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.

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.

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.

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.

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.

Comparison of Quadriceps-Sparing and Medial Parapatellar Approaches in Total Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The quadriceps-sparing (QS) technique for total knee arthroplasty (TKA) was introduced to improve outcomes associated with the medial parapatellar (MP) approach. There is no clear consensus on what advantages, if any, QS provides. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing the QS and MP techniques. PubMed, Ovid, and Scopus were assessed for relevant literature. Long-term (primary) outcomes and short-term (secondary) outcomes from 8 RCTs (579 TKAs) were analyzed using OpenMetaAnalyst (2016). RESULTS: The QS approach did not demonstrate clinically significant advantages, but was associated with statistically and clinically significant increases in the primary outcomes of femoral (odds ratio [OR] 4.92, P = .005), tibial (OR 4.34, P = .01), and mechanical axis outliers (OR 4.77, P = .004). Secondary outcome assessments demonstrated increased surgical (mean differences [MD] 19.54, P < .001) and tourniquet time (MD 23.30, P < .001) for QS. Although statistically significant advantages for QS were identified in Knee Society Function scores at 1.5-3 months (MD 2.31, P = .004) and 2 years (MD 1.86, P < .001), these were not clinically significant (fell below the 6-point minimal clinically important difference). CONCLUSION: The QS approach to TKA fails to demonstrate clinically significant advantages, but shows increased malalignment. This increased incidence of implant malalignment may predispose QS patients to early prosthesis failure. Because the QS approach may increases the risk of malalignment while providing no clear benefit compared to MP, we recommend against the routine use of the QS TKA approach.

The Leukocyte Esterase Test Strip Is a Poor Rule-Out Test for Periprosthetic Joint Infection.

BACKGROUND: The urinary leukocyte esterase (LE) test strip has been suggested as a good screening test for periprosthetic joint infection (PJI). The purpose of this study is to compare the diagnostic profile of LE assays from different manufacturers and determine whether the LE test strip is a good rule-out test. METHODS: Synovial fluid samples (N = 344), sent to 1 laboratory for PJI testing, were used in this prospective study. Four different tests for synovial fluid LE were simultaneously evaluated for their performance in detecting white blood cell (WBC) positive samples (>3000 cells/µL). RESULTS: Both neutrophil elastase immunoassays demonstrated greater sensitivity than urinary LE test strips (92.0% and 90.8% vs 72.4% and 80.3%; all P < 0.011). Fifty-three percent of false-negative urinary LE test strip results clearly missed the presence of elevated levels of synovial fluid LE. Invalid urinary LE test strip results were 4-fold more likely among WBC (+) compared with WBC (-) samples (27.0% vs 6.8%; P < 0.0001). The combined failure to detect an elevated WBC count, because of either false-negative or invalid results, was 47.1% and 41.4% for the Roche and Siemens test strips, respectively. CONCLUSIONS: This study agrees with the existing literature demonstrating that the LE test strips are among the lowest sensitivity tests for PJI. The urinary LE tests strips should not be used to rule-out PJI, as they often fail to detect abundant levels of LE in synovial fluid. Instead, it is more appropriate to use the (++) LE test strip result as a secondary confirmatory rule-in test for PJI because of its high specificity.

Utility of Synovial White Blood Cell Count and Differential Before Reimplantation Surgery.

BACKGROUND: Determining optimal timing of reimplantation during 2-stage exchange for periprosthetic joint infection (PJI) remains elusive. Joint aspiration for synovial white blood cell (WBC) count and neutrophil percentage (PMN%) before reimplantation is widely performed; yet, the implications are rarely understood. Therefore, this study investigates (1) the diagnostic yield of synovial WBC count and differential analysis and (2) the calculated thresholds for persistent infection. METHODS: Institutional PJI databases identified 129 patients undergoing 2-stage exchange arthroplasty who had joint aspiration before reimplantation between February 2005 and May 2014. Persistent infection was defined as a positive aspirate culture, positive intraoperative cultures, or persistent symptoms of PJI-including subsequent PJI-related surgery. Receiver-operating characteristic curve was used to calculate thresholds maximizing sensitivity and specificity. RESULTS: Thirty-three cases (33 of 129; 25.6%) were classified with persistent PJI. Compared with infection-free patients, these patients had significantly elevated PMN% (62.2% vs 48.9%; P = .03) and WBC count (1804 vs 954 cells/µL; P = .04). The receiver-operating characteristic curve provided thresholds of 62% and 640 cells/µL for synovial PMN% and WBC count, respectively. These thresholds provided sensitivity of 63% and 54.5% and specificity of 62% and 60.0%, respectively. The risk of persistent PJI for patients with PMN% >90% was 46.7% (7 of 15). CONCLUSION: Synovial fluid analysis before reimplantation has unclear utility. Although statistically significant elevations in synovial WBC count and PMN% are observed for patients with persistent PJI, this did not translate into useful thresholds with clinical importance. However, with little other guidance regarding the timing of reimplantation, severely elevated WBC count and differential analysis may be of use.

A Current Procedural Terminology Code for "Knee Conversion" Is Needed to Account for the Additional Surgical Time Required Compared to Total Knee Arthroplasty.

BACKGROUND: Previous knee injury requiring surgical intervention increases the rate of future arthroplasty. Coding modifiers for removal of previous hardware or increased complexity offer inconsistent results. A Current Procedural Terminology code for knee conversion does not currently exist as it does for conversion hip arthroplasty. We investigate the extra time associated with conversion knee arthroplasty. METHODS: Sixty-three total knee arthroplasty (TKA) cases in the setting of previous knee hardware were identified from our institution between 2008 and 2015. Knee conversions were matched to primary TKA by age, gender, body mass index, Charlson Comorbidity Index, and surgeon, in a 3:1 ratio. Patients who underwent knee conversions were compared to matched TKA with regard to operative time, length of stay, discharge destination, readmission, and repeat procedures within 90 days from index procedure. RESULTS: The mean operating room time for primary TKA was 71.7 minutes (range 36-138). The mean operating room time for knee conversion was significantly greater by an additional 31 minutes; mean 102.1 minutes (range 56-256 minutes, P < .0001). Rates of readmission, 0.5% vs 3.2%, and repeat procedures, 5.3% vs 12.7%, within 90 days were greater for knee conversions. There was no difference in length of stay or discharge destination. CONCLUSION: Total knee conversion results in a 43% increase in operative time and more than twice the rate of readmission and repeat procedures within 90 days compared to TKA. This suggests the need for an additional Current Procedural Terminology code for knee conversion arthroplasty to compensate surgeons for the extra time required for conversions.

The Alpha-defensin Test for Periprosthetic Joint Infections Is Not Affected by Prior Antibiotic Administration.

BACKGROUND: Previous studies have demonstrated that the administration of antibiotics to patients before performing diagnostic testing for periprosthetic joint infection (PJI) can interfere with the accuracy of test results. Although a single-institution study has suggested that alpha-defensin maintains its concentration and sensitivity even after antibiotic treatment, this has not yet been demonstrated in a larger multiinstitutional study. QUESTIONS/PURPOSES: (1) For the evaluation of PJI, is prior antibiotic administration associated with decreased alpha-defensin levels? (2) When prior antibiotics are given, is alpha-defensin a better screening test for PJI than the traditional tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fluid white blood cells, fluid polymorphonuclear cells [PMNs], and fluid culture)? METHODS: This retrospective study included data from 106 hip and knee arthroplasties with Musculoskeletal Infection Society-defined PJI from four centers. Of the 106 patients in this study, 30 (28%) were treated with antibiotics for PJI before diagnostic workup (ABX group), and 76 (72%) were not treated before the diagnostic workup (NO-ABX group). There were no differences in age, sex, joint, culture-negative rate, or bacteriology between groups. The patients in the ABX group had antibiotics initiated by physicians who commenced care before assessment for PJI by the treating surgeon's service. We compared the alpha-defensin levels and sensitivity between the ABX and NO-ABX groups. Additionally, the sensitivity of the alpha-defensin test was compared to that of traditional tests for PJI among patients on antibiotics. RESULTS: The administration of antibiotics before performing the alpha-defensin test for PJI was not associated with a decreased median alpha-defensin level (ABX group, median 4.2 [range, 1.79-12.8 S/CO] versus NO-ABX, median 4.9 [range, 0.5-16.8 S/CO], difference of medians: 0.68 S/CO [95% confidence interval {CI}, -0.98 to 1.26], p = 0.451). Furthermore, the alpha-defensin test had a higher sensitivity (100%; 95% CI, 88.4%-100.0%) in diagnosing PJI among patients on antibiotics when compared with the ESR (69.0% [95% CI, 49.17%-84.72%], p = 0.001), the CRP (79.3% [95% CI, 60.3%-92.0%], p = 0.009), the fluid PMN% (79.3% [95% CI, 60.3%-92.0%), p = 0.009), and fluid culture (70.0% [95% CI, 50.6%-85.3%], p = 0.001). CONCLUSIONS: The alpha-defensin test maintains its concentration and sensitivity for PJI even in the setting of antibiotic administration. Furthermore, among patients with PJI on antibiotics, the alpha-defensin tests demonstrated a higher sensitivity in detecting PJI when compared with the ESR, CRP, fluid PMN%, and fluid culture. The high sensitivity of the alpha-defensin test, even in the setting of prior antibiotic treatment, provides excellent utility as a screening test for PJI. LEVEL OF EVIDENCE: Level III, diagnostic study.

Prospective Evaluation of Sleep Disturbances After Total Knee Arthroplasty.

Sleep disturbance after total knee arthroplasty (TKA) has not been studied 6 months after surgery. A prospective study was conducted on 34 primary, unilateral TKA patients preoperatively until 6 months postoperatively. Sleep quality was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Pain was measured on a visual analog scale. Sleep quality worsened from baseline during the first 6 weeks postoperatively (P = .03), but improved at 3 and 6 months (P = .003). Pain scores decreased from baseline over all time points, and there was no correlation between sleep quality and pain. The Epworth Sleepiness Scale did not change over time. This study can be used to counsel TKA patients to expect initial sleep disturbances that improve by 3 months.

The C-Reactive Protein May Not Detect Infections Caused by Less-Virulent Organisms.

BACKGROUND: The aim of the present study was to evaluate the influence of organism type on the performance of the synovial fluid C-reactive protein (CRP) test. METHODS: We retrospectively reviewed the results of 21,422 synovial fluid samples sent to one common laboratory for the purpose of diagnostic testing for periprosthetic joint infection. Both a synovial fluid CRP result and a positive culture were present for 1789 submitted samples. The cultured organisms were grouped by species, virulence, and gram type; and the median CRP level was determined for each group. RESULTS: The median synovial fluid CRP level was significantly lower for less-virulent organisms, when compared to those organisms classified as virulent (15.10 mg/L vs 32.70 mg/L; P < .0001). Some less-virulent species such as yeast and Staphylococcus epidermidis were associated with a 4-10 times lower CRP response than those of virulent organisms such as Streptococcus agalactiae and Staphylococcus aureus (P < .0001). Bacterial gram type had no influence on the median CRP result. The rate of false-negative CRP values was 50.9% for yeast, 29.4% for S. epidermidis, 28.5% for all less-virulent organisms, and 11.6% for all virulent organisms. CONCLUSION: The CRP response appears to be highly dependent on the infecting organism and is more likely to provide false-negative results in the setting of less-virulent organisms. Although the use of a CRP level is an important part of the workup for periprosthetic joint infection, surgeons must be aware that this protein may yield a false-negative result in the setting of less-virulent organisms.

The Alpha-defensin Test for Periprosthetic Joint Infection Responds to a Wide Spectrum of Organisms.

BACKGROUND: The alpha-defensin test has been previously demonstrated to be highly accurate in the diagnosis of prosthetic joint infection (PJI), nearly matching the Musculoskeletal Infection Society definition for PJI. However, the relationship between alpha-defensin levels and differing infecting organism has not yet been investigated. QUESTIONS/PURPOSES: The purpose of this study is to describe the breadth of organisms that can trigger a positive synovial fluid alpha-defensin test result in the setting of PJI and also to assess the magnitude of the alpha-defensin result in terms of various pathogen characteristics. METHODS: Between December 2012 and March 2014, one laboratory processed 2319 synovial fluid samples for alpha-defensin testing. The present study reviewed the results of the 1937 samples that simultaneously had a synovial fluid culture performed; these came from 418 surgeons in 42 states. The overall culture-positive rate was 49% (244 of 498) among alpha-defensin-positive synovial fluids and 1% (19 of 1439) among alpha-defensin-negative synovial fluids. The organisms recovered from 244 alpha-defensin-positive, culture-positive fluids were recorded and grouped based on various characteristics, including Gram type, species, virulence, oral pathogenicity, and source joint. Alpha-defensin-negative samples served as uninfected controls. Median alpha-defensin levels were calculated for each group, and Dunn's multiple comparison test for nonparametric data was used to identify any statistically significant (p < 0.05) organism-specific differences in the alpha-defensin level. RESULTS: The alpha-defensin test for PJI was positive in the setting of a wide spectrum of organisms typically causing PJI. The median alpha-defensin level for all 244 alpha-defensin-positive, culture-positive samples (4.7 [interquartile range {IQR}, 3.7-5.3]) was higher than negative controls (0.26 [IQR, 0.22-0.33]) with a median difference of 4.4 (p < 0.001). There were no differences in the median alpha-defensin levels when performing a multiple comparison test among Gram-positive organisms (4.7 [IQR, 3.6-5.3]), Gram-negative organisms (4.8 [IQR, 4.2-5.3]), yeast (4.1 [IQR, 2.2-5.1]), virulent organisms (4.7 [IQR, 3.8-5.2]), less virulent organisms (4.8 [IQR, 3.6-5.4]), oral pathogens (4.5 [IQR, 3.2-5.2]), knees (4.7 [IQR, 3.7-5.3]), hips (4.9 [IQR, 4.1-5.8]), or shoulders (5.3 [IQR, 4.0-10.7]) with all comparisons having a p > 0.999. CONCLUSIONS: The alpha-defensin test provides consistent results regardless of the organism type, Gram type, species, or virulence of the organism and should be seriously considered to be a standard diagnostic tool in the evaluation for PJI. Future research should focus on the performance of this test in specific clinical scenarios such as the immediate postoperative period in the setting of severe immunocompromise and in the setting of a native joint. LEVEL OF EVIDENCE: Level III, diagnostic study.

Premature Therapeutic Antimicrobial Treatments Can Compromise the Diagnosis of Late Periprosthetic Joint Infection.

BACKGROUND: In the absence of positive cultures and draining sinuses, the diagnosis of periprosthetic joint infection (PJI) relies on laboratory values. It is unknown if administration of antibiotics within 2 weeks before diagnostic evaluations can affect these tests in patients with PJI. QUESTIONS/PURPOSES: The purpose of this study was to investigate the correlation of antibiotic administration with (1) fluctuations in the synovial fluid and serology laboratory values; and (2) sensitivity of the diagnostic tests in patients with late PJI (per Musculoskeletal Infection Society [MSIS] criteria). METHODS: Synovial white blood cell (WBC) count, polymorphonuclear neutrophil (PMN) percentage, and serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as culture results were investigated in 161 patients undergoing total knee arthroplasty with late PJI diagnosed with the MSIS criteria. Depending on whether presampling antibiotics were used, patients were divided in two groups (53 [33%] patients were on antibiotics). The median laboratory values and the false-negative rates were compared between the two groups. RESULTS: The median of all variables were lower in the antibiotic group compared with the other group: ESR (mm/hr): 70 versus 85, difference of medians (DOM) = 15 mm/hr, p = 0.018; CRP (mg/L): 72 versus 130, DOM = 58 mg/L, p = 0.038; synovial WBC (cells/µL): 29,170 versus 46,900, DOM = 17,730, p = 0.022; and synovial PMN%: 88.5% versus 92.5%, DOM = 4%, p = 0.012. Furthermore, using the MSIS cutoffs, the false-negative rates of several parameters were higher in the antibiotic group; ESR: 19.2% (nine of 47) versus 6.1% (six of 99) (relative risk, 3.1; 95% confidence interval [CI], 1.2-8.3; p = 0.020); CRP: 14.9% (seven of 47) versus 2.00% (two of 100) (relative risk, 7.4; 95% CI, 1.6-34.4); PMN%: 23.1% (12 of 52) versus 9.4% (10 of 106) (relative risk, 2.4; 95% CI, 1.1-5.2; p = 0.027). Patients in the antibiotic group also had higher rates of negative cultures: 26.4% (14 of 53) versus 12.9% (14 of 108) (relative risk, 2.0; 95% CI, 1.05-3.9; p = 0.046). CONCLUSIONS: It appears that premature antibiotic treatments are associated with lower medians of diagnostic laboratory values. Thus, and in line with the guideline recommendations of the American Academy of Orthopaedic Surgeons, patients with suspected late-PJI should not receive antibiotics until the diagnosis is reached or refuted. LEVEL OF EVIDENCE: Level III, diagnostic study.

The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip.

BACKGROUND: Synovial fluid biomarkers have demonstrated diagnostic accuracy surpassing the currently used diagnostic tests for periprosthetic joint infection (PJI). QUESTIONS/PURPOSES: The purpose of this study is to directly compare the sensitivity and specificity of the synovial fluid α-defensin immunoassay to the leukocyte esterase (LE) colorimetric test strip. METHODS: Synovial fluid was collected from 46 patients meeting the inclusion criteria of this prospective diagnostic study. Synovial fluid samples were tested with both a novel synovial-fluid-optimized immunoassay for α-defensin and the LE colorimetric test strip. The Musculoskeletal Infection Society (MSIS) definition was used to classify 23 periprosthetic infections and 23 aseptic failures; this classification was used as the standard against which the two diagnostic tests were compared. RESULTS: The synovial fluid α-defensin immunoassay correctly predicted the MSIS classification of all patients in the study, demonstrating a sensitivity and specificity of 100% for the diagnosis of PJI. The α-defensin assay could be read for all samples, including those with blood in the synovial fluid. The leukocyte esterase test strip could not be interpreted in eight of 46 samples (17%) as a result of blood interference. Analysis of the LE strips that could be interpreted yielded a sensitivity of 69% and a specificity of 100%. CONCLUSIONS: The synovial fluid α-defensin immunoassay outperformed the LE colorimetric test strip in this study and provided reliable results even when the LE test strip failed as a result of blood interference. The simple analytic results provided by the α-defensin immunoassay, compared with the more complex and interpretive nature of both the MSIS criteria and LE colorimetric test strip, make it a highly attractive diagnostic tool. LEVEL OF EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Medicare fails to compensate additional surgical time and effort associated with revision arthroplasty.

In comparison to primary total knee arthroplasty, surgical time was 1.8 times greater for all knee revisions and 2.4 times greater for complex knee revisions. Knee revisions had an 8.5% higher rate of 90-day repeat procedures. In comparison to primary total hip arthroplasty, surgical time was 1.8 greater for all hip revisions and 2.6 fold greater for complex hip revisions. Hip revisions had a 3.4% higher rate of 90-day repeat procedures. Practices based on revisions or complex revisions alone would see a 32% and 50% decrease in reimbursement respectively compared to the ones based on primary arthroplasty. The projected future increase in primary arthroplasties and the relative incentive to perform primary arthroplasty may soon put patient access to physicians willing to perform revision arthroplasty at risk.

Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) remains a serious clinical challenge. There is a pressing need for improved diagnostic testing methods; biomarkers offer one potentially promising approach. QUESTIONS/PURPOSES: We evaluated the diagnostic characteristics of 16 promising synovial fluid biomarkers for the diagnosis of PJI. METHODS: Synovial fluid was collected from 95 patients meeting the inclusion criteria of this prospective diagnostic study. All patients were being evaluated for a revision hip or knee arthroplasty, including patients with systemic inflammatory disease and those already receiving antibiotic treatment. The Musculoskeletal Infection Society (MSIS) definition was used to classify 29 PJIs and 66 aseptic joints. Synovial fluid samples were tested by immunoassay for 16 biomarkers optimized for use in synovial fluid. Sensitivity, specificity, and receiver operating characteristic curve analysis were performed to assess for diagnostic performance. RESULTS: Five biomarkers, including human α-defensin 1-3, neutrophil elastase 2, bactericidal/permeability-increasing protein, neutrophil gelatinase-associated lipocalin, and lactoferrin, correctly predicted the MSIS classification of all patients in this study, with 100% sensitivity and specificity for the diagnosis of PJI. An additional eight biomarkers demonstrated excellent diagnostic strength, with an area under the curve of greater than 0.9. CONCLUSIONS: Synovial fluid biomarkers exhibit a high accuracy in diagnosing PJI, even when including patients with systemic inflammatory disease and those receiving antibiotic treatment. Considering that these biomarkers match the results of the more complex MSIS definition of PJI, we believe that synovial fluid biomarkers can be a valuable addition to the methods utilized for the diagnosis of infection. LEVEL OF EVIDENCE: Level II, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Clostridium difficile is common in patients with postoperative diarrhea after hip and knee arthroplasty.

Clostridium difficile is an antibiotic-associated gastrointestinal infection that has detrimental consequences. We sought to determine the incidence of C. difficile in TJA patients with postoperative diarrhea, to determine risk factors for C. difficile infection, and to establish the incidence of C. difficile-related complications. Our institutional protocol includes screening for C. difficile in all patients with diarrhea after TJA. We identified 121 such patients over four years with twenty-eight (23%) testing positive for C. difficile. Revision arthroplasty and prolonged postoperative antibiotic use were risk factors for C. difficile infection. With our protocol of screening and immediate treatment of C. difficile positive patients, we found no C. difficile-associated complications.