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      Clinical characteristics and prognostic significance of EBER positivity in diffuse large B-cell lymphoma: A meta-analysis

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          Abstract

          Recent studies show that Epstein-Barr virus (EBV) positivity might be related to adverse prognosis in patients with diffuse large B-cell lymphoma (DLBCL), but the results are still inconclusive. We conducted this meta-analysis to define the clinical value of EBV infection in DLBCL. All potential articles in PubMed, Web of Science, Medline, and Embase were retrieved. Using the random-effects or fixed-effect model, pooled hazard ratios (HRs) or relative risk (RR) with 95% confidence intervals (CIs) were used to calculate the correlation between EBER and prognosis and clinical features in DLBCL. A total of 13 qualified studies with 4111 patients were identified in our meta-analysis based on the inclusion and exclusion criteria. The overall estimates revealed that EBV-encoded small RNAs (EBER) positivity was significantly correlated with worse overall survival (HR = 2.43, 95% CI: 1.73–3.36) and progression-free survival (HR = 3.60, 95% CI: 2.07–6.26). In addition, EBER positivity was associated with age older than 60 years (RR = 1.51, 95% CI: 1.02–2.24), male sex (RR = 1.34, 95% CI: 1.05–1.71), more advanced stage (RR = 2.25, 95% CI: 1.72–2.96), high international prognostic index (RR = 2.20, 95% CI: 1.71–2.82), more than one extranodal involvement (RR = 1.69, 95% CI: 1.27–2.26), presence of B symptom (RR = 1.75, 95% CI: 1.30–2.35), non-germinal center B-cell subtype (RR = 1.35, 95% CI: 1.03–1.78), and elevated lactate dehydrogenase levels (RR = 1.30, 95% CI: 0.98–1.72). EBER positivity was correlated with worse outcomes, worse clinical course, and adverse clinicopathologic features among patients with DLBCL.

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          Most cited references 34

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          Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.

           Andreas Stang (2010)
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            Practical methods for incorporating summary time-to-event data into meta-analysis

            Background In systematic reviews and meta-analyses, time-to-event outcomes are most appropriately analysed using hazard ratios (HRs). In the absence of individual patient data (IPD), methods are available to obtain HRs and/or associated statistics by carefully manipulating published or other summary data. Awareness and adoption of these methods is somewhat limited, perhaps because they are published in the statistical literature using statistical notation. Methods This paper aims to 'translate' the methods for estimating a HR and associated statistics from published time-to-event-analyses into less statistical and more practical guidance and provide a corresponding, easy-to-use calculations spreadsheet, to facilitate the computational aspects. Results A wider audience should be able to understand published time-to-event data in individual trial reports and use it more appropriately in meta-analysis. When faced with particular circumstances, readers can refer to the relevant sections of the paper. The spreadsheet can be used to assist them in carrying out the calculations. Conclusion The methods cannot circumvent the potential biases associated with relying on published data for systematic reviews and meta-analysis. However, this practical guide should improve the quality of the analysis and subsequent interpretation of systematic reviews and meta-analyses that include time-to-event outcomes.
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              A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project.

              The recognition of several new types of non-Hodgkin's lymphoma (NHL) in recent years has led to proposals for changing lymphoma classifications, including a new proposal put forth by the International Lymphoma Study Group (ILSG). However, the clinical significance of the new entities and the practical utility of this new proposal have not been studied. Therefore, we performed a clinical evaluation of the ILSG classification. A cohort of 1,403 cases of NHL was organized at nine study sites around the world and consisted of consecutive patients seen between 1988 and 1990 who were previously untreated. A detailed protocol for histologic and clinical analysis was followed at each site, and immunologic characterization as to T- or B-cell phenotype was required. Five expert hematopathologists visited the sites and each classified each case using the ILSG classification. A consensus diagnosis was also reached in each case, and each expert rereviewed a 20% random sample of the cases. Clinical correlations and survival analyses were then performed. A diagnosis of NHL was confirmed in 1,378 (98.2%) of the cases. The most common lymphoma types were diffuse large B-cell lymphoma (31%) and follicular lymphoma (22%), whereas the new entities comprised 21% of the cases. Diagnostic accuracy was at least 85% for most of the major lymphoma types, and reproducibility of the diagnosis was 85%. Immunophenotyping improved the diagnostic accuracy by 10% to 45% for a number of the major types. The clinical features of the new entities were distinctive. Both the histologic types and the patient characteristics as defined by the International Prognostic Index predicted for patient survival. In conclusion we found that the ILSG classification can be readily applied and identifies clinically distinctive types of NHL. However, for clinical application, prognostic factors as defined by the International Prognostic Index must be combined with the histologic diagnosis for appropriate clinical decisions.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: SupervisionRole: Validation
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Validation
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 June 2018
                2018
                : 13
                : 6
                Affiliations
                [1 ] Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
                [2 ] Faculty of Laboratory Medicine, Zhengzhou University, Zhengzhou, P. R. China
                [3 ] Key Laboratory Medicine of Henan Province, Faculty of Laboratory Medicine of Zhengzhou University, Zhengzhou, P. R. China
                [4 ] Open Laboratory, Henan Province Key Subject of Clinical Medicine, Zhengzhou, P. R. China
                Fondazione IRCCS Istituto Nazionale dei Tumori, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-18-09906
                10.1371/journal.pone.0199398
                6007832
                29920566
                © 2018 Gao et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 5, Tables: 1, Pages: 13
                Product
                Funding
                The authors received no specific funding for this work.
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                Physical Sciences
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