The present meta-analysis was written according to the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines [28]. Ethical approval and acquisition of informed consent from participants were not required because all data were based on already published studies and were anonymously analyzed without any potential harm to the participants.
Literature search
A computerized search of MEDLINE, EMBASE, and Cochrane Library was conducted for studies published before October 2022, which investigated the PJI rates of patients who received IASIs before TKA and patients who did not. The search query included synonyms for total knee arthroplasty, steroid, injection, infection, and complication as follows: ([arthroplasty, replacement, knee] OR [total knee arthroplasty]) AND ([steroids] OR [adrenal cortex hormones] OR [corticosteroid]) AND [injections] AND ([safety] OR [infection] OR [complication]). The search was confined to studies on “humans” in the “English” language. Bibliographies of the studies were checked to identify additional relevant studies.
Inclusion and exclusion criteria
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The included studies fulfilled the following criteria: (1) patients diagnosed with PJI after TKA; (2) patients who had a history of preoperative IASI; (3) follow-up duration more than six months to determine PJI and sufficient data to tabulate 2 × 2 contingency tables for odds ratios; and (4) publication type of original articles. We excluded studies with the following criteria: (1) patients who had arthroplasty other than primary TKA, such as revision TKA, unicompartmental knee arthroplasty, and total hip arthroplasty; (2) intra-articular injection applied perioperatively for pain control purpose; (3) outcomes that did not include PJI rates; and (4) review articles, editorials, letters, and single case studies. The above process was independently performed by two reviewers with consultation from a third reviewer for reaching a consensus when any disagreements were present.
Data extraction and quality assessment
Two reviewers independently extracted data from each study using a standardized data extraction form: patient characteristics such as the size of study population, the number of patients with PJI, and the time points of preoperative IASIs; and study characteristics including authors, institutions, publication year, study design, and follow-up duration.
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The risk of bias was assessed using the Cochrane-recommended Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool because all included studies were non-randomized. The ROBINS-I tool provides signaling questions for reviewers to determine low, moderate, serious, or critical risk of bias among evaluated studies [29].
Data synthesis and analyses
The primary outcome of this study was the association between IASI and PJI. The time point from which IASIs could be applied without risking PJI was also assessed. Two by two tables were made for the odds ratio of PJI in association with IASI. As most primary studies reported time points of IASIs with 3-month intervals, the odds ratios were assessed with the time interval < 3 months and the time interval < 6 months. Although a few studies investigated both superficial infection and deep infection, only the latter was counted in the present study because diagnostic standard for superficial infection was unclear; many factors could affect the incidence of superficial infection; and it was intra-articular infection that led to devastating outcomes.
Summary estimates of odds ratios were calculated with a random-effects model to avoid overestimation of the study results. Heterogeneity was evaluated with forest plots and was quantified by Higgins I2 test, in which 25%, 50%, and 75% were considered as low, moderate, and high heterogeneities, respectively [30]. All statistical analyses were performed using the Review Manager (RevMan) program Version 5.4.1 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014; Copenhagen Denmark).
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