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      MicroRNA expression analysis in peripheral blood and soft-tissue of patients with periprosthetic hip infection : a prospective controlled pilot study

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          Abstract

          Aims

          Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

          Methods

          This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline.

          Results

          Overall, several miRNAs in plasma and tissue were identified to be progressively deregulated according to ongoing PJI. When comparing the plasma samples, patients with a high-grade infection showed significantly higher expression levels for hsa-miR-21-3p, hsa-miR-1290, and hsa-miR-4488, and lower expression levels for hsa-miR-130a-3p and hsa-miR-451a compared to the aseptic group. Furthermore, the high-grade group showed a significantly higher regulated expression level of hsa-miR-1260a and lower expression levels for hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-148b-5p, hsa-miR-301a-3p, hsa-miR-451a, and hsa-miR-454-3p compared to the low-grade group. No significant differences were found between the low-grade and aseptic groups. When comparing the tissue samples, the high-grade group showed significantly higher expression levels for 23 different miRNAs and lower expression levels for hsa-miR-2110 and hsa-miR-3200-3p compared to the aseptic group. No significant differences were found in miRNA expression between the high- and low-grade groups, as well as between the low-grade and aseptic groups.

          Conclusion

          With this prospective pilot study, we were able to identify a circulating miRNA signature correlating with high-grade PJI compared to aseptic patients undergoing hip arthroplasty revision. Our data contribute to establishing miRNA signatures as potential novel diagnostic and prognostic biomarkers for PJI.

          Cite this article: Bone Jt Open 2024;5(6):479–488.

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          Most cited references50

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          Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030.

          Over the past decade, there has been an increase in the number of revision total hip and knee arthroplasties performed in the United States. The purpose of this study was to formulate projections for the number of primary and revision total hip and knee arthroplasties that will be performed in the United States through 2030. The Nationwide Inpatient Sample (1990 to 2003) was used in conjunction with United States Census Bureau data to quantify primary and revision arthroplasty rates as a function of age, gender, race and/or ethnicity, and census region. Projections were performed with use of Poisson regression on historical procedure rates in combination with population projections from 2005 to 2030. By 2030, the demand for primary total hip arthroplasties is estimated to grow by 174% to 572,000. The demand for primary total knee arthroplasties is projected to grow by 673% to 3.48 million procedures. The demand for hip revision procedures is projected to double by the year 2026, while the demand for knee revisions is expected to double by 2015. Although hip revisions are currently more frequently performed than knee revisions, the demand for knee revisions is expected to surpass the demand for hip revisions after 2007. Overall, total hip and total knee revisions are projected to grow by 137% and 601%, respectively, between 2005 and 2030. These large projected increases in demand for total hip and knee arthroplasties provide a quantitative basis for future policy decisions related to the numbers of orthopaedic surgeons needed to perform these procedures and the deployment of appropriate resources to serve this need.
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            Prosthetic-joint infections.

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              Haemolysis during Sample Preparation Alters microRNA Content of Plasma

              The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers.
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                Author and article information

                Contributors
                Role: Orthopaedic Surgery Resident
                Role: Head of the Hip Arthroplasty and Septic Surgery Section
                Role: Medical Student
                Role: Head of Shoulder and Elbow Surgery
                Role: Head of the Infectiology and Septic Surgery Section
                Role: Orthopaedic Surgery Resident
                Role: Chief Physician and Professor of Orthopedic Surgery
                Role: Chief Executive Officer
                Role: Specialist in Orthopedics and Trauma Surgery
                Role: Head of Shoulder and Elbow Surgery
                Journal
                Bone Jt Open
                Bone Jt Open
                BJO
                Bone & Joint Open
                The British Editorial Society of Bone & Joint Surgery (London )
                2633-1462
                6 June 2024
                June 2024
                : 5
                : 6
                : 479-488
                Affiliations
                [1 ] org-divisionCharité University Hospital, Center for Musculoskeletal Surgery , Berlin, Germany
                [2 ] org-divisionSchulthess Klinik , Zurich, Switzerland
                [3 ] org-divisionTAmiRNA GmbH , Vienna, Austria
                [4 ] org-divisionHealthlab , Salzburg, Austria
                Author notes
                Correspondence should be sent to Alp Paksoy. E-mail: alp.paksoy@ 123456charite.de

                The authors have no conflicts of interest to disclose. D. Akgün reports that this study was supported by the Stiftung Endoprothetik.

                Author information
                https://orcid.org/0000-0002-1657-8961
                Article
                BJO-2023-0172.R2
                10.1302/2633-1462.56.BJO-2023-0172.R2
                11152758
                38839054
                06fbdd30-ae68-46a8-985b-9f5dae0a585c
                © 2024 Paksoy et al.

                Open Access This article is distributed under the terms of the Creative Commons Attributions (CC BY 4.0) licence ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original author and source are credited.

                History
                Funding
                Funded by: doi http://dx.doi.org/10.13039/501100005986, org-divisionStiftung Endoprothetik;
                Categories
                Hip
                Hip
                Arthroplasty
                Reverse Hybrid
                Hip, hip
                bj11388, Orthopaedic diseases
                bj1763, Basic science
                bj11416, Orthopaedic treatments
                bj1268, Arthroplasty
                bj731, Anatomy
                bj10165, MicroRNA
                bj2079, Blood
                bj12334, Periprosthetic joint infection
                bj14239, RNA
                bj11640, Other infections
                bj1995, Biomarkers
                bj6871, Hip arthroplasty
                bj12331, Periprosthetic hip infection
                bj15143, Soft tissue
                bj12068, Pathological conditions
                Custom metadata
                2.0
                $2.00
                Charité University Hospital, Center for Musculoskeletal Surgery, Berlin, Germany
                Hip
                The authors have no conflicts of interest to disclose. D. Akgün reports that this study was supported by the Stiftung Endoprothetik.

                biomarker,circulating microrna,periprosthetic hip joint infection,microrna signature,crp,microrna expression level,microrna profiling

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