Synovial Fluid Viscosity Test is Promising for the Diagnosis of Periprosthetic Joint Infection

BackgroundSo far there is no “gold standard” test for the diagnosis of periprosthetic joint infection (PJI), compelling clinicians to rely on several serological and synovial fluid tests with no 100% accuracy. Synovial fluid viscosity is one of the parameters defining the rheology properties of synovial fluid. We hypothesized that patients with PJI may have a different level of synovial fluid viscosity and aimed to investigate the sensitivity and specificity of synovial fluid viscosity in detecting PJI.MethodsThis prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 45 patients undergoing revision for PJI (n = 15), revision for aseptic failure (n = 15), and primary arthroplasty (n = 15). PJI was defined using the Musculoskeletal Infection Society criteria. In all patients, synovial fluid viscosity, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and plasma d-dimer levels were measured preoperatively.ResultsThe synovial fluid viscosity level was significantly lower (P = .0011) in patients with PJI (7.93 mPa·s, range 3.0-15.0) than in patients with aseptic failure (13.11 mPa·s, range 6.3-20.4). Using Youden’s index, 11.80 mPa·s was determined as the optimal threshold value for synovial fluid viscosity for the diagnosis of PJI. Synovial fluid viscosity outperformed CRP, ESR, and plasma d-dimer, with a sensitivity of 93.33% and a specificity of 66.67%.ConclusionSynovial fluid viscosity seems to be on the same level of accuracy with CRP, ESR, and d-dimer regarding PJI detection and to be a promising marker for the diagnosis of PJI.     

Synovial Fluid Absolute Neutrophil Count and Neutrophil-To-Lymphocyte Ratio are not Superior to Polymorphonuclear Percentage in Detecting Periprosthetic Joint Infection

BackgroundSerum and synovial biomarkers are currently used to diagnose periprosthetic joint infection (PJI). Serum neutrophil-to-lymphocyte ratio (NLR) has shown promise as an inexpensive test in diagnosing infection, but there are no reports of synovial NLR or absolute neutrophil count (ANC) for diagnosing chronic PJI. The purpose of this study was to investigate the diagnostic potential of both markers.MethodsA retrospective review of 730 patients who underwent total joint arthroplasty and subsequent aspiration was conducted. Synovial white blood cell (WBC) count, synovial polymorphonuclear percentage (PMN%), synovial NLR, synovial ANC, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), serum WBC, serum PMN%, serum NLR, and serum ANC had their utility in diagnosing PJI examined by area-under-the-curve analyses (AUC). Pairwise comparisons of AUCs were performed.ResultsThe AUCs for synovial WBC, PMN%, NLR, and ANC were 0.84, 0.84, 0.83, and 0.85, respectively. Synovial fluid ANC was a superior marker to synovial NLR (P = .027) and synovial WBC (P = .003) but not PMN% (P = .365). Synovial NLR was inferior to PMN% (P = .006) but not different from synovial WBC (P > .05). The AUCs for serum ESR, CRP, WBC, PMN%, NLR, and ANC were 0.70, 0.79, 0.63, 0.72, 0.74, and 0.67, respectively. Serum CRP outperformed all other serum markers (P < .05) except for PMN% and NLR (P > .05). Serum PMN% and NLR were similar to serum ESR (P > .05).ConclusionSynovial ANC had similar performance to PMN% in diagnosing chronic PJI, whereas synovial NLR was a worse diagnostic marker. The lack of superiority to synovial PMN% limits the utility of these tests compared to established criteria.     

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.     

Utility of Diagnostic Markers in Late Periprosthetic Joint Infection Workup for Total Knee Arthroplasty Patients Who Received Antibiotics 48 Hours Before Aspiration

BackgroundDiagnosing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains challenging despite recent advancements in testing and evolving criteria over the last decade. Moreover, the effects of antibiotic use on diagnostic markers are not fully understood. Thus, this study sought to determine the influence of antibiotic use within 48 hours before knee aspiration on synovial and serum laboratory values for suspected late PJI.MethodsPatients who underwent a TKA and subsequent knee arthrocentesis for PJI workup at least 6 weeks after their index arthroplasty were reviewed across a single healthcare system from 2013 to 2020. Median synovial white blood cell (WBC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum WBC count were compared between immediate antibiotic and nonantibiotic PJI groups. Receiver operating characteristic (ROC) curves and Youden’s index were used to determine test performance and diagnostic cutoffs for the immediate antibiotics group.ResultsThe immediate antibiotics group had significantly more culture-negative PJIs than the no antibiotics group (38.1 versus 16.2%, P = .0124). Synovial WBC count demonstrated excellent discriminatory ability for late PJI in the immediate antibiotics group (area under curve, AUC = 0.97), followed by synovial PMN percentage (AUC = 0.88), serum CRP (AUC = 0.86), and serum ESR (AUC = 0.82).ConclusionAntibiotic use immediately preceding knee aspiration should not preclude the utility of synovial and serum lab values for the diagnosis of late PJI. Instead, these markers should be considered thoroughly during infection workup considering the high rate of culture-negative PJI in these patients.Level of EvidenceLevel III, retrospective comparative study.     

Synovial Fluid d-Lactate—A Novel Pathogen-Specific Biomarker for the Diagnosis of Periprosthetic Joint Infection

BackgroundSynovial fluid d-lactate may be useful for diagnosing periprosthetic joint infection (PJI) as this biomarker is exclusively produced by bacteria. We evaluated the performance of synovial fluid d-lactate using 2 definition criteria and determined its optimal cutoff value for diagnosing PJI.MethodsConsecutive patients undergoing joint aspiration before prosthesis revision were prospectively included. Synovial fluid was collected for culture, leukocyte count, and d-lactate concentration (by spectrophotometry). Youden's J statistic was used for determining optimal d-lactate cutoff value on the receiver operating characteristic curve by maximizing sensitivity and specificity.ResultsA total of 224 patients were included. Using Musculoskeletal Infection Society criteria, 71 patients (32%) were diagnosed with PJI and 153 (68%) with aseptic failure (AF), whereas using institutional criteria, 92 patients (41%) were diagnosed with PJI and 132 (59%) with AF. The optimal cutoff of synovial fluid d-lactate to differentiate PJI from AF was 1.3 mmol/L, independent of the used definition criteria. Synovial fluid d-lactate had a sensitivity of 94.3% (95% confidence interval [95% CI], 86.2-98.4) and specificity of 78.4% (95% CI, 66.8-81.2) using Musculoskeletal Infection Society criteria, whereas its sensitivity was 92.4% (95% CI, 84.9-96.9) and specificity 88.6% (95% CI, 81.9-93.5) using institutional criteria. The concentration of d-lactate was higher in infections caused by Staphylococcus aureus (P < .001) and streptococci (P = .016) than by coagulase-negative staphylococci or in culture-negative PJI.ConclusionThe synovial fluid d-lactate showed high sensitivity (>90%) for diagnosis of PJI using both definition criteria and correlated with the pathogen virulence. The high sensitivity makes this biomarker useful as a point-of-care screening test for PJI.Level of EvidenceDiagnostic level I.     

Can the Leukocyte Esterase Strip Test Predict Persistence of Periprosthetic Joint Infection at Second-Stage Reimplantation?

BackgroundWe evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR.MethodsThe records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP + ESR were calculated.ResultsSensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively.ConclusionThe LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.     

Measurement of Serum Anti-staphylococcal Antibodies Increases Positive Predictive Value of Preoperative Aspiration for Hip Prosthetic Joint Infection

BackgroundPreoperative synovial fluid culture is pivotal in the early diagnosis of prosthetic joint infection (PJI) but may yield false-positive and false-negative results. We evaluated the predictive value of synovial fluid culture results combined with the measurement of serum anti-staphylococcal antibodies (SASA).Questions/purposes(1) For hip and knee PJI, does combining positive SASA results with preoperative synovial culture results improve the positive predictive value (PPV) of preoperative synovial fluid culture alone? (2) Does combining preoperative synovial fluid culture results with a positive cell count and differential result increase the PPV of preoperative synovial fluid culture alone? (3) What proportion of isolated organisms exhibit concordance in antibiotic susceptibility: preoperative aspiration versus intraoperative isolates?MethodsA prospective study was conducted at two French reference centers that manage bone and joint infections and included 481 adult patients who had a revision or resection arthroplasty between June 25, 2012 and June 23, 2014. Exclusion criteria including no serum sample available for immunoassay, the lack of microbiological documentation, and the absence of preoperative aspiration reduced the patient number to 353. Seven patients with an undetermined SASA result were excluded from the analysis. We also excluded patients with PJI involving more than one Staphylococcus species (polystaphylococcal infection) and those in whom more than one Staphylococcus species was recovered from the preoperative synovial fluid culture (polystaphylococcal synovial fluid culture). In total, 340 patients were included in the analysis (no infection, 67% [226 of 340]; staphylococcal infection, 21% [71 of 340]; other infection, 13% [43 of 340]). The preoperative synovial fluid analysis included a cell count and differential and bacterial culture. SASAs were measured using a multiplex immunoassay. The diagnosis of PJI was determined using the Infectious Diseases Society of America (IDSA) criteria [14] and intraoperative tissue culture at the time of revision surgery was used as the gold standard (at least one positive intraoperative sample for a “virulent” organism (such as S. aureus) or two positive samples for a “non-virulent” (for example S. epidermidis).ResultsSASA increased the PPV compared with synovial fluid culture alone (92% [95% CI 82 to 97] versus 79% [95% CI 68 to 87]; p = 0.04); when stratified by site, an increase in PPV was seen in hip infections (100% [95% CI 89 to 100] versus 77% [95% CI 63 to 88]; p = 0.01) but not in knee infections (84% [95% CI 66 to 95] versus 80% [95% CI 64 to 91]; p = 0.75). A positive cell count and differential result increased the PPV of staphylococcal synovial fluid cultures compared with synovial fluid culture alone (86% [95% CI 70 to 95] versus 79% [95% CI 68 to 87]; p = 0.36); when stratified by site, no difference in hip and knee infections was observed (86% [95% CI 67 to 96] versus 77% [95% CI 63 to 88]; p = 0.42) and 86% [95% CI 70 to 95] versus 80% [95% CI 64 to 91]; p = 0.74).ConclusionSASA measurement improves the predictive value of synovial fluid cultures of the hip for all staphylococcal organisms, including coagulase-negative staphylococci, but the PPV of SASA plus synovial fluid culture it is not superior to the PPV of synovial fluid cell count/differential plus synovial culture for the knee.Level of EvidenceLevel III, diagnostic study.     

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.     

The Performance of Diagnostic Tests for Identifying Periprosthetic Joint Infection After Failed Partial Knee Arthroplasty

BackgroundIndications for unicompartmental knee arthroplasty (UKA) and patello-femoral arthroplasty are expanding. Despite the lower published infection rates for UKA and patello-femoral arthroplasty than total knee arthroplasty, periprosthetic joint infection (PJI) remains a devastating complication and diagnostic thresholds for commonly utilized tests have not been investigated recently. Thus, this study evaluated if diagnostic thresholds for PJI in patients who had a failed partial knee arthroplasty (PKA) align more closely with previously reported thresholds specific to UKA or the 2018 International Consensus Meeting on Musculoskeletal Infection.MethodsWe identified 109 knees in 100 patients that underwent PKA with eventual conversion to total knee arthroplasty within a single healthcare system from 2000 to 2021. Synovial fluid nucleated cell count and synovial polymorphonuclear percentage in addition to preoperative serum erythrocyte sedimentation rate, serum C-reactive protein, and serum white blood cell count were compared with Student’s t-tests between septic and aseptic cases. Receiver operating characteristic curves and Youden’s index were used to assess diagnostic performance and the optimal cutoff point of each test.ResultsSynovial nucleated cell count, synovial polymorphonuclear percentage, and serum C-reactive protein demonstrated excellent discrimination for diagnosing PJI with an area under the curve of 0.97 and lower cutoff values than the previously determined UKA specific criteria. Serum erythrocyte sedimentation rateESR demonstrated good ability with an area under the curve of 0.89.ConclusionSerum and synovial fluid diagnostic thresholds for PJI in PKAs align more closely with the thresholds established by the 2018 International Consensus Meeting as compared to previously proposed thresholds specific to UKA.Level of EvidenceLevel III, retrospective comparative study.     

Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infections and Rheumatoid Arthritis: A Prospective Cohort Study

BackgroundInflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA.MethodsThis prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively.ResultsAn increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%.ConclusionCurrent serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.     

Cell-free Deoxyribonucleic Acid: A Potential Biomarker of Chronic Periprosthetic Knee Joint Infection

BackgroundThe correct diagnosis of a chronic periprosthetic joint infection (PJI) is a major challenge in clinical practice, with the “gold standard” for diagnosis yet to be established. Synovial fluid analysis has been proven to be a useful tool for that purpose. Cell-free DNA (cf-DNA) levels have been shown to be increased in several conditions such as cancer, trauma, and sepsis. Therefore, this study was designed to evaluate the potential of synovial fluid cf-DNA quantification for the diagnosis of chronic periprosthetic infections following total knee arthroplasty.MethodsA prospective study with patients undergoing total knee arthroplasty revision surgery for any indication was performed. PJI diagnosis was defined according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. The study cohort consisted of 26 patients classified as infected and 40 as noninfected. Synovial fluid cf-DNA direct quantification by fluorescent staining was made. Sensitivity, specificity, and receiver operating characteristic curve were calculated.ResultsThe cf-DNA levels were significantly higher in patients who had PJIs (122.5 ± 57.2 versus 4.6 ± 2.8 ng/μL, P < .0001). With a cutoff of 15 ng/μL, the area under the receiver operating characteristic, sensitivity, and specificity of cf-DNA were 0.978, 96.2%, and 100%, respectively.ConclusionThe present study has shown that cf-DNA is increased in synovial fluid of patients who have chronic PJIs. It is a promising biomarker for knee PJI diagnosis and further studies are needed to confirm its utility.     

Hospital Costs for Unsuccessful Two-Stage Revisions for Periprosthetic Joint Infection

BackgroundAlthough 2-stage exchange arthroplasty is the preferred surgical treatment for periprosthetic joint infection (PJI) in the United States, little is known about the risk of complications between stages, mortality, and the economic burden of unsuccessful 2-stage procedures.MethodsThe 2015-2019 Medicare 100% inpatient sample was used to identify 2-stage PJI revisions in total hip and knee arthroplasty patients using procedural codes. We used the Fine and Gray sub-distribution adaptation of the conventional Kaplan-Meier method to estimate the probability of completing the second stage of the 2-stage PJI infection treatment, accounting for death as a competing risk. Hospital costs were estimated from the hospital charges using “cost-to-charge” ratios from Centers for Medicare and Medicaid Services.ResultsA total of 5094 total hip arthroplasty and 13,062 total knee arthroplasty patients had an index revision for PJI during the study period. In the first 12 months following the first-stage explantation, the likelihood of completing a second-stage PJI revision was 43.1% (95% confidence interval [CI] 41.7-44.5) for hips and 47.9% (95% CI 47.0-48.8) for knees. Following explantation, 1-year patient survival rates for hip and knee patients were 87.4% (95% CI 85.8-88.9) and 91.4% (95% CI 90.6-92.2), respectively. The median additional cost for hospitalizations between stages was $23,582 and $20,965 per patient for hips and knees, respectively. Hospital volume, Northeast or Midwest region, and younger age were associated with reduced PJI costs (P < .05).ConclusionAlthough viewed as the most preferred, the 2-stage revision strategy for PJI had less than a 50% chance of successful completion within the first year, and was associated with high mortality rates and substantial costs for treatment failure.     

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.     

The Potential Value of Monocyte to Lymphocyte Ratio,Platelet to Mean Platelet Volume Ratio in the Diagnosis of Periprosthetic Joint Infections

ObjectiveTo explore the possibility of obtaining more accurate information from routine blood tests for the diagnosis of periprosthetic joint infection (PJI).MethodsThis is a retrospective study. Between 2017 and 2018, a total of 246 patients who underwent total hip or knee revision surgery were included in this study. There were 146 females and 100 males, and the mean age of the patients was 62.1 ± 12.75 years. Laboratory parameters erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), D‐dimer, plasma fibrinogen, serum white blood cell (WBC), and calculable ratio markers were collected. Based on leukocytes (monocyte count, neutrophil count, lymphocyte count), platelet count, and mean platelet volume Inflammation‐related ratio markers were calculated, which including monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and platelet to mean platelet volume ratio (PMR). Follow‐up of all studied cases for at least 1 year. The diagnostic value of the markers based on the receiver operating characteristic (ROC) analysis. The most optimal combinations of blood markers were selected by the prediction models. Statistical analyses and prediction models were performed using R software.ResultsOf the 246 patients, 125 were diagnosed with PJI and 121 with aseptic loosening. A higher rate of patients underwent revision surgery due to hip prosthesis loosening in the aseptic loosening group (74.4%) compared to the PJI group (45.6%, P < 0.001). ROC curves showed that the area under the curve (AUC) for classical markers, fibrinogen was 0.853 (95% confidence interval [CI], 0.805–0.901), ESR was 0.836 (95% CI, 0.785–0.887) and CRP was 0.825 (95% CI, 0.773–0.878). Followed by the PMR, PLR, NLR and MLR, which showed promising diagnostic performance with AUCs of 0.791, 0.785, 0.736, and 0.733. The AUCs of the ratio markers were higher than those of D‐dimer (0.691;95% CI, 0.6243–0.7584) and serum WBC (0.622; 95% CI, 0.552–0.691). After the predictive model calculation, AUC was up to 0.923 (95% CI, 0.891–0.951) when plasma fibrinogen combined with MLR and PMR and interpreted excellent discriminatory capacity with a sensitivity of 86.40% and a specificity of 84.17%. The new combination significantly increases the accuracy and reliability of the diagnosis of PJI (P < 0.001). The AUC increased to 0.899 (95% CI, 0.861–0.931; P = 0.007) and 0.916 (95% CI, 0.880–0.946; P < 0.001), followed by CRP and ESR, respectively. All plasma fibrinogen, ESR, and CRP combined with both PMR and MLR achieved the highest specificity (89.17%) and PPV (85.34%).ConclusionThe diagnostic performance greatly improved when plasma fibrinogen, ESR, and CRP combined with ratio markers.     

Increased Synovial Inflammatory Markers in Aseptic Total Hip Arthroplasty Dislocation

BackgroundIn cases of total hip arthroplasty (THA) dislocation, a synovial fluid aspiration is often performed to evaluate for periprosthetic joint infection (PJI). It is currently unclear how aseptic dislocation of a THA influences synovial fluid white blood cell (WBC) count and polymorphonuclear percentage (PMN%). The primary aim of this study is to investigate the influence of THA dislocation on synovial WBC count and PMN%.MethodsTwenty-eight patients who underwent a synovial aspiration of a THA between 2014 and 2019 were identified and enrolled in our case-control study. Patients with an aseptic THA dislocation and synovial hip aspiration were matched against patients without dislocation, patients undergoing hip aspiration before aseptic THA revision surgery, and patients undergoing hip aspiration before septic THA revision surgery.ResultsSynovial WBC count was significantly increased in the dislocation vs aseptic THA revision group (P = .015), as well as between the septic revision group vs dislocation and aseptic THA revision group (both P < .001). The PMN% did not differ significantly between the dislocation and aseptic revision groups (P = .294). Mean C-reactive protein values were 12.4 ± 14.9 mg/dL in THA dislocation, 24.1 ± 37.7 mg/dL in THA without infection compared to 85.7 ± 84.9 mg/dL in THA infection group (P < .001).ConclusionThis study shows that THA dislocation has a significant impact on synovial WBC count in joint aspiration. Our data suggest that in the setting of THA dislocation, synovial WBC and PMN% may not be the best method to evaluate for PJI. Further research should be performed to establish new thresholds for these synovial inflammatory markers in the setting of THA dislocation and PJI.Level of evidenceLevel III; retrospective trial.     

Proinflammatory biomarkers' level and functional genetic polymorphisms in periprosthetic joint infection

Objective

The aims of this study were 1) to identify the level of inflammatory biomarkers interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-17, C-reactive protein (CRP), granulocyte colony-stimulating factor (GCSF), ferritin, and tumor necrosis factor (TNF)-α in serum and synovial fluid samples of patients who underwent revision arthroplasty surgery; 2) to establish the relationship between serum and synovial fluid levels; 3) to determine if any of the 11 genetic polymorphisms of TNFα, IL-1, IL-6, IL-8, IL-17, and GCSF on the encoding genes was associated with periprosthetic joint infection (PJI).

Periprosthetic joint infection diagnosis: a complete understanding of white blood cell count and differential

Recent research has raised doubts regarding the utility of serum white blood cell count (WBC) for diagnosis of periprosthetic joint infection (PJI). As synovial WBC and neutrophil (PMN) percentage have been adopted as accurate markers of PJI, this study investigated the correlation of WBC in serum versus joint fluid and diagnostic value of all WBC levels for failed arthroplasty patients. 153 patients (73 PJI) undergoing revision knee arthroplasty were identified. Weak correlations between joint fluid and serum for WBC (R = 0.19), PMN count (R = 0.31), and lymphocyte count (R = -0.22) were observed. Diagnostic accuracy of PMN (93%) and WBC (93%) synovial count relative to serum was similar to synovial WBC (93%) and PMN% (95%) alone. Serum WBC analysis does little to improve the accurate diagnosis of PJI.     

Preoperative Opioid Use Is Associated With Higher Revision Rates in Total Joint Arthroplasty: A Systematic Review

BackgroundAlthough preoperative opioid use has been associated with poor postoperative patient-reported outcome measures and delayed return to work in patients undergoing total joint arthroplasty, direct surgery-related complications in patients on chronic opioids are still not clear. Thus, we sought to perform a systematic review of the literature to evaluate the influence of preoperative opioid use on postoperative complications and revision following primary total joint arthroplasty.MethodsFollowing the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we queried PubMed, EMBASE, the Cochrane Library, and the ISI Web of Science for studies investigating the influence of preoperative opioid use on postoperative complications following total hip arthroplasty and total knee arthroplasty up to May 2020.ResultsAfter applying exclusion criteria, 10 studies were included in the analysis which represented 87,165 opioid users (OU) and 5,214,010 nonopioid users (NOU). The overall revision rate in the OU group was 4.79% (3846 of 80,303 patients) compared to 1.21% in the NOU group (43,719 of 3,613,211 patients). There was a higher risk of aseptic loosening (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.11-1.53, P = .002), periprosthetic fractures (OR 1.89, 95% CI 1.53-2.34, P < .00001), and dislocations (OR 1.26, 95% CI 1.14-1.39, P < .00001) in the OU group compared to the NOU group. Overall, 5 of 6 studies reporting on periprosthetic joint infection (PJI) rates showed statistically significant correlation between preoperative opioid use and higher PJI rates.ConclusionThere is strong evidence that preoperative opioid use is associated with a higher overall revision rate for aseptic loosening, periprosthetic fractures, and dislocation, and an increased risk for PJI.Level of EvidenceLevel III, systematic review.     

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.