Synovial White Blood Cell Research Articles

Which Minor Criteria is the Most Accurate Predictor for the Diagnosis of Hip and Knee Periprosthetic Joint Infection in the Asian Population?

BackgroundThe aim of this study was to evaluate the diagnostic performance of minor criteria from the 2018 International Consensus Meeting (ICM) for the diagnosis of chronic periprosthetic joint infection (PJI) in an Asian population. MethodsWe retrospectively reviewed 76 patients who underwent a revision knee or hip arthroplasty at an academic institution between September 2018 and December 2019. All major and minor 2018 ICM criteria were available for all patients included. Cases with at least 1 major criterion or score ≥6 in minor criteria were considered as infected. The diagnostic performance was evaluated by a receiver operative characteristic curve analysis and area under the curve (AUC) for each minor criterion. An AUC value of more than 0.9 was considered outstanding and 0.8-0.9 as excellent. ResultsWhen using 2018 ICM threshold, the diagnostic performance ranked based on AUC was the following: alpha defensin (0.92), positive histology (0.83), leukocyte esterase (0.82), synovial white blood cell (0.81), serum erythrocyte sedimentation rate (0.78), synovial polymorphonuclear neutrophils (0.77), serum C-reactive protein (0.74), D-dimer (0.59), single positive culture (0.53), and positive intraoperative purulence (0.51). Alpha defensin was considered as an outstanding test among the 2018 ICM minor criteria. Positive histology, leukocyte esterase, and synovial white blood cell were considered as excellent tests. ConclusionBased on our findings, alpha-defensin has the best diagnostic performance in Asian population among the minor criteria of 2018 ICM.

Synovial calprotectin is a reliable biomarker for periprosthetic joint infections in acute-phase inflammation — a prospective cohort study

PurposeDiagnosing periprosthetic joint infections (PJI) are challenging and may be hampered by the presence of other causes of local inflammation. Conventional synovial and serum markers are not reliable under these circumstances. Synovial calprotectin has been recently shown as a promising biomarker for PJI in total hip (THA) and total knee arthroplasty (TKA). The aim of this study is to investigate if calprotectin is reliable for PJI diagnosis in cases with accompanying inflammation due to recent surgery, dislocation or implant breakage in primary and revision TKA and THA.MethodsThirty-three patients were included in this prospective study between July 2019 and October 2021 (17 patients undergoing surgery < 9 months, 11 dislocations, five implant breakage, respectively). Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin, using a lateral-flow-assay, were analysed. These parameters were tested against a modified European-Bone-and-Joint-Infection-Society (EBJIS) definition with adjusted thresholds to account for the local inflammation. Statistic quality criteria were calculated and compared using a binary classification test.ResultsSeventeen patients were classified as confirmed infections according to the modified EBJIS definition (13 THA and 4 TKA). The calprotectin assay yielded a sensitivity of 0.88 (0.64, 0.99), a specificity of 0.81 (0.54, 0.96), a positive predictive value (PPV) of 0.83 (0.59, 0.96) and a negative predictive value (NPV) of 0.87 (0.60, 0.98).ConclusionsEven in the presence of local inflammation due to other, non-infectious causes, calprotectin is a reliable diagnostic parameter for the detection of a PJI in primary and revision THA and TKA.

How Does a "Dry Tap" Impact the Accuracy of Preoperative Aspiration Results in Predicting Chronic Periprosthetic Joint Infection?

Periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is challenging to diagnose. We aimed to evaluate the impact of dry taps requiring saline lavage during preoperative intra-articular hip aspiration on the accuracy of diagnosing PJI before revision surgery. A retrospective review was conducted for THA patients with suspected PJI who received an image-guided hip aspiration from May 2016 to February 2020. Musculoskeletal Infection Society (MSIS) diagnostic criteria for PJI were compared between patients who had dry tap (DT) vs successful tap (ST). Sensitivity and specificity of synovial markers were compared between the DT and ST groups. Concordance between preoperative and intraoperative cultures was determined for the 2 groups. In total, 335 THA patients met inclusion criteria. A greater proportion of patients in the ST group met MSIS criteria preoperatively (30.2% vs 8.3%, P < .001). Patients in the ST group had higher rates of revision for PJI (28.4% vs 17.5%, P= .026) and for any indication (48.4% vs 36.7%, P= .039). MSIS synovial white blood cell count thresholds were more sensitive in the ST group (90.0% vs 66.7%). There was no difference in culture concordance (67.9% vs 65.9%, P= .709), though the DT group had a higher rate of negative preoperative cultures followed by positive intraoperative cultures (85.7% vs 41.1%, P= .047). Our results indicate that approximately one third of patients have dry hip aspiration, and in these patients cultures are less predictive of intraoperative findings. This suggests that surgeons considering potential PJI after THA should apply extra scrutiny when interpreting negative results in patients who require saline lavage for hip joint aspiration.

The role of synovial fluid aspiration in shoulder joint infections

BackgroundJoint aspiration with analysis of synovial fluid white blood cell count (WBC) and microbiological culture is a widely established aspect in the diagnosis of shoulder joint infections (SJI). In case of a two stage revision for SJI, joint aspiration before re−/implantation of a total shoulder arthroplasty (TSA) was used to rule out persistent infection for years but its value is under debate. Shoulder specific data on all aspects is rare. The current study aims to answer the following research questions: Does joint aspiration have an insufficient predictive value in the diagnosis of SJI in (1) initial workup and (2) before definite arthroplasty with polymethylmethacrylate (PMMA)-Spacer in place?MethodsThis retrospective evaluation investigates 35 patients that were treated for SJI with a two staged implantation of a TSA after debridement and implantation of an PMMA-Spacer. Joint aspirations were performed preoperatively (PA) and before re−/implantation of the prosthesis while spacer was in place (interstage aspiration, IA). Samples were taken for microbiological culture and analysis of WBC. Sensitivity and specificity were calculated with reference to intraoperative microbiological samples. Receiver Operating Characteristic (ROC), Area-Under-Curve analysis (AUC) and calculation of the Youden index were performed to find optimum cut-off for WBC.ResultsThe sensitivity of microbiological cultures from PA was 58.3% and the specificity was 88.9%. The mean WBC was 27,800 leucocytes/mm3 (range 400-96,300). The maximum Youden index (0.857) was a cut-off of 2600 leucocytes/mm3 with a sensitivity of 85.7% and a specificity of 100.0%. The sensitivity and specificity of IA were 0.0% and 88.5%, respectively.ConclusionsPreoperative aspiration is likely to miss Cutibacteria spp. and CoNS and cannot rule out infection for sure. However, we recommend it for its advantages of targeted antibiotic therapy in case of germ identification. Empiric antibiotic therapy should cover Cutibacteria and CoNS even if aspiration showed negative microbiological cultures. In contrast, the diagnostic value of interstage aspiration does not qualify for its routine use.

Laboratory Value Effectiveness in Predicting Early Postoperative Periprosthetic Joint Infection After Total Hip Arthroplasty.

Diagnosing early periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) remains challenging. We sought to validate optimal laboratory value cutoffs for detecting early PJIs in a series of primary THAs from one institution. We retrospectively identified 22,795 primary THAs performed between 2000 and 2019. Within 12 weeks, 43 hips (43 patients) underwent arthrocentesis. Patients were divided into 2 groups: evaluation ≤6 weeks or 6-12 weeks following THA. The 2011 Musculoskeletal Infection Society major criteria for PJI diagnosed PJI in 15 patients. Mann-Whitney U-tests were used to compare median laboratory values and receiver operating characteristic curve analysis was used to evaluate optimal cutoff values. Both within 6 weeks and between 6 and 12 weeks postoperatively, median C-reactive protein (CRP), erythrocyte sedimentation rate, synovial white blood cell (WBC) count, neutrophil percentage, and absolute neutrophil count (ANC) values were significantly higher in infected THAs. Optimal cutoffs within 6 weeks were: CRP ≥100 mg/L, synovial WBCs ≥4390 cells/μL, neutrophil percentage ≥74%, and ANC ≥3249 cells/μL. Between 6 and 12 weeks, optimal cutoffs were: CRP ≥33 mg/L, synovial WBCs ≥26,995 cells/μL, neutrophil percentage ≥93%, and ANC ≥25,645 cells/μL. Early PJI following THA should be suspected within 6 weeks with CRP ≥100 mg/L or synovial WBCs ≥4390 cells/μL. Between 6 and 12 weeks postoperatively, cutoffs of CRP ≥33 mg/L, synovial fluid WBC ≥26,995 cells/μL, and neutrophil percentage ≥93% diagnosed PJI with high accuracy. Level IV Diagnostic.

Complete blood platelet and lymphocyte ratios increase diagnostic accuracy of periprosthetic joint infection following total hip arthroplasty.

Systemically, changes in serum platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte (MLR) represent primary responses to early inflammation and infection. This study aimed to determine whether PLR, PVR, NLR, and MLR can be useful in diagnosing periprosthetic joint infection (PJI) in total hip arthroplasty (THA) patients. A total of 464 patients that underwent revision THA with calculable PLR, PVR, NLR, and MLR in 2 groups was evaluated: 1) 191 patients with a pre-operative diagnosis of PJI, and 2) 273 matched patients treated for revision THA for aseptic complications. The sensitivity and specificity of PLR combined with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial white blood cell count (WBC) and synovial polymorphonuclear leukocytes (PMN) (97.9%; 98.5%) is significantly higher than only ESR combined with CRP, synovial WBC and synovial PMN (94.2%; 94.5%; p < 0.01). The sensitivity and specificity of PVR combined with ESR, CRP and synovial WBC, and synovial PMN (98.4%; 98.2%) is higher than only ESR combined with CRP, synovial WBC and synovial PMN (94.2%; 94.5%; p < 0.01). The study results demonstrate that both PLR and PVR calculated from complete blood counts when combined with serum and synovial fluid markers have increased diagnostic sensitivity and specificity in diagnosing periprosthetic joint infection in THA patients. III, case-control retrospective analysis.

Urine Dipstick Leukocyte Esterase in the Rapid Diagnosis of Septic Arthritis.

This study aimed to evaluate the sensitivity and specificity of the leukocyte esterase (LE) band in two groups of patients receiving and not receiving antibiotics and compare the results. This prospective cross-sectional study was conducted on 105 joints with clinical suspicion of infectious arthritis (based on Kocher criteria) admitted in Shohada Hospital, Tabriz, Iran, within 2017-2018. Patients were divided into two groups, including receiving antibiotics (n=29; group 1) and not receiving antibiotics (n=76; group 2). Articular fluid aspiration was performed under sterile conditions with an 18-gauge angiocath with at least 1 ml volume of the hip, knee, ankle, elbow, and shoulder joints. Polymorphonuclear cell percentage count, cell count, Gram staining (GS), culture, and leukocyte esterase test were performed immediately after the aspiration of the specimens. Levels of synovial fluid white blood cell count, serum white blood cell count, PMN, serum glucose, erythrocyte sedimentation rate, C-reactive protein, and time of aspiration (TOA) were significantly higher in the group receiving antibiotics (P<0.05). Synovial glucose levels were significantly lower in the group receiving antibiotics. Furthermore, the positive frequency of glucose esterase, blood culture, GS, serum culture, and ultimate diagnosis of septic arthritis tests were significantly lower in the antibiotic receiving group (P<0.05). The sensitivity, and positive predictive value of the leukocyte esterase test were obtained at 100%, and 96.55% in the antibiotic receiving group, respectively. Moreover, in the group not receiving antibiotics, the sensitivity, specificity, positive predictive value, and negative predictive value of the leukocyte esterase test were estimated at 72.22%, 92.50%, 89.66%, 78.72%, respectively. Antibiotic use and the prolongation of TOA lead to increased inflammatory products, which is interfering with lab variables. As a result, they increase the sensitivity of the test. The sensitivity and specificity of the leukocyte esterase test in patients who did not receive antibiotics showed that this was a suitable and reliable laboratory method for the rapid detection of infectious arthritis that required an emergency rescue procedure.

Defining a Synovial Fluid White Blood Cell Count Threshold to Predict Periprosthetic Infection after Shoulder Arthroplasty.

Background: The diagnosis of periprosthetic shoulder infection (PSI) requires a thorough diagnostic workup. Synovial fluid aspiration has been proven to be a reliable tool in the diagnosis of joint infections of the lower extremity, but shoulder specific data is limited. This study defines a threshold for synovial fluid white blood cell count (WBC) and assesses the reliability of microbiological cultures. Methods: Retrospective study of preoperative and intraoperative fluid aspiration of 31 patients who underwent a revision of a shoulder arthroplasty (15 with PSI defined by IDSA criteria, 16 without infection). The threshold for WBC was calculated by ROC/AUC analysis. Results: WBC was significantly higher in patients with PSI than in other patients. A threshold of 2800 leucocytes/mm3 showed a sensitivity of 87% and a specificity of 88% (AUROC 0.92). Microbiological cultures showed a sensitivity of 76% and a specificity of 100%. Conclusions: A threshold of 2800 leucocytes/mm3 in synovial fluid can be recommended to predict PSI. Microbiological culture has an excellent specificity and allows for targeted antibiotic therapy. Joint aspiration presents an important pillar to diagnose PSI.

Apport de l’analyse du liquide synovial au diagnostic des infections articulaires

Synovial fluid analysis is essential for the diagnosis and management of septic arthritis (SA). It allows to identify the pathogen (mainly bacterial) and to study the antibiotics sensitivity (essential for the therapeutic management). Nevertheless, the direct examination is often negative (positive in 15–40% of the cases) and the bacterial culture can be taken in default (positive in 75–85% of the cases) because of an antibiotic therapy set up before the joint puncture, a too small bacterial inoculum or in case of fragile/fastidious bacterial species. Molecular biology techniques (DNAr16S PCR or multiplex PCR) are only of value if positive, and do not seem to increase the sensitivity of bacterial detection during SA. Synovial biomarkers are therefore necessary to allow a diagnosis of SA without bacteriological documentation or to formally eliminate this diagnosis. A synovial white blood cells threshold≥50,000/mm3 seems insufficient to discriminate SA from another diagnosis (metabolic, crystal-induced or reactive arthritis). Synovial biochemical parameters seem to be of particular interest (lactate, glucose, calprotectin, procalcitonin) while others should be abandoned (protides, LDH). This article reviews the performance of cytological, bacteriological and biochemical parameters of synovial fluid for the diagnosis of SA.

What Is the Impact of Automated Synovial Cell Counting on Different Aseptic Causes and Periprosthetic Conditions Associated With Revision THA?

Studies have suggested that automated synovial cell counting may overestimate the white blood cell (WBC) count, resulting in false positive tests when evaluating patients for the possibility of periprosthetic joint infection (PJI) after THA. However, associations between WBC counts high enough to mimic PJI in patients whose arthroplasties are not infected but rather are experiencing a variety of aseptic problems-including but not limited to metallosis, polyethylene wear, and recurrent dislocation-have not, to our knowledge, been adequately addressed. In addition, there is a lack of analyses about the polymorphonuclear percentage (PMN%) when assessed by automated analyzers in this context. In the context of different indications for aseptic revision and different periprosthetic hip pathologic findings, we asked: (1) What were the synovial WBC count levels, and what proportion of values were above the 2018 International Consensus Meeting (ICM) cutoff (3000 cells/μL)? (2) What were the synovial PMN% levels, and what proportion of values were above the 2018 ICM (70%)? We retrospectively studied the preoperative cell count analyses of synovial fluid in patients who underwent revision THA for aseptic reasons at our tertiary referral arthroplasty center between January 2015 and December 2017. We considered all revisions performed on patients during that time potentially eligible, and after prespecified exclusions were applied (exclusions mainly included 15% [197 of 1306] sporadic missing data and 12% [155 of 1306] insufficient synovial fluid obtained in the aspirate), a total of 702 patients undergoing revision THA for aseptic reasons remained for the final analysis. As far as we know, no patients underwent re-revision for PJI at a mean follow-up of 46 ± 11 months, which tends to confirm our impression that indeed these hips did not have PJI. Cell count analyses were conducted using an automated analyzer. Clinical findings, preoperative radiographs, and surgical reports--confirmed by available histologic results--were used to establish diagnoses. We evaluated these hips considering the recommendations of the 2018 ICM (WBC count of 3000 cells/μL and PMN% of 70%) to see what proportion of them would have been characterized as likely having PJI on basis of those cutoff values. The mean WBC count for the entire cohort was 2120 ± 2395 cells/μL. The mean PMN% for the entire cohort was 36% ± 22%. Compared with aseptic loosening and recurrent dislocation, polyethylene wear had the highest mean WBC count (3817 ± 3711 cells/μL; p < 0.001). Of the investigated periprosthetic conditions, wear-induced synovitis had the highest value (4464 ± 3620 cells/μL; p < 0.001). Considering the ICM threshold, polyethylene wear showed the highest proportion of WBC counts above 3000 cells/μL among the indications for aseptic revision (60% [25 of 42]; p < 0.001). Of the periprosthetic conditions, wear-induced synovitis showed the highest proportion beyond the ICM cutoff (60% [50 of 83]; p < 0.001). The mean PMN% for aseptic causes ranged between 28% and 44% without differences among them (p = 0.12). Patients with metallosis had the highest mean PMN% of the periprosthetic conditions investigated (45% ± 25%; p = 0.007). Regarding the ICM threshold, metallosis resulted in the largest proportion of patients with a PMN% above 70% (21% [10 of 47]; p = 0.003), and that for wear-induced synovitis was 6% (5 of 83; p = 0.42) and for osteolysis was 3% (1 of 33; p = 0.51). There were no differences among aseptic loosening, recurrent dislocation, and polyethylene wear in terms of the proportion above 70% among the aseptic revision causes. Using automated cell counting, we found that WBC counts differ widely across indications for aseptic revision THA, and a high proportion of patients who underwent revision THA for aseptic reasons had WBC counts above the commonly used threshold of 3000 cells/μL. However, the PMN% was much less affected in several common indications for aseptic revision THA, making this measure more reliable for interpreting aspiration results using an automated analyzer. Based on the data distributions we observed, manual counting techniques might be considered in particular among patients with polyethylene wear, metal-on-metal bearing surfaces, or suspected metallosis. However, an elevated WBC count alone, observed using an automated analyzer in the context of polyethylene wear, should not be considered to be strongly suggestive of PJI, since that finding occurred so commonly among patients without infection. Level III, diagnostic study.

Diagnosis of Chronic Infection at Total Hip Arthroplasty Revision Is a Question of Definition.

Purpose Contradicting definitions of periprosthetic joint infection (PJI) are in use. Joint aspiration is performed before total hip arthroplasty (THA) revision. This study investigated the influence of PJI definition on PJI prevalence at THA revision. Test quality of prerevision aspiration was evaluated for the different PJI definitions. Methods 256 THA revisions were retrospectively classified to be infected or not infected. Classification was performed according to the 4 different definitions proposed by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), the International Consensus Meeting (ICM), and the European Bone and Joint Infection Society (EBJIS). Only chronic PJIs were included. Results PJI prevalence at revision significantly correlated with the applied PJI definition (p = 0.01, Cramer's V = 0.093). PJI prevalence was 20.7% for the MSIS, 25.4% for the ICM, 28.1% for the IDSA, and 32.0% for the EBJIS definition. For synovial fluid white blood cell count, the best ROC-AUC for predicting PJI was 0.953 in combination with the MSIS definition. Conclusion PJI definition significantly influences the rate of diagnosed PJIs at THA revision. Synovial fluid white blood cell count is a reliable means to rule out PJI. In cases with a borderline high synovial white blood cell count before THA revision as the only sign of chronic PJI, an extended diagnostic work-up should be considered.

The Diagnostic Value of Synovial Fluid Lymphocytes in Gout Patients.

Objective This study is aimed at investigating the diagnostic value of synovial fluid cell counts in gout patients. Methods A total of 185 gout, 64 rheumatoid arthritis (RA), 26 axial spondyloarthritis (axSpA), and 24 osteoarthritis (OA) patients were included in the study. According to serum uric acid (sUA) levels on attack, gout patients were divided into normal sUA gout patients and high sUA gout patients. The laboratory data were recorded. ROC curves were generated to evaluate the diagnostic value of the variables for gout patients and normal sUA gout patients compared with RA, axSpA, and OA patients. Results The synovial fluid white blood cell (WBC), peripheral blood mononuclear cell (PBMC), monocyte, polymorphonuclear (PMN), and neutrophil counts in gout patients were higher than those in OA patients (P < 0.05). The synovial fluid PBMC and lymphocyte counts in gout patients were lower than those in RA and axSpA patients (P < 0.05). ROC curve results showed that the AUC values of lymphocytes and sUA for gout patients were 0.728 and 0.881, respectively, which were higher than those of other variables. The optimal cutoff value of lymphocytes for gout was 1.362, with a Youden index of 0.439, a sensitivity of 83.3%, and a specificity of 60.6%. The AUC values of lymphocytes, sUA, and CRP for normal sUA gout patients were 0.694, 0.643, and 0.700, respectively, which were higher than those of other variables. The optimal cutoff value of lymphocytes for normal sUA gout patients was 1.362, with a Youden index of 0.422, a sensitivity of 81.6%, and a specificity of 60.6%. Conclusions The synovial fluid cell counts of gout patients were different from those of RA, axSpA, and OA patients. Synovial fluid lymphocytes had a higher diagnostic value for gout.

Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints

There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.

Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis.

The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar's test and area under the receiver operating characteristic curve (AUC) analysis. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J2021;103-B(6):1119-1126.

Accidental Arthrotomy Causing Aseptic Monoarthritis Due to Agave Sap: A Case Report

IntroductionAseptic inflammatory arthritis has been reported from thorns or cactus needles after inadvertent arthrotomy. Agave sap irritants may cause an aseptic inflammatory arthritis mimicking a septic joint.Case ReportA 27-year-old male presented with left knee pain and swelling two hours after suffering an accidental stab wound to his left lateral knee by an agave plant spine. Synovial fluid white blood cell count was 92,730 mm3 with 75% neutrophils and no crystals. Surgical washout was remarkable for turbid fluid and no foreign body. Synovial fluid and blood cultures remained without growth. At two-week follow-up, the patient had recovered.ConclusionPenetrating injuries from agave thorns can cause an inflammatory arthritis that mimics septic arthritis.

Positive frozen section during reimplantation increases the risk of treatment failure in two-stage exchange arthroplasty even in patients with normal ESR and CRP.

It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure. Treatment failure occurred in eight (30.77%) of the 26 PJI patients with positive frozen sections at reimplantation, compared with 13 (9.49%) of 137 patients with negative results. In the multivariate analysis, positive frozen section increased the risk of failure (odds ratio 4.70; 95% confidence interval (CI) 1.64 to 13.45). The mean number of months to reinfection was lower in the positive frozen section group than in the control group (p = 0.041). While there were nine (34.62%) patients with positive frozen section and 25 (18.25%) patients with negative frozen section who had prolonged antibiotic use (p = 0.042), the mean duration of antibiotic use was comparable in two groups. Synovial white blood cell count (p = 0.137) and polymorphonuclear leucocyte percentage (p = 0.454) were not associated with treatment failure in logistic regression model. Positive frozen section at reimplantation was independently associated with subsequent failure and earlier reinfection, despite normal ESR and CRP levels pre-reimplantation. Surgeons should be aware of the risk of treatment failure in patients with positive frozen sections and carefully consider benefits of reimplantation. Cite this article: Bone Joint J2021;103-B(5):916-922.

Variability and Interpretation of Synovial Cell Count and Differential: A Perspective in Hip and Knee Arthroplasty.

Multiple threshold values have been proposed for synovial leukocyte count (white blood cell count) and synovial neutrophil percentage (percent polymorphonuclear neutrophils) in the diagnosis of periprosthetic joint infection (PJI). The objective of this study was to elucidate the variability of these criteria under diverse patient/surgical settings. Hip PJIs yield higher synovial white blood cell counts and percent polymorphonuclear neutrophils than knee PJIs. Periprosthetic joint infection of failed unicompartmental knee arthroplasty produces a higher white blood cell count than that of failed total knee arthroplasty. Synovial white blood cell count and percent polymorpho-nuclear neutrophils PJI thresholds also vary in patients with antibiotic cement spacers and depend on the timing from primary arthroplasty (<6 weeks vs >6 weeks). Similarly, test results should be carefully interpreted for patients with comorbidities so that PJI is not missed or falsely identified. [Orthopedics. 2021;44(3):e320-e325.].

Local and systemic effects following intraarticular injection of MM-II liposomes. Results from two nonclinical toxicity studies in rabbits and dogs

Purpose: MM-II is a suspension of large multilamellar liposomes composed of two phospholipids, DMPC and DPPC, for intra-articular administration, under development for treatment of osteoarthritic pain. Due to their unique characteristics, MM-II liposomes are retained on the cartilage surface, providing long-term lubrication and leading to a reduction in wear of the cartilage. The purpose of these preclinical studies was to evaluate the toxicity of MM-II, when administered via intra-articular (IA) injection into the stifle joint of rabbits and dogs. Methods: In two GLP compliant studies, Rabbits or Beagle dogs were administered IA injection of placebo, saline or low (22 mg/kg and 20 mg/kg for rabbits and dogs respectively), mid (44 mg/kg and 39 mg/kg for rabbits and dogs respectively) and high (66 mg/kg and 59 mg/kg for rabbits and dogs respectively) doses of MM-II. Animals were assessed post dose for 4 days, 14 weeks, or 18 weeks. Assessment of toxicity was based on mortality, clinical observations, body weight change, food consumption, ophthalmic observations, electrocardiographic (ECG) measurements (dogs only), and clinical and anatomic pathology. As part of this study, blood samples were collected for toxicokinetic (TK) evaluation and synovial fluid samples were collected for clinical pathology evaluations. Results: Rabbits: No MM-II-related mortality, MM-II-related clinical observations; effects on qualitative food consumption; findings during ophthalmic examinations; effects in hematology, coagulation, clinical chemistry, or urinalysis test results; or organ weight effects or macroscopic findings were noted. MM-II related findings were limited to a non-adverse moderate increase in body weights for the females at all dose levels and reversible, non-adverse microscopic findings of synovial hyperplasia and mixed cell inflammation in the injected stifle of all groups administered MM-II. After MM-II administration, DMPC exposure, as assessed by mean Cmax and AUC0-72, was higher than its endogenous baseline level and the placebo and saline control groups. After reaching Cmax, DMPC concentrations declined largely, through 144 or 552 hours post dosing. DPPC exposure was relatively similar to its endogenous baseline level and to their levels in the placebo and saline control groups. Dogs: No MM-II-related mortality, MM-II-related clinical observations; effects on qualitative food consumption; findings during ophthalmic examinations; effects in hematology, coagulation, clinical chemistry, or urinalysis test results; or organ weight effects or macroscopic findings were noted. MM-II related findings were limited to reversible, transient, non-adverse, minimally to mildly higher synovial fluid white and red blood cell counts and microscopic findings of synovial hyperplasia and mixed cell inflammation in the injected stifle of all groups administered MM-II. After MM-II administration, DMPC exposure as assessed by mean Cmax and AUC0-72 was higher than its endogenous baseline levels and the placebo and saline control groups. After reaching Cmax, mean DMPC concentrations declined largely through 312 or 552 hours post dosing. DPPC exposure was relatively similar to its endogenous baseline level and to their levels in the placebo and saline control groups. Conclusions: In both studies, MM-II related findings were considered non-adverse at all dose levels. The NOAEL was determined as 59 mg/kg in the dogs study and 66 mg/kg in the rabbit study. Toxicokinetic findings in both studies indicated that DMPC exposure appears to be impacted by MM-II administration, but DPPC is not. The highest doses employed in these studies provide a maximal local safety margin of 11.9-fold for dogs and 22.9-fold for MM-II in rabbits of the highest dose to be administered in MM-II phase 2 clinical trial. To conclude, MM-II was found safe with no adverse events and with a NOAEL of highest dose employed in the study.

Optimal Synovial Fluid Leukocyte Count Cutoff for Diagnosing Native Joint Septic Arthritis After Antibiotics: A Receiver Operating Characteristic Analysis of Accuracy.

Urgent treatment of septic arthritis is key in preventing devastating morbidity or mortality. Accurate diagnosis is critical, and the standard diagnostic cutoff of 50,000 synovial leukocytes may be altered by previous administration of antibiotics. Our objective was to identify and compare a cutoff synovial leukocyte count with a high sensitivity and specificity for diagnosis of septic arthritis in patients who received antibiotics and those who had not. A receiver operating characteristic (ROC) curve was used to provide a discriminate cutoff value for diagnosing septic arthritis. A retrospective chart review of 383 patients was done over a 13-year period including those who had arthrocentesis of any joint. Two groups were created, those who had not been given antibiotics within 2 weeks (control) and those who received intravenous or oral antibiotics within 2 weeks before arthrocentesis. Relevant data included synovial leukocyte count and differential cell count. Additional metrics included temperature, erythrocyte sedimentation rate, and C-reactive protein. A ROC curve determined the optimal synovial white blood cell cutoff for diagnosing septic arthritis in native joints for each group. The ROC curve determined that patients who received antibiotics had an optimal cutoff of >16,000 cells (sensitivity = 82%, specificity = 76%), and a neutrophil percentage cutoff of >90% (sensitivity = 73%, specificity = 74%). The control group had an optimal synovial leukocyte cutoff of >33,000 cells (sensitivity = 96%, specificity = 95%). The optimal neutrophil percentage cutoff in the control group was >83% neutrophils (sensitivity = 89%, specificity = 79%). When a patient is given antibiotics before arthrocentesis, a diagnostic value of >16,000 synovial leukocytes should be used to guide treatment of septic arthritis. A diagnostic value of >33,000 synovial leukocytes yields the highest accuracy for diagnosis of septic arthritis in patients who have not been given antibiotics before arthrocentesis. III.

Presentation and Outcomes of Peri-Prosthetic Joint Infection: A Comparison of Culture-Positive and Culture-Negative Disease.

Background: Peri-prosthetic joint infection (PJI) is a debilitating and costly complication of joint replacement. Synovial fluid cultures are negative in up to 25% of PJI cases. The purpose of this study was to compare the clinical characteristics and outcomes of culture negative and culture positive PJI. Patients and Methods: We conducted a retrospective study including all patients aged 18 and older admitted to a single tertiary-care hospital between 1998 and 2015 diagnosed with PJI and treated with antibiotic agents and surgery. Results: One hundred ninety-six patients with PJI were identified; 48 (24.5%) were culture-negative (CN) and 148 (75.5%) were culture-positive (CP). The groups were similar in age and presence of associated comorbidities. Fever was more common among the CP patients (CN, 23.8%; CP, 38.4%; p = 0.03) as was sepsis defined by Sepsis-2 criteria (CN, 12.8%; CP, 28.7%; p = 0.03). Patients who were CP had higher synovial white blood cell (WBC) count (CN, 30,500 per milliliter; CP, 95,400 per milliliter; p < 0.01), a longer length of stay (CN, 3.8%; CP,7.9%; p = 0.02), and fewer alternative diagnoses established within one year (CN, 25.0%; CP, 2.7%; p < 0.01). Our logistic regression models also found that CP patients had an adjusted odds ratio (OR) of 2.59 for rehabilitation placement with 95% confidence interval (CI) of 1.15-5.83 and adjusted OR of 0.04 for an alternative diagnosis within one year with 95% CI, 0.009-0.22 compared with their CN counterparts. Conclusions: This study suggests that patients with CN PJI have less severe disease, better outcomes, and higher rates of alternative diagnoses within one year.