Concomitant Hip and Knee Periprosthetic Joint Infection in Periprosthetic Fracture: Diagnostic Utility of Serum and Synovial Fluid Markers

BackgroundDiagnosing periprosthetic joint infection (PJI) in patients with a periprosthetic fracture can be challenging due to concerns regarding the reliability of commonly used serum and synovial fluid markers. This study aimed at determining the diagnostic performance of serum and synovial fluid markers for diagnosing PJI in patients with a periprosthetic fracture of a total joint arthroplasty.MethodsA total of 144 consecutive patients were included: (1) 41 patients with concomitant PJI and periprosthetic fracture and (2) 103 patients with periprosthetic fracture alone. Serum markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and synovial markers white blood cell (WBC) count and polymorphonuclear percentage were assessed.ResultsESR demonstrated 87% sensitivity and 48% specificity at the Musculoskeletal Infection Society threshold, area under the curve (AUC) of 0.74, and optimal threshold of 45.5 mm/h (76% sensitivity, 68% specificity). CRP showed 94% sensitivity and 40% specificity, AUC of 0.68 with optimal threshold of 16.7 mg/L (84% sensitivity, 51% specificity). Synovial WBC count demonstrated 87% sensitivity and 78% specificity, AUC of 0.90 with optimal threshold of 4552 cells/μL (86% sensitivity, 85% specificity). Polymorphonuclear percentage showed 79% sensitivity and 63% specificity, AUC of 0.70 with optimal threshold of 79.5% (74% sensitivity, 63% specificity). The AUC of all combined markers was 0.90 with 84% sensitivity and 79% specificity.ConclusionThe diagnostic utility of the serum and synovial markers for diagnosing PJI was lower in the setting of concomitant periprosthetic fracture compared to PJI alone. Using the Musculoskeletal Infection Society thresholds, ESR, CRP, and WBC count showed high sensitivity, yet low specificity, thus higher thresholds and utilizing all serum and synovial markers in combination should be considered.     

Synovial Fluid Calprotectin for the Preoperative Diagnosis of Chronic Periprosthetic Joint Infection

BackgroundThe diagnosis of periprosthetic joint infection (PJI) represents a challenge in clinical practice and the analysis of synovial fluid is a useful diagnostic tool. Calprotectin is an inflammatory biomarker widely used in the evaluation of chronic inflammatory diseases; however, little is known about its role in PJI. The purpose of this study is to determine the reliability of synovial calprotectin in the diagnosis of PJI.MethodsSeventy-six patients with painful knee arthroplasty were included in this prospective observational study. Synovial fluid was analyzed for cell count, percentage of polymorphonuclear neutrophils, microbiological culture, leukocyte esterase strip test, alpha-defensin rapid test, and calprotectin immunoassay dosage. The 2018 Consensus Statements criteria for PJI were used as standard reference to define the presence of infection. Sensitivity, specificity, positive and negative likelihood ratio, and receiver-operation characteristic curve were calculated for calprotectin immunoassay test.ResultsBy 2018 Consensus Statements criteria for PJI, 28 patients were considered infected, 44 patients were considered not infected, and 4 patients were classified as inconclusive. The calprotectin synovial fluid test resulted in 2 false-positive results and no false-negative results. The calprotectin synovial fluid test demonstrated a sensitivity of 100% (95% confidence interval [CI] 99.96-100) and specificity of 95% (95% CI 89.4-100) for the diagnosis of PJI. The positive likelihood ratio was 22 (95% CI 5.680-85.209) and the negative likelihood ratio was 0 (95% CI 0-0.292). The area under the receiver-operation characteristic curve was 0.996 (95% CI 94.3-100).ConclusionThe present study suggests that synovial calprotectin immunoassay test has a high sensitivity and specificity in the diagnosis of knee PJI. Moreover, it is easily applied, quick and valuable in clinical practice.     

Synovial Fluid Alpha-Defensin Is an Adjunctive Tool in the Equivocal Diagnosis of Periprosthetic Joint Infection

Background

Synovial fluid alpha-defensin has shown to be a reliable diagnostic test for the diagnosis of periprosthetic joint infection (PJI), but its use in equivocal cases has yet to be established. The purpose of this study was to determine the reliability of alpha-defensin testing in patients, where the diagnosis of PJI was unclear.

Diagnostic Utility of Platelet Count/Lymphocyte Count Ratio and Platelet Count/Mean Platelet Volume Ratio in Periprosthetic Joint Infection Following Total Knee Arthroplasty

BackgroundDiagnosing a periprosthetic joint infection (PJI) can be challenging and often requires a combination of clinical and laboratory findings. Monocyte/lymphocyte ratio, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio (PLR), and platelet/mean platelet volume ratio (PVR) are simple predictors for inflammation that can be readily obtained from complete blood count. The aim of this study is to evaluate the diagnostic utility of these markers in predicting PJI in total knee arthroplasty (TKA) patients.MethodsA total of 538 patients who underwent revision TKA with calculable marker ratios prerevision in 2 groups were evaluated: (1) 206 patients with a preoperative diagnosis of PJI (group I) and (2) 332 patients treated for revision TKA for aseptic failures (group II). The diagnostic abilities of the markers were assessed via receiver operator characteristic curve analysis.ResultsThe optimal threshold of PVR at 30.82 had the highest sensitivity of 87.7%, while the optimal threshold of PLR at 234.13 had the highest specificity of 82.5%. Both PLR and PVR, when combined with Musculoskeletal Infection Society thresholds for erythrocyte sedimentation rate, C-reactive protein, synovial WBC, and PMN%, achieve significantly higher sensitivity and specificity rates for PJI at or above 97% (PLR: 99.03%; 98.80%; PVR: 98.54%;97.89%).ConclusionOur study demonstrates that PVR and PLR, which are readily available and inexpensive to obtain from complete blood counts, when combined with serum and synovial fluid markers have increased sensitivity and specificity comparable to that of alpha defensin. This suggests that PVR and PLR can be used together with other hematologic and aspirate markers to increase the accuracy of PJI diagnosis in TKA patients.     

Diagnosing Periprosthetic Joint Infection in Inflammatory Arthritis: Assumption Is the Enemy of True Understanding

Background

Despite concern over the interpretation of serum and synovial fluid tests to screen and diagnose periprosthetic joint infection (PJI) in patients with inflammatory arthritis, only a single study has investigated this area. We aimed to assess accuracy of clinical and laboratory markers for PJI diagnosis in the context of underlying inflammatory arthritis.

Diagnostic Utility and Thresholds for Commonly Obtained Serum and Synovial Markers Prior to Reimplantation in Periprosthetic Joint Infection

BackgroundAccurate diagnosis of persistent periprosthetic joint infection (PJI) during 2-stage exchange remains a challenge. This study evaluated the diagnostic performance and thresholds of several commonly obtained serum and synovial markers to better guide reimplantation timing.MethodsThis was a retrospective review of 249 patients who underwent 2-stage exchange with antibiotic spacers for PJI. Serum and synovial markers analyzed included white blood cell (WBC) count, polymorphonuclear percentage (PMN%), neutrophil-to-lymphocyte ratio (NLR), and absolute neutrophil count (ANC). Serum markers analyzed were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), as well as percentage change in ESR and CRP from initial diagnosis to reimplantation. Area under the curve (AUC) analyses were performed to determine diagnostic accuracy of detecting PJI.ResultsIn TKAs, synovial ANC and WBC had the highest AUCs (0.76), with thresholds of 2,952 and 3,800 cells/μL, respectively. The next best marker was serum CRP (0.73) with a threshold of 5.2 mg/dL. In THAs, serum CRP had the highest AUC (0.84) with a threshold of 4.3 mg/dL, followed by synovial PMN% (0.80) with a threshold of 77%. Percentage change in serum ESR or CRP provided low diagnostic value overall.ConclusionRegarding serum markers, CRP consistently performed well in detecting persistent PJI in patients with antibiotic spacers. Absolute values of serum CRP and ESR had better diagnostic value than trends for guiding reimplantation timing. Diagnostic performance differed with joint type; however, synovial markers outperformed serum counterparts. No marker alone can be utilized to diagnose residual PJI in these patients, and further work is needed in this domain.     

Mortality During Total Knee Periprosthetic Joint Infection

Background

Periprosthetic joint infections (PJIs) are fraught with multiple complications including poor patient-reported outcomes, disability, reinfection, disarticulation, and even death. We sought to perform a systematic review asking the question: (1) What is the mortality rate of a PJI of the knee undergoing 2-stage revision for infection? (2) Has this rate improved over time? (3) How does this compare to a normal cohort of individuals?

A Novel Adjunct Indicator of Periprosthetic Joint Infection: Platelet Count and Mean Platelet Volume

BackgroundDiagnosing a periprosthetic joint infection (PJI) is difficult and often requires a combination of objective findings. The purpose of this study is to determine whether platelets, a known acute phase reactant, would be able to further aid in the diagnosis of PJI.MethodsA single-institution retrospective review study was performed on all revision total hip and knee arthroplasties done between 2000 and 2016 (n = 4939). PJI was defined by Musculoskeletal Infection Society criteria (n = 949). Platelet count and mean platelet volume were assessed from each patient’s preoperative complete blood count. These values were then assessed as a ratio via receiver operating characteristic (ROC) curve analysis.ResultsThe platelet count to mean platelet volume ratio for PJI patients was 33.45 compared to 25.68 for patients in the aseptic revision cohort (P < .001). ROC curve analysis demonstrates that a ratio of 31.70 has a sensitivity of 48.10 (95% confidence interval 44.9-51.4) and a specificity of 80.85 (95% confidence interval 79.6-82.1). This specificity was higher than that of both estimated sedimentation ratio (ESR) and C-reactive protein (CRP) for the same cohorts using optimal values determined via ROC curve analysis. When used in conjunction with ESR and CRP, there was a statistically significant increase in the diagnostic performance of the model used to assess PJI relative to the model that just employed ESR and CRP (P < .05).ConclusionOur study demonstrates that platelets and their associated serum biomarkers are associated with PJI and warrant consideration in patients who are being evaluated for potential PJI.     

Plasma Fibrinogen and Platelet Count Are Referable Tools for Diagnosing Periprosthetic Joint Infection: A Single-Center Retrospective Cohort Study

BackgroundAlthough the MusculoSkeletal Infection Society has suggested a series of markers to diagnose periprosthetic joint infection (PJI), no single marker can accurately identify infection before revision hip or knee arthroplasty, and exploring promising markers to easily and reliably diagnose PJI is ongoing. The aim of this study was to evaluate the diagnostic value of plasma fibrinogen and platelet count for diagnosing PJI.MethodsWe retrospectively included 439 patients who underwent revision arthroplasty from January 2008 to December 2018; 79 patients with coagulation-related comorbidities were evaluated separately. The remaining 360 patients constituted 153 PJI and 207 non-PJI patients. Receiver operating characteristic curves were used to evaluate the maximum sensitivity and specificity of the tested markers.ResultsThe receiver operating characteristic curves showed that the areas under the curve for plasma fibrinogen, platelet count, and serum C-reactive protein and erythrocyte sedimentation rate were 0.834, 0.746, 0.887, and 0.842, respectively. Based on Youden's index, the optimal predictive cutoffs for fibrinogen and platelet count were 3.57 g/L and 221 × 10⁹/L, respectively. The sensitivity and specificity, respectively, were 68.6% and 86.0% (fibrinogen) and 57.5% and 83.1% (platelet count) for diagnosing PJI. The sensitivity and specificity, respectively, were 76.7% and 72.2% (fibrinogen) and 48.8% and 63.9% (platelet count) for diagnosing PJI in patients with coagulation-related comorbidities.ConclusionPlasma fibrinogen performed well for diagnosing PJI before revision arthroplasty, and its value neared that of traditional inflammatory markers. Although the diagnostic value of the platelet count was inferior to traditional markers, its diagnostic value was fair for diagnosing PJI. Fibrinogen also may be useful for diagnosing PJI in patients with coagulation-related comorbidities.     

Development and Validation of an Evidence-Based Algorithm for Diagnosing Periprosthetic Joint Infection

BackgroundThe guidelines for diagnosis of periprosthetic joint infection (PJI) introduced by the American Academy of Orthopaedic Surgeons served the orthopedic community well. However, they have never been validated and do not account for newer diagnostic modalities. Our aim was to update current guidelines and develop an evidence-based and validated diagnostic algorithm.MethodsThis multi-institutional study examined total joint arthroplasty patients from 3 institutions. Patients fulfilling major criteria for infection as defined by Musculoskeletal Infection Society were considered infected (n = 684). Patients undergoing aseptic revision for a noninfective indication and did not show evidence of PJI or undergo reoperation within 2 years served as a noninfected control group (n = 820). The algorithm was validated on a separate cohort of 422 cases.ResultsThe first step in evaluating PJI should include a physical examination, followed by serum C-reactive protein, erythrocyte sedimentation rate, and D-dimer. If at least one of these tests are elevated, or if high clinical suspicion exists, joint aspiration should be performed, sending the fluid for a white blood cell count, leukocyte esterase, polymorphonuclear percentage, and culture. Alpha defensin did not show added benefit as a routine diagnostic test. In inconclusive cases, intraoperative findings including gross purulence, histology, and next-generation sequencing or a single positive culture can aid in making the diagnosis. The proposed algorithm demonstrated a high sensitivity (96.9%) and specificity (99.5%).ConclusionThis validated, evidence-based algorithm for diagnosing PJI should guide clinicians in the workup of patients undergoing revision arthroplasty and improve clinical practice. It also has the potential to reduce cost.     

Periprosthetic Joint Infection in Patients with Inflammatory Joint Disease: a Review of Risk Factors and Current Approaches to Diagnosis and Management

Background

Prevention, early identification, and effective management of periprosthetic joint infection (PJI) in patients with inflammatory joint disease (IJD) present unique challenges for physicians. Discontinuing disease-modifying anti-rheumatoid drugs (DMARDs) perioperatively may reduce immunosuppression and infection risk at the expense of increasing disease flares. Interpreting traditional diagnostic markers of PJI can be difficult due to disease-related inflammation.

Purposes

This review is designed to answer how to (1) manage immunosuppressive/DMARD therapy perioperatively, (2) diagnose PJI in patients with IJD, and (3) treat PJI in this population.

Methods

The PubMed database was searched for relevant articles with subsequent review by independent authors.

Results

While there is evidence to support the use of methotrexate perioperatively in RA patients, it remains unclear whether using anti-tumor necrosis factor medications perioperatively increases the risk of surgical site infections. Serum erythrocyte sedimentation rate and C-reactive protein can be useful for diagnosis of PJI in this population, but only as part of comprehensive workup that ultimately relies upon sampling of joint fluid. Management of PJI depends on several clinical factors including duration of infection and the likelihood of biofilm presence, the infecting organism, sensitivity to antibiotic therapy, and host immune status. The evidence suggests that two-stage revision or resection arthroplasty is more likely to eradicate infection, particularly when MRSA is the pathogen.

Conclusion

Immunosuppression and baseline inflammatory changes in the IJD population can complicate the prevention, diagnosis, and treatment of PJI. Understanding the increase in risk associated with IJD and its treatment is essential for proper management when patients undergo lower extremity arthroplasty.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9338-8) contains supplementary material, which is available to authorized users.     

Diagnostic Value of Synovial White Blood Cell Count and Serum C-Reactive Protein for Acute Periprosthetic Joint Infection After Knee Arthroplasty

Background

The diagnosis of periprosthetic joint infection (PJI) remains difficult, particularly in acute postoperative stage. The purpose of this study was to investigate the optimal cutoff value of synovial white blood cell (WBC) count, percentage of polymorphonuclear cells, erythrocyte sedimentation rate, and C-reactive protein (CRP) for diagnosing early postoperative infection after knee joint arthroplasty.

D-Dimer,Erythrocyte Sedimentation Rate,and C-Reactive Protein Sensitivities for Periprosthetic Joint Infection Diagnosis

BackgroundThere is contradicting evidence on the diagnostic value of inflammatory biomarkers for periprosthetic joint infection (PJI). We sought to quantify the sensitivity of D-dimer for acute and chronic PJI diagnosis and evaluate D-dimer lab values in the 90-day postoperative window in a control cohort of primary joint arthroplasty patients for comparison.MethodsAn institutional database was queried for patients undergoing revision procedures for PJI after total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2014 to present. CRP, ESR, and D-dimer were collected within 90 days pre and postoperatively and sensitivities for the diagnosis of PJI were calculated. The control group included patients who underwent a negative diagnostic workup for deep venous thrombosis (DVT) or pulmonary embolus (PE) and had a D-dimer lab collected within 90 days postoperatively from primary total joint arthroplasty (TJA).ResultsA total of 604 PJI patients were identified, and 81 patients had D-dimer, ESR, and CRP collected. There were 50/81 acute PJI patients and 31/81 chronic PJI patients who had median D-dimer values of 2,136.5 ng/mL [interquartile range (IQR): 1,642-3,966.5] and 3,336 ng/mL [IQR: 1,976-5,594]. Only the chronic PJI group had significantly higher D-dimer values when compared to the control cohort (P = .009). The sensitivity of D-dimer was calculated to be 92% and 93.5% in the acute and chronic PJI groups, respectively.ConclusionSerum D-dimer may not have high diagnostic utility for acute PJI, especially in the setting of recent surgery; however, it still may be useful for patients who have chronic PJI.     

Synovial Biomarkers to Detect Chronic Periprosthetic Joint Infection: A Pilot Study to Compare Calprotectin Rapid Test,Calprotectin ELISA Immunoassay and Leukocyte Esterase Test

BackgroundPeriprosthetic joint infection (PJI) is a devastating complication after joint replacement surgery, and making diagnosis is often far from obvious. Calprotectin was recently proposed as a promising synovial biomarker to detect PJI. To our knowledge, no comparative study exists between enzyme-linked immunosorbent assay (ELISA) and rapid calprotectin test (CalFAST). Our purpose was to compare these methods with leukocyte esterase (LE) test from synovial fluid of painful knee arthroplasty subjected to infectious workup.MethodsNinety-three patients were included in this prospective observational study. They underwent synovial fluid aspiration that was analyzed for cell count, microbiological culture, LE test, calprotectin rapid test, and calprotectin immunoassay dosage. The 2018 Consensus Statements criteria for PJI were used to diagnose PJI. Sensitivity, specificity, positive and negative likelihood ratio, and receiver operating characteristic were calculated for detection methods and compared.ResultsWe categorized 39 patients as infected and 50 patients as not infected. The sensitivity comparing the ELISA test and CalFAST test was similar, 92.3% and 97.4%, respectively. LE rapid test showed 46% of sensitivity and 94% of specificity. The highest specificity was found with ELISA test (100%). Comparing the receiver operating characteristic curves by z-test, there were statistically significant differences between LE strip test and the other two methods. Otherwise, no statistically significant differences were present between ELISA and CalFAST test.ConclusionSynovial calprotectin detection has high accuracy in knee PJI diagnosis, both ELISA and rapid test. LE strip test remains a good test to confirm the diagnosis of PJI in case of positivity. In clinical practice, the calprotectin rapid test can be considered an excellent point-of-care test.     

In-Hospital Mortality in Patients With Periprosthetic Joint Infection

Background

While periprosthetic joint infection (PJI) has a huge impact on patient function and health, only a few studies have investigated its impact on mortality. The purpose of this large-scale study was to (1) determine the rate and trends of in-hospital mortality for PJI and (2) compare the in-hospital mortality rate of patients with PJI and those undergoing revision arthroplasty for aseptic failure and patients undergoing other nonorthopedic major surgical procedures.

Synovial C-Reactive Protein is a Useful Adjunct for Diagnosis of Periprosthetic Joint Infection

BackgroundThe diagnostic utility of synovial C-reactive protein (CRP) has been debated for a while. Existing studies are limited by small sample sizes and using outdated criteria for periprosthetic joint infection (PJI). Furthermore, the relationship between synovial and serum CRP has rarely been investigated in the setting of PJI. This study aimed to evaluate the diagnostic utility of synovial CRP and to assess its relationship with serum CRP and other common biomarkers.MethodsWe reviewed 621 patients who underwent evaluation for PJI prior to revision arthroplasty from 2014 to 2021. Biomarkers, including serum CRP and erythrocyte sedimentation rate, synovial CRP, polymorphonuclear leukocyte percentage, white blood cell count, and alpha-defensin, were evaluated using the 2018 International Consensus Meeting criteria.ResultsIn total, 194 patients had a PJI; 394 were considered aseptic failures and 33 were inconclusive. Synovial CRP showed an area under the curve (AUC) of 0.951 (95% CI, 0.932-0.970) with 74.2% sensitivity and 98.0% specificity, whereas, serum CRP had an AUC of 0.926 (95% CI, 0.903-0.949) with 83.5% sensitivity and 88.3% specificity. There was a good correlation between synovial and serum CRP (R = 0.703; 95% CI, 0.604-0.785). The combination of serum and synovial CRP yielded a significantly higher AUC than that obtained when using serum CRP alone (AUC 0.964 versus 0.926, P = .016).ConclusionSynovial CRP demonstrated excellent accuracy when used to determine the presence of PJI. There was a good correlation between serum and synovial CRP levels in revision arthroplasty patients and the combined use of serum and synovial CRP proved to be more accurate than the serum test alone. These findings support the use of synovial CRP as an adjunct in the workup of PJI.     

Management of Periprosthetic Joint Infection: The More We Learn,the Less We Know

BackgroundDespite the tremendous and long-standing success of total hip arthroplasty and total knee arthroplasty as treatments for end-stage arthritis, periprosthetic joint infection (PJI) remains a rare but feared complication of these procedures.MethodsThis review highlights some of the difficulties inherent to studying PJI. These include the difficulty in powering studies to capture this relatively uncommon complication, as well as the heterogeneity in clinical presentation and manifestations associated with the diagnosis and treatment of PJI.ConclusionWe suggest an algorithm for moving forward with new research in an attempt to answer the challenging questions facing the arthroplasty community regarding PJI.     

Longer Operative Time Results in a Higher Rate of Subsequent Periprosthetic Joint Infection in Patients Undergoing Primary Joint Arthroplasty

Background

Whether prolonged operative time is an independent risk factor for subsequent surgical site infection (SSI) and periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) remains a clinically significant and underexplored issue. The aim of this study is to investigate the association between operative time and the risk of subsequent SSI and PJI in patients undergoing primary TJA.

The Utility of Serum d-Dimer for the Diagnosis of Periprosthetic Joint Infection in Revision Total Hip and Knee Arthroplasty

BackgroundThere is scarce and contradicting evidence supporting the use of serum d-dimer for the diagnosis of periprosthetic joint infection in revision total hip (THA) and knee (TKA) arthroplasty. Therefore, the purpose of this study is to test the accuracy of serum d-dimer against the 2013 International Consensus Meeting (ICM) criteria.MethodsA retrospective review was performed on a consecutive series of 172 revision THA/TKA surgeries performed by 3 fellowship-trained surgeons at a single institution (August 2017 to May 2019) and that had d-dimer performed during their preoperative workup. Of this cohort, 111 (42 THAs/69 TKAs) cases had complete 2013 ICM criteria tests and were included in the final analysis. Septic and aseptic revisions were categorized per 2013 ICM criteria (“gold standard”) and compared against serum d-dimer using an established threshold (850 ng/mL). Sensitivity, specificity, likelihood ratios, and positive/negative predictive values were determined. Independent t-tests, Fisher’s exact tests, chi-squared tests, and receiver operating characteristic curve analysis were performed.ResultsThere was no statistically significant difference in baseline demographics between septic and aseptic cases per 2013 ICM criteria. When compared to ICM criteria, d-dimer demonstrated high sensitivity (95.9%) and negative predictive value (90.9%) but low specificity (32.3%), positive predictive value (52.8%), and overall, poor accuracy (61%) to diagnose periprosthetic joint infection. Positive likelihood ratio was 1.42 while negative likelihood ratio was 0.13. The area under the curve (AUC) was 0.742.ConclusionSerum d-dimer has poor accuracy to discriminate between septic and aseptic cases using a described threshold in the setting of revision THA and TKA.