Risk scores for allograft failure: Are they still useful in liver recipients from donation after circulatory death?

BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.

Age,blood tests and comorbidities and AIMS65 risk scores outperform Glasgow-Blatchford and pre-endoscopic Rockall score in patients with upper gastrointestinal bleeding

BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hospital mortality,intervention(endoscopic or surgical)and length of admission(≥7 d).METHODS We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021.We calculated and compared the area under the receiver operating characteristics curves(AUROCs)of Glasgow-Blatchford score(GBS),pre-endoscopic Rockall score(PERS),albumin,international normalized ratio,altered mental status,systolic blood pressure,age older than 65(AIMS65)and age,blood tests and comorbidities(ABC),including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts.We subsequently analyzed through a logistic binary regression model,if addition of lactate increased the score performance.RESULTS All scores had discriminative ability in predicting in-hospital mortality irrespective of study group.AIMS65 score had the best performance in the variceal bleeding group(AUROC=0.772;P<0.001),and ABC score(AUROC=0.775;P<0.001)in the non-variceal bleeding group.However,ABC score,at a cut-off value of 5.5,was the best predictor(AUROC=0.770,P=0.001)of inhospital mortality in both populations.PERS score was a good predictor for endoscopic treatment(AUC=0.604;P=0.046)in the variceal population,while GBS score,(AUROC=0.722;P=0.024),outperformed the other scores in predicting surgical intervention.Addition of lactate to AIMS65 score,increases by 5-fold the probability of in-hospital mortality(P<0.05)and by 12-fold if added to GBS score(P<0.003).No score proved to be a good predictor for length of admission.CONCLUSION ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population.PERS and GBS should be used to determine need for endoscopic and surgical intervention,respectively.Lactate can be used as an additional tool to risk scores for predicting inhospital mortality.

Untangling the difficult interplay between ischemic and hemorrhagic risk:The role of risk scores

BACKGROUND Bleedings are an independent risk factor for subsequent mortality in patients with acute coronary syndromes(ACS)and in those undergoing percutaneous coronary intervention.This represents a hazard equivalent to or greater than that for recurrent ACS.Dual antiplatelet therapy(DAPT)represents the cornerstone in the secondary prevention of thrombotic events,but the benefit of such therapy is counteracted by the increased hemorrhagic complications.Therefore,an early and individualized patient risk stratification can help to identify high-risk patients who could benefit the most from intensive medical therapies while minimizing unnecessary treatment complications in low-risk patients.AIM To review existing literature and gain better understanding of the role of ischemic and hemorrhagic risk scores in patients with ischemic heart disease(IHD).METHODS We used a combination of terms potentially used in literature describing the most common ischemic and hemorrhagic risk scores to search in PubMed as well as references of full-length articles.RESULTS In this review we briefly describe the most important ischemic and bleeding scores that can be adopted in patients with IHD,focusing on GRACE,CHA2DS2-Vasc,PARIS CTE,DAPT,CRUSADE,ACUITY,HAS-BLED,PARIS MB and PRECISE-DAPT score.In the second part of this review,we try to define a possible approach to the IHD patient,using the most suitable scores to stratify patient risk and decide the most appropriate patient treatment.CONCLUSION It becomes evident that risk scores by themselves can’t be the solution to balance the ischemic/bleeding risk of an IHD patient.Instead,some risk factors that are commonly associated with an elevated risk profile and that are already included in risk scores should be the focus of the clinician while he/she is taking care of a patient affected by IHD.

Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores:evidence from the China Kadoorie Biobank

Background:Several studies have reported that polygenic risk scores(PRSs)can enhance risk prediction of coronary artery disease(CAD)in European populations.However,research on this topic is far from sufficient in non-European countries,including China.We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.Methods:Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training(n=28,490)and testing sets(n=72,150).Ten previously developed PRSs were evaluated,and new ones were developed using clumping and thresholding or LDpred method.The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set.Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms.Prediction of the 10-year first CAD events was assessed using hazard ratios(HRs)and measures of model discrimination,calibration,and net reclassification improvement(NRI).Hard CAD(nonfatal I21-I23 and fatal I20-I25)and soft CAD(all fatal or nonfatal I20-I25)were analyzed separately.Results:In the testing set,1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years.The HR per standard deviation of the optimal PRS was 1.26(95%CI:1.19-1.33)for hard CAD.Based on a traditional CAD risk prediction model containing only non-laboratory-based information,the addition of PRS for hard CAD increased Harrell’s C index by 0.001(-0.001 to 0.003)in women and 0.003(0.001 to 0.005)in men.Among the different high-risk thresholds ranging from 1%to 10%,the highest categorical NRI was 3.2%(95%CI:0.4-6.0%)at a high-risk threshold of 10.0%in women.The association of the PRS with soft CAD was much weaker than with hard CAD,leading to minimal or no improvement in the soft CAD model.Conclusions:In this Chinese population sample,the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD.Therefore,this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.

Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection

Hepatocellular carcinoma(HCC)accounts for the majority of primary liver cancers and represents a global health challenge.Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide.HCC most commonly occurs in patients with underlying liver disease,especially chronic hepatitis B virus(HBV)infection in highly endemic areas.Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple,effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC.We examined 23 HCC risk scores published worldwide in CHB patients with(n=10)or without(n=13)antiviral treatment.We also described the characteristics of the risk score’s predictive performance and application status.In the future,higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.

Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality.Methods: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk stratification.Results: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups.Conclusions: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

Importance of risk assessment,endoscopic hemostasis,and recent advancements in the management of acute non-variceal upper gastrointestinal bleeding

Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)is a common medical emergency in clinical practice.While the incidence has significantly reduced,the mortality rates have not undergone a similar reduction in the last few decades,thus presenting a significant challenge.This editorial outlines the key causes and risk factors of ANVUGIB and explores the current standards and recent updates in risk assessment scoring systems for predicting mortality and endoscopic treatments for achieving hemostasis.Since ANUVGIB predominantly affects the elderly population,the impact of comorbidities may be responsible for the poor outcomes.A thorough drug history is important due to the increasing use of antiplatelet agents and anticoagulants in the elderly.Early risk stratification plays a crucial role in deciding the line of management and predicting mortality.Emerging scoring systems such as the ABC(age,blood tests,co-morbidities)score show promise in predicting mortality and guiding clinical decisions.While conventional endoscopic therapies remain cornerstone approaches,novel techniques like hemostatic powders and over-the-scope clips offer promising alternatives,particularly in cases refractory to traditional modalities.By integrating validated scoring systems and leveraging novel therapeutic modalities,clinicians can enhance patient care and mitigate the substantial morbidity and mortality associated with ANVUGIB.

Evaluation of polygenic risk score for risk prediction of gastric cancer

Genetic variations are associated with individual susceptibility to gastric cancer.Recently,polygenic risk score(PRS)models have been established based on genetic variants to predict the risk of gastric cancer.To assess the accuracy of current PRS models in the risk prediction,a systematic review was conducted.A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models.The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823.Incorporation of epidemiological factors or Helicobacter pylori(H.pylori)status increased the accuracy for risk prediction,while selection of single nucleotide polymorphism(SNP)and number of SNPs appeared to have little impact on the model performance.To further improve the accuracy of PRS models for risk prediction of gastric cancer,we summarized the association between gastric cancer risk and H.pylori genomic variations,cancer associated bacteria members in the gastric microbiome,discussed the potentials for performance improvement of PRS models with these microbial factors.Future studies on comprehensive PRS models established with human SNPs,epidemiological factors and microbial factors are indicated.

Clinical validity and utility of genetic risk scores in prostate cancer

Current issues related to prostate cancer （PCa） clinical care （e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa） call for risk assessment tools that can be combined with family history （FH） to stratify disease risk among men in the general population. Since 2007, genome-wide association studies （GWASs） have identified more than 100 SNPs associated with PCa susceptibility. In this review, we discuss （1） the validity of these PCa risk-associated SNPs, individually and collectively; （2） the various methods used for measuring the cumulative effect of multiple SNPs, including genetic risk score （GRS）; （3） the adequate number of SNPs needed for risk assessment; （4） reclassification of risk based on evolving numbers of SNPs used to calculate genetic risk, （5） risk assessment for men from various racial groups, and （6） the clinical utility of genetic risk assessment. In conclusion, data available to date support the clinical validity of PCa risk-associated SNPs and GRS in risk assessment among men with or without FH. PCa risk-associated SNPs are not intended for diagnostic use; rather, they should be used the same way as FH. Combining GRS and FH can significantly improve the performance of risk assessment. Improved risk assessment may have important clinical utility in targeted PCa testing. However, clinical trials are urgently needed to evaluate this clinical utility as well as the acceptance of GRS by patients and physicians.

Polygenic risk scores:the future of cancer risk prediction,screening,and precision prevention

Genome-wide association studies(GWASs)have shown that the genetic architecture of cancers are highly polygenic and enabled researchers to identify genetic risk loci for cancers.The genetic variants associated with a cancer can be combined into a polygenic risk score(PRS),which captures part of an individual’s genetic susceptibility to cancer.Recently,PRSs have been widely used in cancer risk prediction and are shown to be capable of identifying groups of individuals who could benefit from the knowledge of their probabilistic susceptibility to cancer,which leads to an increased interest in understanding the potential utility of PRSs that might further refine the assessment and management of cancer risk.In this context,we provide an overview of the major discoveries from cancer GWASs.We then review the methodologies used for PRS construction,and describe steps for the development and evaluation of risk prediction models that include PRS and/or conventional risk factors.Potential utility of PRSs in cancer risk prediction,screening,and precision prevention are illustrated.Challenges and practical considerations relevant to the implementation of PRSs in health care settings are discussed.

Polygenic risk scores: effect estimation and model optimization

Background:Polygenic risk score(PRS)derived from summary statistics of genome-wide association studies(GWAS)is a useful tool to infer an individuaPs genetic risk for health outcomes and has gained increasing popularity in human genetics research.PRS in its simplest form enjoys both computational efficiency and easy accessibility,yet the predictive performance of PRS remains moderate for diseases and traits.Results:We provide an overview of recent advances in statistical methods to improve PRS's performance by incorporating information from linkage disequilibrium,functional annotation,and pleiotropy.We also introduce model validation methods that fine-tune PRS using GWAS summary statistics.Conclusion:In this review,we showcase methodological advances and current limitations of PRS,and discuss several emerging issues in risk prediction research.

Comparison of different risk scores in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background The early detection of high-risk patients with primary percutaneous coronary intervention（PPCI） is important in reducing the risk of death in patients with acute ST elevation myocardial infarction（STEMI）. We aimed to compare the prognostic value of validated risk scores for in-hospital and one-year death. Methods This study enrolled a series of patients with acute STEMI who underwent PPCI. Thrombolysis in Myocardial Infarction（TIMI） risk score, Korea Acute Myocardial Infarction Registry（KAMIR） score, Canada Acute Coronary Syndrome（C-ACS） and Age, Glomerular filtration rate, and Ejection Fraction（AGEF） were calculated. The prognostic accuracy of the 4 scores for in-hospital and one-year death was assessed. Results A total of 489 patients with acute STEMI were retrospectively included in the present study. There were 16（3.3%） patients died while in hospital. AGEF had higher predictive power for in-hospital death than KAMIR score（0.894 vs. 0.816,P = 0.048） and C-ACS（0.894 vs. 0.728, P = 0.038）. No statistical significance was found when comparing with TIMI risk score（0.894 vs. 0.795, P = 0.124）. There were 33 patients died in 459（93.9%） included patients completed one-year follow up. The AUC of TIMI risk score, KAMIR score, C-ACS and AGEF in predicting one-year death was 0.728, 0.718, 0.681 and 0.772, respectively. They had similarly prognostic value for one-year mortality（P 〉 0.05）. Conclusion The AGEF risk scores appear to have slightly better prognostic value for the in-hospital and one-year mortality in patients with acute STEMI receiving PPCI.

Stair climbing,genetic predisposition,and the risk of incident type 2 diabetes:A large population-based prospective cohort study

Background:Cross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation.However,few studies have examined the long-term association between stair climbing and the incidence of type 2 diabetes(T2D).We aimed to prospectively evaluate the association of stair climbing with T2D and assess modifications by genetic predisposition to T2D.Methods:We included 451,699 adults(mean age=56.3±8.1 years,mean±SD;55.2%females)without T2D at baseline in the UK Biobank and followed up to March 31,2021.Stair climbing information was collected through the touchscreen questionnaire.Genetic risk score for T2D consisted of 424 single nucleotide polymorphisms.Results:During a median follow up of 12.1 years,14,896 T2D cases were documented.Compared with participants who reported no stair climbing,those who climbed stairs regularly had a lower risk of incident T2D(10-50 steps/day:hazard ratio(HR)=0.95,95%confidence interval(95%CI):0.89-1.00;60-100 steps/day:HR=0.92,95%CI:0.87-0.98;110-150 steps/day:HR=0.86,95%CI:0.80-0.91;>150 steps/day:HR=0.93,95%CI:0.87-0.99,p for trend=0.0007).We observed a significant interaction between stair climbing and genetic risk score on the subsequent T2D risk(p for interaction=0.0004),where the risk of T2D showed a downward trend in subjects with low genetic risk and those who reported stair climbing activity of 110-150 steps/day appeared to have the lowest overall T2D risk among those with intermediate to high genetic risk.Conclusion:A higher number of stairs climbed at home was associated with lower T2D incidence risk,especially among individuals with a low genetic predisposition to T2D.These findings highlight that stair climbing,as incidental physical activity,offers a simple and low-cost complement to public health interventions for T2D prevention.

Genetic susceptibility loci of lung cancer are associated with malignant risk of pulmonary nodules and improve malignancy diagnosis based on CEA levels

Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study

BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited.AIM To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity.METHODS Data from Dryad database were used in this study.Patients in the Gastroen-terology Department of Sapporo General Hospital,Sapporo,Japan,were enrolled.The starting and ending dates of the enrollment were January 1,2008 and January 5,2015,respectively.The cutoff date for follow-up was May 31,2016.The inde-pendent and dependent(target)variables were the baseline measured using the KRS and final all-cause mortality,respectively.The KRS was categorized into three groups:Low-risk group(=0 score),intermediate-risk group(1-2 score),and high-risk group(≥3 score).RESULTS Men and patients with Eastern Cooperative Oncology Group Performance Status(ECOG PS)≥2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS.The higher the score,the higher the risk of early death;however,the relevance of this independent prediction decreased with longer survival.The overall survival of each patient was recorded via real-world follow-up and retrospective observations,and this study yielded the overall relationship between KRS and all-cause mortality.CONCLUSION The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years;however,this independent predictive relationship weakened as survival time increased.

New scoring system for acute chest pain risk stratification: Is it worth SVEAT-ing it?

The emergency room is a very potent environment in the hospital.With the growing demands of the population,improved accessibility to health resources,and the onslaught of the triple pandemic,it is extremely crucial to triage patients at presentation.In the spectrum of complaints,chest pain is the commonest.Despite it being a daily ailment,chest pain brings concern to every physician at first.Chest pain could span from acute coronary syndrome,pulmonary embolism,and aortic dissection(all potentially fatal)to reflux,zoster,or musculoskeletal causes that do not need rapid interventions.We often employ scoring systems such as GRACE/PURSUIT/TIMI to assist in clinical decision-making.Over the years,the HEART score became a popular and effective tool for predicting the risk of 30-d major adverse cardiovascular events.Recently,a new scoring system called SVEAT was developed and compared to the HEART score.We have attempted to summarize how these scoring systems differ and their generalizability.With an increasing number of scoring systems being introduced,one must also prevent anchorage bias;i.e.,tools such as these are only diagnosis-specific and not organ-specific,and other emergent differential diagnoses must also be kept in mind before discharging the patient home without additional workup.

Higher Plasma Potassium Level Reduces 10-Year Cardiovascular Disease Risk Predicted by the Framingham Risk Score among Taxi-Motorbike Drivers Residing and Working in Cotonou, Benin

Hypertension, obesity, smoking, dyslipidemia, and type 2 diabetes (T2D) are the major risk factors for developing cardiovascular diseases (CVD). Recent studies revealed that taxi-motorbike drivers (TMDs) in Cotonou had higher rates of CVD risk factors, but their impacts on cardiovascular events have rarely been studied. The Framingham risk score (FRS) is an algorithm that considers CVD risk factors and estimates the risk of developing CVD in the next 10 years. Our objectives were to assess the 10-year CVD risk predicted by the FRS, and to examine the relationships of 10-year CVD risk with plasma iron and potassium levels among TMDs. We included 134 TMDs (22 - 59 years old) who had no prior diagnosis of CVD or T2D, and not taking medications affecting iron and potassium homeostasis. Conventional cardiovascular risk factors were used to calculate the 10-year CVD risk, which was categorized as low (20%). FRS > 2%, which corresponded to the 75th percentile of FRS distribution in our study population, was used as a cut-off value to classify participants into two groups. Plasma iron and potassium levels were segregated into tertiles and their associations with 10-year CVD risk were quantified by multivariate-adjusted logistic regression to calculate the odd ratios (ORs) to being above the 75th percentile of 10-year CVD risk with the corresponding 95% confidence intervals (CIs). We found that 62.0% of participants had at least one of cardiovascular risk factors. Approximately 97.8% of TMDs had 10-year CVD risk 4.8 mmol/L led to an 83% risk reduction of having 10-year CVD risk > 2% (OR = 0.17, 95% CI: 0.04 - 0.82, P = 0.027). In conclusion, our findings showed that high plasma potassium levels associate with reduced 10-year CVD risk among TMDs. Interventions focused on monitoring of plasma potassium, particularly in those with existing cardiovascular risk factors, may help prevent CVD.

Genome-wide associations, polygenic risk, and Mendelian randomization reveal limited interactions between John Henryism and cynicism

BACKGROUND John Henryism(JH)is a strategy for dealing with chronic psychological stress characterized by high levels of physical effort and work.Cynicism is a belief that people are motivated primarily by self-interest.High scores on the JH scale and cynicism measures correlate with an increased risk of cardiovascular disease.High cynicism is also a hallmark of burnout syndrome,another known risk factor for heart disease.AIM To evaluate possible interactions between JH and cynicism hoping to clarify risk factors of burnout.METHODS We analyzed genetic and psychological data available from the Database of Genotypes and Phenotypes for genome-wide associations with these traits.We split the total available samples and used plink to perform the association studies on the discovery set(n=1852,80%)and tested for replication using the validation set(n=465).We used scikit-learn to perform supervised machine learning for developing genetic risk algorithms.RESULTS We identified 2,727,and 204 genetic associations for scores on the JH,cynicism and cynical distrust(CD)scales,respectively.We also found 173 associations with high cynicism,109 with high CD,but no associations with high JH.We also produced polygenic classifiers for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7.CONCLUSION We found significant genetic components to these traits but no evidence of an interaction.Therefore,while there may be a genetic risk,JH is not likely a burnout risk factor.

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.

Frailty and cardiovascular disease： potential role of gait speed in surgical risk stratification in older adults

Frailty is a state of late life decline and vulnerability, typified by physical weakness and decreased physiologic reserve. The epidemiology and pathophysiology of frailty share features with those of cardiovascular disease. Gait speed can be used as a measure of frailty and is a powerful predictor of mortality. Advancing age is a potent risk factor for cardiovascular disease and has been associated with an increased risk of adverse outcomes. Older adults comprise approximately half of cardiac surgery patients, and account for nearly 80% of the major complications and deaths following surgery. The ability of traditional risk models to predict mortality and major morbidity in older patients being considered for cardiac surgery may improve if frailty, as measured by gait speed, is included in their assessment. It is possible that in the future frailty assessment may assist in choosing among therapies （e.g., surgical vs. percutaneous aortic valve replacement for patients with aortic stenosis）.