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      Can biomarkers be used to improve diagnosis and prediction of metabolic syndrome in childhood cancer survivors? A systematic review

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          Summary

          Childhood cancer survivors (CCS) are at increased risk to develop metabolic syndrome (MetS), diabetes, and cardiovascular disease. Common criteria underestimate adiposity and possibly underdiagnose MetS, particularly after abdominal radiotherapy. A systematic literature review and meta‐analysis on the diagnostic and predictive value of nine newer MetS related biomarkers (adiponectin, leptin, uric acid, hsCRP, TNF‐alpha, IL‐1, IL‐6, apolipoprotein B (apoB), and lipoprotein(a) [lp(a)]) in survivors and adult non‐cancer survivors was performed by searching PubMed and Embase. Evidence was summarized with GRADE after risk of bias evaluation (QUADAS‐2/QUIPS). Eligible studies on promising biomarkers were pooled. We identified 175 general population and five CCS studies. In the general population, valuable predictive biomarkers are uric acid, adiponectin, hsCRP and apoB (high level of evidence), and leptin (moderate level of evidence). Valuable diagnostic biomarkers are hsCRP, adiponectin, uric acid, and leptin (low, low, moderate, and high level of evidence, respectively). Meta‐analysis showed OR for hyperuricemia of 2.94 (age‐/sex‐adjusted), OR per unit uric acid increase of 1.086 (unadjusted), and AUC for hsCRP of 0.71 (unadjusted). Uric acid, adiponectin, hsCRP, leptin, and apoB can be alternative biomarkers in the screening setting for MetS in survivors, to enhance early identification of those at high risk of subsequent complications.

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          QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

          In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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            AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both

            The number of published systematic reviews of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions. Systematic reviews are subject to a range of biases and increasingly include non-randomised studies of interventions. It is important that users can distinguish high quality reviews. Many instruments have been designed to evaluate different aspects of reviews, but there are few comprehensive critical appraisal instruments. AMSTAR was developed to evaluate systematic reviews of randomised trials. In this paper, we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic reviews, including those based on non-randomised studies of healthcare interventions.
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              Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.

              A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.
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                Author and article information

                Contributors
                v.g.pluimakers@prinsesmaximacentrum.nl
                Journal
                Obes Rev
                Obes Rev
                10.1111/(ISSN)1467-789X
                OBR
                Obesity Reviews
                John Wiley and Sons Inc. (Hoboken )
                1467-7881
                1467-789X
                13 July 2021
                November 2021
                : 22
                : 11 ( doiID: 10.1111/obr.v22.11 )
                : e13312
                Affiliations
                [ 1 ] Princess Máxima Center for Pediatric Oncology Utrecht Netherlands
                [ 2 ] Department of Medicine, Endocrinology Erasmus Medical Center Rotterdam Netherlands
                [ 3 ] Medical Statistics, Department of Biomedical Data Science Leiden UMC Leiden Netherlands
                [ 4 ] Mathematical Institute Leiden University Leiden Netherlands
                [ 5 ] Department of Medicine University Medical Center Utrecht Netherlands
                Author notes
                [*] [* ] Correspondence

                V.G. Pluimakers, Princess Máxima Centre for Pediatric Oncology, Heidelberglaan 25, Utrecht 3584 CS, Netherlands.

                Email: v.g.pluimakers@ 123456prinsesmaximacentrum.nl

                Author information
                https://orcid.org/0000-0002-3066-3951
                https://orcid.org/0000-0001-8818-6759
                https://orcid.org/0000-0001-5588-0277
                https://orcid.org/0000-0002-1059-0126
                https://orcid.org/0000-0002-7760-879X
                https://orcid.org/0000-0002-7698-0282
                Article
                OBR13312
                10.1111/obr.13312
                8596408
                34258851
                6655e32d-cdb3-47fc-99f6-63367d6e4020
                © 2021 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 May 2021
                : 19 March 2021
                : 09 June 2021
                Page count
                Figures: 4, Tables: 2, Pages: 22, Words: 21115
                Funding
                Funded by: Erasmus Medisch Centrum , doi 10.13039/501100003061;
                Funded by: Princess Máxima Center for Pediatric Oncology
                Categories
                Pediatric Obesity/Obesity Comorbidity
                Pediatric Obesity/Obesity Comorbidity
                Custom metadata
                2.0
                November 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.9 mode:remove_FC converted:17.11.2021

                Medicine
                biomarker,childhood cancer survivors,systematic review,the metabolic syndrome
                Medicine
                biomarker, childhood cancer survivors, systematic review, the metabolic syndrome

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