Development and validation of a questionnaire-based risk scoring system to identify individuals at high risk for gastric cancer in Chinese populations

Objective:This study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening.Methods:A gastric cancer risk scoring system(GC-RSS)was developed based on questionnaire-based predictors for gastric cancer derived from systematic literature review.To assess the capability of this system for discrimination,risk scores for 8,214 and 7,235 outpatient subjects accepting endoscopic examination in two endoscopy centers,and 32,630 participants in a community-based cohort in China were calculated to plot receiver operating characteristic curves and generate area under the curve(AUC).To evaluate the performance of GC-RSS,the screening proportion,sensitivity and detection rate ratio compared to universal screening were used under different risk score cutoff values.Results:GC-RSS comprised nine predictors including advanced age,male gender,low body mass index(<18.5 kg/m^(2)),family history of gastric cancer,cigarette smoking,consumption of alcohol,preference for salty food,irregularity of meals and consumption of preserved food.This tool performed well in determining the risk of malignant gastric lesions with AUCs of 0.763,0.706 and 0.696 in three validation sets.When subjects with risk scores≥5 were evaluated with endoscopy,nearly 50%of these endoscopies could be saved with a detection rate of over 1.5 times achieved.When the cutoff was set at 8,only about 10%of subjects with the highest risk would be offered endoscopy,and detection rates for gastric cancer could be increased 2-4 fold compared to universal screening.Conclusions:An effective questionnaire-based GC-RSS was developed and validated.This tool may play an important role in establishing a tailored screening strategy for gastric cancer in China.

Estimation of Physiologic Ability and Surgical Stress scoring system for predicting complications following abdominal surgery: A metaanalysis spanning 2004 to 2022

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.

Predictive utility of the Rockall scoring system in patients suffering from acute nonvariceal upper gastrointestinal hemorrhage

BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)represents a sig-nificant clinical challenge due to its unpredictability and potentially severe out-comes.The Rockall risk score has emerged as a critical tool for prognostic asse-ssment in patients with ANVUGIB,aiding in the prediction of rebleeding and mo-rtality.However,its applicability and accuracy in the Chinese population remain understudied.AIM To assess the prognostic value of the Rockall risk score in a Chinese cohort of patients with ANVUGIB.METHODS A retrospective analysis of 168 ANVUGIB patients’medical records was condu-cted.The study employed statistical tests,including the t-test,χ^(2) test,spearman correlation,and receiver operating characteristic(ROC)analysis,to assess the re-lationship between the Rockall score and clinical outcomes,specifically focusing on rebleeding events within 3 months post-assessment.RESULTS Significant associations were found between the Rockall score and various clinical outcomes.High Rockall scores were significantly associated with rebleeding events(r=0.735,R2=0.541,P<0.001)and strongly positively correlated with adverse outcomes.Low hemoglobin levels(t=2.843,P=0.005),high international normalized ratio(t=3.710,P<0.001),active bleeding during endoscopy(χ^(2)=7.950,P=0.005),large ulcer size(t=6.348,P<0.001),and requiring blood transfusion(χ^(2)=6.381,P=0.012)were all significantly associated with rebleeding events.Furthermore,differences in treatment and management strategies were identified between patients with and without rebleeding events.ROC analysis indicated the excellent discriminative power(sensitivity:0.914;specificity:0.816;area under the curve:0.933;Youden index:0.730)of the Rockall score in predicting rebleeding events within 3 months.CONCLUSION This study provides valuable insights into the prognostic value of the Rockall risk score for ANVUGIB in the Chinese population.The results underscore the potential of the Rockall score as an effective tool for risk strati-fication and prognostication,with implications for guiding risk-appropriate management strategies and optimizing care for patients with ANVUGIB.

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.

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.

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.

A new scoring system to evaluate adjuvant chemotherapy for patients with T2N0M0 gastric cancer after D2 gastrectomy

BACKGROUND At present,there is insufficient medical evidence to determine whether adjuvant chemotherapy is necessary for T2N0M0 gastric cancer.AIM To obtain a risk score to assess the need for adjuvant chemotherapy in patients with T2N0M0 gastric cancer.METHODS We identified 325 patients with pathological T2N0M0 stage primary gastric cancer at the National Cancer Center between 2011 and 2018.Univariate and multivariate Cox regression analyses were performed to predict factors affecting prognosis.Vascular invasion,tumor site,and body mass index were assessed,and a scoring system was established.We compared the survival outcomes and benefits of adjuvant chemotherapy between the different subgroups.RESULTS Five-year survival rates of the score 0,1,2,and 3 groups were 92%,95%,80%,and 50%,respectively(P<0.001).In the score 2-3 group,five-year survival rates for patients in the adjuvant chemotherapy group and postoperative observation group were 95%and 61%,respectively(P=0.021).CONCLUSION For patients with T2N0M0 stage gastric cancer and two or more risk factors,adjuvant chemotherapy after D2 gastrectomy may have a survival benefit.

Development and Validation of a Prognostic Risk Score System for COVID-19 Inpatients:A Multi-Center Retrospective Study in China

Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.

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.

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.

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.

Novel CABIN score outperforms other prognostic models in predicting in-hospital mortality after salvage transjugular intrahepatic portosystemic shunting

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is now established as the salvage procedure of choice in patients who have uncontrolled or severe recurrent variceal bleeding despite optimal medical and endoscopic treatment.AIM To analysis compared the performance of eight risk scores to predict in-hospital mortality after salvage TIPS(sTIPS)placement in patients with uncontrolled variceal bleeding after failed medical treatment and endoscopic intervention.METHODS Baseline risk scores for the Acute Physiology and Chronic Health Evaluation(APACHE)II,Bonn TIPS early mortality(BOTEM),Child-Pugh,Emory,FIPS,model for end-stage liver disease(MELD),MELD-Na,and a novel 5 category CABIN score incorporating Creatinine,Albumin,Bilirubin,INR and Na,were calculated before sTIPS.Concordance(C)statistics for predictive accuracy of inhospital mortality of the eight scores were compared using area under the receiver operating characteristic curve(AUROC)analysis.RESULTS Thirty-four patients(29 men,5 women),median age 52 years(range 31-80)received sTIPS for uncontrolled(11)or refractory(23)bleeding between August 1991 and November 2020.Salvage TIPS controlled bleeding in 32(94%)patients with recurrence in one.Ten(29%)patients died in hospital.All scoring systems had a significant association with in-hospital mortality(P<0.05)on multivariate analysis.Based on in-hospital survival AUROC,the CABIN(0.967),APACHE II(0.948)and Emory(0.942)scores had the best capability predicting mortality compared to FIPS(0.892),BOTEM(0.877),MELD Na(0.865),Child-Pugh(0.802)and MELD(0.792).CONCLUSION The novel CABIN score had the best prediction capability with statistical superiority over seven other risk scores.Despite sTIPS,hospital mortality remains high and can be predicted by CABIN category B or C or CABIN scores>10.Survival was 100%in CABIN A patients while mortality was 75%for CABIN B,87.5%for CABIN C,and 83%for CABIN scores>10.

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.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Comprehensive assessment of the association between tumorinfiltrating immune cells and the prognosis of renal cell carcinoma

BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal malignancies.Increasing evi-dence has shown an association between immune infiltration in RCC and clinical outcomes.To discover possible targets for the immune system,we investigated the link between tumor-infiltrating immune cells(TIICs)and the prognosis of RCC.AIM To investigate the effects of 22 TIICs on the prognosis of RCC patients and iden-tify potential therapeutic targets for RCC immunotherapy.METHODS The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions.Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC.A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes.Furthermore,multi-variate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC.A value of P<0.05 was regarded as statistically significant.RESULTS Compared to normal tissues,RCC tissues exhibited a distinct infiltration of im-mune cells.An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC.High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve(P=1E-05).The immunological risk score model was demonstrated to be a dependable predictor of survival risk(area under the curve=0.747)via the receiver operating characteristic curve.According to multivariate Cox regression analysis,the immune risk score model independently predicted RCC patients'prognosis(hazard ratio=1.550,95%CI:1.342–1.791;P<0.001).Finally,we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.CONCLUSION TIICs play various roles in RCC prognosis.The immunological risk score is an independent predictor of poor survival in kidney cancer cases.