Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification

Background:There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma(HCC)recurrence.Recent studies suggest that postoperative adjuvant transarterial chemoembolization(PA-TACE)is beneficial for patients at high risk of tumor recurrence.However,it is difficult to select the patients.The present study aimed to develop an easy-to-use score to identify these patients.Methods:A total of 4530 patients undergoing liver resection were recruited.Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization(PDTE)scoring system was established.Results:The scoring system was composed of ten risk factors including alpha-fetoprotein(AFP),albuminbilirubin(ALBI)grade,operative bleeding loss,resection margin,tumor capsular,satellite nodules,tumor size and number,and microvascular and macrovascular invasion.Using 5 points as risk stratification,the patients with PA-TACE had higher recurrence-free survival(RFS)compared with non-TACE in>5 points group(P<0.001),whereas PA-TACE patients had lower RFS compared with non-TACE in≤5 points group(P=0.013).In the training and validation cohorts,the C-indexes of PDTE scoring system were 0.714[standard errors(SE)=0.010]and 0.716(SE=0.018),respectively.Conclusions:The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance.Patients with>5 points may benefit from PA-TACE.

Relationship between multi-slice computed tomography features and pathological risk stratification assessment in gastric gastrointestinal stromal tumors

BACKGROUND Computed tomography(CT)imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors(GISTs).AIM To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs.METHODS The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed.All patients had received dynamic contrast-enhanced CT(CECT)followed by surgical resection.According to the modified National Institutes of Health criteria,147 lesions were classified into the low malignant potential group(very low and low risk;101 lesions)and high malignant potential group(medium and high-risk;46 lesions).The association between malignant potential and CT characteristic features(including tumor location,size,growth pattern,contour,ulceration,cystic degeneration or necrosis,calcification within the tumor,lymphadenopathy,enhancement patterns,unenhanced CT and CECT attenuation value,and enhancement degree)was analyzed using univariate analysis.Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential.The receiver operating curve(ROC)was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification.RESULTS There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs.Univariate analysis showed no significant differences in age,gender,tumor location,calcification,unenhanced CT and CECT attenuation values,and enhancement degree between the two groups(P>0.05).However,a significant difference was observed in tumor size(3.14±0.94 vs 6.63±3.26 cm,P<0.001)between the low-grade and high-grade groups.The univariate analysis further revealed that CT imaging features,including tumor contours,lesion growth patterns,ulceration,cystic degeneration or necrosis,lymphadenopathy,and contrast enhancement patterns,were associated with risk stratification(P<0.05).According to binary logistic regression analysis,tumor size[P<0.001;odds ratio(OR)=26.448;95%confidence interval(CI):4.854-144.099)],contours(P=0.028;OR=7.750;95%CI:1.253-47.955),and mixed growth pattern(P=0.046;OR=4.740;95%CI:1.029-21.828)were independent predictors for risk stratification of gastric GISTs.ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919(95%CI:0.863-0.975)and 0.940(95%CI:0.893-0.986),respectively.The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm,and the sensitivity and specificity were 93.5%and 84.2%,respectively.CONCLUSION CT features,including tumor size,growth patterns,and lesion contours,were predictors of malignant potential for primary gastric GISTs.

MRD-directed and risk-adapted individualized stratified treatment of AML

Measurable residual disease(MRD)has been widely recognized as a biomarker for deeply evaluating complete remission(CR),predicting relapse,guiding pre-emptive interventions,and serving as an endpoint surrogate for drug testing.However,despite the emergence of new technologies,there remains a lack of comprehensive understanding regarding the proper techniques,sample materials,and optimal time points for MRD assessment.In this review,we summarized the MRD methods,sample sources,and evaluation frequency according to the risk category of the European Leukemia Net(ELN)2022.Additionally,we emphasize the importance of properly utilizing and combining these technologies.We have also refined the flowchart outlining each time point for preemptive interventions and intervention paths.The evaluation of MRD in acute myeloid leukemia(AML)is sophisticated,clinically applicable,and technology-dependent,and necessitates standardized approaches and further research.

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.

Cancer risk stratification system and classification of gastritis:Perspectives

Kyoto global consensus reports that the current ICD-10 classification for gastritis is obsolete.The Kyoto classification of gastritis states that severe mucosal atrophy has a high risk of gastric cancer,while mild to moderate atrophy has a low risk.The updated Kimura-Takemoto classification of atrophic gastritis considers five histological types of multifocal corpus atrophic gastritis according to stages C2 to O3.This method of morphological diagnosis of atrophic gastritis increases sensitivity by 2.4 times for severe atrophy compared to the updated Sydney system.This advantage should be considered when stratifying the high risk of gastric cancer.The updated Kimura-Takemoto classification of atrophic gastritis should be used as a reference standard(gold standard)in studies of morphofunctional relationships to identify serological markers of atrophic gastritis with evidence-based effectiveness.The use of artificial intelligence in the serological screening of atrophic gastritis makes it possible to screen a large number of the population.During serological screening of atrophic gastritis and risk stratification of gastric cancer,it is advisable to use the Kyoto classification of gastritis with updated Kimura-Takemoto classification of atrophic gastritis.

Long-Term Outcomes after Coronary Artery Bypass Grafting with Risk Stratification

Background: Risk stratification of long-term outcomes for patients undergoing Coronary artery bypass grafting has enormous potential clinical importance. Aim: To develop risk stratification models for predicting long-term outcomes following coronary artery bypass graft (CABG) surgery. Methods: We retrospectively revised the electronic medical records of 2330 patients who underwent adult Cardiac surgery between August 2016 and December 2022 at Madinah Cardiac Center, Saudi Arabia. Three hundred patients fulfilled the eligibility criteria of CABG operations with a complete follow-up period of at least 24 months, and data reporting. The collected data included patient demographics, comorbidities, laboratory data, pharmacotherapy, echocardiographic parameters, procedural details, postoperative data, in-hospital outcomes, and follow-up data. Our follow-up was depending on the clinical status (NYHA class), chest pain recurrence, medication dependence and echo follow-up. A univariate analysis was performed between each patient risk factor and the long-term outcome to determine the preoperative, operative, and postoperative factors significantly associated with each long-term outcome. Then a multivariable logistic regression analysis was performed with a stepwise, forward selection procedure. Significant (p < 0.05) risk factors were identified and were used as candidate variables in the development of a multivariable risk prediction model. Results: The incidence of all-cause mortality during hospital admission or follow-up period was 2.3%. Other long-term outcomes included all-cause recurrent hospitalization (9.8%), recurrent chest pain (2.4%), and the need for revascularization by using a stent in 5 (3.0%) patients. Thirteen (4.4%) patients suffered heart failure and they were on the maximum anti-failure medications. The model for predicting all-cause mortality included the preoperative EF ≤ 35% (AOR: 30.757, p = 0.061), the bypass time (AOR: 1.029, p = 0.003), and the duration of ventilation following the operation (AOR: 1.237, p = 0.021). The model for risk stratification of recurrent hospitalization comprised the preoperative EF ≤ 35% (AOR: 6.198, p p = 0.023), low postoperative cardiac output (AOR: 3.622, p = 0.007), and the development of postoperative atrial fibrillation (AOR: 2.787, p = 0.038). Low postoperative cardiac output was the only predictor that significantly contributed to recurrent chest pain (AOR: 11.66, p = 0.004). Finally, the model consisted of low postoperative cardiac output (AOR: 5.976, p < 0.001) and postoperative ventricular fibrillation (AOR: 4.216, p = 0.019) was significantly associated with an increased likelihood of the future need for revascularization using a stent. Conclusions: A risk prediction model was developed in a Saudi cohort for predicting all-cause mortality risk during both hospital admission and the follow-up period of at least 24 months after isolated CABG surgery. A set of models were also developed for predicting long-term risks of all-cause recurrent hospitalization, recurrent chest pain, heart failure, and the need for revascularization by using stents.

Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit

BACKGROUND Cirrhotic patients with acute-on-chronic liver failure(ACLF)in the intensive care unit(ICU)have a poor but variable prognoses.Accurate prognosis evaluation can guide the rational management of patients with ACLF.However,existing prognostic scores for ACLF in the ICU environment lack sufficient accuracy.AIM To develop a new prognostic model for patients with ACLF in ICU.METHODS Data from 938 ACLF patients in the Medical Information Mart for Intensive Care(MIMIC)database were used to develop a new prognostic model(MIMIC ACLF)for ACLF.Discrimination,calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve(AUROC),calibration curve and decision curve analysis(DCA),respectively.MIMIC ACLF was then externally validated in a multiple-center cohort,the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in China.RESULTS The MIMIC ACLF score was determined using nine variables:ln(age)×2.2+ln(white blood cell count)×0.22-ln(mean arterial pressure)×2.7+respiratory failure×0.6+renal failure×0.51+cerebral failure×0.31+ln(total bilirubin)×0.44+ln(internationalized normal ratio)×0.59+ln(serum potassium)×0.59.In MIMIC cohort,the AUROC(0.81/0.79)for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF(0.76/0.74),Model for End-stage Liver Disease(MELD;0.73/0.71)and MELD-Na(0.72/0.70)(all P<0.001).The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing scores.The net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50%threshold probability.The superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external cohorts.CONCLUSION We developed and validated a new prognostic model with satisfactory accuracy for cirrhotic patients with ACLF hospitalized in the ICU.The model-based risk stratification and online calculator might facilitate the rational management of patients with ACLF.

Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.

Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

Cracking the silent gallstone code:Wait or operate?

The widespread availability of abdominal ultrasound has revealed the common occurrence of asymptomatic gallstones.While the treatment for symptomatic gallstones is clear,the benefits of minimally invasive laparoscopic cholecystectomy have sparked debate about the best approach to managing silent gallstones.The potential for asymptomatic gallstones to become symptomatic or lead to complications complicates the decision-making process regarding surgical intervention,as it's uncertain when or which patients might develop complications.Consequently,risk stratification appears to play a critical role in guiding decisions about silent gallstones.However,there is no definitive evidence to direct management,and a consensus-based on high-quality evidence is yet to be established.

Serum cystatin C,monocyte/high-density lipoprotein-C ratio,and uric acid for the diagnosis of coronary heart disease and heart failure

BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.

Oncological results, functional outcomes and health-related quality-of-life in men who received a radical prostatectomy or external beam radiation therapy for localized prostate cancer： a study on long-term patient outcome with risk stratification

Health-related quality-of-life （HRQOL） after a radical prostatectomy （RP） or extemal beam radiation therapy （EBRT） has not been studied in conjunction with oncological outcomes in relation to disease risk stratification. Moreover, the long-term outcomes of these treatment approaches have not been studied. We retrospectively analyzed oncological outcomes between consecutive patients receiving RP （n = 86） and EBRT （n = 76） for localized prostate cancer. HRQOL and functional outcomes could be assessed in 62 RP （79%） and 54 EBRT （79%） patients over a 3-year follow-up period （median： 41 months） using the Medical Outcomes Study Short Form-36 （SF-36） and the University of Califomia Los Angeles Prostate Cancer Index （UCLA PCI）. The 5-year biochemical progression-free survival did not differ between the RP and EBRT groups for low-risk （74.6% vs. 75.0%, P = 0.931） and intermediate-risk （61.3% vs. 71.1%, P = 0.691） patients. For high-risk patients, progression-free survival was lower in the RP group （45.1%） than in the EBRT group （79.7%） （P = 0.002）. The general HRQOL was comparable between the two groups. Regarding functional outcomes, the RP group reported lower scores on urinary function and less urinary bother and sexual bother than the EBRT group （P 〈 0.001, P 〈 0.05 and P 〈 0.001, respectively）. With risk stratification, the low- and intermediate-risk patients in the RP group reported poorer urinary function than patients in the EBRT group （P 〈 0.001 for each）. The sexual function of the high-risk patients in the EBRT group was better than that of the same risk RP patients （P 〈 0.001）. Biochemical recurrence was not associated with the UCLA PCI score in either group. In conclusion, low- to intermediate-risk patients treated with an RP may report relatively decreased urinary function during long-term follow-up. The patient＇s HRQOL after treatment did not depend on biochemical recurrence.

Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening:A cross-sectional population-based analysis

Objective:Integration of risk stratification into fecal immunochemical test(FIT)might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer(CRC)screening.A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment(QRA)and FIT,FIT-only and QRA-only strategies in a CRC screening program in China.Methods:The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China.Participants were first invited to undertake QRA and one-time FIT(OC-sensor).Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy.Participation,detection rate,and resource demand for colonoscopy were calculated and compared.Results:Of the 29,626 invitees,20,203 completed the parallel combination,8,592 completed the QRA-only,and11 completed the FIT-only strategy.For the parallel combination,FIT-only,and QRA-only strategies,the overall positivity rates were 10.2%(2,928/28,806),5.4%(1,096/20,214),and 6.8%(1,944/28,795),respectively;the yield of advanced neoplasm per 10,000 invitees were 46.9[95%confidence interval(95%CI):39.8-55.4],36.8(95%CI:30.5-44.4),and 12.2(95%CI:8.8-16.8),respectively;the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7%(95%CI:4.0%-5.6%),9.9%(95%CI:8.3%-11.9%),and 1.9%(95%CI:1.3%-2.6%),respectively;the number of colonoscopies required to detect one advanced neoplasm was 11.4(95%CI:9.8-13.4),5.7(95%CI:4.8-6.7),and 28.4(95%CI:20.7-39.2),respectively.Conclusions:The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.

Multi-slice spiral computed tomography in differential diagnosis of gastric stromal tumors and benign gastric polyps,and gastric stromal tumor risk stratification assessment

BACKGROUND The biological characteristics of gastric stromal tumors are complex,and their incidence has increased in recent years.Gastric stromal tumors(GST)have potential malignant tendencies,and the probability of transformation into malignant tumors is as high as 20%-30%.AIM To investigate the value of multi-slice spiral computed tomography(MSCT)in the differential diagnosis of GST and benign gastric polyps,and GST risk stratification assessment.METHODS We included 64 patients with GST(GST group)and 60 with benign gastric polyps(control group),confirmed by pathological examination after surgery in PLA General Hospital,from January 2016 to June 2021.The differences in the MSCT imaging characteristic parameters and enhanced CT values between the two groups before surgery were compared.According to the National Institutes of Health’s standard,GST is divided into low-and high-risk groups for MSCT imaging characteristic parameters and enhanced CT values.RESULTS The incidences of extraluminal growth,blurred boundaries,and ulceration in the GST group were significantly higher than those in the control group(P<0.05).The CT values and enhanced peak CT values in the arterial phase in the CST group were higher than those in the control group(P<0.05).The MSCT differential diagnosis of GST and gastric polyp sensitivity,specificity,misdiagnosis rate,missed diagnosis rate,and areas under the curve(AUCs)were 73.44%,83.33%,26.56%,16.67%,0.784,respectively.The receiver operating characteristic curves were plotted with the arterial CT value and enhanced peak CT value,with a statistical difference.The results showed that the sensitivity,specificity,misdiagnosis rate,missed diagnosis rate,and AUC value of arterial CT in the differential diagnosis of GST and gastric polyps were 80.18%,62.20%,19.82%,37.80%,and 0.710,respectively.The sensitivity,specificity,misdiagnosis rate,missed diagnosis rate,and AUC value of the enhanced peak CT value in the differential diagnosis of GST and gastric polyps were 67.63%,60.40%,32.37%,39.60%,and 0.710,respectively.The incidence of blurred lesion boundaries and ulceration in the high-risk group was significantly higher than that in the low-risk group(P<0.05).The arterial phase and enhanced peak CT values in the high-risk group were significantly higher than those in the low-risk group(P<0.05).CONCLUSION Presurgical MSCT examination has important value in the differential diagnosis of GST and gastric benign polyps and can effectively evaluate the risk grade of GST patients.

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features

AIM To investigate the association between 16 insertiondeletions(INDEL) polymorphisms, colorectal cancer(CRC) risk and clinical features in an admixed population.METHODS O n e h u n d re d a n d fo r ty p a t i e n t s w i t h C R C a n d 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on Gene Mapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology scoring.RESULTS Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis(TNM) stage risk, the Ins alleles of ACE, HLAG and TP53(6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk.CONCLUSION The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

Role of Immune Microenvironmental Factors for Improving the IPI-related Risk Stratification of Aggressive B Cell Lymphoma

Objective To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. Methods A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CDS, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. Results Significant differences in 11 factors （age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8＋ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum l^2-microglobulin） were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index （IPI）, revised IPI, and NCCN-IPI models] （P 〈 0.05）. Concordance rates were high （81.4%-100.0%） when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. Conclusion We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.

Presepsin as a biomarker for risk stratification for acute cholangitis in emergency department: A single-center study

BACKGROUND Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk.The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage.With the introduction of white blood cell(WBC)count,C-reactive protein(CRP),and total bilirubin(T-Bil)into the diagnostic criteria and severity grading for acute cholangitis,the diagnosis rate and grading have significantly improved.However,early risk stratification assessments are challenging in the emergency department.Therefore,we hope to find an ideal predictive biomarker for cholangitis grade.Presepsin is a promising biomarker for the early diagnosis,severity,and prognosis of acute bacterial infections.AIM To assess the grading value of presepsin in patients with acute cholangitis.METHODS This clinical study was conducted at the Beijing Friendship Hospital,a 2000-bed teaching hospital with approximately 200000 emergency admissions per year.In this prospective observational study,336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed.WBC count,CRP,procalcitonin(PCT),presepsin,T-Bil,and blood culture results were collected.The values were compared using the Pearsonχ2 test,Fisher’s exact test,or Mann-Whitney U test.The area under the receiver operating characteristic curve(AUC)of the value was examined using the Delong test.The correlations among the key research indicators were determined using Pearson correlation.RESULTS In total,336 patients were examined,which included 107,106,and 123 patients classified as having mild,moderate,and severe cholangitis,respectively.WBC count,CRP,PCT,presepsin,T-Bil,direct bilirubin,and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients(P=0.000).The AUC of presepsin in predicting moderate acute cholangitis was 0.728,which was higher than that of CRP(0.631,P=0.043)and PCT(0.585,P=0.002),and same as that of WBC count(0.746,P=0.713)and T-Bil(0.686,P=0.361).The AUC of presepsin in predicting severe acute cholangitis was 0.715,which was higher than that of WBC count(0.571,P=0.008),CRP(0.590,P=0.009),PCT(0.618,P=0.024),and T-Bil(0.559,P=0.006).The presepsin levels in the positive blood culture group were higher(2830.8pg/mLvs1987.8pg/mL,P=0.000),and the AUC of presepsin(0.688)proved that it was a good biomarker for predicting positive bacterial culture.CONCLUSION Presepsin can predict positive blood culture in patients with acute cholangitis.It is superior to WBC count,CRP,PCT,and T-Bil for the risk stratification of acute cholangitis.

Arrhythmic risk stratification in ischemic,non-ischemic and hypertrophic cardiomyopathy:A two-step multifactorial,electrophysiology study inclusive approach

Annual arrhythmic sudden cardiac death ranges from 0.6%to 4%in ischemic cardiomyopathy(ICM),1%to 2%in non-ischemic cardiomyopathy(NICM),and 1%in hypertrophic cardiomyopathy(HCM).Towards a more effective arrhythmic risk stratification(ARS)we hereby present a two-step ARS with the usage of seven non-invasive risk factors:Late potentials presence(≥2/3 positive criteria),premature ventricular contractions(≥30/h),non-sustained ventricular tachycardia(≥1episode/24 h),abnormal heart rate turbulence(onset≥0%and slope≤2.5 ms)and reduced deceleration capacity(≤4.5 ms),abnormal T wave alternans(≥65μV),decreased heart rate variability(SDNN<70ms),and prolonged QT_(c)interval(>440 ms in males and>450 ms in females)which reflect the arrhythmogenic mechanisms for the selection of the intermediate arrhythmic risk patients in the first step.In the second step,these intermediate-risk patients undergo a programmed ventricular stimulation(PVS)for the detection of inducible,truly high-risk ICM and NICM patients,who will benefit from an implantable cardioverter defibrillator.For HCM patients,we also suggest the incorporation of the PVS either for the low HCM Risk-score patients or for the patients with one traditional risk factor in order to improve the inadequate sensitivity of the former and the low specificity of the latter.

Risk stratification of patients who present with chest pain and have normal troponins using a machine learning model

BACKGROUND Risk stratification tools exist for patients presenting with chest pain to the emergency room and have achieved the recommended negative predictive value(NPV)of 99%.However,due to low positive predictive value(PPV),current stratification tools result in unwarranted investigations such as serial laboratory tests and cardiac stress tests(CSTs).AIM To create a machine learning model(MLM)for risk stratification of chest pain with a better PPV.METHODS This retrospective cohort study used de-identified hospital data from January 2016 until November 2021.Inclusion criteria were patients aged>21 years who presented to the ER,had at least two serum troponins measured,were subsequently admitted to the hospital,and had a CST within 4 d of presentation.Exclusion criteria were elevated troponin value(>0.05 ng/mL)and missing values for body mass index.The primary outcome was abnormal CST.Demographics,coronary artery disease(CAD)history,hypertension,hyperlipidemia,diabetes mellitus,chronic kidney disease,obesity,and smoking were evaluated as potential risk factors for abnormal CST.Patients were also categorized into a high-risk group(CAD history or more than two risk factors)and a low-risk group(all other patients)for comparison.Bivariate analysis was performed using a χ^(2) test or Fisher’s exact test.Age was compared by t test.Binomial regression(BR),random forest,and XGBoost MLMs were used for prediction.Bootstrapping was used for the internal validation of prediction models.BR was also used for inference.Alpha criterion was set at 0.05 for all statistical tests.R software was used for statistical analysis.RESULTS The final cohort of the study included 2328 patients,of which 245(10.52%)patients had abnormal CST.When adjusted for covariates in the BR model,male sex[risk ratio(RR)=1.52,95%confidence interval(CI):1.2-1.94,P<0.001],CAD history(RR=4.46,95%CI:3.08-6.72,P<0.001),and hyperlipidemia(RR=3.87,95%CI:2.12-8.12,P<0.001)remained statistically significant.Incidence of abnormal CST was 12.2%in the high-risk group and 2.3%in the low-risk group(RR=5.31,95%CI:2.75-10.24,P<0.001).The XGBoost model had the best PPV of 24.33%,with an NPV of 91.34%for abnormal CST.CONCLUSION The XGBoost MLM achieved a PPV of 24.33%for an abnormal CST,which is better than current stratification tools(13.00%-17.50%).This highlights the beneficial potential of MLMs in clinical decision-making.