Identification of digital twins to guide interpretable AI for diagnosis and prognosis in heart failure.

Heart failure (HF) is a highly heterogeneous condition, and current methods struggle to synthesize extensive clinical data for personalized care. Using data from 343 HF patients, we developed mechanistic computational models of the cardiovascular system to create digital twins. These twins, consisting of optimized measurable and unmeasurable parameters alongside simulations of cardiovascular function, provided comprehensive representations of individual disease states.

Pre-Diagnostic Plasma Metabolites are Associated with Incident Hepatocellular Carcinoma: A Prospective Analysis.

Despite increasing incidence of hepatocellular carcinoma (HCC) in vulnerable populations, accurate early detection tools are lacking. We aimed to investigate the associations between pre-diagnostic plasma metabolites and incident HCC in a diverse population. In a prospective, nested case-control study within the Southern Community Cohort Study (SCCS), we conducted pre-diagnostic liquid chromatography-mass spectrometry metabolomics profiling in 150 incident HCC cases (median time to diagnosis 7.

Metabolomic epidemiology offers insights into disease aetiology.

Metabolomic epidemiology is the high-throughput study of the relationship between metabolites and health-related traits. This emerging and rapidly growing field has improved our understanding of disease aetiology and contributed to advances in precision medicine. As the field continues to develop, metabolomic epidemiology could lead to the discovery of diagnostic biomarkers predictive of disease risk, aiding in earlier disease detection and better prognosis.

High triglyceride-glucose (TyG) index is associated with poor prognosis of heart failure with preserved ejection fraction.

Background: The impact of insulin resistance on the prognosis of heart failure with preserved ejection fraction (HFpEF) remains unknown. This study aimed to investigate the association between the triglyceride-glucose (TyG) index, an easily calculated marker of insulin resistance, and the long-term prognosis of HFpEF.

Methods: A total of 823 patients with HFpEF were enrolled in the study.

Genome-wide study of genetic polymorphisms predictive for outcome from first-line oxaliplatin-based chemotherapy in colorectal cancer patients.

We conducted the first large genome-wide association study to identify novel genetic variants that predict better (or poorer) prognosis in colorectal cancer patients receiving standard first-line oxaliplatin-based chemotherapy vs chemotherapy without oxaliplatin. We used data from two phase III trials, NCCTG N0147 and NCCTG N9741 and a population-based patient cohort, DACHS. Multivariable Cox proportional hazards models were employed, including an interaction term between each SNP and type of treatment for overall survival (OS) and progression-free survival.

The impact of the stress hyperglycemia ratio on mortality and rehospitalization rate in patients with acute decompensated heart failure and diabetes.

Background: The relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes.

Methods: We consecutively enrolled 1904 ADHF patients.

Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort.

Background: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.

Predictive Polygenic Score for Outcome after First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients Using Supervised Principal Component Analysis.

Background: Associations between candidate germline genetic variants and treatment outcome of oxaliplatin, a drug commonly used for patients with colorectal cancer, have been reported but not robustly established. This study aimed to construct polygenic hazard scores (PHSs) as predictive markers for oxaliplatin treatment outcome by using a supervised principal component approach (PCA).

Methods: Genome-wide association analysis for overall survival, including interaction terms (SNP*treatment type) was carried out using two phase III trials, 3,098 resected stage III colon cancer (rCC) patients of NCCTG N0147 and 506 metastatic colorectal cancer (mCRC) patients of NCCTG N9741, separately.

Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome.

Evidence has linked exogenous and endogenous sex hormones with the human microbiome. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.

Smoking Behaviour Changes After Diagnosis of Inflammatory Bowel Disease and Risk of All-cause Mortality.

Background And Aims: We examined smoking behaviour changes after diagnoses of Crohn's disease [CD] and ulcerative colitis [UC] and evaluated their impact on mortality.

Methods: Study population included incident CD or UC cases from three cohorts of the Nurses' Health Study [NHS], NHSII, and Health Professionals Follow-up Study. Smoking and other risk factors were prospectively assessed.

Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival.

Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies.

Genetic variants associated with circulating C-reactive protein levels and colorectal cancer survival: Sex-specific and lifestyle factors specific associations.

Elevated blood levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. Our study included 16 142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium.

Association between post-treatment circulating biomarkers of inflammation and survival among stage II-III colorectal cancer patients.

Background: Biomarker studies on colorectal cancer (CRC) prognosis are limited to pre-diagnostic or pre-operative measures. Post-treatment biomarkers are not well understood for their associations with CRC survival.

Methods: We included 306 eligible incident stage II-III CRC cases from the population-based Seattle Colon Cancer Family Registry.

Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study.

Background: A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer-specific survival.

Methods: We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium.

Genetic Predictors of Severe Skin Toxicity in Patients with Stage III Colon Cancer Treated with Cetuximab: NCCTG N0147 (Alliance).

Background: Cetuximab, an EGFR inhibitor used to treat multiple cancer types, including colon cancer, causes severe skin toxicity in 5%-20% of patients, leading to decreased quality of life and treatment delays. Our understanding of which patients have an increased risk of severe toxicities is limited. We conducted a genome-wide association study to identify germline variants predictive of cetuximab-induced severe skin toxicity.

Genetic Variants in the Regulatory T cell-Related Pathway and Colorectal Cancer Prognosis.

Background: High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4 T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis.

Methods: In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer-specific survival using Cox regression models.

Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia.

Purpose: BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia.

Methods: Study subjects included Kaiser Permanente Washington members aged 20-75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review.

A New Comprehensive Colorectal Cancer Risk Prediction Model Incorporating Family History, Personal Characteristics, and Environmental Factors.

Purpose: Reducing colorectal cancer incidence and mortality through early detection would improve efficacy if targeted. We developed a colorectal cancer risk prediction model incorporating personal, family, genetic, and environmental risk factors to enhance prevention.

Methods: A familial risk profile (FRP) was calculated to summarize individuals' risk based on detailed cancer family history (FH), family structure, probabilities of mutation in major colorectal cancer susceptibility genes, and a polygenic component.

Genetic Variant Associated With Survival of Patients With Stage II-III Colon Cancer.

Background & Aims: Many genetic variants have been associated with colorectal cancer risk, although few have been associated with survival times of patients. Identification of genetic variants associated with survival times might improve our understanding of disease progression and aid in outcome prediction. We performed a genome-wide association study to identify variants associated with colon cancer survival time.

The association between colorectal sessile serrated adenomas/polyps and subsequent advanced colorectal neoplasia.

Purpose: Colorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia.

Methods: This case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review.