Clinical Endpoint Events Research Articles

Soluble ST2 for predicting heart failure, atrial fibrillation and death in patients with coronary heart disease with or without renal insufficiency

BackgroundThis study aimed to investigate the relationship between baseline soluble suppression of tumorigenesis-2 (sST2) concentration and the outcomes of heart failure (HF), atrial fibrillation (AF) or death in patients with coronary heart disease (CHD) with or without renal insufficiency (RI). MethodsBetween March 2011 and December 2015, 3454 patients with CHD from the Chinese PLA General Hospital were enrolled in this cohort study. The patients were followed up until October 2021. AF, HF, and death events were recorded. Associations between baseline sST2 concentrations and clinical outcomes were assessed using Kaplan-Meier (K-M) curves, and Cox regression and generalised additive models. Subgroup analysis were carried out between RI and non-RI groups. ResultsAmong the patients with CHD (61.5 ± 11.8 years; 78.6 % men), 415 (12.02 %) had RI. During a median follow-up of 8.37 years, HF and AF were reported in 216 (6.25 %) and 174 (5.04 %) patients, respectively, and 297 (8.60 %) died. The K-M curves indicated that patients in the higher quartiles of sST2 concentrations were correlated with a poor survival rate of HF, AF, or death (all Ps < 0.001). Generalised additive model (GAM) demonstrated a nonlinear positive association between sST2 concentration and the risk of HF, AF, and death in CHD patients. The cut-off value of sST2 for predicting HF, AF and death were 32.1, 25.4 and 28.6 ng/mL, respectively. CHD patients with sST2 higher than the cut-off value had higher risks of HF (HR: 3.02, 95%CI: 2.24–4.05), AF (HR: 2.86; 95%CI: 2.10–3.90), and death (HR:2.11, 95%CI: 1.67–2.67). Furthermore, in patients with RI (12.02 %, n = 415), the prognostic value of sST2 over the cut-off value for HF and death remained unchanged (HR: 3.21 and 2.35; P < 0.05). In patients with CHD with or without RI, sST2 improved the area under the curve (AUC) of traditional risk models for predicting clinical endpoint events. ConclusionsThe biomarker sST2 may be useful for predicting HF, AF, and death in patients with CHD. The predicted value was not affected by renal function.

MIR145 Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome.

The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non-muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.

Prediction of survival and analysis of prognostic factors for patients with AFP negative hepatocellular carcinoma: a population-based study

PurposeHepatocellular carcinoma (HCC) has a poor prognosis, and alpha-fetoprotein (AFP) is widely used to evaluate HCC. However, the proportion of AFP-negative individuals cannot be disregarded. This study aimed to establish a nomogram of risk factors affecting the prognosis of patients with AFP-negative HCC and to evaluate its diagnostic efficiency.Patients and methodsData from patients with AFP-negative initial diagnosis of HCC (ANHC) between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database for model establishment and validation. We randomly divided overall cohort into the training or validation cohort (7:3). Univariate and multivariate Cox regression analysis were used to identify the risk factors. We constructed nomograms with overall survival (OS) and cancer-specific survival (CSS) as clinical endpoint events and constructed survival analysis by using Kaplan-Meier curve. Also, we conducted internal validation with Receiver Operating Characteristic (ROC) analysis and Decision curve analysis (DCA) to validate the clinical value of the model.ResultsThis study included 1811 patients (1409 men; 64.7% were Caucasian; the average age was 64 years; 60.7% were married). In the multivariate analysis, the independent risk factors affecting prognosis were age, ethnicity, year of diagnosis, tumor size, tumor grade, surgery, chemotherapy, and radiotherapy. The nomogram-based model related C-indexes were 0.762 (95% confidence interval (CI): 0.752–0.772) and 0.752 (95% CI: 0.740–0.769) for predicting OS, and 0.785 (95% CI: 0.774–0.795) and 0.779 (95% CI: 0.762–0.795) for predicting CSS. The nomogram model showed that the predicted death was consistent with the actual value. The ROC analysis and DCA showed that the nomogram had good clinical value compared with TNM staging.ConclusionThe age(HR:1.012, 95% CI: 1.006–1.018, P-value < 0.001), ethnicity(African-American: HR:0.946, 95% CI: 0.783–1.212, P-value: 0.66; Others: HR:0.737, 95% CI: 0.613–0.887, P-value: 0.001), tumor diameter(HR:1.006, 95% CI: 1.004–1.008, P-value < 0.001), year of diagnosis (HR:0.852, 95% CI: 0.729–0.997, P-value: 0.046), tumor grade(Grade 2: HR:1.124, 95% CI: 0.953–1.326, P-value: 0.164; Grade 3: HR:1.984, 95% CI: 1.574–2.501, P-value < 0.001; Grade 4: HR:2.119, 95% CI: 1.115–4.027, P-value: 0.022), surgery(Liver Resection: HR:0.193, 95% CI: 0.160–0.234, P-value < 0.001; Liver Transplant: HR:0.102, 95% CI: 0.072–0.145, P-value < 0.001), chemotherapy(HR:0.561, 95% CI: 0.471–0.668, P-value < 0.001), and radiotherapy(HR:0.641, 95% CI: 0.463–0.887, P-value:0.007) were independent prognostic factors for patients with ANHC. We developed a nomogram model for predicting the OS and CSS of patients with ANHC, with a good predictive performance.

Direct oral anticoagulants compared with warfarin in patients with left ventricular thrombus: a cohort study from China.

Current guidelines recommend vitamin K antagonist (VKA) for left ventricular (LV) thrombus. This study aimed to compare the effectiveness and safety of direct oral anticoagulant (DOAC) and warfarin in Chinese patients with LV thrombus. Patients with LV thrombus admitted to Beijing Anzhen Hospital of Capital Medical University between January 2018 and January 2022, were enrolled in this cohort study. The primary endpoint was defined as thrombus resolution within 90 days. The secondary endpoints included thrombus resolution within 180 days, major bleeding events, and minor bleeding events. All patients were followed up for at least 90 days after diagnosis of LV thrombus. Patients were divided into the VKA and DOAC groups according to the anticoagulants. Differences in clinical endpoint events between the two groups were compared. This study included 129 and 111 patients in the VKA and DOAC groups, respectively. After adjusting for gender and smoking status, no significant difference was observed in thrombus resolution within 90 days between the VKA and DOAC groups. Additionally, there was no difference between the two groups in the secondary endpoints of thrombus resolution within 180 days, major bleeding, and minor bleeding. In subgroup analysis, rivaroxaban and dabigatran did not show significant differences in primary and secondary endpoints. This study showed no significant difference in thrombus resolution between DOAC and warfarin. DOAC might be an alternative to warfarin for the treatment of LV thrombus. However, further large prospective studies are required to explore the efficacy and safety of DOAC in patients with LV thrombus.

Regression of Liver Fibrosis in Patients on Hepatitis B Therapy Is Associated With Decreased Liver-Related Events

Background and AimsLiver fibrosis in patients with chronic hepatitis B (CHB) can regress with successful antiviral therapy. However, the long-term clinical benefits of fibrosis regression have not been fully elucidated. This study investigated the association between biopsy-proven fibrosis regression by P-I-R score and liver-related events (LREs) in CHB patients. MethodsPatients with on-treatment liver biopsy and significant fibrosis/cirrhosis (Ishak ≥ stage 3) were included in this analysis. Fibrosis regression was evaluated according to the P-I-R score of the Beijing Classification. LREs were defined as decompensations, hepatocellular carcinoma (HCC), liver transplantation, or death. Cox proportional hazards model was used to determine associations of fibrosis regression with LREs. ResultsA total of 733 patients with Ishak stage 3/4 (n = 456, 62.2%) and cirrhosis (Ishak stage 5/6, n = 277, 37.8%) by on-treatment liver biopsy were enrolled. According to the P-I-R score, fibrosis regression, indeterminate and progression were observed in 314 (42.8%), 230 (31.4%), and 189 (25.8%) patients, respectively. The 7-year cumulative incidence of LREs was 4.1%, 8.7%, and 18.1% in regression, indeterminate, and progression, respectively (Log-rank, P < .001). Compared to patients with fibrosis progression, those with fibrosis regression had a lower risk of LREs (adjusted HR = 0.40, 95%CI: 0.16-0.99, P = .047), followed by indeterminate group (adjusted HR = 0.86, 95%CI: 0.40 - 1.85, P = .691). Notably, this favorable association was also observed in patients with cirrhosis or low platelet counts (< 150×109/L). ConclusionsAntiviral therapy-induced liver fibrosis regression assessed by P-I-R score is associated with reduced liver-related events. This shows the utility of histologic fibrosis regression assessed by on-treatment P-I-R score as a surrogate endpoint for clinical events in patients with HBV-related fibrosis or early cirrhosis.

Loss of Mir-221/222 Cluster Expression Results in Short-Term Disease Progression and Poor Post-Treatment Outcome in Multiple Myeloma

Despite the notable progress that has been achieved in the realm of MM treatment, the persistence of elevated relapse rates and therapy resistance remain a substantial hindrance to effective management of the patients. Therefore, the development of modern tools to ameliorate patients' prognosis and predict treatment outcome is of first clinical priority. MicroRNAs (miRNAs) have emerged as powerful post-transcriptional regulators of gene expression, while recent advances in high-throughput sequencing techniques have unveiled their prognostic utility in numerous pathologies. Herein, using a miRNA-seq we have investigated miRNA profiles in association with Revised International Staging System (R-ISS), aiming to reveal potential MM-related miRNAs able to improve patients' risk stratification. Bone marrow (BM) aspiration samples were collected from 120 MM patients at diagnosis (screening cohort). Mononuclear cells were isolated using Ficoll-Paque, while CD138 + plasma cells were positively selected using anti-CD138 mAbs magnetic beads. miRNA-seq was performed in CD138 + cells from 8 R-ISS I, 8 R-ISS II and 8 R-ISS III MM patients. Following 3‘-end polyadenylation of total RNA, miR-221/222 levels were quantified in our screening cohort by RT-qPCR. Disease progression (relapse and/or death) and patients’ mortality were assessed as clinical endpoint events, while internal validation was accomplished by bootstrap Cox proportional regression analysis. Aash et al. 2023 (n=86) and Kruykov et al. 2016 (n=149) served as external validation cohorts. miRNA-seq revealed miR-221/222 to be concurrently downregulated in R-ISS III versus R-ISS I/II MM patients (miR-221: FC=0.356; miR-222: FC=0.357; Fig.1B,C). The analysis of our screening cohort documented that CD138 + miR-221/222 loss is significantly associated with higher risk for short-term disease progression ( p=0.010; Fig.1D) and poor survival ( p=0.001; Fig.1E) of MM patients. Furthermore, the analysis of the two independent validation cohorts (Aass et al. cohort A, p=0.019; and Kryukov et al. cohort B, p=0.013) clearly confirmed the worse treatment outcome of the patients with miR-221/222 loss (Fig.1F,G). Moreover, miR-221/222-fitted multivariate models demonstrated the ability of miR-221/222 cluster to ameliorate the clinical routine of the established MM prognostic markers, including “R-ISS stage”, “high-risk cytogenetics” [+1q21, t (4;14) del(17p13), t(14;16), t(11;14), del(13q)] and “response to 1 st line therapy” (IMWG guidelines). In this context, the evaluation of CD138 + miR-221/222 levels significantly improved the risk-stratification of MM patients, resulting in the advanced positive prediction of patients' poor treatment outcome within R-ISS III (PFS: p=0.006, OS: p=0.019; Fig.2A,B) and high-risk cytogenetics groups (PFS: p=0.025, OS: p=0.022; Fig.2C,D). Finally, focusing on patients' response to 1 st line therapy stratification, loss of miR-221/222 could efficiently define optimal (sCR/CR/VGPR) and poor (PR/SD/PD) responders' subgroups (PFS: p&amp;lt;0.001, OS: p&amp;lt;0.001; Fig.2E,F). In conclusion, we identified miR-221/222 loss in CD138 + plasma cells as a powerful independent predictor of patients' risk for disease progression and poor treatment outcome, while miR-221/222-fitted multivariate prognostic models resulted to improved patients' risk-stratification and prediction of MM treatment outcome.

Abstract 15640: Long Term Event-Free Survival in Patients With Ischemic and Non-Ischemic Cardiomyopathy up to Thirteen Years Following Cell-Based Therapy: Results From the Hyperion Observational Cohort

Introduction: The long-term clinical outcomes of cell-based therapies to treat ischemic (ICM) and non-ischemic dilated cardiomyopathy (NIDCM) are unknown. We therefore prospectively followed patients (pts) with ICM/NICDM treated by targeted transcatheter endocardial mesenchymal stromal cell (MSC) injections (TESI). Methods: Of the 155 pts enrolled in prior MSC TESI studies, 111 were eligible to be contacted. Of these, 47 (42%) agreed to participate and have periodic follow-up assessments (Cardiac MRI/CT, 6MWT, labs, PE, EKG, and MLHFq) for up to 13 years following their index procedure. Time-to-event information was captured from all 155 former participants. Endpoints included event-free survival, changes in left ventricular ejection fraction (EF), and ventricular remodeling. Clinical endpoint events were defined as the composite of: Death (all-cause mortality), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Descriptive statistics were used to classify the sample, and Kaplan-Meier survival analysis was generated to examine time-to-event trends. Results: There were 134 men and 21 women, mean age 60.0±11.0 years, including 121 (78%) with ICM, and 34 (22%) with NIDCM. In pts with ICM, mean EF at baseline was 31 %±10.8% and after 1 year was 32.6%±11.8% (P=0.08). In pts with NIDCM baseline EF was 27%±10% and increased to 34%±13% after 1 year (P=0.002). Overall, 40% of pts had a decrease in LVEF, 26% had &lt;5% increase, 34% had a ≥5% increase, and 17% had a ≥10% increase in LVEF after 1 year. Increases of ≥5% LVEF post-therapy were associated with longer event-free survival in NIDCM (OR: 2.57; 95% CI: 0.6, 11.1) but not ICM (OR: 1.25; 95% CI: 0.4, 3.6). Conversely, reductions in LVEDV were associated with longer event-free survival in ICM (OR: 7.23; 95% CI: 1.9, 27.1) but not NIDCM (OR: 1.88; 95% CI: 0.4, 10.0). Conclusion: In this long-term observational cohort analysis, improvement of EF and/or reduction in LVEDV was associated with survival benefits among pts with NIDCM and ICM respectively. Future studies are needed with placebo controls to determine which pts are most likely to respond to MSC therapy. Clinical Trial Registration: URL: http://www.clinicaltrials.gov.; Unique ID: NCT03071835.

Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

The contributionof genotype-guided selection of P2Y12 inhibitor on prognosis in ACS /CCS patients undergoing percutaneous coronary intervention: aretrospective cohort study.

We aimed to explore the contribution of genotype-guided selection of P2Y12 inhibitors on prognosis in Chinese patients with acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Totally, 2063 patients were included. They were divided into empiric treatment group (n = 1025) and individualized treatment group (n = 1038) depending on whether taken CYP2C19 genetic testing. The incidences of clinical endpoint events were compared in two groups at 1-year follow-up. The effective endpoint events were major adverse cardiovascular events (MACEs), including all-cause mortality, in-stent restenosis, nonfatal myocardial infarction, nonfatal stroke and severe recurrent ischemia. Meanwhile, the safe endpoint was bleeding events defined by the Bleeding Academic Research Consortium (BARC) criteria. Finally, 66.83% patients were diagnosed with ACS and 33.17% patients were diagnosed with CCS in empiric group. 68.11% patients were diagnosed with ACS and 31.89% patients were diagnosed with CCS in individualized group. At 1-year follow-up, individualized group showed lower MACEs rate than empiric group (19.61% vs. 10.69%, HR: 1.915; 95% CI: 1.534 to 2.392; P < 0.0001, log-rank test; adjusted HR: 1.983; 95% CI: 1.573 to 2.501; P = 0.000, cox proportional hazards regression models), while bleeding events were significantly less common in empiric group than in individualized group (7.32% vs. 10.40%, HR: 0.693; 95% CI: 0.519 to 0.926; P = 0.0132, log-rank test; adjusted HR: 0.695; 95% CI: 0.518 to 0.933; P = 0.016, cox proportional hazards regression models). It was mainly manifested in BARC class 1 bleeding, which did not warrant the interruption of antiplatelet therapy (ITA). Further, subgroup analyses illustrated that no significant difference existed in cumulative MACEs-free survival rate between all treatment arms of individualized group (P = 0.6579 by log-rank test), and CYP2C19 intermediate metabolizer (IM) genetype appeared to be significantly associated with bleeding events for patients treated with ticagrelor (clopidogrel vs. ticagrelor: 6.80% vs. 14.88%; adjusted HR:0.440; 95% CI: 0.246 to 0.787; adjusted P = 0.006). Genotype-guided selection of P2Y12 inhibitor made a very positive contribution on the prognosis in Chinese ACS/CCS patients undergoing PCI. Instead of intensifying antiplatelet strategies, conventional-dose clopidogrel could be recommended as P2Y12 inhibitor after weighing MACEs and bleeding events in CYP2C19 IM patients.

Effect of different blood pressure levels on short-term outcomes in hospitalized heart failure patients

BackgroundTo investigate the influence of blood pressure (BP) level on short-term prognosis of heart failure (HF), the effect of the BP level on clinical end point events 3 months after discharge was observed. MethodsA retrospective cohort study was performed on 1492 hospitalized HF patients. All patients were divided according to systolic blood pressure (SBP) per 20 mmHg and diastolic blood pressure (DBP) per 10 mmHg. Logistic regression analysis was used to analyze the relationship between BP level and heart failure rehospitalization, cardiac death, all-cause death and a composite end point of heart failure rehospitalization/all-cause death at 3 month follow-up after discharge. ResultsAfter multivariable adjustment, the relationship between SBP and DBP levels and outcomes followed an inverted J curve relationship. Compared with the reference group (110 < SBP≤130 mmHg), the risk of all end point events significantly increased in the SBP≤90 mmHg group included heart failure rehospitalization (OR 8.16, 95%CI 2.88–23.11, P < 0.001), cardiac death (OR 5.43, 95%CI 1.97–14.96, P = 0.001), all-cause death (OR 4.85, 95%CI 1.76–13.36, P = 0.002), and composite end point (OR 2.76, 95%CI 1.03–7.41, P = 0.044). SBP>150 mmHg significantly increased the risk of heart failure rehospitalization (OR 2.67, 95%CI 1.15–6.18, P = 0.022). Compared with.the reference group (65 < DBP≤75 mmHg), cardiac death (OR 2.64, 95%CI 1.15–6.05, P = 0.022) and all-cause death (OR 2.67, 95%CI 1.20–5.93, P = 0.016) was significantly increased in DBP≤55 mmHg group. There was no significant difference among subgroups according to left ventricular ejection fraction (P > 0.05). ConclusionsThere is a significant difference in the short-term prognosis 3 months after discharge in HF patients with different BP levels at discharge. There was an inverted J curve relationship between BP levels and prognosis.

Clinical Efficacy Protocol of Yinhuapinggan Granules: A Randomized, Double-Blind, Parallel, and Controlled Clinical Trial Program for the Intervention of Community-Acquired Drug-Resistant Bacterial Pneumonia as a Complementary Therapy.

Background: Community-acquired bacterial pneumonia (CABP) is an important health care concern in the worldwide, and is associated with significant morbidity, mortality, and health care expenditure. Streptococcus pneumoniae is the most frequent causative pathogen of CABP. Common treatment for hospitalized patients with CABP is empiric antibiotic therapy using β-lactams in combination with macrolides, respiratory fluoroquinolones, or tetracyclines. However, overuse of antibiotics has led to an increased incidence of drug-resistant S. pneumoniae, exacerbating the development of community-acquired drug-resistant bacterial pneumonia (CDBP) and providing a challenge for physicians to choose empirical antimicrobial therapy. Methods: Traditional Chinese medicine (TCM) is widely used as a complementary treatment for CDBP. Yinhuapinggan granules (YHPG) is widely used in the adjuvant treatment of CDBP. Experimental studies and small sample clinical trials have shown that YHPG can effectively reduce the symptoms of CDBP. However, there is a lack of high-quality clinical evidence for the role of YHPG as a complementary drug in the treatment of CDBP. Here, we designed a randomized, double-blind, placebo-controlled clinical trial to explore the efficacy and safety of YHPG. A total of 240 participants will be randomly assigned to the YHPG or placebo group in a 1:1 ratio. YHPG and placebo will be added to standard treatment for 10 days, followed by 56 days of follow-up. The primary outcome is the cure rate of pneumonia, and the secondary outcomes includes conversion rate of severe pneumonia, lower respiratory tract bacterial clearance, lactic acid (LC) clearance rate, temperature, C-reactive protein (CRP), criticality score (SMART-COP score), acute physiological and chronic health assessment system (APACHEII score) and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed according to a pre-defined statistical analysis plan. This research will disclose the efficacy of YHPG in acquired drug-resistant pneumonia. Clinical Trial Registration: https://clinicaltrials.gov, identifier ChiCTR2100047501

Long-term prognosis of patients with hepatitis B virus\u2013related acute-on-chronic liver failure: a retrospective study

BackgroundThe long-term prognosis of patients with hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF) is not well characterised. We assessed long-term outcomes and the associated risk factors of HBV-ACLF patients in southern China.MethodsWe retrospectively analysed clinical data, adverse events, and clinical endpoint events of HBV-ACLF patients treated at our department between January 2014 and December 2018.ResultsA total of 616 (52.3%) patients with cirrhosis and 561 (47.7%) patients without cirrhosis were included. In 973 (83%) patients, the disease was associated only with HBV, while 204 (17%) patients had two or more aetiological factors. The proportion of patients receiving antiviral treatment for HBV was low (20.3%). Further analyses indicated that patients without cirrhosis had a significantly lower 90-day liver transplantation–free mortality and higher 5‐year survival rate than those with cirrhosis (59.5% vs. 27.6%; 62% vs. 36%; P < 0.05). Remarkably, self-withdrawal of nucleos(t)ide analog (NA) was an independent risk factor for short-term prognosis. Age, cirrhosis at admission, and platelet level were closely related to long-term prognosis of HBV-ACLF patients.ConclusionThe proportion of HBV-ACLF patients receiving antiviral treatment is very low in south China. Cirrhosis at admission has a significant effect on both short-term and long-term prognosis. No significant improvement in the short-term prognosis of HBV-ACLF patients was observed compared with previous studies. More comprehensive access to antiviral treatment and long-term surveillance of HBV patients are key imperatives to reduce the incidence of HBV-ACLF and improve the prognosis.Trial Registration The trial was registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565) on May 13, 2020: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009OZY&selectaction=Edit&uid=U00036P1&ts=2&cx=27seqt

Effects of Home-Based Baduanjin Exercise on Left Ventricular Remodeling in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction: Study Protocol for a Randomized Controlled Trial.

BackgroundLeft ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is a major pathological basis associated with heart failure and increased mortality. Exercise-based cardiac rehabilitation has been verified to significantly improve prognosis and quality of life. As a traditional Chinese Qigong, Baduanjin exercise has effectively alleviated adverse LV remodeling in STEMI patients. Despite this, participation in exercise rehabilitation remains low, and home-based exercise rehabilitation may be an alternative approach. Besides, anterior STEMI is reported to have higher risk of adverse LV remodeling. However, the efficiency regarding home-based Baduanjin exercise on LV remodeling in anterior STEMI patients remains uncertain currently.Methods/DesignA single-blind, randomized controlled clinical trial was conducted to explore the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients compared with moderate intensity aerobic walking. A total of 114 participants were assigned randomly to the Baduanjin group or walking control group at a 1:1 ratio. Eligible participants practiced Baduanjin or walking exercise (5 times a week) for 12 weeks, and then followed up for another 12 weeks. The primary outcome is a relative change in the LV end-diastolic volume. The secondary outcomes include the plasma levels of hypersensitive C-reactive protein and interleukin 6, health-related quality of life measured by EQ-5D-5L, LV ejection fraction, patient health questionnaire-9, generalized anxiety disorder screener-7, short physical performance battery score, and clinical endpoint events. The proportion of circulating regulatory T-cells were also assessed. Adverse events were recorded throughout the trial for safety evaluation. Data were be analyzed by researchers blinded to the treatment allocation.DiscussionThis study provided powerful evidence for the use of home-based Baduanjin exercise in anterior STEMI patients in alleviating LV remodeling and improving clinical outcomes.Trial RegistrationThe Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine has approved this study (ZYYECK[2020]045). Written informed consent of patients were required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2100047298).DisseminationOur results will be published in peer-reviewed journals and disseminated through academic conferences and the Internet.

MiRNA-seq and clinical evaluation in multiple myeloma: miR-181a overexpression predicts short-term disease progression and poor post-treatment outcome.

Despite significant advances in multiple myeloma (MM) therapy, disease relapse and treatment resistance remain major obstacles in clinical management. Herein, we have studied the clinical utility of miRNAs in improving patients' risk-stratification and prognosis. miRNA-seq was performed in CD138+ plasma cells of MM, smoldering multiple myeloma (sMM) and monoclonal gammopathy of undetermined significance (MGUS) patients. The screening MM cohort consisted of 138 patients. miRNA levels of CD138+ plasma cells were quantified by RT-qPCR following 3'-end RNA polyadenylation. Disease progression and patients' death were used as clinical end-point events. Internal validation was conducted by bootstrap analysis. Clinical net benefit on disease prognosis was assessed by decision curve analysis. Kruykov et al. 2016 served as validation cohort (n = 151). miRNA-seq highlighted miR-181a to be upregulated in MM vs. sMM/MGUS, and R-ISS III vs. I patients. Screening and validation cohorts confirmed the significantly higher risk for short-term progression and worse survival of the patients overexpressing miR-181a. Multivariate models integrating miR-181a with disease established markers led to superior risk-stratification and clinical benefit for MM prognosis. CD138+ overexpression of miR-181a was strongly correlated with inferior disease outcome and contributed to superior prediction of MM patients early progression, supporting personalised prognosis and treatment decisions.

Experience with various occluder types for endovascular hemodynamic isolation of the left atrium appendage in patients with non-valvular atrial fibrillation

The aimof our study was to evaluate implantation efficacy and safety across various occluder types and to identify factors determining device selection.Methods. This single-site prospective observational study included patients above the age of 40 years with non-valvular atrial fibrillation (AF) and high thromboembolic risk, undergoing endovascular isolation of the left atrium appendage (LAA) with Watchman or Amplatzer Cardiac Plug/Amulet devices. Occluders were implanted to patients without either had contraindications to anticoagulant therapy (ACT) or refused ACT. We evaluated technical aspects of device implantation, short- and long-term outcomes of the intervention over 3 years of follow-up.Results. 90 patients were enrolled in the study (62 into the Watchman arm and 28 into the Amplatzer arm). Interventions were technically successful in 89 cases. In 1 patient (1/90, 1.1%) technical success was not achieved due to device migration (Amplatzer Amulet). The incidence of early (occurring within˂ 24 hours) implantation complications was 0% in the Watchman arm, and 3.6% in the Amplatzer arm (1/28) (р=0.135) (device migration). The cumulative incidence of all in-hospital complications was 11.3% and 14.3%, respectively (р=0.734). No significant differences between arms were found in the incidence of device thrombosis within 90 days post-implantation (3.3% in the Watchman’s arm and 8.3% in the Amplatzer arm, р=0.316). During the observation period, there were no significant differences in comparison groups in the incidence of net clinical efficacy endpoint events (р=0.58). The bleeding rate was 17.7% and 14.3%, respectively, р=0.769. No factors influencing the choice of the device could be identified reliably; however, there was a trend towards Watchman preference for appendage anatomic variants such as broccoli and cactus. Amplatzer was preferred in patients with contraindications to ACT.Conclusion.Implantation of Watchman and Amplatzer Amulet occluders is equally effective and safe in preventing thromboembolism in patients with AF not receiving ACT for various reasons. The individual choice of a device may be influenced by appendage anatomy and indications to occluder implantation.

P-059: miRNA profiling of CD138+ plasma cells identifies miR-181a-5p overexpression as independent predictor of short-term progression and poor treatment outcome in multiple myeloma

<h3>Background</h3> The considerable progress made in multiple myeloma (MM) treatment nowadays resulted in significantly prolonged survival. However, the high heterogeneity of patients' response to treatment outlines the need for novel prognostic molecular markers able to support individualized treatment. microRNAs (miRNAs) have emerged as powerful post-transcriptional regulators of gene expression with a crucial role in cancer, while recent advances in high-throughput techniques have unveiled their prognostic utility. Herein, using a miRNA-seq approach we investigated miRNA profiles in association with MM and its precursor states, aiming to reveal potential MM-related miRNAs able to improve patients' risk stratification. <h3>Methods</h3> Bone marrow aspiration (BMA) samples were collected from 138 MM, 30 smoldering MM (sMM) and 25 monoclonal gammopathy of undetermined significance (MGUS) patients at diagnosis. Mononuclear cells were isolated using Ficoll-Paque, while CD138+ plasma cells were positively selected using magnetic beads with anti-CD138 mAbs. Next, miRNA-seq was performed in CD138+ plasma cells from MGUS (n=4), sMM (n=4) and MM (n=20) patients. Based on miRNA-seq, target prediction and Gene Ontology (GO) enrichment analysis, miR-181a-5p was further evaluated for the first time in CD138+ plasma cells from the total study population. Following RNA extraction and 3'-end polyadenylation, miR-181a-5p levels were quantified using RT-qPCR. Disease progression and patients' death were assessed as clinical endpoint events. Internal validation was performed by bootstrap analysis, while decision curve analysis was utilized to evaluate clinical benefit. Kruykov et al. 2016 served as an external validation cohort (n=151). <h3>Results</h3> miRNA-seq revealed miR-181a-5p to be concurrently upregulated in MM vs. MGUS/sMM as well as R-ISS III vs. R-ISS I patients. Hematopoietic cell differentiation and apoptosis were significantly enriched following GO analysis. In our screening cohort, miR-181a-5p overexpression was associated with a significantly higher risk of short-term disease progression (HR=2.524; p=0.006) and poor overall survival following treatment (HR=2.629; p=0.027) of MM patients. Consistent with our results, Kryukov et al. validation cohort confirmed the inferior survival outcome of the MM patients with elevated miR-181a-5p levels. Finally, multivariate prognostic models incorporating miR-181a-5p with established disease markers, including R-ISS stage and high-risk cytogenetics offered superior risk-stratification specificity and clinical benefit in MM prognosis. More specifically, Kaplan-Meier analysis showed that the combination of R-ISS stage with miR-181a-5p overexpression could provide a better stratification of MM patients' OS (p=0.001) as well as PFS (p=0.016). <h3>Conclusions</h3> We identified miR-181a-5p overexpression in CD138+ plasma cells as a powerful independent predictor of adverse disease outcome and higher risk for post-treatment progression.

Safety and Effectiveness of the SVELTE Fixed-Wire and Rapid Exchange Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Systems for the Treatment of Atherosclerotic Lesions: Results of the OPTIMIZE Randomized Study

[Figure: see text].

Effects of Guanxinshutong Capsules as Complementary Treatment in Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial.

Chronic heart failure (CHF) is a common cardiovascular disease with high mortality and a poor prognosis, which places heavy burdens upon society and families. Traditional Chinese medicine (TCM) has been used extensively as complementary treatment for CHF. Guanxinshutong (GXST) capsules are used commonly for the treatment of coronary heart disease (CHD). Experimental research and small-sample clinical trials have shown that GXST can attenuate CHF. However, the effects of GXST as complementary medicine in CHF treatment lack high-quality clinical evidence. We have designed a multicenter, randomized, double-blind, placebo-controlled clinical trial that explores the efficacy and safety of using GXST compared with placebo for patients with CHF with reduced left ventricular ejection fraction (LVEF). A total of 480 participants will be assigned randomly to the GXST group or placebo group at a 2:1 ratio. GXST and placebo will be added to standard treatment for 12 weeks, and then followed up for another 40 weeks. The primary outcome is the improvement value of 6-min walk distance, and the secondary outcomes include plasma levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association classification, Minnesota Living with Heart Failure Questionnaire scores, echocardiographic parameters, and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed following a predefined statistical analysis plan. This study will show the effects of the specific use of GXST in CHF patients with reduced LVEF. The Research Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University has approved this study (2019-Y-003-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1900023877). Our results will be disseminated to the public through peer-reviewed journals, academic conferences, and the Internet.

TRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5'-tRF-LysCTT Results in Disease Early Progression and Patients' Poor Treatment Outcome.

Simple SummaryBladder cancer (BlCa) management relies on lifelong surveillance strategies with invasive interventions that adversely affect patients’ quality-of-life and lead to a high economic burden for healthcare systems. Exploitation of bladder tumors’ molecular background could lead to modern precision medicine. tRNA-derived fragments (tRFs), rather than degradation debris, are novel functional small ncRNAs that have emerged as key regulators of cellular homeostasis. This is the first study of the clinical utility of tRFs in BlCa. Using in silico analysis of the TCGA-BLCA project, we identified 5′-tRF-LysCTT (5′-tRF of tRNALysCTT) to be significantly deregulated in BlCa, and we have studied its clinical value in our cohort of 230 BlCa patients. Elevated 5′-tRF-LysCTT levels were significantly associated with aggressive tumor phenotype as well as early disease progression and poor treatment outcome. Integration of 5′-tRF-LysCTT with established disease markers resulted in superior prediction of patients’ prognosis, supporting personalized treatment and monitoring decisions.The heterogeneity of bladder cancer (BlCa) prognosis and treatment outcome requires the elucidation of tumors’ molecular background towards personalized patients’ management. tRNA-derived fragments (tRFs), although originally considered as degradation debris, represent a novel class of powerful regulatory non-coding RNAs. In silico analysis of the TCGA-BLCA project highlighted 5′-tRF-LysCTT to be significantly deregulated in bladder tumors, and 5′-tRF-LysCTT levels were further quantified in our screening cohort of 230 BlCa patients. Recurrence and progression for non-muscle invasive (NMIBC) patients, as well as progression and patient’s death for muscle-invasive (MIBC) patients, were used as clinical endpoint events. TCGA-BLCA were used as validation cohort. Bootstrap analysis was performed for internal validation and the clinical net benefit of 5′-tRF-LysCTT on disease prognosis was assessed by decision curve analysis. Elevated 5′-tRF-LysCTT was associated with unfavorable disease features, and significant higher risk for early progression (multivariate Cox: HR = 2.368; p = 0.033) and poor survival (multivariate Cox: HR = 2.151; p = 0.032) of NMIBC and MIBC patients, respectively. Multivariate models integrating 5′-tRF-LysCTT with disease established markers resulted in superior risk-stratification specificity and positive prediction of patients’ progression. In conclusion, increased 5′-tRF-LysCTT levels were strongly associated with adverse disease outcome and improved BlCa patients’ prognostication.

T1 mapping and late gadolinium enhancement for the diagnosis of dilated cardiomyopathy

To explore the role of T1 mapping and late gadolinium enhancement (LGE) for detection of dilated cardiomyopathy (DCM). Thirty-two DCM patients detected by ultrasonic testing with unknown origin heart failure from April 2018 to November 2019 were involved. In addition, they were compared with 18 physical examiner under cardiac magnetic resonance imaging (CMRI) in the same period. Phillip's Ingenia 3.0T MRI was used to examine heart function, plain scan included cine, T2 weighted imaging (T2WI) and pre-contrast native T1 mapping. The enhancement scan included perfusion weighted imaging, LGE imaging and post-contrast post T1 mapping. Using gadolinium injection, a bolus of 0.1 mL/kg of gadolinium-based contrast followed by a 20 mL saline flush was administered. After a 7-minute later start scanning, delay enhance sequence was started, including 4 layers, 2 cavities and 4 cavities. LGE and T1 mapping results were observed, including cardiac function indexes [left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), valvular regurgitation], cardiac morphological indexes [left ventricular mass (LVM)], histological characteristics (T2WI myocardial signal, presence of perfusion defect and its position and scope, presence of delayed enhancement and its position, shape and scope, pre- and post-contrast T1 values), extracellular volume (ECV) and the accompanying signs (pericardial effusion and pleural effusion). The receiver-operating characteristic curve (ROC) was drawn, the diagnostic value of T1 value of pre-contrast T1 mapping for DCM was evaluated, and the occurrence of clinical endpoint events was observed. There were no statistically significant differences in DCM patients with gender, age, body mass index (BMI), blood pressure, heart rate (HR), hematocrit (HCT), creatinine (Cr), family history of hypertension or heart disease. In DCM group N-terminal brain natriuretic peptide precursor (NT-proBNP) level and proportion of patients with heart function level III, diabetes, smoking history, drinking history and medication history were significantly higher than those in control group. Compared with control group, LVEDV (mL/m2: 234.9±35.9 vs. 121.8±27.6), LVESV (mL/m2: 189.7±42.8 vs. 54.8±17.0), LVM (g: 197.6±56.3 vs. 110.5±22.9), pre-contrast T1 values (ms: 1 332.1±35.9 vs. 1 272.0±47.0), ECV [(45.7±4.9)% vs. (28.0±2.1)%] were significantly increased in the DCM group; LVEF (0.191±0.107 vs. 0.554±0.103), post-contrast T1 values (ms: 453.9±72.7 vs. 493.5±43.9) were significantly decreased (all P < 0.05). In DCM group, the proportions of valvular regurgitation, pericardial effusion and pleural effusion were 25.0%, 18.8% and 25.5%, respectively. ROC curve analysis showed that the cutoff value of pre-contrast T1 values was 1 220.22 ms, the area under ROC curve (AUC) was 0.84 (P = 0.015), the sensitivity and specificity were 77.8% and 88.9%, indicating that pre-contrast T1 values may be a certain prediction for diagnosis of DCM. In 32 patients with DCM, 22 cases (68.8%) had LGE in position wall, interventricular septum, inferior wall or under the epicardium, with local or multiple diffuse, 9 cases (28.1%) were both interventricular septum and inferior wall involved. During an average of 16 months follow-up, 3.1% patients appeared sudden cardiac death. One-stop CMRI can improve the diagnostic efficacy of DCM, and T1 mapping with LGE imaging can improve the diagnostic accuracy, which is very meaningful for diagnosis and follow-up of patients.