroke Genomics: Current Knowledge, Clinical Applications and Future Possibilities

The pathophysiology of stoke involves many complex pathways and risk factors. Though there are several ongoing studies on stroke, treatment options are limited, and the prevalence of stroke is continuing to increase. Understanding the genomic variants and biological pathways associated with stroke could offer novel therapeutic alternatives in terms of drug targets and receptor modulations for newer treatment methods. It is challenging to identify individual causative mutations in a single gene because many alleles are responsible for minor effects. Therefore, multiple factorial analyses using single nucleotide polymorphisms (SNPs) could be used to gain new insight by identifying potential genetic risk factors. There are many studies, such as Genome-Wide Association Studies (GWAS) and Phenome-Wide Association Studies (PheWAS) which have identified numerous independent loci associated with stroke, which could be instrumental in developing newer drug targets and novel therapies. Additionally, using analytical techniques, such as meta-analysis and Mendelian randomization could help in evaluating stroke risk factors and determining treatment priorities. Combining SNPs into polygenic risk scores and lifestyle risk factors could detect stroke risk at a very young age and help in administering preventive interventions

Obstetric outcomes during delivery hospitalizations among obese pregnant women in the United States

The rates of both maternal and fetal adverse outcomes increase significantly with higher body mass index. The aim of this study was to calculate national estimates of adverse maternal and fetal outcomes and associated hospitalization cost among obese pregnant women using a national database. This study was a retrospective analysis of data retrieved from Nationwide Inpatient Sample database, collected during 2010–2014. The primary outcomes of this study were adverse maternal and fetal outcomes, hospital length of stay, and hospitalization cost. There was a total of 18,687,217 delivery-related hospitalizations, of which 1,048,323 were among obese women. Obese women were more likely to have cesarean deliveries (aOR 1.70, 95% CI 1.62–1.79) and labor inductions (aOR 1.51, 95% CI 1.42–1.60), greater length of stay after cesarean deliveries (aOR 1.14, 95% CI 1.08–1.36) and vaginal deliveries (aOR 1.48, 95% CI 1.23–1.77). They were also more likely to have pregnancy-related hypertension, preeclampsia, gestational diabetes, premature rupture of membranes, chorioamnionitis, venous thromboembolism, excessive fetal growth, and fetal distress. Obese pregnant women had significantly greater risk for adverse obstetrical outcomes, which substantially increased the hospital and economic burden. Risk stratification of pregnant patients based on obesity could also help obstetricians to make better clinical decisions and improve patient outcomes

Stroke Genomics: Current Knowledge, Clinical Applications and Future Possibilities

The pathophysiology of stoke involves many complex pathways and risk factors. Though there are several ongoing studies on stroke, treatment options are limited, and the prevalence of stroke is continuing to increase. Understanding the genomic variants and biological pathways associated with stroke could offer novel therapeutic alternatives in terms of drug targets and receptor modulations for newer treatment methods. It is challenging to identify individual causative mutations in a single gene because many alleles are responsible for minor effects. Therefore, multiple factorial analyses using single nucleotide polymorphisms (SNPs) could be used to gain new insight by identifying potential genetic risk factors. There are many studies, such as Genome-Wide Association Studies (GWAS) and Phenome-Wide Association Studies (PheWAS) which have identified numerous independent loci associated with stroke, which could be instrumental in developing newer drug targets and novel therapies. Additionally, using analytical techniques, such as meta-analysis and Mendelian randomization could help in evaluating stroke risk factors and determining treatment priorities. Combining SNPs into polygenic risk scores and lifestyle risk factors could detect stroke risk at a very young age and help in administering preventive interventions

Association between vitamin D deficiency and hypothyroidism: results from the National Health and Nutrition Examination Survey (NHANES) 2007–2012

Purpose: Many smaller studies have previously shown a significant association between thyroid autoantibody induced hypothyroidism and lower serum vitamin D levels. However, these finding have not been confirmed by large-scale studies. In this study, we evaluated the relationship between hypothyroidism and vitamin D levels using a large population-based data. Methods: For this study, we used National Health and Nutrition Examination Survey (NHANES) during the years 2007–2012. We categorized participants into three clinically relevant categories based on vitamin D levels: optimal, intermediate and deficient. Participants were also split into hypothyroid and hyperthyroid. Weighted multivariable logistic regression analyses were used to calculate the odds of being hypothyroid based on vitamin D status. Results: A total of 7943 participants were included in this study, of which 614 (7.7%) were having hypothyroidism. Nearly 25.6% of hypothyroid patients had vitamin D deficiency, compared to 20.6% among normal controls. Adjusted logistic regression analyses showed that the odds of developing hypothyroidism were significantly higher among patients with intermediate (adjusted odds ratio [aOR], 1.7, 95% CI: 1.5–1.8) and deficient levels of vitamin D (aOR, 1.6, 95% CI: 1.4–1.9). Conclusion: Low vitamin D levels are associated with autoimmune hypothyroidism. Healthcare initiatives such as mass vitamin D deficiency screening among at-risk population could significantly decrease the risk for hypothyroidism in the long-term

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

Dietary factors play an important role in shaping the gut microbiome which, in turn, regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome have been implicated in the development of colorectal cancer (CRC). Diets low in dietary fibers and phytomolecules as well as other lifestyle-related factors may predispose to CRC. Emerging evidence demonstrates that the predominance of microbes, such as Fusobacterium nucleatum, can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. In this study, we aim to present evidence regarding the relationship of dietary factors to the gut microbiome and development of CRC. Keywords: dietary fibers; short chain fatty acid; gut microbiota; colorectal cancer prevention; epigenetic

Sudden Infant Death Syndrome (SIDS) and the routine otoacoustic emission infant hearing screening test: an epidemiological retrospective case-control study

Objectives To investigate whether decreased otoacoustic emission (OAE) signal recordings in the right ear are associated with an increased risk of sudden infant death syndrome (SIDS) and to monitor any temporal changes in risk factors. Design Retrospective case-control study. Setting Telephone interviews with families recruited in England between July 2016 and October 2017 who experienced the unexpected death of a child <4 years old since 2008 and control families recruited from maternity wards in Bristol and Birmingham. Participants We recruited 91 (89%) of the 102 bereaved families who made initial contact, 64 deaths were under 1 year (sudden unexpected death in infancy) of which 60 remained unexplained (SIDS). Of the 220 control families, 194 (88%) follow-up interviews were conducted. We had analysable hearing data for 24 SIDS infants (40%) and 98 controls (51%). Results OAE signals were marginally increased rather than decreased among SIDS infants for the right ear, especially at lower frequencies, but not significantly so. The strongest predictors of SIDS were bed-sharing in hazardous (infant sleeping next to a carer who smoked, drank alcohol or slept on a sofa) circumstances (35% vs 3% controls, p<0.0001), infants found prone (33% vs 3% controls, p<0.0001) and infants whose health in the final week was â € not good' (53% vs 9% controls, p<0.0001). The prevalence of maternal smoking during pregnancy among both SIDS mothers (20%) and controls (10%) was much lower than previous studies. Conclusions Hearing data were difficult to obtain; larger numbers would be needed to determine if asymmetrical differences between the right and left ear were a marker for SIDS. A national prospective registry for monitoring and a renewed campaign to a new generation of parents needs to be considered underlining the initial message to place infants on their backs for sleep and the more recent message to avoid bed-sharing in hazardous circumstances