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-hosp...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.展开更多
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...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.展开更多
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-...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.展开更多
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...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.展开更多
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 asse...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.展开更多
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...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.展开更多
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 c...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.展开更多
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 popularit...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.展开更多
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...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.展开更多
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 betwe...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.展开更多
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 challen...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.展开更多
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...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.展开更多
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...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.展开更多
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 ha...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 75<sup>th</sup> 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.展开更多
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-interes...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.展开更多
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 graduall...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.展开更多
BACKGROUND Postoperative complications remain a paramount concern for surgeons and healthcare practitioners.AIM To present a comprehensive analysis of the Estimation of Physiologic Ability and Surgical Stress(E-PASS)s...BACKGROUND Postoperative complications remain a paramount concern for surgeons and healthcare practitioners.AIM To present a comprehensive analysis of the Estimation of Physiologic Ability and Surgical Stress(E-PASS)scoring system’s efficacy in predicting postoperative complications following abdominal surgery.METHODS A systematic search of published studies was conducted,yielding 17 studies with pertinent data.Parameters such as preoperative risk score(PRS),surgical stress score(SSS),comprehensive risk score(CRS),postoperative complications,post-operative mortality,and other clinical data were collected for meta-analysis.Forest plots were employed for continuous and binary variables,withχ2 tests assessing heterogeneity(P value).RESULTS Patients experiencing complications after abdominal surgery exhibited significantly higher E-PASS scores compared to those without complications[mean difference and 95%confidence interval(CI)of PRS:0.10(0.05-0.15);SSS:0.04(0.001-0.08);CRS:0.19(0.07-0.31)].Following the exclusion of low-quality studies,results remained valid with no discernible heterogeneity.Subgroup analysis indicated that variations in sample size and age may contribute to hetero-geneity in CRS analysis.Binary variable meta-analysis demonstrated a correlation between high CRS and increased postoperative complication rates[odds ratio(OR)(95%CI):3.01(1.83-4.95)],with a significant association observed between high CRS and postoperative mortality[OR(95%CI):15.49(3.75-64.01)].CONCLUSION In summary,postoperative complications in abdominal surgery,as assessed by the E-PASS scoring system,are consistently linked to elevated PRS,SSS,and CRS scores.High CRS scores emerge as risk factors for heightened morbidity and mortality.This study establishes the accuracy of the E-PASS scoring system in predicting postoperative morbidity and mortality in abdominal surgery,underscoring its potential for widespread adoption in effective risk assessment.展开更多
BACKGROUND Prediabetes risk assessment models derived from large sample sizes are scarce.AIM To establish a robust assessment model for prediabetes and to validate the model in different populations.METHODS The China ...BACKGROUND Prediabetes risk assessment models derived from large sample sizes are scarce.AIM To establish a robust assessment model for prediabetes and to validate the model in different populations.METHODS The China National Diabetes and Metabolic Disorders Study(CNDMDS)collected information from 47325 participants aged at least 20 years across China from 2007 to 2008.The Thyroid Disorders,Iodine Status and Diabetes Epidemiological Survey(TIDE)study collected data from 66108 participants aged at least 18 years across China from 2015 to 2017.A logistic model with stepwise selection was performed to identify significant risk factors for prediabetes and was internally validated by bootstrapping in the CNDMDS.External validations were performed in diverse populations,including populations of Hispanic(Mexican American,other Hispanic)and non-Hispanic(White,Black and Asian)participants in the National Health and Nutrition Examination Survey(NHANES)in the United States and 66108 participants in the TIDE study in China.C statistics and calibration plots were adopted to evaluate the model’s discrimination and calibration performance.RESULTS A set of easily measured indicators(age,education,family history of diabetes,waist circumference,body mass index,and systolic blood pressure)were selected as significant risk factors.A risk assessment model was established for prediabetes with a C statistic of 0.6998(95%CI:0.6933 to 0.7063)and a calibration slope of 1.0002.When externally validated in the NHANES and TIDE studies,the model showed increased C statistics in Mexican American,other Hispanic,Non-Hispanic Black,Asian and Chinese populations but a slightly decreased C statistic in non-Hispanic White individuals.Applying the risk assessment model to the TIDE population,we obtained a C statistic of 0.7308(95%CI:0.7260 to 0.7357)and a calibration slope of 1.1137.A risk score was derived to assess prediabetes.Individuals with scores≥7 points were at high risk of prediabetes,with a sensitivity of 60.19%and specificity of 67.59%.CONCLUSION An easy-to-use assessment model for prediabetes was established and was internally and externally validated in different populations.The model had a satisfactory performance and could screen individuals with a high risk of prediabetes.展开更多
BACKGROUND Genetic variants of Helicobacter pylori(H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms(SNPs) of H. pylori that are associated with gastric cancer have been reported. T...BACKGROUND Genetic variants of Helicobacter pylori(H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms(SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear.AIM To assess the performance of a polygenic risk score(PRS) based on H. pylori SNPs in predicting the risk of gastric cancer.METHODS A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest(RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined.RESULTS Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio(OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76(95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve(AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hp Europe strains, with an AUC value of 0.78.CONCLUSION The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.展开更多
Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the ris...Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend 〈 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend 〈 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (C/s)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% C/s) for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17) in men and 4.53 (2.57-7.98) in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.展开更多
文摘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.
文摘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.
基金supported by grants from the National Natural Science Foundation of China(Nos.82192904,82192901,82192900,and 91846303)The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong.The long-term follow-up is supported by grants from the UK Wellcome Trust(Nos.212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,and 088158/Z/09/Z)+2 种基金the National Key Research and Development Program of China(No.2016 YFC0900500)National Natural Science Foundation of China(No.81390540)Chinese Ministry of Science and Technology(No.2011BAI09B01).
文摘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.
文摘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.
基金Supported by the National Natural Science Foundation of China,No.31870777.
文摘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.
文摘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.
基金the National Natural Science Foundation of China(81820108028,81922061,82003530).
文摘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.
文摘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.
文摘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.
基金supported by the National Key Research and Development Program of China(grant number 2020YFC2006300)the Young Scientists Fund of the National Natural Science Foundation of China(grant number 82103835)。
文摘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.
基金supported by the National Natural Science Foundation of China(No.82073628,81871876 and 82173609).
文摘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.
文摘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.
文摘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.
文摘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 75<sup>th</sup> 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.
文摘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.
基金Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0308.
文摘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.
基金Supported by Medical Science and Technology Project of Zhejiang Province of China,No.2020PY053.
文摘BACKGROUND Postoperative complications remain a paramount concern for surgeons and healthcare practitioners.AIM To present a comprehensive analysis of the Estimation of Physiologic Ability and Surgical Stress(E-PASS)scoring system’s efficacy in predicting postoperative complications following abdominal surgery.METHODS A systematic search of published studies was conducted,yielding 17 studies with pertinent data.Parameters such as preoperative risk score(PRS),surgical stress score(SSS),comprehensive risk score(CRS),postoperative complications,post-operative mortality,and other clinical data were collected for meta-analysis.Forest plots were employed for continuous and binary variables,withχ2 tests assessing heterogeneity(P value).RESULTS Patients experiencing complications after abdominal surgery exhibited significantly higher E-PASS scores compared to those without complications[mean difference and 95%confidence interval(CI)of PRS:0.10(0.05-0.15);SSS:0.04(0.001-0.08);CRS:0.19(0.07-0.31)].Following the exclusion of low-quality studies,results remained valid with no discernible heterogeneity.Subgroup analysis indicated that variations in sample size and age may contribute to hetero-geneity in CRS analysis.Binary variable meta-analysis demonstrated a correlation between high CRS and increased postoperative complication rates[odds ratio(OR)(95%CI):3.01(1.83-4.95)],with a significant association observed between high CRS and postoperative mortality[OR(95%CI):15.49(3.75-64.01)].CONCLUSION In summary,postoperative complications in abdominal surgery,as assessed by the E-PASS scoring system,are consistently linked to elevated PRS,SSS,and CRS scores.High CRS scores emerge as risk factors for heightened morbidity and mortality.This study establishes the accuracy of the E-PASS scoring system in predicting postoperative morbidity and mortality in abdominal surgery,underscoring its potential for widespread adoption in effective risk assessment.
基金Supported by the National Key Research and Development Program of China,No.2018YFC1313902。
文摘BACKGROUND Prediabetes risk assessment models derived from large sample sizes are scarce.AIM To establish a robust assessment model for prediabetes and to validate the model in different populations.METHODS The China National Diabetes and Metabolic Disorders Study(CNDMDS)collected information from 47325 participants aged at least 20 years across China from 2007 to 2008.The Thyroid Disorders,Iodine Status and Diabetes Epidemiological Survey(TIDE)study collected data from 66108 participants aged at least 18 years across China from 2015 to 2017.A logistic model with stepwise selection was performed to identify significant risk factors for prediabetes and was internally validated by bootstrapping in the CNDMDS.External validations were performed in diverse populations,including populations of Hispanic(Mexican American,other Hispanic)and non-Hispanic(White,Black and Asian)participants in the National Health and Nutrition Examination Survey(NHANES)in the United States and 66108 participants in the TIDE study in China.C statistics and calibration plots were adopted to evaluate the model’s discrimination and calibration performance.RESULTS A set of easily measured indicators(age,education,family history of diabetes,waist circumference,body mass index,and systolic blood pressure)were selected as significant risk factors.A risk assessment model was established for prediabetes with a C statistic of 0.6998(95%CI:0.6933 to 0.7063)and a calibration slope of 1.0002.When externally validated in the NHANES and TIDE studies,the model showed increased C statistics in Mexican American,other Hispanic,Non-Hispanic Black,Asian and Chinese populations but a slightly decreased C statistic in non-Hispanic White individuals.Applying the risk assessment model to the TIDE population,we obtained a C statistic of 0.7308(95%CI:0.7260 to 0.7357)and a calibration slope of 1.1137.A risk score was derived to assess prediabetes.Individuals with scores≥7 points were at high risk of prediabetes,with a sensitivity of 60.19%and specificity of 67.59%.CONCLUSION An easy-to-use assessment model for prediabetes was established and was internally and externally validated in different populations.The model had a satisfactory performance and could screen individuals with a high risk of prediabetes.
基金Supported by the National Natural Science Foundation of China,No. 31870777。
文摘BACKGROUND Genetic variants of Helicobacter pylori(H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms(SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear.AIM To assess the performance of a polygenic risk score(PRS) based on H. pylori SNPs in predicting the risk of gastric cancer.METHODS A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest(RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined.RESULTS Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio(OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76(95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve(AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hp Europe strains, with an AUC value of 0.78.CONCLUSION The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.
基金supported by Grants from the Ministry of Science and Technology of the People’s Republic of China[2016YFC1305202,2016YFC1305601,2016YFC0901201,2016YFC1304904]the National Natural Science Foundation of China[81670795]
文摘Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend 〈 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend 〈 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (C/s)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% C/s) for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17) in men and 4.53 (2.57-7.98) in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.