Nd:YAG capsulotomy incidence associated with five different single-piece monofocal intraocular lenses: a 3-year Spanish real-world evidence study of 8293 eyes

Objectives To investigate the associations between different single-piece monofocal intraocular lenses (IOLs) and neodymium-doped yttrium aluminum garnet laser (Nd:YAG) capsulotomy incidence 3 years after cataract surgery in a Spanish cohort. Methods This is a longitudinal retrospective cohort study. Data were extracted from the electronic medical records of two large regional hospitals in Spain. Patients aged ≥65 years receiving cataract surgery with placement of five different IOLs and with ≥6 months of baseline data were included. We report the Nd:YAG capsulotomy incidence 3 years post cataract surgery, and the survival plot over the 3 years of follow-up time. The associated adjusted (age, gender, and diabetic retinopathy) multivariate analysis with odds ratios (ORs) and 95% CIs is also presented. Results The cohort (53% female, mean age 75 ± 5.9 years) included 14,519 eyes (Alcon AcrySof = 2968, AJL LLASY60 = 1776, Medicontur Bi-flex = 5176, Zeiss Asphina = 4478, and IOL Tech Stabibag = 121). Of these, 8293 were retained until 3-year follow-up. At 3 years after cataract surgery, the Nd:YAG capsulotomy incidence was 5% for Alcon AcrySof, while it ranged from 21.2% to 31.1% for the other IOLs (p < 0.0001 for each comparison). The odds for Nd:YAG capsulotomy were significantly higher (p < 0.0001) for other IOLs compared with those of Alcon AcrySof (ORs = 8.85, 5.86, 5.74, 5.21 for AJL LLASY60, Medicontur Bi-flex, IOL Tech Stabibag, and Zeiss Asphina, respectively). Conclusions The lower Nd:YAG capsulotomy rates for Alcon AcrySof IOLs compared to the other IOLs support the importance of lens choice in reducing patient burden and treatment costs.

MCRS1 EXPRESSION MORE IN TUMOR PART AND SERVES AS A POOR PROGNOSTIC FACTOR IN EXTRAHEPATIC CHOLANGIOCARCINOMA

INTRODUCTION:Microporous protein 1 (MCRS1) acts as a cancer gene. MCRS1 is associated with poor prognosis in several types of cancer including colorectal cancer, hepatocellular carcinoma, glioma, and non-small cell lung cancer. In the current study, we are trying to shed light on the role of MCRS1 in the extrahepatic cholangiocarcinoma. METHODS: We retrospectively selected 13 patients who diagnosed extrahepatic cholangiocarcinoma. All clinical charts and histopathology reports were reviewed for and recoded for age, gender, tumor size, surgical margin status, lymph node metastasis, distant metastasis and TMN staging. All patients were followed for 1~10 years. The median follow-up period was 3.2 years. RESULTS: The expression level of MCRS1 showed signicantly higher in tumor part than non-tumor part. In the Kaplan-Meier survival plot , the high MCRS1 expression group showed poor survival probability with p value of 0.020. The Hazard ratio of MCRS1 showed 8.393 folds in high MCRS1 expression group when compared with low expression group with the borderline p value of 0.05. CONCLUSION:MCRS1 serves as a poor prognostic factor. Further analysis, no correlation was found in proliferation, apoptosis, angiogenesis and EMT markers. The reason may be the sample size and large-scale study in the future is mandatory

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

Integrative Analysis of Dna Methylation and Gene Expression Profiles to Explore Potential Biomarkers of Glioblastoma

Glioblastoma multiform (GBM) is the most common, most invasive, and malignant type of primary brain tumor with poorly prognosis and poorly survival rate. Using GSE22891 the expression and methylation status of same GBM patients was evaluated to explore key epigenetic genes in GBM. Using |log2FC| > 1 and FDR < 0.05 as the threshold, DEGs including 4910 downregulated and 2478 upregulated were screened and by |log2FC| > 0.2 and p.value < 0.05, 3223 DMCs were detected. By merging the results of DEGs and DMCs, 643 genes were selected for network analysis by WGCNA, and based on expression values three modules and by methylation values, one module was selected. Using STRING and Cytoscape, PPI network of genes of all modules were constructed separately. According to the PPI network, core genes were picked out. The expression status of core genes was evaluated using GSE77043, GSE42656, GSE30563, GSE22891, GSE15824, and GSE122498, and 50 genes were validated. The methylation status of 50 genes was explored using GSE50923, GSE22891, and GSE36245, and finally, 12 hub genes including ARHGEF7, RAB11FIP4, PPP1R16B, OLFM1, CLDN10, BCAT1, C1QB, C1QC, IFI16, NUP37, PARP9, and PCALF were selected. Using GEPIA database, the expression and survival plot, and using cBioportal the scatterplot of methylation versus expression of 12 hub genes were extracted based on TCGA. To determine the diagnostic values of the hub genes, the ROC curve and the area under the curve (AUC) were extracted based on GSE22891.

Potential Effects of Angiogenesis-related Factors on the Severity of APAC and Surgical Outcomes of Trabeculectomy

Background. Acute primary angle closure (APAC) caused by an abrupt closure of trabecular meshwork can develop into angle closure glaucoma due to uncontrolled IOP. Under reduced oxygen tension, hypoxia inducible transcription factors will be accumulated. EPO (erythropoietin) and PDGF (platelet derived growth factor) families are thought to be associated with angiogenesis under hypoxic condition.Methods. Concentrations of EPO, PDGF-AA, -BB, -CC and -DD collected in aqueous humor samples were measured. Before operations, correlations between target proteins and IOP were detected between APAC (acute primary angle closure) and cataract patients. Based on the post-operative follow-up, the effects of EPO and PDGF family members on the successful rate of trabeculectomy were tested. Results. The levels of EPO, PDGF-CC and -DD were significantly elevated in the APAC group compared to the cataract group. During the post-operative follow-up, EPO, PDGF-CC and -DD showed significant differences between the success and failure groups. In multivariable linear regression analyses, failed filtration surgery was more likely in APAC eyes with higher EPO level. The Kaplan-Meier survival plot suggested that the success rate in eyes with low EPO level was significantly higher than that in eyes with high EPO level.Conclusion. The levels of EPO, PDGF-CC and -DD were significantly elevated in failure group. EPO level correlated with preoperative IOP and numbers of eyedrops, and higher EPO level in aqueous humor is a risk factor for trabeculectomy failure. It can be a biomarker to estimate the severity of APAC and the success rate of surgery. The investigation of mechanism of EPO in APAC a may have potential clinical applications for the surgical treatment of APAC.

BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK

Background: Prostate cancer remains one of the most common and deadliest forms of cancer, generally respond well to radical prostatectomy and associated interventions, up to 30% of individuals will suffer disease relapse. Although BUB1B was found to be essential for cell growth and proliferation, even in several kinds of tumor cells, the specific importance and mechanistic role of BUB1B in prostate cancer remain unclear. Methods: Quantitative Real-Time PCR and Western-blot were used in the detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down the target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between the two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett’s posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. Results: In the present report, we found BUB1B expression to be highly increased in prostate cancer tissues relative to normal controls. We further found BUB1B to be essential for efficient tumor cell proliferation, and to correlate with poorer prostate cancer patient outcomes. From a mechanistic perspective, the ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation. Conclusion: Altogether, our data suggest that BUB1B is up-regulated in prostate cancer, suggesting that the growth of cancer cells may depend on BUB1B-dependent regulation of MELK transcription. BUB1B may serve as a clinical prognostic factor and a druggable target for prostate cancer.

FOXM1-Dependent Transcriptional Regulation of EZH2 Induces Proliferation and Progression in Prostate Cancer

Background: Prostate cancer is one of the most commonly diagnosed cancer and one of the most common causes of cancer-related deaths among men world-wide. Patients who are diagnosed with localized prostate cancer and treated with radical prostatectomy often respond well to therapy. The current standard therapy for prostate cancer involves maximal surgical resection followed by radiotherapy and chemotherapy. Clarifying the molecular mechanism of tumor proliferation and recurrence becomes more and more important for clinical therapies of prostate cancer. Methods: Quantitative Real-Time PCR and Western-blot were used in detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett’s posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. Results: In this study, we identified that FOXM1 expression was significantly enriched in prostate cancer compared with normal tissue. Additionally, FOXM1 was functionally required for tumor proliferation and its expression was associated to poor prognosis in prostate cancer patients. Mechanically, FOXM1-dependent regulation of EZH2 is essential for proliferation and progression in prostate cancer. Conclusion: Taken together, our data suggest that oncogenic transcription factor FoxM1 is up-regulated in prostate cancer, suggesting that growth of cancer cells may depend on FOXM1 activity. FOXM1 may serve as a clinical prognostic factor and a therapeutic target for prostate cancer.

A Novel Cell-Free Fluorescent Assay for HDL Function: Low Apolipoprotein A1 Exchange Rate Associated with Increased Incident Cardiovascular Events

Background Cholesterol efflux capacity is a tissue culture assay for HDL function that is not amenable for high-throughput monitoring of risk assessment. Methods We devised a cell-free HDL function assay to measure the exchange rate of exogenous apoA1 into serum HDL using NBD/Alexa647 double-labeled apoA1, whose NBD/Alexa647 emission ratio increased upon exchange into HDL. ApoA1 exchange rate (AER) was assayed by incubating labeled apoA1 with human serum, and the rate of the increase of the NBD/Alexa647 ratio over time was calculated as AER. Results Fast protein liquid chromatography analysis of serum confirmed that the labeled apoA1 selectively exchanged into the HDL lipoprotein fraction. Characterization studies demonstrated that the AER assay had excellent intra- and inter-day reproducibility, was stable over 3 freeze-thaw cycles, and yielded similar results with serum or plasma. We quantified AER in serum from randomly selected stable subjects undergoing elective diagnostic coronary angiography (n = 997). AER was correlated with HDL-cholesterol (r = 0.58, P &lt; 0.0001) and apoA1 levels (r = 0.56, P &lt; 0.0001). Kaplan-Meier survival plot showed subjects in the lowest quartile of AER experienced a significantly higher rate of incident major adverse cardiovascular events (MACE = myocardial infarction, stroke, or death) (P &lt; 0.0069 log rank). Moreover, compared to subjects in the lowest AER quartile, the remaining subjects showed significantly lower incident (3 year) risk for MACE, even after adjustment for traditional risk factors and apoA1 (HR 0.58; 95% CI 0.40–0.85; P = 0.005). Conclusions In a prospective cohort of stable subjects undergoing elective diagnostic cardiac evaluations, low AER was associated with increased incident risk of MACE.

P604 Can we reduce intravenous monoclonal antibody observation times without compromising patient safety? A single centre retrospective observational study

Background Monoclonal antibodies (MAbs) are integral to inflammatory bowel disease (IBD) management. The administration of intravenous (IV) MAbs, infliximab and vedolizumab, for Brighton and Sussex University Hospital patients is via an outpatient clinic. Licensing specifies lengthy observation times; infliximab for induction (infusion 1 to 3) and maintenance (infusion 4 onwards) requires 1 to 2 h observation. Vedolizumab for induction (infusion 1 to 2) requires 2 h observation and maintenance (infusion 3 onwards) 1-h observation. This can affect waiting times; 33% UK patients waited longer than two weeks for infliximab. A reduction in observation times could improve capacity but needs to be done without compromising patient safety. Methods A single centre observational study was conducted. Retrospective data were collected on all current patients receiving infliximab or vedolizumab at BSUH. Data were collected over 12 weeks (April to July 2019); patients seen twice in this period were included once. The presence of reaction from current and previous infusions was determined by patient questioning and patient records review. Reaction occurrence, nature and management were recorded. There is not a grading system for IBD infusion-related reactions. To standardise we used the cancer Common Terminology Criteria for Adverse Events; grade 3 and above is designated severe (grade 5 being death). Results For infliximab 130 patients were reviewed with 2607 infusions administered in total. For vedolizumab 69 patients were reviewed with 557 infusions administered in total. Due to the small sample size significance could not be reached. The survival plot indicates high levels of ‘no reactions’ observed in the first 4 infusions of infliximab 97.7% (+1.6%, -4.7%), and first 3 infusions of vedolizumab 96.9% (+2.3%, −8.8%). Considering capacity over 12 weeks, for infliximab a minimum of 121 could be recouped and 64 h for vedolizumab. Extrapolated this could equate to 740 h per year. Conclusion All reactions occurred within three infusions, were non-severe and managed within the infusion clinic. By removing the observation period from infusion 4 onwards, infusion clinic capacity could be increased but further data from multiple centres are required to prove significance.