Immune-Related lncRNAs to Construct Novel Signature for Predicting Prognosis in Gastric Cancer

Background: Long non coding RNAs (lncRNAs) have many functions, including immune response. The signal irlncRNAs with no requirement of specific expression level seems to be valuable in predicting the prognosis of patients with gastric cancer (GC). Results: Our results suggested that immune related lncRNA signaling is of great value in predicting prognosis, and it may be possible to measure the response to immunotherapy. This feature may guide the choice of immunotherapy for GC. Conclusion: Immune-related lncRNA signals show independent prognostic significance in GC. These results of this research could predict the prognosis of GC patients without detecting specific expression level of lncRNA, providing a possible method for predicting the survival of GC patients, and providing a potential lncRNA target for immunotherapy.

Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group

Background Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. Methods We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). Results Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40–5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25–0.92, p = 0.026). Both parameters maintained their independent prognostic significance. Conclusions ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. Clinical trial identifier NCT04805099

Grading Evolution and Contemporary Prognostic Biomarkers of Clinically Significant Prostate Cancer

Gleason grading remains the strongest prognostic parameter in localized prostate adenocarcinoma. We have here outlined the evolution and contemporary practices in pathological evaluation of prostate tissue samples for Gleason score and Grade group. The state of more observer-independent grading methods with the aid of artificial intelligence is also reviewed. Additionally, we conducted a systematic review of biomarkers that hold promise in adding independent prognostic or predictive value on top of clinical parameters, Grade group and PSA. We especially focused on hard end points during the follow-up, i.e., occurrence of metastasis, disease-specific mortality and overall mortality. In peripheral blood, biopsy-detected prostate cancer or in surgical specimens, we can conclude that there are more than sixty biomarkers that have been shown to have independent prognostic significance when adjusted to conventional risk assessment or grouping. Our search brought up some known putative markers and panels, as expected. Also, the synthesis in the systematic review indicated markers that ought to be further studied as part of prospective trials and in well characterized patient cohorts in order to increase the resolution of the current clinico-pathological prognostic factors.

Chronic obstructive pulmonary disease in heart failure: influence on circulating biomarkers and outcome

Background Chronic obstructive pulmonary disease (COPD) is common in patients with chronic heart failure (CHF). Purpose We aimed to explore the impact of COPD on HF biomarkers (N-terminal fraction of pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hs-TnT], and soluble suppression of tumorigenesis-2 [sST2]) and outcome. Methods Individual data from 14 cohorts of patients with stable chronic HF and NT-proBNP and hs-TnT values were analysed. Patients with known COPD status were evaluated. Results Patients (n=13,178) were aged 67 years (58–75), 75% males, and 76%, 11%, 13% with HF with reduced, mid-range, or preserved ejection fraction (HFrEF/HFmrEF/HFpEF), respectively. Patients with COPD were older than those without COPD (age 71 years [64–77] vs. 66 [57–75]; p<0.001), more frequently males (79% vs. 74%; p<0.001), had more often ischaemic HF (54% vs. 52%; p<0.001), and HFpEF (14% vs. 12%; p=0.011), but not HFpEF (12% vs. 11%; p=0.097). COPD patients had also more severe dyspnoea (44% in NYHA class III-IV vs. 31%; p<0.001), and slightly worse renal function (median estimated glomerular filtration rate [eGFR] 58 mL/min/1.73 m2 [44–74] vs. 60 [46–67]; p<0.001). Patients with COPD had higher NT-proBNP (1501 ng/L [642–3333] vs. 1225 ng/L [476–2902]; p<0.001), hs-TnT (22 ng/L [13–38] vs. 17 ng/L [9–30]; p<0.001), and sST2 (30 ng/mL [22–45] vs. 29 [21–43]; p<0.001). Over a median follow-up of 2.1 years (1.5–3.7, range 0–18 years), 3,865/12,489 patients (31%) died; among them, 2,443/12,450 (20%) died for cardiovascular causes; 3,373/12,469 patients (27%) were hospitalized for HF over 35 months (15–63, range 0–216 months). Patients with COPD had a significantly higher all-cause mortality, cardiovascular mortality, and worse survival free from HF hospitalization (all p<0.001; Figure). In a model including age, gender, ischaemic vs. non-ischaemic aetiology, eGFR, HFrEF/HFmrEF/HFpEF, and NYHA class III-IV, COPD retained independent prognostic significance from NT-proBNP for 1-year all-cause (p=0.009) and cardiovascular mortality (p=0.022), 5-year all-cause (p<0.001) and cardiovascular mortality (p=0.011) as well as 3- (p=0.033), 6- (p=0.019) and 12-month HF hospitalization (p=0.033). COPD lost its independent prognostic significance when hs-TnT and sST2 were included in the model. Conclusions COPD in HF is characterized by higher NT-proBNP, hs-TnT and sST2 levels. COPD adds prognostic significance over NT-proBNP alone, but not over the combination of NT-proBNP, hs-TnT, and sST2. Funding Acknowledgement Type of funding source: None

Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study

Background: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis is not particularly clear.Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed.Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/ml (P<0.001), ALP>187.5IU/L (P=0.032) and ALB<25g/L (P<0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/ml (P=0.030) and Alb<25g/L (P=0.024). The existence of AL amyloidosis especially the heart involvement was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/ml in symptomatic multiple myeloma having independent prognostic significance (RR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P<0.001).Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent prognostic significance (RR=8.741, P=0.002).Conclusions: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma is mainly because involvements of important organs especially the heart. AL amyloidosis probablely has a greater impact on the prognosis of smoldering multiple myeloma than symptomatic multiple myeloma.

P1653Admission high-sensitivity troponin T and NT-proBNP for outcome prediction in acute heart failure

Background High-sensitivity troponin T (hs-TnT) reflects the severity of ongoing myocardial damage and holds independent prognostic significance in chronic heart failure (HF). In acute HF (AHF), its additive prognostic value over natriuretic peptides is unclear. Methods Individual data of 1571 AHF patients with admission hs-TnT were collected from 3 cohorts. Results Patients were aged 78±10 years, and 51% were men. Median hs-TnT and N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP) concentrations were 43 ng/L (interquartile interval 26–69) and 5660 (2693–12466), respectively. Patients experiencing in-hospital death (n=187, 13%) had significantly higher hs-TnT and NT-proBNP on admission (both p<0.001). The risk of in-hospital death increased by 45% per each doubling of hs-TnT (HR 1.45, 95% confidence interval - CI 1.31–1.59, p<0.001), and by 32% per each doubling of NT-proBNP (HR 1.32, 95% CI 1.17–1.50, p<0.001). Patients with hs-TnT ≥43 ng/L and NT-proBNP ≥5660 ng/L had a 2.7-fold higher risk of in-hospital death (relative risk - RR 2.7, 95% CI 1.7–4.5). Among the 1262 patients discharged, 1024 deaths occurred over a median 11-month follow-up (4–22). In a model including NT-proBNP, hs-TnT ≥43 ng/L was a strong, independent predictor of all-cause death at 6, 12 and 24 months, and the composite of cardiovascular death or HF hospitalization at 6 and 24 months. hs-TnT ≥43 ng/L also improved risk reclassification. Conclusions The risk of in-hospital death is almost 3 folds higher with admission hs-TnT ≥43 ng/L and NT-proBNP ≥5660 ng/L, and hs-TnT ≥43 ng/L holds strong independent prognostic significance for post-discharge outcome.

Impact of smokeless tobacco products on myocardial infarction and stroke and it’s prognostic significance

Background: The use of smokeless tobacco (SLT) predates smoking and its effects on the health of the individuals is very much similar tobacco smoking. The present study was done with the aim to find out independent prognostic significance of ST products on disease outcome like myocardial infarction and stroke.Methods: This prospective study was done on the patients attending to the Department of Internal Medicine, Institute of Medical Sciences and SUM Hospital, Bhubaneswar with complaints suggesting of coronary artery disease and stroke during the period from July 2016 to June 2018. The exposure of risk factors and confounding factors are detailed and collected from the patients by using predesigned questionnaire. All the data was analysed by using SPSS version 20.Results: During the study period a total of 423 patients were included in the study. Mean average age of the participants was 56.58±11.23 years. Male preponderance was seen in the study. Out of total patients, myocardial infarction was noticed in 49 and stroke in 64 patients. SLT was used by 323 (76.4%) users. Among SLT both gutkha and pan was most commonly used (55.6%). Among them hypertension and diabetes were seen in 193 and 184 patients respectively. Risk of incidence of CVA and stroke was found to be more among SLT users compared to non-users.Conclusions: SLT is considered to be an important etiological factor for the incidence of myocardial infarction and stroke. There is an urgent need to increase clinical interventions and awareness in public to decrease SLT addiction.

Right Ventricular Function in Left Heart Disease

Right ventricular (RV) function is an independent prognostic factor for short- and long-term outcomes in cardiac surgical patients. Patients with mitral valve (MV) disease are at increased risk of RV dysfunction before and after MV operations. Yet RV function is not part of criteria for decision making or risk stratification in this setting. The role of MV disease in the development of pulmonary hypertension (PHTN) and the ultimate impact of PHTN on RV function have been well described. Nonetheless, there are other mechanisms by which MV disease and MV surgery affect RV performance. Research suggests that PHTN may not be the most important determinant of RV dysfunction. Both RV dysfunction and PHTN have independent prognostic significance. This review explores the unique anatomic and functional features of the RV and the pathophysiologic and prognostic implications of RV dysfunction in patients with MV disease in the perioperative period.