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Bone & Joint Research
Vol. 9, Issue 5 | Pages 236 - 241
1 May 2020
Li R Wang C Ji X Zheng Q Li X Ni M Zhang G Chen J

Aims. The purpose of this study was to validate our hypothesis that centrifugation may eliminate false-positive leucocyte esterase (LE) strip test results caused by autoimmune diseases in the diagnosis of knee infection. Methods. Between January 2016 and May 2019, 83 cases, including 33 cases of septic arthritis and 50 cases of aseptic arthritis, were enrolled in this study. To further validate our hypothesis, another 34 cases of inflammatory arthritis from the Department of Rheumatology of our institution were also included. After aspiration, one drop of synovial fluid was applied to LE strips before and after centrifugation. The results were recorded after approximately three minutes according to the different colour grades on the colour chart. The differences of LE results between each cohort were analyzed. Results. Before centrifugation, 46% (23/50) of the LE strip tests in the aseptic arthritis group were false-positives. Most of the false-positive results were due to inflammatory arthritis; after centrifugation, 78.3% (18/23) of the tests yielded negative results. Similar results were observed in cases from the Department of Rheumatology. The sensitivity of the centrifuged LE strip test was 0.818 (0.639 to 0.924), which is still an acceptable level compared with the uncentrifuged results, which yielded a sensitivity of 0.909 (0.745 to 0.976). However, the specificity was increased from 0.540 (0.395 to 0.679) to 0.900 (0.774 to 0.963) after centrifugation. Conclusion. Although inflammatory arthritis can yield a false-positive LE strip test result in the diagnosis of knee infection, centrifugation may eliminate these false-positive results. Cite this article: Bone Joint Res. 2020;9(5):236–241


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 70 - 70
1 Dec 2017
Benedetto PD Cainero V Gisonni R Beltrame A Causero A
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Aim. The aim of the study is to evaluate the specificity and sensibility of leukocyte esterase for the diagnosis of periposthetic joint infection (PJI). Method. Between October 2016 and April 2017 we enrolled 65 patients underwent to hip and knee revision arthroplasty due to uncertain joint infection. Synovial fluid was obtained from 64 joints that underwent revision arthroplasty. Each patient was evaluated in the preoperative time with CRP, ESR and leukoscan, in the intraoperative time with frozen section and leukocyte esterase strip and post-operative with sonication fluid culture, periprosthetic tissues cultures and histological examination. Results of all of these exams were compared to assess the specificity, the sensibility, the positive and negative predicting values of leukocyte esterase for the diagnosis of PJI. Results. The leukocyte esterase test with a threshold of +/++ had a sensitivity of 80.2%, a specificity of 82.8%, a positive predictive value of 63.8%, and negative predictive value of 92.1%. Using the threshold of ++ as a positive leukocyte esterase result, the specificity reached 97.8%, the positive predictive value 90.8%, and the negative predictive value 89.0%. Conclusions. These results demonstrate that leukocyte esterase is a quite accurate, effective marker of periprosthetic joint infection and that it is a valuable tool that can be used in conjunction with the the other tests for diagnosis of PJI


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 83 - 83
19 Aug 2024
Tarabichi S Lizcano JD Abe EA Olin B Courtney PM Parvizi J
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No single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Leukocyte esterase (LE) is a synovial marker that has proven utility in the diagnosis of PJI. The purpose of this prospective study was to (1) identify the optimal cutoff for the use of LE in the diagnosis of PJI and (2) determine whether performance of the LE strip test varied by infecting organism. This prospective study enrolled 1,015 patients undergoing hip or knee revision arthroplasty at a single institution from 2009 to September 2021. PJI was defined using a modified version of 2018 International Consensus Meeting (ICM) criteria that excluded LE when calculating the ICM score. Receiver operating characteristic curves were used to assess the utility of the LE strip test in the diagnosis of PJI. 973 patients were included in the analyses. 246 (25.4%) were classified as ICM-positive and 727 (74.6%) were classified as ICM-negative. An LE cutoff of “1+” (AUC 0.819, sensitivity 73.2%, specificity 90.6%) had superior accuracy to an LE cutoff of “2+” (AUC 0.713, sensitivity 43.9%, specificity 98.8%) in the overall diagnosis of PJI (p<0.001). When stratifying by organism type, an LE cutoff of “1+” had the best diagnostic utility for PJI caused by methicillin resistant Staphylococcus aureus (AUC 0.888, sensitivity 87.0%, n=23) followed by Streptococcus spp. (AUC 0.882, sensitivity 85.7%, n=28), coagulase negative Staphylococci (AUC 0.836, sensitivity 76.6%, n=47), methicillin sensitive Staphylococcus aureus (AUC 0.806, sensitivity 70.6%, n=34), culture negative (AUC 0.793, sensitivity 67.9%, n=56), and gram negative rods (AUC 0.763, sensitivity 61.9%, n=21). To our knowledge, this is the largest study evaluating the utility of the LE strip test in the diagnosis of PJI. Based on our findings, it appears that a “1+” cutoff has higher diagnostic utility than a cutoff of “2+”


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 104 - 104
1 Dec 2015
De Vecchi E Villa F Agrappi S Toscano M Drago L
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Culture examination is still considered the gold standard for diagnosis of bone and joint infections, including prosthetic ones, even if in up to 20–30% of cases, particularly prosthetic joint infections, it fails to yield microbial growth. To overcome this limitation, determination of markers of inflammation and or infection directly in joint fluid has been proposed. Aim of this study was to evaluate the applicability of measurement of lecukocyte esterase (LE), C-reactive protein (CRP) and glucose in synovial fluid for diagnosis of bone and joint infections. Synovial fluids from 80 patients were aseptically collected and sent to laboratory for microbiological cultures. After centrifugation at 3000 rpm for 10 minutes, pellet was used for cultures, while the surnatant was used for determination of LE, CRP and glucose. LE and glucose were evaluated by means of enzymatic colorimetric strips developed for urinanalysis. One drop of synovial fluid was placed on the LE and on the glucose pads and the results were read after about 120 seconds. A LE test graded + or ++, and a glucose test equal to trace or negative were considered suggestive for infection. CRP was measured by an automated turbidimetric method. On the basis of clinical findings, microbiological, haematological and histological analyses patients were retrospectively divided into 2 groups. Group 1 comprised 19 infected patients (12 males, 7 females age: 70.6 ± 10.3 yrs, range: 47 – 88 yrs) while Group 2 included 61 aseptic patients (32 males and 29 females, age: 61.5 ± 16.3 yrs, range: 15 – 84). Sensitivity of the three tests was 89.5%. 84% and 73,7% for LE, CRP and glucose, respectively. Specificity was 98.4%, 88.5% and 70% for LE, CRP and glucose, respectively. Positive and negative predictive values were 94.4% and 96.8% for LE, 69.6% and 94.6% for CRP and 77.8% and 89.6% for glucose test. When LE was combined with CRP, sensitivity increased to 94.7%, while no differences were observed for LE combined with glucose. Leukocyte esterase has proven to be a rapid, simple and inexpensive test to rule in or out bone and joint infections. Combination of its measurement with that of CRP increased sensitivity. In conclusion, the combination of leukocyte esterase and CRP may represent a simple and useful tool for diagnosis of bone and joint infections


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_11 | Pages 27 - 27
1 Aug 2018
Zagra L Villa F Cappelletti L Gallazzi E Materazzi G De Vecchi E
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Leukocyte esterase (LE) has shown to be an accurate marker of prosthetic joint infections and has been proposed as an alternative to frozen section (FS) for intra-operative diagnosis. In this study, intra-operative determination of LE was compared with FS for the diagnosis of periprosthetic hip infections. One hundred and nineteen patients undergoing hip revision surgery due to prosthetic joint failure from June 2015 to December 2017 were considered. Joint fluids were collected before the arthrotomy for determination of LE which was performed by using enzymatic colorimetric strips. Four to six samples were stained with hematoxylin eosin for FS and considered suggestive for infection when at least 5 polymorphonuclear leukocytes in 5 fields at high power fields were found. Sensitivity and specificity of LE were 100% and 93.8 %, respectively. The positive predictive value was 79.3 %, while the negative predictive value was 100%. Time from collection to response was 20.1 ± 4.4 minutes. Sensitivity and specificity of FS were 83.3 % and 92.1 %, respectively. The positive and negative predictive values were 84.6 % and 97.1%. Time from sample collection response was 27.2 ± 6.9 minutes. LE showed a higher sensitivity and a slightly lower specificity and the same diagnostic accuracy of intraoperative FS. The faster turnaround time (about 20 minutes from receiving of sample by the laboratory), its ease of use and the low costs make this test a valuable alternative to frozen sections and is going to replace FS in our clinical practice


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_5 | Pages 5 - 5
1 Mar 2021
Chapa JAG Peña-Martinez V gonzález GM Cavazos JFV de Jesus Treviño Rangel R Carmona MCS Taraco AGR
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Aim. Septic arthritis (SA) is considered a medical emergency. The most common etiological agents are glucose consuming bacteria, so we evaluated the clinical utility of synovial fluid (SF) glucose levels and other biochemical parameters for supporting the diagnosis of the disease and their association with a positive bacteria culture and joint destruction. Methods. Adult patients with SA diagnose were enrolled prospectively between July 2018 and October 2019. As control group, adults with knee osteoarthritis, meniscus and/or knee ligaments lesions were enrolled. SF samples were obtained from the joints by arthrocentesis/arthrotomy. Microbiological analyses of SF were performed using Brucella broth blood culture flasks, samples were incubated at 37°C with 5% CO. 2. for 24 hours. Gram stain, chocolate and blood agar were used for the identification and growth of the bacteria. SF glucose levels, pH and leukocyte esterase were measured as biochemical parameters using a glucometer and colorimetric test strips. The Outerbridge classification was used for grading the osteochondral injury. Furthermore, blood samples were collected from patients and control subjects for determining glucose levels. Results. We included 8 subjects with knee ligaments lesions, 6 with meniscus lesions and 5 with osteoarthritis as control group, as well as 20 patients with SA diagnose. The mean age of the patients was 57.8 years with a 65% of male predominance. The most common affected joint was the knee (85%). SF culture was positive in 60% of the cases and the most common etiological agent was Staphylococcus aureus (58.3%). SF glucose levels from patients were lower than the controls (P=0.0018) and showed the lowest concentration in patients with a positive culture (P=0.0004). There was also a difference between blood and SF glucose concentration from the positive culture patients (P<0.0001). Leucocyte esterase presented the highest values in positive culture patients (P=<0.0001) and a more acidic pH was found compared to the control group (P<0.0001). Regarding the osteochondral injury, the lowest concentrations of SF glucose were found in patients with a higher grade in the classification (P = 0.0046). Conclusions. SF glucose and leukocyte esterase concentrations might be a quick and cheap useful parameter for the physician for distinguishing between bacterial infection and not infected joint. In addition, the lowest SF glucose levels might give information about the joint damage due to the disease


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 6 - 6
1 Dec 2018
Wouthuyzen-Bakker M Ploegmakers J Ottink K Kampinga G Wagenmakers-Huizenga L Jutte P Kobold AM
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Aim. Diagnosing or excluding a chronic prosthetic joint infection (PJI) prior to revision surgery can be a clinical challenge. To enhance accuracy of diagnosis, several biomarkers were introduced in recent years, but most are either expensive or not available as a rapid test. We compared the diagnostic accuracy of leucocyte esterase (€0.20 per sample), calprotectin (€20 per sample) and alpha defensin (€200 per sample). Method. We prospectively evaluated PJI patients with chronic pain with or without prosthetic loosening between 2017 and 2018. Synovial fluid was collected prior to revision surgery. Leucocyte esterase was measured using a reagent strip (2+ considered as positive), and calprotectin and alpha defensin were measured using a lateral flow immunoassay. Intraoperative cultures (5 periprosthetic tissue samples, synovial fluid and sonication fluid) incubated for 9 days, were used as gold standard. At least two positive cultures of low-grade microorganisms with the same antibiogram were required to diagnose PJI. Results. A total of 19 patients were included (knee =11, hip =8). None of the patients were treated with antibiotics prior to revision surgery. A PJI was diagnosed in 8 patients (42.1%). The diagnostic accuracy of leucocyte esterase vs. calprotectin vs. alpha defensin was as follows; sensitivity 50.0% vs. 87.5% vs. 87.5%, specificity 81.8% vs. 90.9% vs. 100%, positive predictive value 60.0% vs. 87.5% vs. 100% and negative predictive value 75.0% vs. 90.9% vs. 91.6%, respectively. Both calprotectin and alpha defensin were false negative in one PJI caused by Cutibacterium acnes. The other two C. acnes PJIs were correctly diagnosed with both tests. Conclusions. Calprotectin is as accurate as alpha defensin in excluding a chronic PJI at 10% of the costs. Future studies with a large number of patients are necessary to analyze its diagnostic accuracy in very low-grade infections, in particularly caused by C. acnes


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 7 - 7
1 Oct 2022
Bottagisio M Viganò M Zagra L Pellegrini A De Vecchi E
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Aim. The analysis of synovial fluid has proved to be of crucial importance in the diagnostic process of prosthetic joint infections (PJI), suggesting the presence of an infection before the microbiological culture results. In this context, several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI [1, 2]. However, several testing methods have been explored to detect synovial calprotectin levels, emphasizing the need to use a standardized, rapid and rapid test. In this study, synovial calprotectin was analyzed by means of a commercial stool test [3] to explore whether the detected levels might predict PJIs and, therefore, being a promising tool for the fast and reliable diagnosis of this complication. Method. The synovial fluid of 55 patients underwent to revision of the prosthetic implant were analyzed. The measurement of calprotectin was carried out by of commercial stool test, following the protocol for liquid samples. Calprotectin levels were then compared to other synovial biomarkers of PJI such as leucocyte esterase and count and percentage of polymorphonuclear cells. Data analysis were performed using R software v4.1.1 (R Core Team) and package “pROC” [4]. Receiver operator characteristics curves were designed using culture test as gold standard to evaluate the area under curve (AUC) of each method (with DeLong method for confidence-interval calculation). Thresholds were calculated to maximize Youden's index; sensitivity and specificity were reported. One-to-one Pearson's correlations coefficient were calculated for each pair of methods. P value <0.05 were considered statistically significant. Results. Of the 55 synovial fluids analyzed, 13 patients were diagnosed with PJI and 42 with an aseptic failure of the implant. The specificity, sensitivity, and AUC of calprotectin resulted 0.90, 0.85, and 0.86 (95%CI: 0.72–0.99), respectively with a set threshold of 226.5 µg/g. The values of calprotectin had a moderate and statistically relevant correlation with the synovial leucocyte counts (r. s. = 0.54, p = 0.0003) and the percentage of polymorphonuclear cells (r. s. = 0.68, p = 0.0000). Conclusions. From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicator of local infection, delivering a rapid and reliable results and supporting the diagnostic process of PJI


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_10 | Pages 102 - 102
1 Jun 2018
Jones R
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Total knee arthroplasty (TKA) is one of the most common orthopaedic operations performed worldwide and it is largely successful in pain relief and functional recovery. However, when pain persists post-operatively the thorough evaluation must be instituted. Extra-articular causes of knee pain include; hip pathology, lumbar spine degenerative disease or radicular symptoms, focal neuropathy, vascular disease, and chronic regional pain syndrome. Intra-articular causes of knee pain: infection, crepitation/clunk, patella osteonecrosis, patella mal-tracking, soft tissue imbalance, malalignment, arthrofibrosis, component loosening, implant wear, ilio-tibial band irritation, and bursitis. Other causes of pain to rule out are component overhang with soft tissue irritation, recurrent hemarthrosis secondary to synovial impingement or entrapment, non-resurfaced patella, and metal sensitivity. A careful history may reveal previous knee surgeries with delayed healing or prolonged drainage, chronology of sign and symptoms, co-morbid medical conditions, jewel or metal sensitivity. Physical exam should help with specific signs in the operated knee. Targeted local anesthetic blocks are helpful and response to lumbar sympathetic blocks determines presence of CRPS. Lab tests are important: ESR, CRP, WBC, aspiration with manual cell count and diff, leucocyte esterase dipstick, RA titers, metal derm patch testing, nuclear scans, CT best for rotational malalignment, and MARS MRI. More recently patient satisfaction as an outcome measure has shown TKA results not satisfactory in 11- 18% of patients. A discordance of patient vs. surgeon satisfaction exists so the following factors may help improve this: correct patient selection, establishing and correlating surgeon-patient expectations, peri-operative optimization of patient co-morbidities to help avoid preventable complications, use of pre-operative and post-operative pathways. Satisfaction rates can best be improved by addressing the previous points with patients prior to TKA surgery


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_15 | Pages 51 - 51
1 Aug 2017
Jones R
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TKA is one of the most common orthopaedic operations performed worldwide and it is largely successful in pain relief and functional recovery. However, when pain persists post-operatively the thorough evaluation must be instituted. Extra-articular causes of knee pain include; hip pathology, lumbar spine degenerative disease or radicular symptoms, focal neuropathy, vascular disease, and chronic regional pain syndrome. Intra-articular causes of knee pain: infection, crepitation/ clunk, patella osteonecrosis, patella mal-tracking, soft tissue imbalance, malalignment, arthrofibrosis, component loosening, implant wear, ilio-tibial band irritation, and bursitis. Other causes of pain to rule out are component overhang with soft tissue irritation, recurrent hemarthrosis secondary to synovial impingement or entrapment, non-resurfaced patella, and metal sensitivity. A careful history may reveal previous knee surgeries with delayed healing or prolonged drainage, chronology of sign and symptoms, co-morbid medical conditions, jewel or metal sensitivity. Physical exam should help with specific signs in the operated knee. Targeted local anesthetic blocks are helpful and response to lumbar sympathetic blocks determines presence of CRPS. Lab tests are important: ESR, CRP, WBC, aspiration with manual cell count and diff, leukocyte esterase dipstick, RA titers, metal derm patch testing, nuclear scans, CT best for rotational malalignment,, and MARS MRI. More recently patient satisfaction as an outcome measure has shown TKA results not satisfactory in 11 – 18% of patients. A discordance of patient vs. surgeon satisfaction exists so the following factors may help improve this: correct patient selection, establishing and correlating surgeon-patient expectations, peri-operative optimisation of patient comorbidities to help avoid preventable complications, use of pre- and post-operative pathways. Satisfaction rates can best be improved by addressing the previous points with patients prior to TKA surgery


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 17 - 17
1 Dec 2017
Zahar A Citak M Lausmann C Gehrke T
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Aim. Alpha-defensin was recently introduced as a new biomarker having a very high accuracy to rule out periprosthetic joint infection (PJI). A new rapid lateral flow version of the Alpha-defensin test was developed and introduced to detect high levels of Alpha-defensin in synovial fluid quickly and with ease. We conducted a single-centre prospective clinical study to compare the results of the Alpha-defensin rapid test* against the conventional diagnostics according to MSIS criteria. Method. A total of 223 consecutive patients with painful total hip or knee arthroplasty were enrolled into the study. In all patients, blood C-reactive protein was measured and joint aspirations were performed. From the synovial fluid a leukocyte cell count with granulocyte percentage, microbiology cultures and Leukocyte Esterase tests were carried out according to the recommendation of MSIS for diagnosing PJI. At the same time, the Lateral Flow Test* was performed from the aspirate. 191 subjects with 195 joint aspirations (96 hips, 99 knees) were included in final clinical and statistical evaluation. We had 119 joints with an aseptic revision and 76 joints with PJI. Results. After statistical analysis the overall sensitivity of the Lateral Flow Test* was 92.1% (95% confidence interval [CI], 83.6% to 97.1%), the specificity was 100% (95% CI, 97.0% to 100%), the positive predictive value was 100% (95% CI, 94.9% to 100%), and the negative predictive value was 95.2% (95% CI, 89.9% to 98.2%). The overall accuracy of the Lateral Flow Test* was 96.9% (189 of 195, 95% CI, 93.4% to 98.9%). Conclusions. Our results suggest that the PJI test* has a very high accuracy in diagnosing infected THA and TKA. Though the Lateral Flow Test* does not provide information on the identity of the infectious pathogen, the test does have an important role in recognizing PJI early and enables surgeons to start proper therapy without delay. *Synovasure®


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_12 | Pages 18 - 18
1 Oct 2018
Gehrke T Zahar A Lausmann C Citak M
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Introduction. Despite several preventive strategies, periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is still a devastating complication. Early diagnosis and appropriate treatment are crucial to achieve successful infection control, but challenging since there is no test with 100% sensitivity and 100%. Therefore, several national and international guidelines include synovial analysis of joint aspirates as important diagnostic criteria, but cut-off levels for synovial cell count (CC) and polymorphonuclear (granulocyte) percentage (PMN%) are still debatable. The current investigation was performed to analyze the overall accuracy and optimal cut-off of synovial CC and PMN% following total knee (TKA) and total hip arthroplasty (THA). Methods. Between October 2012 and June 2017, all patients with painful TKA or THA, who underwent joint aspiration before revision arthroplasty were included in this retrospective study. From aspirated synovial fluid, leukocyte esterase activity, leukocyte CC and PMN% were determined, and specimens were sent for bacterial culture. A total of 524 preoperative joint aspirations (255 hips, 269 knees) were enrolled for final analysis. For 337 patients, the synovial CC and PMN% could be measured by the laboratory. From those patients, 203 patients were scheduled for aseptic revision, and 134 patients for septic revision arthroplasty according to the MSIS criteria for PJI. Specificity (SP), sensitivity (SE), positive predictive value (PPV), negative predictive and overall accuracy were measured for CC and PMN%. The optimum cut-off value was calculated by the ROC and the value giving the AUC, achieving the best possible level of sensitivity and specificity. Results. The best cut-off level for PJI of all study patients was 2582 leukocytes/μL (Se 80.6%, Sp 85.2%) and a PMN% of 66.1% (Se 80.6%, Sp 83.3%). The chosen cut-off levels for PJI of TKA was 1630 leukocytes/μL (Se 83.6%, Sp 82.2%) and a PMN% of 60.5% (Se 80.3%, Sp 77.1%). The optimal cut-off values for PJI of THA was 3063 leukocytes/μL (Se 78.1%, Sp 80.0%) and a PMN% of 66.1% (Se 82.2%, Sp 82.4%). Conclusions. Synovial cell count and polymorphonuclear percentage are sensitive methods for diagnosing PJI with differences in cut-off levels for THA and TKA. We suggest considering the cut-off levels of CC and PMN% from aspirates of TKA at 1600/μL and 60%, respectively, as possible PJI. For THA, the cut-off levels of CC and PMN% are at 3000/μL and 66%, respectively


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_8 | Pages 59 - 59
1 May 2019
Valle CD
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The AAOS clinical practice guideline for diagnosis of periprosthetic joint infection (PJI) and the MSIS definition of PJI were both “game changers” in terms of diagnosing PJI and the reporting of outcomes for research. However, the introduction of new diagnostic modalities, including biomarkers, prompted a re-look at the diagnostic criteria for PJI. Further there was a desire to develop an evidence-based, validated algorithm for the diagnosis of PJI. This multi-institutional study led by Dr. Jay Parvizi examined revision total joint arthroplasty patients from three academic institutions. For development of the algorithm, infected and aseptic cohorts were defined. PJI cases were defined using only the major criteria from the Musculoskeletal Infection Society (MSIS) definition (n=684). Aseptic cases underwent revision for a non-infective indication and did not show evidence of PJI or undergo a reoperation for any reason within 2 years (n=820). Risk factors, clinical findings, serum and synovial markers as well as intraoperative findings were assessed. A stepwise approach using random forest analysis and multivariate regression was used to generate relative weights for each of the various variables assessed at each stage to create an algorithm for diagnosing PJI using the 3 most important tests from each step. The algorithm was formally validated on a separate cohort of 422 patients, 222 who were treated with a 2-stage exchange for PJI who subsequently failed secondary to PJI within one year and 200 patients who underwent revision surgery for an aseptic diagnosis and had no evidence of PJI within two years and did not undergo a reoperation for any reason. The first step in evaluating PJI should include a physical examination to identify a sinus tract, followed by serum testing for C-reactive protein (cut-off value 1mg/dl), D-dimer (cut-off value 860ng/mL) and/or erythrocyte sedimentation rate (cut-off value 30mm/hr) in that order of importance. If at least one of these are elevated, or if there is a high clinical suspicion, joint aspiration should be performed, sending the fluid obtained for a synovial fluid white blood-cell (cut-off value 3,000 wbc/uL) or leukocyte esterase strip testing, polymorphonuclear percentage (cut-off value 80%) and culture. Alpha defensin did not show added benefit as a routine diagnostic test. Major diagnostic criteria are the same whereby the presence of a sinus tract or (2) positive cultures showing the same organism defines PJI. Special care should be taken in cases of ALTR (failed metal-on-metal bearing), crystalline deposition disease, inflammatory arthritis flares or slow growing organisms. In the rare cases where no fluid is obtained at the time of an attempted aspiration and revision surgery is not planned, then this is the rare scenario where nuclear imaging (my preference is an indium labeled white blood cell scan) or a biopsy can be performed. The updated definition of PJI demonstrated a higher sensitivity of 97.7% when compared to the MSIS criteria (79.3%) and the ICM definition (86.9%), with a similar specificity of 99.5%. However, just over 2% of patients examined do fall into the “inconclusive” category. The proposed diagnostic algorithm demonstrated a high overall sensitivity (96.9%) and specificity (99.5%)


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 73 - 73
1 Dec 2015
Riccio G Carrega G Ronca A Flammini S Antonini A
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Diagnosis of chronic prosthetic joint infection (PJI) is often challenging. Painful prosthesis is frequently due to an infection but to diagnose it is somethimes difficult. All recent guidelines stress the central role of joint punction in diagnosis of PJI if the infection is not demonstrated. However which test on synovial fluid must be carried out is not so clearly defined. Total white blood cell count and differential leukocite count are usually considered useful in diagnosis but cut offs reported by different studies are quite different. Moreover this test needs a relatively large amount of fluid and blood contamination of it largely affects the result. What's more the synovial fluid WBC count may be unreliable in the setting of a metal-on-metal bearing or corrosion reaction. Routine cultures should be maintained between 5 and 14 days, their sensitivity appears low in chronic infection even if witholding antimicrobial therapy before the collection of the fluid can increase the likelihood of recovery an organism. Synovial leukocyte esterase can be performed as a rapid office or intraoperative point of care test using urinalysis strips. It is cheap and easy to perform, but the presence of blood in the sample can affect the result and it needs centrifugation. Recently a new test has been proposed to detect alfa-defensine in synovial fluid. It shows a high sensitivity and an exellent specificity. We performed 25 joint punctions on 25 patients with suspected PJI (enrollment is going on). Synovial fluid collected was tested for: leukocite esterase, WBC count and differential, colture in blood colture bottle for anerobe and aerobes (BacT/ALERT Biomerieux, inc) and detection of alfa-defensine level (Synovasure – Zimmer). In patients who underwent surgery at least 5 samples of periprotesic tissue were collected for microbiologic analysis and the removed implant was sonicated according with the methodic. Furthermore samples for frozen section were sent and a histologic examination was made according to the Moriewitz – Kerr classification. The MSIS criteria was utilized to classify the case as infected or not


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 19 - 19
1 Jan 2017
Gallazzi E Capuano N Scarponi S Morelli I Romanò C
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Infection remains among the first reasons for failure of joint prosthesis. Currently, the golden standard for treating prosthetic joint infections (PJIs) is two-stage revision. However, two-stage procedures have been reported to be associated with higher costs and possible higher morbidity and mortality, compared to one-stage. Furthermore, recent studies showed the ability of a fast-resorbable, antibacterial-loaded hydrogel coating to reduce surgical site infections after joint replacement, by preventing bacterial colonization of implants. Aim of this study was then to compare the infection recurrence rate after a one-stage, cemenless exchange, performed with an antibacterial coated implant versus a standardized two-stage revision procedure. In this two-center prospective study, 22 patients, candidate to revision surgery for PJI, were enrolled to undergo a one-stage revision surgery with cementless implants, coated intra-operatively with a fast-resorbable, antibiotic-loaded hyaluronan and poly-D,L-lactide based hydrogel coating (“Defensive Antibacterial Coating”, DAC, Novagenit, Italy). DAC was reconstructed according to manufacturer indications and loaded with Vancomycin or Vancomycin + Meropenem, according to cultural examinations, and directly spread onto the implant before insertion. This prospective cohort was compared with a retrospective series of 22 consecutive patients, matched for age, sex, host type, site of surgery, that underwent a two stage procedure, using a preformed, antibiotic-loaded spacer (Tecres, Italy) and a cementless implant. The second surgery, for definitive implant placing, was performed only after CRP normalization and no clinical sign of infection. Clinical, laboratory and radiographic evaluation were performed at 3, 6 and 12 months, and every 6 months thereafter. Infection recurrence was defined by the presence of a sinus tract communicating with the joint, or at least two among the following criteria: clinical signs of infections; elevated CRP and ESR; elevated synovial fluid WBC count; elevated synovial fluid leukocyte esterase; a positive cultural examination from synovial fluid; radiographic signs of stem loosening. The two groups did not differ significantly for age, sex, host type and site of surgery (18 knees and 4 hips, respectively). The DAC hydrogel was loaded intra-operatively, according to cultural examination, with vancomycin (14 patients) or vancomycin and meropenem (8 cases). At a mean follow-up of 20.2 ± 6.3 months, 2 patients (9.1%) in the DAC group showed an infection recurrence, compared to 3 patients (13.6%) in the two-stage group. No adverse events associated with the use of DAC or radiographic loosening of the stem were observed at the latest follow-up months. This is the first report on one-stage cementless revision surgery for PJI, performed with a fast-resorbable antibacterial hydrogel coating. Our data, although in a limited series of patients and at a relatively short follow-up, show similar infection recurrence rate after one-stage exchange with cementless, coated implants, compared to two-stage revision. These findings warrant further studies in the possible applications of antibacterial coating technologies to treat implant-related infections


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_15 | Pages 14 - 14
1 Aug 2017
Williams G
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Periprosthetic joint infection (PPJI) following shoulder arthroplasty is uncommon, with an overall rate of 0.98%. However, the rates following revision arthroplasty and reverse arthroplasty are much higher. Given the rapid increase in the prevalence of shoulder arthroplasty and the increasing revision burden, the cost of PPJI to society will likely increase substantially. The most common organisms found in PPJI following shoulder arthroplasty are Staphylococcus aureus, coagulase-negative Staphylococcus, and Propionibacterium acnes (P. acnes). P. acnes is especially common in males. Traditional testing for PPJI includes aspiration, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). Aspiration often yields a dry tap and when fluid is obtained for culture, a positive result is helpful but a negative result does not rule out PPJI. Although WBC, ESR, and CRP are often positive with PPJI in the lower extremity, they are most often negative in shoulder PPJI. Although bone scans and WBC labeled scans are used, they are expensive and have low sensitivity and specificity. New testing and techniques have been reported in an attempt to improve sensitivity and specificity for PPJI. These techniques can be divided into tests on serum, synovial fluid, and tissue. Serum Interleukin-6 (IL-6) is highly specific (94%) for shoulder PPJI but has low sensitivity (14%). Synovial fluid can be tested for leukocyte esterase using a simple and cheap technique. In lower extremity PPJI it has shown to be helpful. It is not as helpful in shoulder PPJI with 30% sensitivity and 67% specificity. Alpha defensin has been reported to be more sensitive (63%) and as specific (95%) as traditional techniques but still lacks predictive value. Testing for specific cytokines (IL-2, IL-6, TNF- α) within synovial fluid is not widely used as yet but has shown promise with 80% sensitivity and 90% specificity. Obtaining tissue for culture and other testing is probably the most reliable way of confirming PPJI for the shoulder. Frozen sections taken at the time of revision can be helpful but is very pathologist dependent and institution specific. With a dedicated musculoskeletal pathologist, the finding of 10 or more WBCs per high powered field has been reported to be 72% sensitive and 100% specific for P. acnes and 63% sensitive and 100% specific for other organisms. Cultures from arthroscopic tissue biopsy have also been found to have high sensitivity (100%) and specificity (100%). Genetic testing of tissue biopsy specimens (PCR/NGS) has recently been reported and shows great promise. The significance of positive cultures and other tests, especially for P. acnes is unclear. There is a high rate of positive intra-operative cultures in primary cases of shoulder arthroplasty. In addition, intra-operative cultures taken at the time of revision, even in cases in which infection is not suspected, are frequently positive for P. acnes with weak correlation with rates of post-operative clinical infection. In conclusion, shoulder PPJI is a difficult problem to deal with. The definition of shoulder PPJI is currently unclear and further study is needed. There is no ideal test to confirm it. A reasonable approach is to aspirate for culture, and perform serum tests for WBC, ESR, and C-reactive protein. If any of these is positive in the setting of a painful arthroplasty, PPJI should be assumed until proven otherwise. Operative tissue cultures are probably the most reliable test but the clinical significance is not always obvious. Synovial fluid cytokine profiles and tissue PCR/NGS show promise for the future


Bone & Joint Open
Vol. 4, Issue 11 | Pages 881 - 888
21 Nov 2023
Denyer S Eikani C Sheth M Schmitt D Brown N

Aims

The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI.

Methods

A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated.


Bone & Joint 360
Vol. 8, Issue 4 | Pages 42 - 44
1 Aug 2019


Bone & Joint Research
Vol. 12, Issue 2 | Pages 113 - 120
1 Feb 2023
Cai Y Liang J Chen X Zhang G Jing Z Zhang R Lv L Zhang W Dang X

Aims

This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%).

Methods

In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared.


Bone & Joint 360
Vol. 8, Issue 1 | Pages 40 - 42
1 Feb 2019