Aim. Quantitative assessment of alpha-Defensin offers a promising approach for diagnosing a periprosthetic joint infection (PJI) with sensitivities and specificities ranging from 97% to 100% and 95% to 100%, respectively. However, to the best of our knowledge and after due inquiry little information exists concerning qualitative measurements of alpha-Defensin. The aim of this study was to assess the diagnostic accuracy of the alpha-Defensin test, a lateral flow test for the qualitative detection of alpha-Defensin. Method. In this study, 50 patient with indicated revision surgery met the inclusion criteria due to septic or aseptic loosening. In addition to clinical standard diagnostics of PJI, the alpha-Defensin test. *. for the assessment of the qualitative alpha-Defensin in the synovial fluid was performed. The results were compared with the sensitivity and specificity of currently available clinical tests, specifically C-reactive protein (CRP), frozen section, definitive histology, bacteriology and sonication. Results. Based on the Musculoskeletal Infection Society's (MSIS) definition of PJI, 36 cases were categorized as aseptic and 13 as septic revisions. Due to the lack of an indicated control line (“C”), one alpha-Defensin test. *. was inconclusive. Qualitative alpha-Defensin had an area under the curve, sensitivity, specificity, and positive and negative likelihood ratios of 0.82, 69%, 94%, 12.46, and 0.33, respectively. Adjusted p-values using the method of Hochberg showed that the alpha-Defensin test. *. is significantly at least as good when diagnosing PJI as histology (p=0,0042) and bacteriology with at least one positive culture (p=0,0327). Conclusions. Qualitative alpha-Defensin tests could be an effective supplement in diagnosing PJI with a diagnostic accuracy comparable to histology and bacteriology (≥ 1 positive culture)

Aim. Alpha-defensin is a new synovial fluid biomarker for the diagnosis of periprosthetic joint infections (PJI). We compared the performance of two different alpha-defensin assays: quantitative ELISA test and qualitative lateral flow test. Method. In this prospective cohort study, consecutive patients with a painful prosthesis of the lower limb were eligible for inclusion. In addition to standard diagnostics of PJI, alpha-defensin was determined in the aspirated synovial fluid between October 2016 and April 2017. PJI was defined according to the modified Zimmerli criteria, the Musculoskeletal Infection Society (MSIS) criteria and the Infectious Disease Society of America (IDSA) criteria. A positive quantitative alpha-defensin test was defined at a cut-off value of 5.2 mg/L. The sensitivity, specificity, accuracy and area under the curve of each test were determined and the AUCs were compared among each other. Results. We included 72 patients (55 knee, 27 hip prosthesis) with a median age of 70 years (range: 41 – 85 years). Based on the modified Zimmerli criteria, 23 cases (32%) were categorized as septic and 49 (68%) as aseptic prosthesis failure. The sensitivity, specificity, accuracy, and AUC of quantitative alpha-Defensin were 48%, 98%, 82%, and 0.73, respectively; for qualitative alpha-Defensin, results were 48%, 100%, 83%, and 0.74, respectively. When the IDSA criteria were applied, the sensitivity of the quantitative and qualitative alpha-defensin test was 83% and 75%, respectively; when the MSIS criteria were applied, the sensitivity of the quantitative and qualitative alpha-Defensin was 92% and 83%, respectively. The comparison between the qualitative and quantitative alpha-defensin tests showed no statistically significant difference regardless of the used infection classification (modified Zimmerli: [difference AUC −0.01; p = 0.792], IDSA: [difference AUC 0.04; p = 0.317], MSIS: [difference AUC 0.04; p = 0.264]). Conclusions. The sensitivity of the alpha-defensin test in synovial fluid showed poor sensitivity (48%) for diagnosing PJI when modified Zimmerli criteria were used. No difference were observed between the qualitative and quantitative alpha-defensin test

Aim. A key of success in the treatment of prosthetic joint infection (PJI) is the proper diagnosis. There is a lack of diagnostic tools able to diagnose a PJI with high accuracy. Alpha-defensin has been proposed as possible solution but the available literature is still limited. This prospective study was carried out in order to determine (1) what is the sensitivity, the specificity, the positive and the negative predictive value of the Alpha-defensin immunoassay test in diagnosing PJI; (2) which clinical features may be responsible for false positive and false negative results?. Method. Preoperative aspiration was performed in patients presenting with a painful hip/knee arthroplasty. Metallosis, other inflammatory comorbidities and previous/concomitant antibiotic therapy were not considered as exclusion criteria. Patients with inadequate amount of synovial fluid for culture were excluded. At time of revision synovial fluid samples were taken in the OR in order to perform Alpha-defensin assay. During surgical debridement tissue samples for cultures were obtained. Prospectively, 156 patients (65 knees and 91 hips) were included. A diagnosis of PJI was confirmed in 29 patients. Results. The sensitivity of the Alpha-defensin immunoassay was 97% (95% CI, 92% – 99%), the specificity was 97% (95% CI, 92% – 99%), the positive predictive value was 88% (95% CI, 81% – 92%) and the negative predictive value was 99% (95% CI, 96% – 99%). Among four false positive patients two had a metallosis and one had a polyethylene wear. The false negative case presented with a draining sinus, and intraoperative cultures were also negative. Conclusions. Alpha-defensin assay may have a significant role in PJI diagnosis. Negative tests may exclude the diagnosis of PJI. Positive tests are very much likely to confirm PJI, but other conditions (metallosis, poly wear) should be excluded

Prosthetic joint infection continues to remain a diagnostic challenge for unhappy primary arthroplasty of hip and knees. There is increasing dependence upon alpha-defensin test to make key decisions like whether to revise or not & to decide between one-stage versus two-stage. Aim. This study aims to assess diagnostic accuracy of alpha-defensin test in determining prosthetic hip & knee infection and to provide guidance for appropriate use of this novel but expensive investigation. Methods. Retrospective review of all alpha-defensin investigated patients in an orthopaedic institute between February 2015 & March 2017 was performed. Clinical and radiological outcomes including re-infections, re-operations were analysed and alpha-defensin outcomes were compared with that of other available investigations. Results. Of total 52 tests performed (17 hips & 35 knees), 3 were positive. On comparison with intra-operative culture (gold standard), sensitivity is 100%. All suspected prosthetic hip infections have good clinical outcomes following their decisions being made based upon alpha-defensin test. Among the negative knee test results, 6 patients developed signs of infection in the post-operative period, 4 of which have been revised with washout, poly exchange or full revision. Conclusion. No single clinical investigation can accurately predict prosthetic joint infection in revision for suspected infection. Alpha-defensin test, however, is a useful adjunct to intra-operative surgeon's findings & pre-operative investigations to decide for crucial decisions like whether to revise or not & for deciding between single and two stage

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®

Purpose. Unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic revision-total-knee-arthroplasties (rTKA) are common, and the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, an identification of an underlying pathogen was not possible, so called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate alpha defensin (AD) levels in these patient populations. Methods. In this retrospective analysis of our prospectively maintained biobank, we evaluated synovial AD levels from 143 rTKAs. The 2018-Musculoskeletal Infection Society score (MSIS) was used to define our study groups. Overall, 20 rTKA with UPIC with a minimum of one positive intraoperative culture with MSIS 2-≥6 and 14 UNIC samples with MSIS≥6 were compared to 34 septic culture-positive samples (MSIS ≥6) and 75 aseptic culture-negative (MSIS 0–1) rTKAs. Moreover, we compared the performance of both AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) to test the presence of AD in native and centrifuged synovial fluid. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were considered. Results. AD was detected in 31/34 (91.2%) samples from the infected-group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly (p<0.001) associated with culture positive and infection related histopathological results. Moreover, we found significantly (p=0.001) more high-virulent microorganisms 19/34 (55.9%) in the infected-group compared to the UPIC-group (0/20). Samples from the infected group with high virulent microorganisms 17/19 (89.5%) showed a positive AD. The presence of methicillin resistant Staphylococcus epidermis (MRSE) led to increased AD (p=0.003) levels when compared to those determined in samples positive for methicillin susceptible S. epidermdis (MSSE). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. Conclusion. AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnostic of UPIC and UNIC associated to rTKAs. AD levels produced by patients with PJIs caused by high-virulent microorganisms and MRSE are significantly higher compared to those in patients with PJIs caused by either low-virulent or antibiotic susceptible microorganisms. Centrifugation of synovial fluid had no influence in the outcome of ADLF quantification. Keywords: Alpha-defensin, UPIC, UNIC, revision-knee-arthroplasty

Aim

The aim of the study was to assess the accuracy of the alpha defensin lateral flow test for diagnosis of periprosthetic joint infection (PJI) using an optimized diagnostic algorithm and three classification systems. In addition, we compared the performance with synovial fluid leukocyte count, the most sensitive preoperative test.

Background. The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice and the analysis of synovial fluid (SF) is a useful diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase (LE) strip test, alpha-defensin (AD)) have been introduced into the MSIS (MusculoSkeletal Infection Society) algorithm for the diagnosis of PJI. AD, although promising with high sensitivity and specificity, remains expensive. Calprotectin is another protein released upon activation of articular neutrophils. The determination of calprotectin and joint CRP is feasible in a routine laboratory practice with low cost. Purpose. Our objective was to evaluate different synovial biomarkers (calprotectin, LE, CRP) for the diagnosis of PJI. Methods. In this monocentric study, we collected SF from hip, knee, ankle and shoulder joints of 42 patients who underwent revision or puncture for diagnostic purposes. Exclusion criteria included a joint surgery in the previous 3 months and a diagnosis of a systemic inflammatory disease. PJI was diagnosed in a multidisciplinary consultation meeting (RCP) of the Reference Centers for Osteoarticular Infections of the Great West (CRIOGO). SF was analysed for LE, CRP and calprotectin. The cut-off values used were 50 mg/L for calprotectin, 8.8 mg/L for CRP and 125 WBC/µL for LE. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for these different synovial markers. Results. Of the 42 patients included, 28 were considered as infected and 14 uninfected. The statistical parameters are presented in Table 1. Conclusion. The present study shows that the synovial calprotectin assay has an excellent sensitivity and a 100% NPV for the diagnosis of PJI, suggesting that a result < 50 mg/L could exclude PJI. This promising study suggests that calprotectin should be included with synovial CRP in a new decision algorithm for the diagnosis of PJI. For any tables or figures, please contact the authors directly

Introduction. Periprosthetic joint infection (PJI) is considered one of the most feared causes of implant failure, due to the difficulty in formulating a proper and timely diagnosis. In the diagnostic workup are often used test with a low specificity, such as the dosage of ESR and CRP, or sensitivity, such as cultures or the leukocyte count of the synovial fluid. Radiological investigations are expensive and unreliable to play a direct role in the diagnosis of PJI. The alpha-defensin is an antimicrobial peptide released by neutrophils in response to pathogens and it is an ideal biomarker for the diagnosis of PJI. It is now possible to verify the presence of alpha-defensin in periprosthetic synovial fluid with an ELISA (Synovasure® PJI, Zimmer) that provides results in 10 minutes, with a sensitivity of 97% and a specificity of 96%, without being affected by systemic inflammatory diseases or by the assumption of antibiotics. The purpose of this study is to assess the applicability and reliability of Synovasure® PJI, correlating its results with microbiological analyzes, laboratory tests and imaging studies of the patient. Materials and Methods. Patients recruited are those who have undergone a previous total hip or knee arthroplasty where there is suspicion of PJI. The test can be performed either during surgery or during the diagnostic iter, through the execution of an arthrocentesis. The synovial fluid is partly used for Synovasure® PJI and partly put in culture for microbiological analyzes. Once ready, culture results are compared with the results of the test to get a confirmation of its reliability or reference to identify the microorganism responsible for PJI. These data are then compared, with laboratory tests and radiological investigations performed by the patient. Results. Up to now we have full results in 10 patients (11 implants). In four cases, the test showed the presence of alpha-defensin in the synovial fluid, while in seven cases the test result were negative. In case of negative test culture of synovial fluid showed no growth of microorganisms that could indicate the presence of false negatives. All patients with positive test have arthrocentesis positive for pathogenic microorganisms. We are waiting for culture results of two other patients (one with positive test and one with negative test). In the next few months will be tested other patients with suspicion of PJI. Discussion. Timeliness and accuracy in the diagnosis are essential for the proper management of the patient with suspected PJI. Diagnostic tools currently available are often sensitive but not very specific or conversely, specific but insensitive. New synovial markers such as alpha-defensin and rapid ELISA tests for their dosage open new horizons in the diagnosis of periprosthetic infections. Conclusions. Synovasure® PJI is a practical and reliable tool in the diagnosis of periprosthetic joint infections. Thanks to the quick response and the ease of execution the test can be used both during the diagnostic iter and during the revision surgery helping the orthopedic to apply the most appropriate measures to each case

While advances in laboratory and imaging modalities facilitate the diagnosis of periprosthetic joint infection (PJI), clinical suspicion and a thorough history and physical remain the basis of evaluation. If clinical suspicion is high, the evaluation should be more vigorous, and vice versa. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inexpensive as well as ubiquitous, and should be obtained as a preliminary screening tool. These tests have been found to be cost-effective and highly sensitive. If both tests are negative, there is a low risk of periprosthetic joint infection (i.e., good negative predictive value). Positive results on both tests, in contrast, are not as specific but again raise suspicion. When either the ESR or CRP is elevated, or if the clinical suspicion for infection is high, aspiration of the knee joint is suggested. Synovial fluid should be sent for a synovial fluid white blood cell count (WBC), differential and culture. Given the ability to get three data points from one intervention, arthrocentesis, is the best single maneuver the physician can perform to rule in or out PJI. The synovial fluid WBC count has demonstrated in multiple studies excellent specificity and sensitivity in the diagnosis of infection. Based on multiple recent studies, the proceedings of the International Consensus on PJI recommend cut-offs for the synovial fluid WBC count as >3000 cells/mL and > 80% neutrophils for the differential. Synovial fluid biomarkers represent an expanding area of clinical interests based on the unique cascade of gene expression that occurs in white blood cells in response to pathogens. Deirmegian et al. described the unique gene expression and biomarker production by neutrophils in response to bacteria that are detectable in synovial fluid. Specifically, alpha-defensin is one such antimicrobial peptide. Along with synovial CRP, alpha-defensin can be measured in a currently commercially-available immunoassays. The diagnosis of PJI can be difficult to make in spite of the variety of tests available. That being said, the diagnosis is easily made in our experience in 90% of patients by getting an ESR and CRP followed by selective aspiration of the joint if these values are elevated or if the clinical suspicion is high. Synovial fluid obtained should be sent for a synovial fluid WBC count, differential and cultures

Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease. However, the Periprosthetic Joint Infection (PJI) remains one of the biggest challenges facing orthopaedics today. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. The most common symptom of PJI is pain. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

INTRODUCTION. Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. However, infection of these implants, called Periprosthetic Joint Infection (PJI), remains one of the biggest challenges facing orthopaedics today. PJI can lead to additional surgeries, revision, fusion and amputation. Diagnosis of PJI. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. These include the erythrocyte sedimentation rate (ESR), the serum C-reactive protein (CRP), the synovial fluid white blood cell count and the leukocyte differential. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The Synovasure® Test for Periprosthetic Joint Infection (PJI). The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. These biomarkers include inflammatory proteins, cytokines, and microbicidal peptides / proteins that are known to be involved in the host response to infection. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. DISCUSSION. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. CONCLUSIONS. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

Introduction. In revision surgery, detection of periprosthetic joint infection is of prime importance. Valuable preoperative and intraoperative diagnostic tests and tools are necessary. The classical standard procedures are puncture and bacteriology examination, frozen section intraoperative and powerfield micro analysis. Since autumn 2014 a new device for detection of periprosthetic joint infection is available, named Synovasure. It is a fast test for the detection of Alpha defensing, which plays a major role in the antimicrobial defence and only occurs in inflammatory processes. „The alpha-defensin test is an immunoassay that measures the concentration of the alpha-defensin peptide in human synovialfluid. A-Defensin is an antimicrobial peptide that is secreted into the synovial fluid by human cells in response to pathogenic presence” (Deirmengian C et al., CORR 2014). Summarized, the evidence of Alpha defensin indicates infection. It is produced by CD Diagnostics (Wynnewood, PA, USA) and merchandised by Zimmer (Warsaw, IL, USA). We are using Synovasure in daily routine at our department since September 2014. The aim of this conducted study is to present our first clinical experience and to report our results of the first 54 cases. Material and Methods. At our department Synovasure is standardly used in hip and knee revision surgery. Additionally an intraoperative frozen section and a standard bacteriology were performed. The explanted endprosthesis were sent to examination by sonification in order to gain culture of the sonification fluid and were further examined by Multiplex PCR. A pathologist with more than 15 years of experience conducted the frozen section. The results of Synovasure were matched with all above examinations in order to describe specifity and sensitivity of it. Results. A negative Synovasure Test during surgery and a negative PCR were observed in 3 patients, however, the bacterial culture was positive (after 14 days of breeding) as well as the Multiplex PCR. One patient had a negative frozen section and a negative culture but a positive PCR. Another patient with a high CRP level, all clinical signs of infection and a positive Synovasure Test, had 6 negative cultures. This patient suffered from a Metallosis as well, due to a broken PE inlay of the TKA, which supports the previously stated that Metallosis may interfere this new tool. Unfortunately in this patient neither a frozen section nor a PCR are available. One patient, who had explanation due to infection, underwent reimplantation. During surgery the Synovasure Test and the frozen section were negative (Synovial Fluid), but postoperatively a positive culture and a positive histological report for infection were assessed. Furthermore, a total of 5 tests showed an application error and the test did not show any control line. Conclusion. In conclusion Synovasure helps to detect perprosthetic joint infection in an easy and fast manner. It is simple to integrate into daily routine, nevertheless all standardized examinations for infection need to be conducted

Aim. Apart from other biomarkers isolated in the synovial fluid, alpha-defensin appears to be a promising diagnostic tool to confirm a periprosthetic joint infection (PJI) in the hip or knee. The purpose of this study was to evaluate the sensitivity and specificity of an alpha defensin lateral flow (ADLF) test compared to usual standard classifications in the diagnostic management of PJI. Method. This investigation was set up as a multicenter prospective cohort study. Synovial fluid was obtained by means of joint aspiration or intra-operative tissue biopsies. A presumptive PJI diagnosis was made according to criteria outlined by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA) and the European Bone and Joint Infection Society (EBJIS). The intention to treat by the surgeon was logged. Sensibility and specificity for the ADLF test was plotted for each aforementioned diagnostic algorithm. Spearman correlations between all scores were analyzed. Multiple logistic regression was used to determine the contribution of independent variables to the probability of PJI. Results. Hundred thirty-six patients with a painful arthroplasty were assessed for infection and rated by the treating surgeon as potentially infected or not on the basis of clinical and laboratory information. According to the EBJIS criteria sixty-eight patients were deemed infected, fifty according to the IDSA criteria, forty-one according to the MSIS criteria and forty according to the ADLF test. However, the sensitivity of ADLF test was 87.8% for MSIS, 70% for IDSA and 55.8% for EBJIS. The specificity of ADLF test was between 94% – 97%. Good correlation was observed between synovial fluid culture and ADLF test (r = 0.73). Low to excellent correlations between the ADLF test and the EBJIS (r = 0.58), IDSA (r = 0.68), and MSIS score (r = 0.84) were observed. The surgeon's intention to treat correlated well with the MSIS score (r = 0.86), and moderately with the EBJIS (r = 0.59). Conclusions. ADLF test sensibility was variable, but its specificity was excellent. Most of the cases, not retained by MSIS but classified by EBJIS as infected, got a negative microbiological result. Considering an accepted 20% negative microbiological result rate in PJI diagnostic, EBJIS is clearly overestimating the number of infected cases. MSIS score correlates with the surgeon intention to treat and ADLF test

In years past, the most common reason for revision following knee replacement was polyethylene wear. A more recent study indicates that polyethylene wear is relatively uncommon as a cause for total knee revision counting for only 10% or fewer of revisions. The most common reason for revision currently is aseptic loosening followed closely by instability and infection. The time to revision was surprisingly short. In a recent series only 30% of knees were greater than 5 years from surgery at the time of revision. The most common time interval was less than 2 years. This is likely because of the higher incidence of infection and instability that occurs most commonly at a relatively early time frame. Evaluation of a painful total knee should take into account these findings. All total knees that are painful within 5 years of surgery should be assumed to be infected until proven otherwise. Therefore, virtually all should be aspirated for cell count, differential, and culture. Alpha-defensin is also available in cases in which a patient may have been on antibiotics within a month or less, as well as cases in which diagnosis is a challenge for some reason. Instability can be diagnosed with physical exam focusing on mid-flexion instability which can be usually determined with the patient seated and the knee in mid-flexion, with the foot flat on the floor at which point sagittal plane laxity can be discerned. This is also frequently associated with symptoms of giving way and recurring effusions and difficulty descending stairs. A new phenomenon of tibial de-bonding has been described, which can be a challenge to diagnose. Radiographs can appear normal when loosening occurs between the implant and the cement mantle. This seems to be more common with the use of higher viscosity cement. Obviously this is technique dependent since good results have been reported with the use of high viscosity cement. Component malposition can cause stiffness and pain and relatively good results have been reported by component revision when malrotation has been confirmed with CT scan. When infection, instability and loosening are not present, extra-articular causes should be ruled out including lumbar spine, vascular compromise, complex regional pain syndromes and fibromyalgia, and peri-articular causes such as bursitis, tendonitis, tendon impingement among others. One of the most common causes of pain following total knee is unrealistic patient expectations. Performing total knee replacement in early stages of arthritis with only mild to moderate symptoms and radiographic changes has been associated with persistent pain and dissatisfaction. It may be prudent to obtain the immediate preoperative x-rays to determine if early intervention was undertaken and patients have otherwise normal appearing total knee x-rays and a negative work up. A recent study indicated that this was likely a cause or a major contributing factor to persistent pain following otherwise a well performed knee replacement. A national multicenter study of the appropriateness of indications for TKA also indicated that early intervention was a major cause of persistent pain, dissatisfaction, and failure to improve following total knee replacement

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Metal Ion Levels Not Useful in Failed M-O-M Hips: Systematic Review; Revision of Failed M-O-M THA at a Tertiary Center; Trunnionosis in Metal-on-Poly THA?; Do Ceramic Heads Eliminate Trunnionosis?; Iliopsoas Impingement After 10 THA; Pain in Young, Active Patients Following THA; Pre-operative Injections Increase Peri-prosthetic THA Infection; Debridement and Implant Retention in THA Infection; THA after Prior Lumbar Spinal Fusion; Lumbar Back Surgery Prior to THA Associated with Worse Outcomes; Raising the Joint Line Causes Mid-Flexion Instability in TKA; No Improvement in Outcomes with Kinematic Alignment in TKA; Botox For TKA Flexion Contracture; Intra-operative Synovitis Predicts Worse Outcomes After TKA for OA; When is it Safe for Patients to Drive After Right TKA?; Alpha-Defensin for Peri-prosthetic Joint Infection; Medial Tibia Overhang and Pain Score After TKA

Effectiveness of Liposomal Bupivacaine for Post-Operative Pain Control in Total Knee Arthroplasty: A Prospective, Randomised, Double Blind, Controlled Study. Pericapsular Injection with Free Ropivacaine Provides Equivalent Post-Operative Analgesia as Liposomal Bupivacaine following Unicompartmental Knee Arthroplasty. Total Knee Arthroplasty in the 21st Century: Why Do They Fail? A Fifteen-Year Analysis of 11,135 Knees. Cryoneurolysis for Temporary Relief of Pain in Knee Osteoarthritis: A Multi-Center, Prospective, Double-Blind, Randomised, Controlled Trial. Pre-Operative Freezing of Sensory Nerves for Post-TKA Pain: Preliminary Results from a Prospective, Randomised, Double-Blind Controlled Trial. Proximalization of the Tibial Tubercle Osteotomy: A Solution for Patella Infera during Revision Total Knee Arthroplasty. Treatment of Periprosthetic Joint Infection Based on Species of Infecting Organism: A Decision Analysis. Alpha-Defensin Test for Diagnosis of PJI in the Setting of Failed Metal-on-Metal Bearings or Corrosion. Risk of Reinfection after Irrigation and Debridement for Treatment of Acute Periprosthetic Joint Infection following TKA. Serum Metal Levels for the Diagnosis of Adverse Local Tissue Reaction Secondary to Corrosion in Metal-on-Polyethylene Bearing Total Hip Arthroplasty. Intra-Articular Injection for Painful Hip OA - A Randomised, Double-Blinded Study. Six-Year Follow-up of Hip Decompression with Concentrated Bone Marrow Aspirate to Treat Femoral Head Osteonecrosis. No Benefit of Computer-Assisted TKA: 10-Year Results of a Prospective Randomised Study