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      Umbilical cord blood-derived therapy for preterm lung injury: a systematic review and meta-analysis

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          Abstract

          Introduction

          Lung injuries, such as bronchopulmonary dysplasia (BPD), remain a major complication of preterm birth, with limited therapeutic options. One potential emerging therapy is umbilical cord blood (UCB)-derived therapy.

          Objectives

          To systematically assess the safety and efficacy of UCB-derived therapy for preterm lung injury in preclinical and clinical studies.

          Methods

          A systematic search of MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO International Trials Registry Platform was performed. A meta-analysis was conducted with Review Manager (5.4.1) using a random effects model. Data was expressed as standardized mean difference (SMD) for preclinical data and pooled relative risk (RR) for clinical data, with 95% confidence intervals (CI). Potential effect modifiers were investigated via subgroup analysis. Certainty of evidence was assessed using the GRADE system.

          Results

          Twenty-three preclinical studies and six clinical studies met eligibility criteria. Statistically significant improvements were seen across several preclinical outcomes, including alveolarization (SMD, 1.32, 95%CI [0.99, 1.65]), angiogenesis (SMD, 1.53, 95%CI [0.87, 2.18]), and anti-inflammatory cytokines (SMD, 1.68, 95%CI [1.03, 2.34]). In clinical studies, 103 preterm infants have received UCB-derived therapy for preterm lung injury and no significant difference was observed in the development of BPD (RR, 0.93, 95%CI [0.73, 1.18]). Across both preclinical and clinical studies, administration of UCB-derived therapy appeared safe. Certainty of evidence was assessed as “low.”

          Conclusions

          Administration of UCB-derived therapy was associated with statistically significant improvements across several lung injury markers in preclinical studies. Early clinical studies demonstrated the administration of UCB-derived therapy as safe and feasible but lacked data regarding efficacy.

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          Graphical Abstract

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions

            Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I (“Risk Of Bias In Non-randomised Studies - of Interventions”), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.
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              The PRISMA 2020 statement: An updated guideline for reporting systematic reviews

              The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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                Author and article information

                Contributors
                Journal
                Stem Cells Transl Med
                Stem Cells Transl Med
                stcltm
                Stem Cells Translational Medicine
                Oxford University Press (US )
                2157-6564
                2157-6580
                July 2024
                31 May 2024
                31 May 2024
                : 13
                : 7
                : 606-624
                Affiliations
                Department of Paediatrics, Monash University , VIC 3168, Melbourne, Australia
                Department of Paediatrics, Monash University , VIC 3168, Melbourne, Australia
                Department of Paediatrics, Monash University , VIC 3168, Melbourne, Australia
                Department of Paediatrics, Monash University , VIC 3168, Melbourne, Australia
                Department of Paediatrics, Monash University , VIC 3168, Melbourne, Australia
                The Ritchie Centre, Hudson Institute of Medical Research , VIC 3168, Melbourne, Australia
                Monash Newborn, Monash Children’s Hospital , VIC 3168, Melbourne, Australia
                The Ritchie Centre, Hudson Institute of Medical Research , VIC 3168, Melbourne, Australia
                Department of Obstetrics and Gynaecology, Monash University , VIC 3168, Melbourne, Australia
                The Ritchie Centre, Hudson Institute of Medical Research , VIC 3168, Melbourne, Australia
                Department of Obstetrics and Gynaecology, Monash University , VIC 3168, Melbourne, Australia
                Department of Paediatrics, Monash University , VIC 3168, Melbourne, Australia
                The Ritchie Centre, Hudson Institute of Medical Research , VIC 3168, Melbourne, Australia
                Monash Newborn, Monash Children’s Hospital , VIC 3168, Melbourne, Australia
                Author notes
                Corresponding author: Atul Malhotra, Department of Paediatrics, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia ( atul.malhotra@ 123456monash.edu ).
                Author information
                https://orcid.org/0000-0001-6380-8160
                https://orcid.org/0000-0002-3013-5040
                https://orcid.org/0000-0001-9664-4182
                Article
                szae033
                10.1093/stcltm/szae033
                11227974
                38819251
                f03ace96-b3d0-4f0a-9ec0-5f7c1b9e35cd
                © The Author(s) 2024. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

                History
                : 17 January 2024
                : 14 April 2024
                Page count
                Pages: 19
                Funding
                Funded by: National Health and Medical Research Council, DOI 10.13039/501100000925;
                Categories
                Concise Reviews
                AcademicSubjects/MED00770
                AcademicSubjects/SCI00960

                bronchopulmonary dysplasia,cord blood stem cell transplantation,lung injury,premature birth,systematic review,translational research

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