Synovial Fluid Cutibacterium acnes Antigen Is Detected Among Shoulder Samples with High Inflammation and Early Culture Growth.

BACKGROUND: An emerging paradigm suggests that positive Cutibacterium acnes shoulder cultures can result from either true infection or contamination, with true infections demonstrating a host inflammatory response and early culture growth. This clinical retrospective study examines the relationship between C. acnes antigen, C. acnes culture results, and inflammation. METHODS: From January 2021 to July 2023, 1,365 periprosthetic synovial fluid samples from 347 institutions were tested for shoulder infection at a centralized clinical laboratory. A biomarker scoring system based on the 2018 International Consensus Meeting (ICM) definition was utilized to assign each sample an inflammation score. Associations between inflammation, culture results, and C. acnes antigen results were assessed utilizing cluster and correlation analyses. RESULTS: Of 1,365 samples, 1,150 were culture-negative and 215 were culture-positive (94 C. acnes and 121 other organisms). Among the 94 C. acnes culture-positive samples, unsupervised clustering revealed 2 distinct sample clusters (silhouette coefficient, 0.83): a high-inflammation cluster (n = 67) and a low-inflammation cluster (n = 27). C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation (Spearman ρ, 0.60), with 166-fold higher levels of C. acnes antigen in high-inflammation samples (16.6 signal/cutoff [S/CO]) compared with low-inflammation samples (0.1 S/CO) (p < 0.0001). The days to C. acnes culture positivity demonstrated weak-inverse correlation with inflammation (Spearman ρ = -0.38), with 1.5-fold earlier growth among the 67 high-inflammation samples (6.7 compared with 10.4 days; p < 0.0001). Elevated C. acnes antigen was observed in only 4 (0.38%) of 1,050 low-inflammation culture-negative samples and in only 5 (4.9%) of 103 high-inflammation non-C. acnes-positive cultures. However, 19.0% of high-inflammation, culture-negative samples demonstrated elevated C. acnes antigen. CONCLUSIONS: Synovial fluid C. acnes antigen was detected among shoulder samples with high inflammation and early culture growth, supporting the emerging paradigm that these samples represent true infection. Future research should explore antigen testing to differentiate contamination from infection and to identify culture-negative C. acnes infections. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The False-Positive Rate of Synovial Fluid Culture at a Single Clinical Laboratory Using Culture Bottles.

Introduction Synovial fluid (SF) cultures can yield false-positive or negative results when diagnosing periprosthetic joint infection (PJI). False-positives may arise during sample collection or from laboratory contamination. Understanding false-positive SF culture rates is crucial for interpreting PJI laboratory data, yet clinical laboratories rarely report these rates. This study aimed to define the false-positive SF culture rate at a major specialized clinical laboratory. Methods This study retrospectively analyzed prospectively collected data at a single clinical laboratory that receives SF for clinical testing for PJI. A total of 180,317 periprosthetic SF samples from the hip, knee, and shoulder were identified from January 2016 to December 2023, which met the inclusion criteria for this study. Samples were classified by both a modified 2018 International Consensus Meeting (ICM) score and an inflammation score that combined the SF-C-reactive protein, alpha-defensin, SF-white blood cell count, and SF-polymorphonuclear% into one standardized metric. Logistic regression was utilized to evaluate the impact of various collection-based characteristics on culture positivity, including inflammation biomarkers, the source joint, quality control metrics, and days of specimen transport to the laboratory. SF culture false-positivity was calculated based on the ICM category of "not-infected" or low inflammation score. Results Overall, 13.3% (23,974/180,317) of the samples were associated with a positive culture result: 12.5% for knee samples, 20.3% for hip samples, and 14.7% for shoulder samples. The false-positive SF culture rate among 131,949 samples classified as "not-infected" by the modified 2018 ICM definition was 0.47% (95%CI: 0.43 to 0.51%). Stratification by joint revealed a false-positive rate of 0.34% (95%CI: 0.31 to 0.38%) for knee samples, 1.24% (95%CI: 1.05 to 1.45%) for hip samples, and 3.02% (95%CI: 2.40 to 3.80%) for shoulder samples, with p < 0.0001 for all comparisons. The false-positive SF culture rate among 90,156 samples, representing half of all samples with the lowest standardized inflammation scores, was 0.47% (95%CI: 0.43 to 0.52%). Stratification by joint revealed a false-positive rate of 0.33% (95%CI: 0.29 to 0.37%) for knee samples, 1.45% (95%CI: 1.19 to 1.77%) for hip samples, and 3.09% (95%CI: 2.41 to 3.95%) for shoulder samples, with p<0.0001 for all comparisons. Multivariate logistic regression demonstrated the joint source (hip, shoulder) and poor sample quality as collection-based factors associated with a false-positive culture. Evaluation of a cohort of samples selected to minimize collection-based causes of false-positive culture demonstrated a false-positive rate of 0.30%, representing the ceiling limit for laboratory-based SF culture false-positivity. Conclusions This study utilizes two methods to estimate the false-positive SF culture rate at a single specialized clinical laboratory, demonstrating an overall false-positive rate of approximately 0.5%. Stratification of samples by source joint demonstrated that periprosthetic SF from the shoulder and hip have a substantially higher false-positive culture rate than that of the knee. The lowest false-positive SF culture rate (0.30%) was observed among samples from the knee-passing quality control. Culture positivity due to contamination at this specific laboratory is less than 0.30% because all specimens undergo identical processing.

Synovial Fluid C-reactive Protein Clinical Decision Limit and Diagnostic Accuracy for Periprosthetic Joint Infection.

Introduction C-reactive protein (CRP) has long served as a prototypical biomarker for periprosthetic joint infection (PJI). Recently, synovial fluid (SF)-CRP has garnered interest as a diagnostic tool, with several studies demonstrating its diagnostic superiority over serum CRP for the diagnosis of PJI. Although previous studies have identified diagnostic thresholds for SF-CRP, they have been limited in scope and employed various CRP assays without formal validation for PJI diagnosis. This study aimed to conduct a formal single clinical laboratory validation to determine the optimal clinical decision limit of SF-CRP for the diagnosis of PJI. Methods A retrospective analysis of prospectively collected data was performed using receiver operating characteristic (ROC) and area under the curve (AUC) analyses. Synovial fluid samples from hip and knee arthroplasties, received from over 2,600 institutions, underwent clinical testing for PJI at a single clinical laboratory (CD Laboratories, Zimmer Biomet, Towson, MD) between 2017 and 2022. Samples were assayed for SF-CRP, alpha-defensin, white blood cell count, neutrophil percentage, and microbiological culture. After applying selection criteria, the samples were classified with the 2018 ICM PJI scoring system as "infected," "not infected," or "inconclusive." Data were divided into training and validation sets. The Youden Index was employed to optimize the clinical decision limit. Results A total of 96,061 samples formed the training (n = 67,242) and validation (n = 28,819) datasets. Analysis of the biomarker median values, culture positivity, anatomic distribution, and days from aspiration to testing revealed nearly identical specimen characteristics in both the training set and validation set. SF-CRP demonstrated an AUC of 0.929 (95% confidence interval (CI): 0.926-0.932) in the training set, with an optimal SF-CRP clinical decision limit for PJI diagnosis of 4.45 mg/L. Applying this cutoff to the validation dataset yielded a sensitivity of 86.1% (95% CI: 85.0-87.1%) and specificity of 87.1% (95% CI: 86.7-87.5%). No statistically significant difference in diagnostic performance was observed between the validation and training sets. Conclusion This study represents the largest single clinical laboratory evaluation of an SF-CRP assay for PJI diagnosis. The optimal CRP cutoff (4.45 mg/L) for PJI, which yielded a sensitivity of 86.1% and a specificity of 87.1%, is specific to the assay methodology and laboratory performing the assay. We propose that an SF-CRP test with a laboratory-validated optimal clinical decision limit for PJI may be preferable, in a clinical diagnostic setting, to serum CRP tests that do not have laboratory-validated clinical decision limits for PJI.

Achieving High Accuracy in Predicting the Probability of Periprosthetic Joint Infection From Synovial Fluid in Patients Undergoing Hip or Knee Arthroplasty: The Development and Validation of a Multivariable Machine Learning Algorithm.

Background and objective The current periprosthetic joint infection (PJI) diagnostic guidelines require clinicians to interpret and integrate multiple criteria into a complex scoring system. Also, PJI classifications are often inconclusive, failing to provide a clinical diagnosis. Machine learning (ML) models could be leveraged to reduce reliance on these complex systems and thereby reduce diagnostic uncertainty. This study aimed to develop an ML algorithm using synovial fluid (SF) test results to establish a PJI probability score. Methods We used a large clinical laboratory's dataset of SF samples, aspirated from patients with hip or knee arthroplasty as part of a PJI evaluation. Patient age and SF biomarkers [white blood cell count, neutrophil percentage (%PMN), red blood cell count, absorbance at 280 nm wavelength, C-reactive protein (CRP), alpha-defensin (AD), neutrophil elastase, and microbial antigen (MID) tests] were used for model development. Data preprocessing, principal component analysis, and unsupervised clustering (K-means) revealed four clusters of samples that naturally aggregated based on biomarker results. Analysis of the characteristics of each of these four clusters revealed three clusters (n=13,133) with samples having biomarker results typical of a PJI-negative classification and one cluster (n=4,032) with samples having biomarker results typical of a PJI-positive classification. A decision tree model, trained and tested independently of external diagnostic rules, was then developed to match the classification determined by the unsupervised clustering. The performance of the model was assessed versus a modified 2018 International Consensus Meeting (ICM) criteria, in both the test cohort and an independent unlabeled validation set of 5,601 samples. The SHAP (SHapley Additive exPlanations) method was used to explore feature importance. Results The ML model showed an area under the curve of 0.993, with a sensitivity of 98.8%, specificity of 97.3%, positive predictive value (PPV) of 92.9%, and negative predictive value (NPV) of 99.8% in predicting the modified 2018 ICM diagnosis among test set samples. The model maintained its diagnostic accuracy in the validation cohort, yielding 99.1% sensitivity, 97.1% specificity, 91.9% PPV, and 99.9% NPV. The model's inconclusive rate (diagnostic probability between 20-80%) in the validation cohort was only 1.3%, lower than that observed with the modified 2018 ICM PJI classification (7.4%; p<0.001). The SHAP analysis found that AD was the most important feature in the model, exhibiting dominance among >95% of "infected" and "not infected" diagnoses. Other important features were the sum of the MID test panel, %PMN, and SF-CRP. Conclusions Although defined methods and tools for diagnosis of PJI using multiple biomarker criteria are available, they are not consistently applied or widely implemented. There is a need for algorithmic interpretation of these biomarkers to enable consistent interpretation of the results to drive treatment decisions. The new model, using clinical parameters measured from a patient's SF sample, renders a preoperative probability score for PJI which performs well compared to a modified 2018 ICM definition. Taken together with other clinical signs, this model has the potential to increase the accuracy of clinical evaluations and reduce the rate of inconclusive classification, thereby enabling more appropriate and expedited downstream treatment decisions.

Mechanical Complications of Hip and Knee Spacers Are Common.

Introduction Two-stage revision is frequently used for the treatment of periprosthetic joint infection (PJI). Because antibiotic-loaded cement spacers are constructed and implanted as temporary devices, mechanical complications are possible. The purpose of our study was to define the incidence of such mechanical complications, determine associated risk factors, and establish if such complications influence the subsequent success of PJI treatment. Methods We identified patients who received an antibiotic spacer for the treatment of PJI at a single center over a six-year timeframe. Medical records and all radiographs were collected and reviewed. Radiographic changes over time were recorded, and mechanical complications were noted. We used multivariate logistic regression analysis to assess risk factors for mechanical spacer complications and assess whether such complications influence the likelihood of subsequent reimplantation and ultimate component retention. Results A total of 236 patients were included in the study. There were 82 hip spacers (28% dynamic and 72% static) with a mechanical complication rate of 8.5% and 154 knee spacers (44% dynamic and 56% static) with a mechanical complication rate of 18.2%. Knee spacers were significantly more likely to have mechanical complications than hip spacers. Other risk factors for mechanical complications included bone loss and elevated body mass index (BMI). Bone loss and advanced age were found to be independent risk factors for failure to undergo second-stage reimplantation. Mechanical spacer failure was not an independent risk factor for the likelihood of subsequent reimplantation or ultimate component retention. Conclusions Mechanical complications of antibiotic spacers are common but do not appear to negatively impact the likelihood of subsequent reimplantation or component retention. In knee spacers and in patients with bone loss or elevated BMI, appropriate patient counseling and strategies to prevent such complications are recommended.

Mitigating Concerns Over Transport Delays: An Analysis of Synovial Fluid Culture Results in Arthroplasty.

INTRODUCTION:  There is a concern in the field of arthroplasty that synovial fluid transport delays may reduce the accuracy of synovial fluid culture. However, synovial fluid samples collected in the office, and sometimes in a hospital setting, often require transport to a third-party central or specialty laboratory, causing delays in the initiation of culture incubation. This study investigated the impact of transportation delays on synovial fluid culture results. METHODS:  A retrospective review of prospectively collected data at one clinical laboratory, from 2016 to 2022, was conducted. A total of 125,270 synovial fluid samples from knee arthroplasties, from 2,858 different US institutions, were transported to a single clinical laboratory for diagnostic testing including synovial fluid culture (blood culture bottles). Synovial fluid to be cultured was transported in red top tubes without additives. Samples were grouped into six-time cohorts based on the number of days between aspiration and culture initiation (1-day-delay to 6-day-delay). Metrics such as culture positivity, false-positive culture rate, culture sensitivity, and proportional growth of top genera of organisms were assessed across the cohorts. RESULTS:  Of the 125,270 samples in this study, 71.2% were received the day after aspiration (1-day-delay), with an exponential decrease in samples received on each subsequent day. Culture-positive rates for synovial fluid samples received after 1, 2, 3, 4, 5, and 6 days of transport time were 12.2%, 13.3%, 13.5%, 13.1%, 11.6%, and 11.0%, respectively. The maximum absolute difference in culture-positive rate compared to the 1-day-delay cohort was an increase of 1.3% in the 3-day-delay cohort, which was not considered a clinically meaningful difference. The estimated false-positive culture rate remained relatively consistent across time cohorts, with values of 0.3%, 0.4%, 0.3%, 0.2%, 0.5%, and 0.5% for 1, 2, 3, 4, 5, and 6 days of transport time, respectively. None of the cohorts showed a statistically significant difference after adjustment for multiplicity compared to the 1-day-delay cohort. Culture sensitivity was estimated at 68.2%, 67.2%, 70.5%, 70.7%, 65.9%, and 70.7% for 1, 2, 3, 4, 5, and 6 days of transport time, respectively. None of the cohorts showed a statistically significant difference after adjustment for multiplicity compared to the 1-day-delay cohort. Organism proportions were consistent across time cohorts, with Staphylococcus being the most commonly identified organism. No statistically significant differences were found in the proportional contribution of major genera across the cohorts. CONCLUSIONS:  Synovial fluid culture exhibited surprisingly consistent results despite variable transport time to the destination laboratory, with differences that have minimal clinical importance. While the authors of this study advocate for short transport times as a best practice to expedite diagnosis, it appears that concerns regarding the rapid degradation of culture results due to synovial fluid transportation is unwarranted.

A Video Teaching Tool Is Effective for Training Residents in Hip Arthroplasty Templating.

Work hour restrictions imposed on orthopedic surgery residents since the early 2000s have reduced educational opportunities at the workplace and encouraged alternative strategies for teaching outside the clinical setting. Preoperative templating is essential for safe and effective total hip arthroplasty (THA) and is accurate in predicting final implants. We sought to determine the effectiveness of a video tool for teaching orthopedic residents basic THA templating skills. We developed a video-based teaching tool with instructions on proper THA templating techniques. Ten cases were selected for testing, after excluding patients with severe hip deformities and poor-quality radiographs and only retaining those with concordance between templating by the senior authors and implanted components. The study subjects included three postgraduate year 1 (PGY-1), three PGY-2, and three PGY-5 residents, and three adult reconstruction fellows (PGY-6). Templating skills were assessed before and after watching the instructional video. The evaluation included the size and positioning of femoral and acetabular components, as well as the restoration of leg length. Each templating session was repeated twice. Variance was measured to evaluate consistency in measurements. A linear mixed model and F-test were used for statistical analyses. The number of years in training significantly affected performance prior to exposure to the instructional video. Post-exposure, there was a significant improvement in the accuracy of sizing and positioning of acetabular and femoral components for PGY-1, PGY-2, and PGY-5 residents. The results achieved were comparable to PGY-6 examiners, who did not gain substantial performance benefits from the instructional video. Limb length restoration was less affected by experience or exposure to the video. Component positioning and sizing, as well as leg length discrepancy (LLD), showed a significant decrease in variance after the intervention in all study groups. Video learning is reliable in teaching invaluable skills to orthopedic surgery residents without encroaching on work hours. We conceived a concise video to train orthopedic residents to perform THA templating with proper technique and demonstrated its efficiency and reproducibility.

Systemic Manifestation of Periprosthetic Joint Infection Is Associated With Increased In-Hospital Mortality.

Introduction Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. Systemic symptoms of infection may indicate a patient who is at a higher risk of serious complications. The goal of this study was to determine if systemic symptoms of infection in the setting of PJI were associated with greater in-hospital mortality. Materials and methods We used our institutional database to identify all patients urgently treated for deep PJI from 2002-2012. Records were reviewed to collect demographics, surgical data, vital signs prior to surgical intervention, blood and intraoperative culture results, preoperative intensive care unit (ICU) admissions, and deaths that occurred during the hospital admission. Patients were classified as having systemic inflammatory response syndrome (SIRS) based on the criteria established by the American College of Chest Physicians and the Society of Critical Care Medicine. Results During the 10-year timeframe of our study, 484 patients were treated emergently for deep infection, with 130 (27%) meeting SIRS criteria preoperatively and 31 (6%) of the patients with SIRS having positive blood cultures. Patients with positive blood cultures and SIRS demonstrated a higher in-hospital mortality rate (p < 0.001). Neither SIRS nor SIRS with positive blood cultures were associated with ICU admission. Discussion Occasionally, PJI can spread beyond the affected joint, showing physical symptoms of systemic illness and bacteremia. This study demonstrates that patients with SIRS and positive blood cultures are at an increased risk of in-hospital mortality. These patients should be monitored closely before definitive treatment in order to minimize their mortality risk.

Not All Patients Need Supervised Physical Therapy After Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

Although postoperative physical therapy (PT) has long been considered essential to successful total knee arthroplasty (TKA) recovery, recent literature has suggested that unsupervised home exercise regimens may offer similar benefits to formal supervised sessions. We aimed to compare objectively measured physical function and subjective patient-reported outcomes (PROs) between primary TKA patients who received formal supervised physical therapy sessions and those who received unsupervised home exercise regimens after discharge. Six electronic databases were queried to identify randomized controlled trials comparing supervised physical therapy to unsupervised home exercise regimens in primary TKA patients after discharge. Outcomes of interest included change from baseline in objective measures (knee flexion range of motion (ROM), lower extremity strength, and aerobic capacity) and PROs (physical function and quality of life scores). These outcomes were subdivided into short-term (<6 months from surgery; closest data point to three months is used if multiple measurements were made in this time period) and long-term (≥6 months from surgery; closest data point to 12 months is used if multiple measurements were made in this time period) assessments. A total of 1,884 cases performed in 11 studies were included in this review. There were no significant differences between cohorts with regard to short-term knee flexion ROM (p = 0.7), lower extremity strength (p = 0.6), or patient-reported quality of life (p = 0.5), as well as long-term knee flexion ROM (p = 0.7), patient-reported quality of life (p = 0.2), or patient-reported physical outcome scores (p = 0.3). A small difference in short-term patient-reported physical outcomes was observed in favor of the supervised cohort (standardized mean difference (SMD): 0.3 (95% confidence interval (CI): 0.01, 0.6); I2 = 82%; p = 0.04). Formal supervised physical therapy regimens do not confer clinically significant benefits over unsupervised home exercise regimens following primary TKA. The routine use of supervised physical therapy after discharge may not be warranted. Further study is needed to determine the subset of patients that may benefit from supervised care.

Nationwide Results of Microorganism Antigen Testing as a Component of Preoperative Synovial Fluid Analysis.

BACKGROUND: Antigen immunoassays to detect synovial fluid (SF) microorganisms have recently been made available for clinical use. The purpose of this study was to determine the sensitivity and specificity of an SF microorganism antigen immunoassay detection (MID) panel, evaluate the panel's capability to detect microorganisms in the setting of culture-negative periprosthetic joint infection (PJI), and determine diagnostic predictive values of the MID panel for PJI. METHODS: This study included 67,441 SF samples obtained from a hip or knee arthroplasty, from 2,365 institutions across the United States, submitted to 1 laboratory for diagnostic testing. All data were prospectively compiled and then were analyzed retrospectively. Preoperative SF data were used to classify each specimen by the International Consensus Meeting (2018 ICM) definition of PJI: 49,991 were not infected, 5,071 were inconclusive, and 12,379 were infected. The MID panel, including immunoassay tests to detect Staphylococcus, Candida, and Enterococcus, was evaluated to determine its diagnostic performance. RESULTS: The MID panel demonstrated a sensitivity of 94.2% for infected samples that yielded positive cultures for target microorganisms (Staphylococcus, Candida, or Enterococcus). Among infected samples yielding positive cultures for their respective microorganism, individual immunoassay test sensitivity was 93.0% for Staphylococcus, 92.3% for Candida, and 97.2% for Enterococcus. The specificity of the MID panel for samples that were not infected was 98.4%, yielding a false-positive rate of 1.6%. The MID panel detected microorganisms among 49.3% of SF culture-negative infected samples. For PJI as a diagnosis, the positive predictive value of the MID panel was 91.7% and the negative predictive value was 93.8%. Among MID-positive PJIs, 16.2% yielded a discordant cultured organism instead of that detected by the antigen test. CONCLUSIONS: SF microorganism antigen testing provides a timely adjunct method to detect microorganisms in the preoperative SF aspirate, yielding a low false-positive rate and enabling the detection of a microorganism in nearly one-half of SF culture-negative PJIs. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Physician Use of Multiple Criteria to Diagnose Periprosthetic Joint Infection May Be Less Accurate Than the Use of an Individual Test.

Introduction Multiple-criterion scoring systems for periprosthetic joint infection (PJI) can be algorithmically implemented in research, diagnostically outperforming individual tests. This improved performance may be lost in the practice setting, where clinicians rarely utilize strict algorithms. The ability of physicians to interpret multiple criteria for PJI and confront the complexity of combining them into a final diagnosis has never been studied. This study assessed the diagnostic characteristics of physicians using multiple criteria to diagnose PJI and compared the physicians' diagnostic accuracy to that of individual tests. Methods A total of 12 physicians, including academic arthroplasty surgeons (N=4), community arthroplasty surgeons (N=4), and infectious disease (ID) specialists (N=4) were asked to use their routine clinical diagnostic practice to assign a diagnosis to 277 clinical vignettes using multiple preoperative laboratory criteria for PJI. The undecided rate, interobserver agreement, and accuracy of physicians were characterized relative to the 2013 Musculoskeletal Infection Society (MSIS) gold standard and compared to the accuracy of each individual laboratory test for PJI. Results Physicians interpreting multiple criteria for PJI demonstrated high undecided diagnosis rates (mean=23.5%), poor interobserver agreement (kappa range=0.49-0.63), and mean accuracy of 90.8% (range:85.8%-97.4%) compared to the 2013 MSIS gold standard. The group of academic arthroplasty surgeons had a lower rate of undecided diagnoses than community arthroplasty surgeons (16.2% vs. 29.1%; p<0.0001) or ID specialists (16.2% vs. 25.1%; p<0.0001). Academic arthroplasty surgeons also exhibited a higher interobserver agreement than community arthroplasty surgeons (kappa = 0.63 (95%CI:0.59-0.68) vs. 0.49 (95%CI:0.44-0.54)). Mean physician accuracy (90.8%) was inferior to the alpha-defensin laboratory test (96.0%;p=0.0034) and the alpha-defensin lateral-flow test (94.6%;p=0.036), comparable to synovial fluid white blood cells (SF-WBC) (93.3%;p=0.17) and synovial fluid polymorphonuclear cell % (SF-PMN%) (94.0%;p=0.11), and superior to the erythrocyte sedimentation rate (ESR) (86.2%;p<0.0001) and C-reactive protein (CRP) (84.6%;p<0.0001). Only two academic arthroplasty surgeons in this study were able to outperform every individual test for PJI by combining multiple criteria to make a diagnosis. Conclusion Although multiple-criterion scoring systems may outperform individual tests for diagnosing PJI in the research setting, it appears that the complexity of using multiple tests to diagnose PJI causes indecision and variability among physicians. Physician use of multiple preoperative criteria to diagnose PJI is less accurate than the strict algorithmic calculation of the diagnosis as achieved in research. In fact, most physicians in this study would have improved their diagnostic accuracy for PJI by simply utilizing a single good test to make the diagnosis, instead of trying to combine multiple tests into a decision. We propose that less complex diagnostic criteria should be explored for routine clinical utilization.

Unsupervised Home Exercises Versus Formal Physical Therapy After Primary Total Hip Arthroplasty: A Systematic Review.

Historically, postoperative exercise and physical therapy (PT) have been viewed as crucial to a successful outcome following primary total hip arthroplasty (THA). This systematic review and meta-analysis aimed to assess differences in both short- and long-term objective and self-reported measures between primary THA patients with formal supervised physical therapy versus unsupervised home exercises after discharge. A search was conducted of six electronic databases from inception to December 14, 2020, for randomized controlled trials (RCTs) comparing changes from baseline in lower extremity strength (LES), aerobic capacity, and self-reported physical function and quality of life (QoL) between supervised and unsupervised physical therapy/exercise regimens following primary THA. Outcomes were separated into short-term (<6 months from surgery, closest to 3 months) and long-term (≥6 months from surgery, closest to 12 months) measures. Meta-analyses were performed when possible and reported in standardized mean differences (SMDs) with 95% confidence intervals (CI). Seven studies (N=398) were included for review. No significant differences were observed with regard to lower extremity strength (p=0.85), aerobic capacity (p=0.98), or short-term quality of life scores (p=0.18). Although patients in supervised physical therapy demonstrated improved short-term self-reported outcomes compared to those performing unsupervised exercises, this was represented by a small effect size (SMD 0.23 [95% CI, 0.02-0.44]; p=0.04). No differences were observed between groups regarding long-term lower extremity strength (p=0.24), physical outcome scores (p=0.37), or quality of life (p=0.14). The routine use of supervised physical therapy may not provide any clinically significant benefit over unsupervised exercises following primary THA. These results suggest that providers should reconsider the routine use of supervised physical therapy after discharge.

Laboratory-Reported Normal Value Ranges Should Not Be Used to Diagnose Periprosthetic Joint Infection.

INTRODUCTION: Clinical laboratories offer several multipurpose tests, such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which are not intended to diagnose any specific disease but are used by clinicians in multiple fields. The results and laboratory interpretation (normal/abnormal) of these multipurpose tests are based on laboratory-reported normal thresholds, which vary across clinical laboratories. In 2018, the International Consensus Meeting on Musculoskeletal Infection (2018 ICM) provided a gold-standard definition to diagnose periprosthetic joint infection (PJI) which included many multipurpose laboratory tests, along with thresholds optimized to diagnose PJI. The discrepancy between laboratory-reported normal thresholds and 2018 ICM-recommended PJI-optimized test thresholds has never been studied. The purpose of this study was to assess the existing variation in laboratory-reported normal thresholds for tests commonly used to diagnose PJI and evaluate the potential diagnostic impact of using laboratory-reported normal thresholds instead of 2018 ICM-recommended PJI-optimized thresholds. METHODS: Clinical laboratories (N=85) were surveyed to determine the laboratory-reported units of measure and normal thresholds for common multipurpose tests to diagnose PJI, including the ESR, CRP, D-dimer, synovial fluid white blood cells (SF-WBC), and polymorphonuclear cell percent (SF-PMN%). The variability of units of measure and normal thresholds for each test was then assessed among the 85 included clinical laboratories. A representative dataset from patients awaiting a revision arthroplasty was used to determine the clinical significance of the existing discrepancy between laboratory-reported normal test interpretations and 2018 ICM-recommended PJI-optimized test interpretations. RESULTS: Two units of measure for the CRP and six units of measure for the D-dimer were observed, with only 59% of laboratories reporting the CRP in terms of mg/L and only 16% reporting the D-dimer in ng/ml, as needed to utilize the 2018 ICM definition of PJI. Across clinical laboratories surveyed, the mean laboratory-reported normal thresholds for the ESR (20 mm/h), CRP (7.69 mg/L), D-dimer (500 ng/mL), SF-WBC (5 cells/uL), and SF-PMN% (25%) were substantially lower than the 2018 ICM-recommended PJI-optimized thresholds of 30 mm/h, 10 mg/L, 860 ng/mL, 3,000 cells/uL, and 70%, respectively. Interpretation of test results from a representative PJI dataset using each laboratory's normal test thresholds yielded mean false-positive rates of 14% (ESR), 18% (CRP), 42% (D-dimer), 93% (SF-WBC), and 36% (SF-PMN%) versus the ICM-recommended PJI-optimized thresholds. CONCLUSION: When reporting the results for multipurpose laboratory tests, such as the ESR, CRP, D-dimer, SF-WBC, and SF-PMN%, clinical laboratories utilize laboratory-reported units of measure and normal thresholds that are not intended to diagnose PJI, and therefore may not match the 2018 ICM recommendations. Our findings reveal that laboratory-reported normal thresholds for these multipurpose tests are well below the 2018 ICM recommendations to diagnose PJI. Clinical reliance on laboratory-reported results and interpretations, instead of strict use of the 2018 ICM-recommended units and PJI-optimized thresholds, may lead to false-positive interpretation of multipurpose laboratory tests.

Validation of the Alpha Defensin Lateral Flow Test for Periprosthetic Joint Infection.

BACKGROUND: The synovial fluid test for alpha defensin has been reported to have an excellent performance in diagnosing periprosthetic joint infection (PJI). The purpose of this study was to evaluate the performance of the lateral flow test for synovial fluid alpha defensin by using the methods of a formal diagnostic accuracy study and to compare its performance with that of the laboratory-based alpha defensin test for PJI. METHODS: We conducted a diagnostic accuracy study of the index lateral flow immunoassay for synovial fluid alpha defensin relative to the reference 2013 Musculoskeletal Infection Society (MSIS) multicriteria definition of PJI. The study included a prospective multicenter cohort of outpatients with a failed hip or knee arthroplasty and a supplemental control cohort of fresh synovial fluid specimens submitted by physicians for diagnostic PJI testing. RESULTS: Among 57 patients with PJI and 248 patients without PJI in the overall prospective patient cohort, the sensitivity and specificity of the alpha defensin lateral flow test were 89.5% (95% confidence interval [CI]: 78.5% to 96.0%) and 94.8% (95% CI: 91.2% to 97.2%), respectively. The sensitivity increased to 94.3% (95% CI: 84.3% to 98.8%) after exclusion of 17 patients with grossly bloody aspirates (>1 million red blood cells/µL). Among the supplemental control cohort of fresh synovial fluid samples, including 65 samples from patients with PJI and 397 from patients without PJI, the sensitivity and specificity of the alpha defensin lateral flow test were 98.5% (95% CI: 91.7% to 100.0%) and 98.2% (95% CI: 96.4% to 99.3%), respectively. A comparison of the sensitivity and specificity of the alpha defensin lateral flow test with those of the alpha defensin enzyme-linked immunosorbent assay (ELISA) in the combined cohort did not demonstrate a significant difference in sensitivity (94.3% [95% CI: 88.5% to 97.7%] compared with 93.0% [95% CI: 87.1% to 96.7%]) or specificity (96.9% [95% CI: 95.3% to 98.1%] compared with 97.8% [95% CI: 96.4% to 98.8%]) (both p > 0.05). CONCLUSIONS: The results of this study demonstrate the solid diagnostic performance of the alpha defensin test and have resulted in the U.S. Food and Drug Administration (FDA) authorization of the lateral-flow test with an intended use as an aid in the clinical diagnosis of PJI. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Prior Manipulation under Anesthesia is a Predictor of Contralateral Manipulation in Staged Bilateral Total Knee Arthroplasty.

BACKGROUND: There are many risk factors for arthrofibrosis and manipulation under anesthesia (MUA) following total knee arthroplasty (TKA). However, no study has elucidated whether a history of MUA increases the risk of contralateral MUA in patients undergoing staged bilateral TKA. METHODS: A retrospective review of an institutional database of TKAs was performed. All patients aged ≥18 years who underwent primary staged bilateral TKAs were screened for inclusion. Staged bilateral TKAs were viewed as 2 distinct events based on the temporal order in which they occurred: TKA#1 (occurred first) and TKA#2 (occurred second). Following TKA#1, patients were split into 2 groups: those who underwent MUA (Group MANIP) and those who did not (Group NO MANIP). The subsequent risk of undergoing MUA following TKA#2 was then assessed and compared between the 2 groups. Chi-squared tests were used for comparison. RESULTS: A total of 5,330 patients who underwent primary uncomplicated staged bilateral TKAs (10,660 knees) during the study period were identified. Overall, 2.1% of patients underwent MUA following TKA#1 and 1.9% of patients underwent MUA following TKA#2. In the MANIP group, 21.4% of patients underwent MUA following TKA#2, while only 1.5% underwent MUA in the NO MANIP group. This 14.3-fold increase in the risk of MUA in the MANIP group following TKA#2 was statistically significant (21.4% vs 1.5%, absolute risk reduction = 19.9%, relative risk reduction = 93.0%, P < .0001). CONCLUSION: Patients who undergo MUA during the first TKA of a staged bilateral TKA are 14.3 times more likely to undergo a subsequent MUA than those who did not undergo MUA following their first TKA.

Adverse Local Tissue Reaction due to Mechanically Assisted Crevice Corrosion Presenting as Late Instability Following Metal-on-Polyethylene Total Hip Arthroplasty.

BACKGROUND: Mechanically assisted crevice corrosion (MACC) at modular junctions can cause a spectrum of adverse local tissue reactions (ALTRs) in patients who have undergone total hip arthroplasty (THA). The purpose of this study is to describe the presentation, treatments, and related complications of a cohort of patients presenting with late instability following metal-on-polyethylene THA due to underlying MACC and ALTR. METHODS: This multicenter retrospective case series presents 17 patients (12 women, mean age 62.6, range 42-73) presenting with late instability secondary to ALTR and MACC. All patients had a metal (Cobalt Chrome)-on-polyethylene bearing surface. Patients experienced a mean 2.7 dislocations (range 1-6) at mean 4.3 years (range 0.4-17.0) following their index surgery. Serum metal levels (n = 12) demonstrated a greater elevation of cobalt (mean 6.9, range 0.13-20.88 ng/mL) than chromium (mean 1.9, range 0.13-3.23 ng/mL). RESULTS: Patients were revised for instability at a mean of 6.8 years (range 2.1-19.4) following their index surgery. ALTR was encountered in every case and the modular head-neck junction demonstrated visible corrosion. An exchange of the CoCr head to a ceramic head with a titanium sleeve and placement of a constrained liner was performed for a majority of patients (n = 15, 88.2%). Five patients (29.4%) had complications postoperatively including peroneal palsy (n = 2), periprosthetic joint infection (n = 2), and ALTR recurrence (n = 1). CONCLUSION: Recurrent instability in the setting of otherwise well-positioned THA components and without another obvious cause should raise concern for ALTR as a potential underlying etiology.

Synovial Fluid Aspirates Diluted with Saline or Blood Reduce the Sensitivity of Traditional and Contemporary Synovial Fluid Biomarkers.

BACKGROUND: Recent criteria-based diagnostic tools to diagnose periprosthetic infection (PJI), such as the International Consensus Meeting (ICM) definition of PJI, are heavily reliant on synovial fluid laboratory results. Despite the importance of synovial fluid in PJI diagnosis, the effect of the quality of synovial fluid aspirate on testing results has not been studied. Our laboratory has established quality control parameters to identify synovial fluid aspirates that are highly diluted by saline or blood, which appear to degrade the diagnostic performance of synovial fluid laboratory tests. QUESTIONS/PURPOSES: (1) What proportion of synovial fluid aspirates analyzed at one laboratory are of poor quality (defined as having a red blood count > 1M cells/uL or an optical density at 280 nm < 0.324 or > 1.19)? (2) Does a poor-quality aspirate decrease the sensitivities of International Consensus Meeting-based scores and other synovial fluid biomarker tests in terms of their ability to anticipate a positive culture? METHODS: From January 2016 to July 2019, a total of 123,549 synovial fluid samples were submitted to one laboratory for the purpose of diagnostic testing. Of these, 14% (16,773 of 123,549) samples were excluded because they were from a site other than a hip, knee, or shoulder arthroplasty, and an additional 33% (35,660 of 106,776) were excluded due to insufficient requested tests, resulting in 58% (71,116 of 123,549) samples included in this study. Specimens diluted with extreme levels of saline or blood were identified (defined as having a red blood count >1 M cells/uL or an optical density at 280 nm < 0.324 or > 1.19) as poor-quality aspirates. The sensitivities of synovial fluid C-reactive protein, alpha defensin, neutrophil elastase, white blood cell count, polymorphonuclear cell percentage, and the 2018 ICM-based tool were assessed in good-quality versus poor-quality synovial fluid samples. To avoid bias from using these evaluated tests within the reference definition of PJI in this study, a positive culture resulting from the synovial fluid served as the reference diagnosis defining a control cohort of PJI-positive samples. Although the low false-positive rate of synovial fluid culture allows for the valid estimation of synovial fluid test sensitivity, the high false-negative rate of synovial fluid culture prevents the valid estimation of test specificity, which was not evaluated in this study. RESULTS: Of the samples analyzed, 8% (6025 of 71,116) were found to have poor quality, in that they were substantially compromised by saline and/or blood. The sensitivity of all tests to detect culture-positive synovial fluid was lower in poor-quality than in good-quality samples: 2018 International Consensus Meeting-based tool (83% [95% CI 80 to 86] versus 97% [95% CI 96 to 97]), synovial fluid C-reactive protein (65% [95% CI 61 to 69] versus 88% [95% CI 87 to 89]), alpha defensin (70% [95% CI 66 to 73] versus 93% [95% CI 93 to 94]), neutrophil elastase (80% [95% CI 77 to 83] versus 96% [95% CI 96 to 97]), synovial fluid white blood cell count (69% [95% CI 65 to 73] versus 93% [95% CI 93 to 94]), and the polymorphonuclear cell percentage (88% [95% CI 85 to 91] versus 95% [95% CI 94 to 95]), with all p < 0.001. CONCLUSIONS: When synovial fluid is substantially diluted with saline or blood, the biomarkers and cells being measured are also diluted, decreasing the sensitivity of laboratory testing. We recommend that future diagnostic studies exclude these samples because an artificial reduction in test sensitivity will be observed. CLINICAL RELEVANCE: Clinicians should avoid relying on negative synovial fluid testing to rule out PJI when the fluid submitted is substantially constituted of saline or blood. Further studies are necessary to understand the diagnostic utility, if any, of these diluted aspirate samples.

False-Positive Automated Synovial Fluid White Blood Cell Counting Is a Concern for Both Hip and Knee Arthroplasty Aspirates.

BACKGROUND: Although false elevation of automated leukocyte (white blood cell [WBC]) counts has been described in the setting of hip corrosion, the more general correlation between manual and automated cell counts among synovial fluid aspirates from hip and knee arthroplasties has not been studied. METHODS: This retrospective review at one laboratory identified 8607 consecutive synovial fluid samples from arthroplasties and 812 from native knees, each with an automated WBC count > 3000 cells/µL and a corresponding paired reflex manual count. The correlation between automated and manual counts was evaluated, as was the rate of false-positive automated WBC counts. RESULTS: The correlation between automated WBC counts for native knees, total knee arthroplasties, and total hip arthroplasties was near-perfect, strong, and moderate, respectively. The false-positive rates for automated counts were 4.4%, 10.1%, and 34.3%, respectively (P < .0001). International Consensus Meeting scores and culture positivity demonstrated that manual counts, not automated counts, were correct. CONCLUSION: The presence of a hip or knee arthroplasty appears to substantially increase the risk of a false-positive automated synovial fluid WBC count. Clinicians evaluating an arthroplasty should exercise caution when interpreting positive automated WBC counts, and consider requesting a reflex manual count, to verify the accuracy of automated cell counting.

Musculoskeletal Infection Society (MSIS) Update on Infection in Arthroplasty.

Periprosthetic joint infection (PJI) continues to be a devastating problem in the field of total joint arthroplasty, and recent literature can be used to make the preoperative diagnosis of PJI, guide nonsurgical and surgical treatment, and provide postoperative antimicrobial management of PJI patients. The diagnosis of PJI relies on traditional serum and synovial fluid tests, with newer biomarkers and molecular tests. Surgical treatment depends on the duration of infection, host qualities, and surgeon factors, and procedures include débridement, antibiotics, and implant retention, one-stage exchange arthroplasty, two-stage exchange arthroplasty, resection arthroplasty, fusion, or amputation. Appropriate management of PJI involves coordination with infectious disease consultants, internal medicine physicians, and orthopaedic surgeons. Antimicrobial management is guided by the organisms involved, whether it is a new or persistent infection, and antibiotic suppression should be administered on an individual case basis. The goals of this instructional course lecture are to review the most relevant recent literature and provide treating physicians and surgeons with the most up-to-date armamentarium to reduce the recurrence of PJI.