BACKGROUND: The aim of this study was to investigate the correlation between m6A methylation regulators and cell infiltration characteristics in tumor immune microenvironment (TIME), so as to help understand the immune mechanism of early-stage lung adenocarcinoma (LUAD).
METHODS: The expression and consensus cluster analyses of m6A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed.
RESULTS: Expression of m6A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m6A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells.
CONCLUSIONS: This work reveals that m6A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.

Population-wide impacts of new guidelines in the primary prevention of atherosclerotic cardiovascular disease (ASCVD) should be explored in independent cohorts. Assess and compare the lipid-lowering therapy eligibility and predictive classification performance of 2016 and 2021 European Society of Cardiology (ESC), 2019 American Heart Association/American College of Cardiology (AHA/ACC), and 2022 US Preventive Services Task Force (USPSTF) guidelines.
Participants from the CoLaus|PsyCoLaus study, without ASCVD and not taking lipid-lowering therapy at baseline. Derivation of 10-year risk for ASCVD using Systematic COronary Risk Evaluation (SCORE1), SCORE2 [including SCORE2-Older Persons (SCORE2-OP)], and pooled cohort equation. Computation of the number of people eligible for lipid-lowering therapy based on each guideline and assessment of discrimination and calibration metrics of the risk models using first incident ASCVD as an outcome. Among 4,092 individuals, 158 (3.9%) experienced an incident ASCVD during a median follow-up of 9 years (interquartile range, 1.1). Lipid-lowering therapy was recommended or considered in 40.2% (95% confidence interval, 38.2-42.2), 26.4% (24.6-28.2), 28.6% (26.7-30.5), and 22.6% (20.9-24.4) of women and in 62.1% (59.8-64.3), 58.7% (56.4-61.0), 52.6% (50.3-54.9), and 48.4% (46.1-50.7) of men according to the 2016 ESC, 2021 ESC, 2019 AHA/ACC, and 2022 USPSTF guidelines, respectively. 43.3 and 46.7% of women facing an incident ASCVD were not eligible for lipid-lowering therapy at baseline according to the 2021 ESC and 2022 USPSTF, compared with 21.7 and 38.3% using the 2016 ESC and 2019 AHA/ACC, respectively.
Both the 2022 USPSTF and 2021 ESC guidelines particularly reduced lipid-lowering therapy eligibility in women. Nearly half of women who faced an incident ASCVD were not eligible for lipid-lowering therapy.
Compared with previous European and US guidelines, what are the population-wide impacts of the 2021 European Society of Cardiology (ESC) and 2022 US Preventive Services Task Force (USPSTF) guidelines for primary cardiovascular prevention in terms of lipid-lowering therapy eligibility and risk classification performance?
In a population-based cohort study comprising 4069 adults free from cardiovascular disease and lipid-lowering treatment, the implementation of both guidelines resulted in a lower proportion of treatment-eligible individuals compared with the 2016 ESC and 2019 American Heart Association/American College of Cardiology guidelines, especially among women. In women, nearly half of 10-year incident cardiovascular events occurred in those for whom a lipid-lowering therapy was not recommended. Meanings: The 2021 ESC and 2022 USPSTF guidelines reduced overtreatment but did not improve the identification of individuals who will develop atherosclerotic cardiovascular disease. There is a need to better stratify the cardiovascular risk in women.

BACKGROUND: The assessment of VTE likelihood with VTE risk scores is essential prior to imaging examinations during VTE diagnostic procedure. Little is known with respect to the disparity of predictive power for VTE diagnosis among VTE risk scores in guidelines for nonsurgical hospitalized patients with clinically suspected VTE.
METHODS: A retrospective study was performed to compare the predictive power for VTE diagnosis among the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores in the leading authoritative guidelines in nonsurgical hospitalized patients with suspected VTE.
RESULTS: Among 3168 nonsurgical hospitalized patients with suspected VTE, VTE was finally excluded in 2733(86.3%) ones, whereas confirmed in 435(13.7%) ones. The sensitivity and specificity resulted from the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores were (90.3%, 49.8%), (88.7%, 53.6%), (73.8%, 50.2%), (97.7%,16.9%), (80.9%, 44.0%), and (78.2%, 47.0%), respectively. The YI were 0.401, 0.423, 0.240, 0.146, 0.249, and 0.252 for the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores, respectively. The C-index were 0.694(0.626-0.762), 0.697(0.623-0.772), 0.602(0.535-0.669), 0.569(0.486-0.652), 0.607(0.533-0.681), and 0.609(0.538-0.680) for the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores, respectively. Consistency was significant in the pairwise comparison of Wells vs Geneva(Kappa 0.753, P = 0.565), YEARS vs Padua(Kappa 0.816, P = 0.565), YEARS vs IMPROVE(Kappa 0.771, P = 0.645), and Padua vs IMPROVE(Kappa 0.789, P = 0.812), whereas it did not present in the other pairs. The YI was improved to 0.304, 0.272, and 0.264 for the PERC(AUC 0.631[0.547-0.714], P = 0.006), Padua(AUC 0.613[0.527-0.700], P = 0.017), and IMPROVE(AUC 0.614[0.530-0.698], P = 0.016), with a revised cutoff of 5 or less, 6 or more, and 4 or more denoting the VTE-likely, respectively.
CONCLUSIONS: For nonsurgical hospitalized patients with suspected VTE, the Geneva and Wells scores perform best, the PERC scores performs worst despite its significantly high sensitivity, whereas the others perform intermediately, albeit the absolute predictive power of all isolated scores are mediocre. The predictive power of the PERC, Padua, and IMPROVE scores are improved with revised cutoffs.

Dementia prevention is a global health priority. In 2019, the World Health Organisation published its first evidence-based guidelines on dementia risk reduction. We are now at the stage where we need effective tools and resources to assess dementia risk and implement these guidelines into policy and practice. In this paper we review dementia risk scores as a means to facilitate this process. Specifically, we (a) discuss the rationale for dementia risk assessment, (b) outline some conceptual and methodological issues to consider when reviewing risk scores, (c) evaluate some dementia risk scores that are currently in use, and (d) provide some comments about future directions. A dementia risk score is a weighted composite of risk factors that reflects the likelihood of an individual developing dementia. In general, dementia risks scores have a wide range of implementations and benefits including providing early identification of individuals at high risk, improving risk perception for patients and physicians, and helping health professionals recommend targeted interventions to improve lifestyle habits to decrease dementia risk. A number of risk scores for dementia have been published, and some are widely used in research and clinical trials e.g., CAIDE, ANU-ADRI, and LIBRA. However, there are some methodological concerns and limitations associated with the use of these risk scores and more research is needed to increase their effectiveness and applicability. Overall, we conclude that, while further refinement of risk scores is underway, there is adequate evidence to use these assessments to implement guidelines on dementia risk reduction.

Hypertension, the commonest noncommunicable disease globally, is an important risk factor for cardiovascular disease and renal failure. Theoretically, while it is easy to diagnose and manage by simple measures, practically it has been observed that not only treatment but also diagnosis and its preventive measures are inadequate in developing as well as developed nations. Several guidelines by various international organizations are available to guide clinicians for hypertension management. Though the basic principles of hypertension management are similar in all the guidelines, subtle differences are there. In this article, we compare the two most widely accepted guidelines for hypertension, that is, American College of Cardiology/American Heart Association 2017 Hypertension Guidelines and 2018 European Society of Cardiology and European Society of Hypertension Guidelines on Hypertension. Both the differences and similarities between these two widely followed guidelines are presented.

BACKGROUND: ALT ≥ 80 U/L and HBV DNA ≥ 2000 IU/ml are treatment criteria of APASL guidelines for chronic hepatitis B (CHB) patients. The need of antiviral therapy for patients in gray zone (ALT < 80 U/L or HBV DNA < 2000 IU/ml) is controversial. This study aimed to develop a scoring system to predict hepatocellular carcinoma (HCC) and evaluate the benefit of antiviral therapy in these patients.
METHODS: Seven hundred and forty-nine patients were analyzed. Significant variables were weighted to develop a scoring system for HCC prediction. The area under receiver operating curves (AUROC) were estimated and validated by REVEAL-HBV cohort (n = 3527).
RESULTS: Older age (p < 0.001), male sex (p = 0.036), family history of HCC (p = 0.002) and HBV DNA ≥ 2000 IU/ml (p = 0.045) were independently associated with HCC. A 14-point risk score system predicts 3 and 5-years HCC risk to be 0.866 and 0.868 of AUROC, respectively in the derivation cohort; 0.821 and 0.820, in the REVEAL-HBV cohort. The cumulative HCC incidence was higher in the high risk (score ≥ 8) group both in derivation and validation cohorts (p < 0.001). Patients with antiviral therapy had lower HCC incidence compared to those without (p = 0.016). Of note, antiviral therapy significantly decreased HCC in the high risk group (p = 0.005), but not in the low risk group (p = 0.705).
CONCLUSIONS: A risk scoring system is established and validated. Of CHB patients in gray zone of APASL guidelines, those with risk scores ≥ 8 had higher risk of HCC, but the risk could be significantly reduced by antiviral therapy.

OBJECTIVE: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness.
METHODS: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35-74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: \"Category I (Low risk),\" \"Category II (Middle risk),\" and \"Category III (High risk).\"
RESULTS: The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61-5.43) and 7.33 (4.03-13.3) for males and 3.99 (2.55-6.24) and 3.34 (2.16-5.16) for females, respectively.
CONCLUSIONS: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

Background The cardiac intensive care unit (CICU) population is no longer composed of only patients with acute coronary syndromes, and includes those with acute heart failure and multiple comorbidities. We hypothesized that the GWTG-HF (Get With The Guidelines-Heart Failure) risk score that predicts inpatient mortality in hospitalized patients with heart failure would predict mortality in CICU patients. Methods and Results We retrospectively analyzed CICU patients at a tertiary care hospital from 2007 to 2015. The GWTG-HF risk score was calculated at CICU admission. As a secondary analysis, the EFFECT (Enhanced Feedback for Effective Cardiac Treatment), OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure), and ADHERE (Acute Decompensated Heart Failure National Registry) risk scores were calculated. Kaplan-Meier survival analysis and the area under the receiver operating characteristic curve value were determined for inpatient and 1-year mortality. The GWTG-HF risk score was calculated in 9532 (95%) patients, with a median value of 40 (interquartile range, 35-47). Inpatient mortality occurred in 824 (8.6%) patients, and 2075 (21.8%) patients died by 1 year. Patients who died in hospital had a significantly higher mean GWTG-HF score (47.7 versus 40.2; P<0.001). Inpatient and 1-year mortality increased in each GWTG-HF risk score quartile (P<0.0001). Discrimination of the GWTG-HF, EFFECT, OPTIMIZE-HF, and ADHERE risk scores was assessed using area under the receiver operating characteristic curve values for hospital mortality, and were similar for all risk scores (0.72-0.74; P>0.05). The Hosmer-Lemeshow statistic suggested poor calibration for hospital mortality by the GWTG-HF risk score (P<0.001). Conclusions The GWTG-HF risk score and other heart failure prediction tools demonstrate good discrimination for inpatient and 1-year mortality in a heterogeneous cohort of CICU patients. Our study emphasizes that prognostic variables overlap in cardiac patients, regardless of the admission diagnosis.

To promote uniformity in measuring adherence to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, a reporting guideline for diagnostic and prognostic prediction model studies, and thereby facilitate comparability of future studies assessing its impact, we transformed the original 22 TRIPOD items into an adherence assessment form and defined adherence scoring rules. TRIPOD specific challenges encountered were the existence of different types of prediction model studies and possible combinations of these within publications. More general issues included dealing with multiple reporting elements, reference to information in another publication, and non-applicability of items. We recommend our adherence assessment form to be used by anyone (eg, researchers, reviewers, editors) evaluating adherence to TRIPOD, to make these assessments comparable. In general, when developing a form to assess adherence to a reporting guideline, we recommend formulating specific adherence elements (if needed multiple per reporting guideline item) using unambiguous wording and the consideration of issues of applicability in advance.

Background Patients who have had an acute coronary syndrome ( ACS ) are at increased risk of recurrent cardiovascular events; however, paradoxically, high-risk patients who may derive the greatest benefit from guideline-recommended therapies are often undertreated. The aim of our study was to examine the management, clinical outcomes, and temporal trends of patients after ACS stratified by the Thrombolysis in Myocardial Infarction (TIMI) risk score for secondary prevention, a recently validated clinical tool that incorporates 9 clinical risk factors. Methods and Results Included were patients with ACS enrolled in the biennial Acute Coronary Syndrome Israeli Surveys ( ACSIS ) between 2008 and 2016. Patients were stratified by the TIMI risk score for secondary prevention to low (score 0-1), intermediate (2), or high (≥3) risk. Clinical outcomes included 30-day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Of 6827 ACS patients enrolled, 35% were low risk, 27% were intermediate risk, and 38% were high risk. Compared with the other risk groups, high-risk patients were older, were more commonly female, and had more renal dysfunction and heart failure ( P<0.001 for each). High-risk patients were treated less commonly with guideline-recommended therapies during hospitalization (percutaneous coronary intervention) and at discharge (statins, dual-antiplatelet therapy, cardiac rehabilitation). Overall, high-risk patients had higher rates of 30-day major adverse cardiac events (7.2% low, 8.2% intermediate, and 15.1% high risk; P<0.001) and 1-year mortality (1.9%, 4.6%, and 15.8%, respectively; P<0.001). Over the past decade, utilization of guideline-recommended therapies has increased among all risk groups; however, the rate of 30-day major adverse cardiac events has significantly decreased among patients at high risk but not among patients at low and intermediate risk. Similarly, the 1-year mortality rate has decreased numerically only among high-risk patients. Conclusions Despite an improvement in the management of high-risk ACS patients, they are still undertreated with guideline-recommended therapies. Nevertheless, the outcome of high-risk patients after ACS has significantly improved in the past decade, thus they should not be denied these therapies.