Supplementary Material for: The different prognosis of hepatocellular carcinoma with previous tenofovir vs entecavir treatment for chronic hepatitis B virus: analysis based on 15 propensity score–matched studies

Background: This meta-analysis of high-quality PSM studies was designed to provide robust estimates for comparative HCC prognosis between groups receiving tenofovir or entecavir. Methods: PubMed, Embase, Cochrane Library and Web of Science were searched from inception to July 10, 2022 for relevant studies that comparing the different prognosis of HCC between TDF and ETV. Results: A total of 15 PSM studies were identified, with 24035 sample sizes in tenofovir group and 61410 sample sizes in entecavir group respectively. Pooled data indicated that, compared with entecavir, patients receiving tenofovir experienced significantly lower overall death or liver transplantation, with a pooled OR of 0.55 (95% CI 0.45 ‒ 0.68). Subgroup analysis by population also found similar results with pooled ORs of 0.52 (95% CI 0.38 ‒ 0.70) in entire cohort and 0.62 (95% CI 0.50 ‒ 0.77) in PSM cohort. Conclusions: Our analysis indicated that there was clinically meaningful difference in prognosis of HCC between patients who received entecavir and patients who received tenofovir. Tenofovir treatment may be one of independent favorable factors of prognosis for HCC patients with CHBV

Supplementary Material for: The relationship between vascular aging phenotypes and renal damage among individuals with type 2 diabetes

Objective: To investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. Methods: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010 to 2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60ml/min/1.73m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. Results: The prevalence of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline was 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46-0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20-1.67) for proteinuria, 1.24 (1.01-1.51) for kidney function decline, and 1.56 (1.18-2.06) for proteinuria combined with kidney function decline. Conclusions: Vascular aging phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline

Supplementary Material for: Predictors and Management of Antiplatelet-Related Bleeding Complications for Acute Coronary Syndrome in Chinese Elderly Patients

Background/Aims: Bleeding complications after percutaneous coronary intervention (PCI) are strongly associated with adverse patient outcomes. However, there are no specific guidelines for the predictors and management of antiplatelet-related bleeding complications in Chinese elderly patients with acute coronary syndrome (ACS). Methods: A retrospective analysis of 237 consecutive patients (aged ≥ 75 years) with ACS who had undergone successful PCI from January 2010 to December 2016 was performed to identify predictors and management of antiplatelet-related bleeding complications. Multivariate logistic regression analysis was conducted to investigate independent predictors of antiplatelet-related bleeding complications. We defined antiplatelet-related bleeding complications as first hospitalization received long-term oral antiplatelet therapy and required hospitalization, including gastrointestinal and intracranial bleedings. Results: After multivariable adjustment, independent risk predictors of antiplatelet-related bleeding complications included female gender (odds ratio [OR]: 2.96; 95% confidence interval [CI]: 1.98 to 4.15; P = 0.011), body mass index (OR: 1.54; 95% CI: 1.06 to 1.94; P = 0.034), previous history of bleeding (OR: 4.03; 95% CI: 1.84 to 6.12; P = 0.004), fasting blood glucose (OR: 2.79; 95% CI: 1.23 to 4.46; P = 0.025), and chronic total occlusion lesion (OR: 4.69; 95% CI: 2.19 to 7.93; P = 0.007). Of 46 patients with antiplatelet-related bleeding complications, 54.3% were treated short-term dual antiplatelet therapy (DAPT) cessation (0–7 days) and 45.7% underwent long-term DAPT cessation (> 7 days). Among these, 14 patients presented major adverse cardiac and cerebrovascular events (MACCE), whereas no re-bleeding happened over all available follow-up. The incidence of MACCE was not significantly different between the two groups one year after PCI (36.0% for short-term DAPT cessation versus 23.8% for long-term DAPT cessation, P = 0.522). Conclusion: For elderly patients with ACS, multiple factors were likely to contribute to antiplatelet-related bleeding complications, especially previous history of bleeding and chronic total occlusion lesion. Better individualized, tailored and risk-adjusted antiplatelet therapy after PCI is urgently needed in this high-risk population

Supplementary Material for: Circular RNA Expression Profiling Identifies Prostate Cancer- Specific circRNAs in Prostate Cancer

Background/Aims: Prostate cancer (PCa) is one of the main cancers that damage males’ health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. Methods: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. Results: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. Conclusion: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer

Supplementary Material for: Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multi-regional phase 2 study, RATIONALE-208, examined single-agent tislelizumab (200 mg intravenously every three weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018 and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. Number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. Disease control rate was 53% and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC

Supplementary Material for: CureGN Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations

Introduction: CureGN is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy (IgAN). We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial and vascular lesions evaluated semi-quantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s AC1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (143 MCD, 185 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6-0.8) reproducibility. Mesangial hypercellularity scored as absent, focal or diffuse had moderate reproducibility (AC1=0.58), but good reproducibility (ACI=0.71) when scored as absent or focal vs diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1=0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis and tubular atrophy with eGFR, foot process effacement with UPCR, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery

Supplementary Material for: CureGN Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations

Introduction: CureGN is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy (IgAN). We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial and vascular lesions evaluated semi-quantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s AC1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (143 MCD, 185 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6-0.8) reproducibility. Mesangial hypercellularity scored as absent, focal or diffuse had moderate reproducibility (AC1=0.58), but good reproducibility (ACI=0.71) when scored as absent or focal vs diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1=0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis and tubular atrophy with eGFR, foot process effacement with UPCR, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery

Supplementary Material for: CureGN Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations

Introduction: CureGN is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy (IgAN). We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial and vascular lesions evaluated semi-quantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s AC1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (143 MCD, 185 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6-0.8) reproducibility. Mesangial hypercellularity scored as absent, focal or diffuse had moderate reproducibility (AC1=0.58), but good reproducibility (ACI=0.71) when scored as absent or focal vs diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1=0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis and tubular atrophy with eGFR, foot process effacement with UPCR, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery