Identification and Comprehensive Prognostic Analysis of a Novel Chemokine-Related lncRNA Signature and Immune Landscape in Gastric Cancer

Gastric cancer (GC) is a malignant tumor with poor survival outcomes. Immunotherapy can improve the prognosis of many cancers, including GC. However, in clinical practice, not all cancer patients are sensitive to immunotherapy. Therefore, it is essential to identify effective biomarkers for predicting the prognosis and immunotherapy sensitivity of GC. In recent years, chemokines have been widely reported to regulate the tumor microenvironment, especially the immune landscape. However, whether chemokine-related lncRNAs are associated with the prognosis and immune landscape of GC remains unclear. In this study, we first constructed a novel chemokine-related lncRNA risk model to predict the prognosis and immune landscape of GC patients. By using various algorithms, we identified 10 chemokine-related lncRNAs to construct the risk model. Then, we determined the prognostic efficiency and accuracy of the risk model. The effectiveness and accuracy of the risk model were further validated in the testing set and the entire set. In addition, our risk model exerted a crucial role in predicting the infiltration of immune cells, immune checkpoint genes expression, immunotherapy scores and tumor mutation burden of GC patients. In conclusion, our risk model has preferable prognostic performance and may provide crucial clues to formulate immunotherapy strategies for GC.

Improved evaluation of left ventricular hypertrophy using the spatial QRS-T angle by electrocardiography

Background: Conventional electrocardiographic (ECG) signs of left ventricular hypertrophy lack sensitivity, The aim was to identify LVH based on an abnormal spatial peaks QRS-T angle, and evaluate its diagnostic and prognostic performance compared to that of conventional ECG criteria for LVH. Methods: This was an observational study with four cohorts, all with a QRS duration <120 ms: (1) Healthy volunteers to define normality (n=921), (2) Separate healthy volunteers to compare test specificity (n=461), (3) Patients with at least moderate LVH by cardiac imaging (Imaging-LVH) to compare test sensitivity (n=225), and (4) Patients referred for cardiovascular magnetic resonance imaging to evaluate the combined outcome of hospitalization for heart failure or all-cause death (Clinical-Consecutive, n=783). Results: An abnormal spatial peaks QRS-T angle was defined as exceeding the upper limit of normal, which was found to be ≥40° for females and ≥55° for males. In healthy volunteers, the specificity of the QRS-T angle to detect LVH was 96% (females) and 98% (males). In Imaging-LVH, the QRS-T angle had a higher sensitivity to detect LVH than conventional ECG criteria (93-97% vs 13-56%, p<0.001 for all). In Clinical-Consecutive, of those who did not have any LVH, 238/556 (43%) had an abnormal QRS-T angle, suggesting it can occur even without LVH. There was an association with outcomes in univariable analysis for the QRS-T angle, Cornell voltage, QRS duration, and Cornell product (hazard ratios 1.68-2.5, p<0.01 for all) that persisted in multivariable analysis only for the QRS-T angle and QRS duration (p<0.001 for both). Conclusions: An increased QRS-T angle rarely occurred in healthy volunteers, was a mainstay of moderate or greater LVH, was common in clinical patients without LVH but with cardiac co-morbidities, associated with outcomes. Thus, an increased QRS-T angle identifies left ventricular electrical remodeling that can occur in the absence of LVH detected by imaging. The improved diagnostic and independent prognostic performance for the QRS-T angle suggests that it should be investigated when ECGs are evaluated.

Patterns of Organ Dysfunction in Critically Ill Children Based on PODIUM Criteria

OBJECTIVES The goal of this study was to determine the incidence, prognostic performance, and generalizability of the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) organ dysfunction criteria using electronic health record (EHR) data. Additionally, we sought to compare the performance of the PODIUM criteria with the organ dysfunction criteria proposed by the 2005 International Pediatric Sepsis Consensus Conference (IPSCC). METHODS Retrospective observational cohort study of critically ill children at 2 medical centers in the United States between 2010 and 2018. We assessed prevalence of organ dysfunction based on the PODIUM and IPSCC criteria for each 24-hour period from admission to 28 days. We studied the prognostic performance of the criteria to discriminate in-hospital mortality. RESULTS Overall, 22 427 PICU admissions met inclusion criteria, and in-hospital mortality was 2.3%. The cumulative incidence of each PODIUM organ dysfunction ranged from 15% to 30%, with an in-hospital mortality of 6% to 10% for most organ systems. The number of concurrent PODIUM organ dysfunctions demonstrated good-to-excellent discrimination for in-hospital mortality (area under the curve 0.87–0.93 for day 1 through 28) and compared favorably to the IPSCC criteria (area under the curve 0.84–0.92, P &lt; .001 to P = .06). CONCLUSIONS We present the first evaluation of the PODIUM organ dysfunction criteria in 2 EHR databases. The use of the PODIUM organ dysfunction criteria appears promising for epidemiologic and clinical research studies using EHR data. More studies are needed to evaluate the PODIUM criteria that are not routinely collected in structured format in EHR databases.

Cardiac and aortic size measures in adult echocardiography should be indexed by body surface area regardless of body mass index

BACKGROUNDBody size indexation is a foundation of the diagnostic interpretation of cardiac size measures used in imaging assessment of cardiovascular health. Body surface area (BSA) is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (body mass index (BMI) <18·5 kg/m2 or ≥30 kg/m2, respectively). We hypothesized that mortality can be used to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than BSA regardless of BMI.METHODSIn this big data, cohort study, adult patients with no prior valve replacement were selected from the National Echo Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint.FINDINGSIndexation of echocardiographic measures (left ventricular diameter [n=337,481] and mass [n=330,959], left atrial area [n=136,989], aortic sinus diameter [n=125,130], right atrial area [n=81,699], right ventricular diameter [n=3,575], right ventricular outflow tract diameter [n=2,841]) by BSA had better prognostic performance vs unindexed measures (healthy/overweight: C-statistic 0·656 vs 0·618, average change in Akaike Information Criteria (ΔAIC) 800; underweight: C-statistic 0·669 vs 0·654, ΔAIC 15; obese: C-statistic 0·630 vs 0·612, ΔAIC 113). Indexation by other body size metrics (lean body mass or height and/or weight raised to various powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase ≤0·01), with smaller differences in higher BMI subgroups. Similar results were obtained using sex-disaggregated analysis, for indexation of other aortic or cardiac dimension or volume measures, and for all-cause mortality.INTERPRETATIONIndexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance.FUNDINGThis research was supported in part by grants (PI Ugander) from New South Wales Health, Heart Research Australia, and the University of Sydney.

Prognostic Performance of Alternative Lymph Node Classification Systems for Patients with Medullary Thyroid Cancer: A Single Center Cohort Study

Background Lymph node ratio (LNR) and the log odds of positive lymph nodes (LODDS) have been proposed as alternative lymph node (LN) classification schemes. Various cut-off values have been defined for each system, with the question of the most appropriate for patients with medullary thyroid cancer (MTC) still remaining open. We aimed to retrospectively compare the predictive impact of different LN classification systems and to define the most appropriate set of cut-off values regarding accurate evaluation of overall survival (OS) in patients with MTC. Methods 182 patients with MTC who were operated on between 1985 and 2018 were extracted from our medical database. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 28 LNR and 28 LODDS classifications and compare them with the N category according to the 8th edition of the AJCC/UICC TNM classification in terms of discriminative power. Regression models were adjusted for age, sex, T category, focality, and genetic predisposition. Results High LNR and LODDS are associated with advanced T categories, distant metastasis, sporadic disease, and male gender. In addition, among 56 alternative LN classifications, only one LNR and one LODDS classification were independently associated with OS, regardless of the presence of metastatic disease. The C-statistic demonstrated comparable results for all classification systems showing no clear superiority over the N category. Conclusion Two distinct alternative LN classification systems demonstrated a better prognostic performance in MTC patients than the N category. However, larger scale studies are needed to further verify our findings.

Evaluating the prognostic performance of a polygenic risk score for breast cancer risk stratification

Background Polygenic risk scores (PRS) could potentially improve breast cancer screening recommendations. Before a PRS can be considered for implementation, it needs rigorous evaluation, using performance measures that can inform about its future clinical value. Objectives To evaluate the prognostic performance of a regression model with a previously developed, prevalence-based PRS and age as predictors for breast cancer incidence in women from the Estonian biobank (EstBB) cohort; to compare it to the performance of a model including age only. Methods We analyzed data on 30,312 women from the EstBB cohort. They entered the cohort between 2002 and 2011, were between 20 and 89 years, without a history of breast cancer, and with full 5-year follow-up by 2015. We examined PRS and other potential risk factors as possible predictors in Cox regression models for breast cancer incidence. With 10-fold cross-validation we estimated 3- and 5-year breast cancer incidence predicted by age alone and by PRS plus age, fitting models on 90% of the data. Calibration, discrimination, and reclassification were calculated on the left-out folds to express prognostic performance. Results A total of 101 (3.33‰) and 185 (6.1‰) incident breast cancers were observed within 3 and 5 years, respectively. For women in a defined screening age of 50–62 years, the ratio of observed vs PRS-age modelled 3-year incidence was 0.86 for women in the 75–85% PRS-group, 1.34 for the 85–95% PRS-group, and 1.41 for the top 5% PRS-group. For 5-year incidence, this was respectively 0.94, 1.15, and 1.08. Yet the number of breast cancer events was relatively low in each PRS-subgroup. For all women, the model’s AUC was 0.720 (95% CI: 0.675–0.765) for 3-year and 0.704 (95% CI: 0.670–0.737) for 5-year follow-up, respectively, just 0.022 and 0.023 higher than for the model with age alone. Using a 1% risk prediction threshold, the 3-year NRI for the PRS-age model was 0.09, and 0.05 for 5 years. Conclusion The model including PRS had modest incremental performance over one based on age only. A larger, independent study is needed to assess whether and how the PRS can meaningfully contribute to age, for developing more efficient screening strategies.

632 Diagnostic and prognostic performance of HFA-PEFF and H2FpEF scores in patients with cardiac amyloidosis

Aims HFA-PEFF and H2FPEF scores were developed to aid the diagnosis of heart failure with preserved ejection fraction (HFpEF) and have been associated with outcomes. We aimed to investigate the diagnostic and prognostic significance of these scores in patients with a specific phenotype of HFpEF, cardiac amyloidosis (CA). Methods and results In a retrospective, double-centre, observational study we included 171 patients with either transthyretin (ATTR) (n = 89, 52%) or light-chain (AL) (n = 82, 48%) cardiac amyloidosis and preserved left ventricular ejection fraction (LVEF). Patients were divided into three groups according to HFA-PEFF score (low, 0–1; intermediate 2–4; high 5–6) and H2FPEF score (low, 0–1; intermediate 2–5; high 6–9). None of the patients had a HFA-PEFF score of 0 or 1 (n = 0, 0%); 57 (33.3%) patients had HFA-PEFF score 2–4 and the majority (n = 114, 66.7%) had a high HFA-PEFF score. Twenty-eight (16.4%), 104 (60.8%), 39 (22.8%) patients had low, intermediate, and high H2FPEF score, respectively. During a median follow-up of 14.5 (6.5–30.2) months after diagnosis, 61 (35.7%) patients died. Patients with a high HFA-PEFF score had higher mortality, compared to those with an intermediate score (47.4% vs. 12.3%, P &lt; 0.001). After adjustment for several clinical variables, including age, sex, comorbidities, natriuretic peptides, troponin levels and echocardiographic parameters, a high HFA-PEFF score was independently associated with mortality (HR: 3.75; 95% CI: 1.61–8.70; P = 0.005). H2FPEF score was not significantly associated with outcomes. Conclusions Our results suggest that a low HFA-PEFF score successfully rules out CA diagnosis, whereas some CA patients present a low H2FPEF score, potentially misleading the diagnosis. HFA-PEFF but not H2FPEF score was associated with outcome in patients with CA.