Preoperative MRSA screening using a simple questionnaire prior elective total joint replacement.

INTRODUCTION: The purpose of this study was to evaluate the management and results of our standarized protocol for preoperative identification of MRSA colonisation in patients undergoing primary total hip and knee replacement procedures. METHODS: Following hospital protocol, between January 2016 and June 2019 37,745 patients awaiting elective joint replacement underwent a standardized questionnaire to assess the risk of MRSA infection, identifying patients requiring preoperative MRSA screening. An evaluation of the questionnaire identified effective questions for identifying infected patients. Furthermore, an analysis evaluated the impact of comorbidities or Charlson Comorbidity Index scores on positive MRSA colonization. Additionally, we evaluated the cost savings of targeted testing compared to testing all surgery patients. RESULTS: Of the 37,745 patients, 8.057 (21.3%) were swabbed, with a total of 65 (0.81%) positive tests. From this group 27 (36.48%) who were treated were negative before surgery. Some of the questionnaire results were consistently associated with a higher chance of colonization, including hospitalization during the past year (47,7%), previous history of MRSA (44,6%), and agriculture or cattle farming related work (15,4%). By selectively testing high-risk patients identified through the questionnaire, we achieved a 79% reduction in costs compared to universal MRSA screening. CONCLUSION: Our results suggest that the simple and standardized questionnaire is a valuable tool for preoperative screening, effectively identifying high-risk patients prone to MRSA colonisation. The risk of periprosthetic joint infection (PJI) and its associated sequelae may be reduced by this approach.

The anatomical shape of the distal femur is an independent risk factor for aseptic loosening following one-stage septic knee revision using rotating hinge knee prosthesis.

PURPOSE: Aseptic loosening (AL) is the second most common reason for failure after one-stage septic knee revision. In this context, the goal of the study is to identify risk factors for AL following one-stage septic knee revision using rotating hinge implants. We aimed to answer the following research question: How does the anatomical shape of the distal femur represent an independent risk factor for AL following one-stage septic knee revision arthroplasty? METHODS: Patients, who had undergone re-revision surgery due to AL of the rotating hinge knee prosthesis after one-stage septic knee revision arthroplasty between January 2008 and December 2018, were included. For this purpose, 41 patients with AL after one-stage septic knee revision using rotating hinge implants and 37 controls without any revision surgery at latest follow-up were included in this study. Using standardized anteroposterior (AP) views of the knee in all patients, we measured the inner diameter of the femur 20 cm proximally from the joint line and at a point 2 cm proximally from the adductor tubercle. RESULTS: Among the vast majority of AL cases, we identified an isolated loosening of the femoral component. The AL group showd a high distribution of the Type C according to the Citak classification with 75.7%. Contrary to this, with 24.3% (p < 0.001) the amount of Type C cases was relatively low in the control group. Consequently, Type C configurations of the distal femur represent an independent risk factor for AL with an approximately sevenfold higher risk for AL compareed to Type A and Type B. CONCLUSIONS: The novel radiological classification system of the distal femur shows that the Type C subtype is an independent and main risk factor for AL after one-stage septic knee revision using rotating hinge knee implants.

Anatomical risk factors for aseptic loosening of full hinge knee prosthesis in primary and revision TKAs.

INTRODUCTION: Risk factors (RF) associated with aseptic loosening (AL) in total knee arthroplasty (TKA) are poorly understood. Therefore, the aim of this study was to investigate the anatomical shape variations in relation to the inner-diameter of the femur and the tibia as prognostic RF for AL of full hinge prosthesis (FHP) in primary and revision TKA. MATERIALS AND METHODS: We retrospectively examined all patients, who underwent revision surgery (2003-2018) due to AL of the FHP in primary (n = 38) and revision TKA (n = 46). Diagnosis-appropriate controls without AL at minimum follow-up of 24 months were randomly collected for each group. Besides other risk factors, we also measured the inner diameter of the femur according to the Citak classification and of the tibia on anteroposterior radiographies. RESULTS: RF for AL are younger age in primary and revision as well as > 1 previous surgeries in revision TKA. The femoral index was shown to be a RF for AL in revision TKA (p = 0.001), but not in primary TKA. The novel tibial index was associated with AL in primary with AUC 0.776 (95% CI 0.67, 0.88), 65.8% sensitivity, 86.6% specificity and in revision TKA with AUC 0.817 (95% CI 0.73, 0.91), 82.6% sensitivity and 71.7% specificity. CONCLUSION: This is the first study to calculate the tibial measurements and the tibial index according to Citak et al. and to identify them as prognostic RF for AL of the full hinge knee prosthesis in TKA and confirm the femoral index as a RF for AL also in revision full hinge knee prosthesis. Therefore, the preoperative radiological evaluation should include the analysis of the anatomical shape variants in order to select the appropriate prosthesis design with a possibly enhanced prognosis.

Twenty-year results of a neck-preserving short-stem prosthesis in primary total hip arthroplasty.

PURPOSE: The use of short-stemmed femoral components with preservation of the femoral neck has been advocated for younger and more active patients undergoing joint replacement. This study reports the long-term outcomes of the Collum Femoris-Preserving (CFP) prosthesis on a previous report. METHODS: Between January 1999 and December 2000, a total of 149 patients underwent total hip arthroplasty procedure using the CFP stem in a single institution. At latest follow-up, 79 patients were available and were included in this study. The mean age of the cohort was 73.4 (range, 44-92 years) with a mean follow-up of 20.7 years (range 20-21). The average age was 52.1 years at index procedure (range, 21-71 years). RESULTS: The Kaplan-Meier survivorship free from revision for any cause at 5, 10 and 20 years was 93.2% (87.8-96.3%), 93.2% (87.8-96.3%) and 83.0% (75.7-88.3%), respectively. At 20 years follow-up, the revision for any cause occurred in 26.6% (21 of 79) of patients. The most common causes for revision surgery were aseptic loosening, dislocation, and polyethylene wear with 6.3% (5 out of 79), respectively. Periprosthetic fracture occurred in four patients (5.1%) followed by periprosthetic joint infection in two patients (2.5%). Revision surgery of the femoral stem was required in four patients (5.1%). There was a statistically significant improvement of the Harris Hip Scores from 53 to 83.7 (range 56-91). CONCLUSION: The long-term outcomes of the CFP stem are excellent, demonstrating a low rate of aseptic loosening with an excellent survivorship within 2 decades.

The anatomical shape of the proximal femur correlates with the distal femur anatomy.

PURPOSE: In the case of stemmed implants for lower limb joint arthroplasty procedures, implant stability and survivorship generally rely on the strength of fixation in the medullary canal regardless of whether the procedure is primary or revision surgery. This study aimed to investigate the relationship between the proximal (Dorr classification) and distal (Citak classification) femoral canal geometry classification systems. METHODS: A total of 200 patients who received standing long leg radiographs (hip to ankle) at our institution were identified using our institutional electronic radiology database. Patients were recruited into 4 groups. There were 100 male and 100 female patients with each of those being split into 50 right-sided and 50 left-sided long-leg standing anteroposterior (AP) radiographs. Two independent, blinded observers reviewed each radiograph on two separate occasions, with a minimum of a one-week interval between sittings to review each respective radiograph. RESULTS: No statistically significant correlation was found between demographic data and clinical measurements. A statistically significant correlation was found between the patient's age and BMI results and Citak and Dorr measurements. There was excellent inter-observer and intra-observer agreement for the Citak and Dorr Classifications. The mean Cronbach's α coefficient was 0.96 (range 0.93-0.98) for the Citak Classification and 0.95 (range 0.83-0.97) for the Dorr Classification. There was also an excellent intra-observer agreement with 95% average pairwise per cent agreement for the Citak Classification and 95% average pairwise per cent agreement for the Dorr classification. A statistically significant positive correlation was found between Dorr Calcar Isthmus and Citak Ratio (p < 0.05). CONCLUSION: In this study, the Dorr and Citak classifications are put into relation to each other for the first time. The morphology of the femur was investigated in its entirety and it was shown that there was a positive correlation between the anatomical shape of the proximal and distal medullary canals.

Septic Failure After One-Stage Exchange for Prosthetic Joint Infection of the Hip: Microbiological Implications.

BACKGROUND: The microbiological implications of septic failure after 1-stage exchange for prosthetic joint infection (PJI) of the hip remain unclear. METHODS: Information was gathered on comorbidities, previous procedures, preoperative and postoperative microbiology results, methods of detection, and antibiotic resistance patterns, for all patients, who developed septic failure after 1-stage exchange for PJI of the hip performed at our institution during 2001-2017. RESULTS: Seventy-seven patients were identified. Septic failure was diagnosed a mean of 1.7 (standard deviation 2.3, range 0-11.8) years later. Although the spectrum of microorganisms was similar to preoperative, in the majority of patients (55%), the initial microorganism(s) was (were) replaced by (a) totally different microorganism(s). Overall, there was a decrease in the number of polymicrobial PJIs. The number of patients with high virulent microorganisms decreased significantly from 52 to 36 (P = .034). The number of PJIs due to gram-negative pathogens remained similar (11 vs 14, P = .491). The number of rifampicin-resistant staphylococci, fluoroquinolone-resistant streptococci, enterococci, and fungi changed from 8 to 15, 0 to 2, 7 to 3, and 1 to 2, respectively, but these changes did not reach statistical significance. CONCLUSION: The majority of reinfections is caused by different infecting bacteria, hence it is essential to perform a new diagnostic workup and not base treatment decisions (solely) on historical cultures. We were furthermore unable to irrefutably prove that, from a microbiological point of view, septic failure after 1-stage exchange comes with increased challenges. Given the time interval to failure, we propose that a longer follow-up of these patients is needed, than previously suggested.

What is the rate of reinfection with different and difficult-to-treat bacteria after failed one-stage septic knee exchange?

PURPOSE: Re-operation after septic failure of a one-stage exchange for prosthetic joint infection (PJI) of the knee is a highly challenging procedure with concerns over residual bone stock, soft tissues, and stability. The associated changes in microbiology in cases of reinfection are still largely unknown. METHODS: A comprehensive analysis was performed of all patients treated at our tertiary institution between 2001 and 2017 who developed reinfection after a one-stage exchange for PJI of the knee. Prerequisites for inclusion were a certain diagnosis of PJI according to the ICM criteria and a minimum follow-up of three years. Data on comorbidities, previous surgical interventions, microbiological findings at the time of the initial one-stage exchange and at the time of reinfection, detection methods, and antibiotic resistance patterns were retrospectively studied. RESULTS: Sixty-six patients were identified that met the inclusion criteria. Reinfection occurred after a mean time interval of 27.7 months (SD ± 33.9, range 1-165). Ten types of bacteria were found that were not present before the one-stage exchange. The causative pathogen remained identical in 22 patients (33%) and additional microorganisms were detected in ten patients (15%). Half of the reinfections were however due to (a) completely different microorganism(s). A significant increase in the number of PJIs on the basis of high-virulent (23 vs 30, p = 0.017) and difficult-to-treat bacteria (13 vs 24, p = 0.035) was found. CONCLUSION: The present study provides a novel insight into the microbiological changes following septic failure after one-stage exchange for PJI of the knee. A higher prevalence of more difficult-to-treat bacteria might increase the complexity of subsequent procedures. Also, a longer follow-up of these patients than previously suggested seems in order.

Arthrofibrosis following primary total hip arthroplasty: a distinct clinical entity.

INTRODUCTION: Arthrofibrosis is a relatively frequent complication after total knee arthroplasty. Although stiffness after total hip arthroplasty (THA), because of formation of heterotopic ossification or other causes, is not uncommon, to the authors' best knowledge, arthrofibrosis after THA has not been described. The aim of this study is to describe the arthrofibrosis of the hip after primary THA using an established clinical and histological classification of arthrofibrosis. MATERIALS AND METHODS: We retrospectively examined all patients who were histologically confirmed to have arthrofibrosis after primary THA during revision surgery by examination of tissue samples in our clinic. Arthrofibrosis was diagnosed according to the histopathological SLIM-consensus classification, which defines seven different SLIM types of the periimplant synovial membrane. The SLIM type V determines the diagnosis of endoprosthesis-associated arthrofibrosis. RESULTS: The study population consists of 66 patients who were revised due to arthrofibrosis after primary THA. All patients had a limitation in range of motion prior to revision with a mean flexion of 90° (range from 40 to 125), mean internal rotation of 10° (range from 0 to 40) and mean external rotation of 20° (range from 0 to 50). All patients had histological SLIM type V arthrofibrosis, corresponding to endoprosthesis-associated arthrofibrosis. Histological examination revealed that seven patients (10.6%) had particle-induced and 59 patients (89.4%) had non-particle-induced arthrofibrosis. CONCLUSION: This is the first description of endoprosthetic-associated arthrofibrosis after primary THA on the basis of a well-established histological classification. Our study results could enable new therapeutic and diagnostic opportunities in patients with such an arthrofibrosis. Surgeons should keep arthrofibrosis as a possible cause for stiffness and pain after primary THA in mind. LEVEL OF EVIDENCE: Diagnostic study, Level of Evidence IV.

What Is the Mid-term Survivorship of Infected Rotating-hinge Implants Treated with One-stage-exchange?

BACKGROUND: Despite the growing number of studies reporting on periprosthetic joint infection (PJI), there is little information on one-stage exchange arthroplasty for the revision of infected rotating-hinge prostheses, which can be among the most difficult PJI presentations to treat. QUESTIONS/PURPOSES: After one-stage direct exchange revision for an infected rotating-hinge TKA prosthesis, and using a multimodal approach for infection control, we asked: (1) What is the survivorship free from repeat revision for infection and survivorship free from reoperation for any cause? (2) What is the clinical outcome, based on the Oxford Knee Score, of these patients at the latest follow-up? METHODS: Between January 2011 and December 2017, we treated 101 patients with infected rotating-hinge knee prostheses at our hospital. All patients who underwent a one-stage exchange using another rotating-hinge implant were potentially eligible for this retrospective study. During that period, we generally used a one-stage approach when treating PJIs. Eighty-three percent (84 of 101) of patients were treated with one-stage exchange, and the remainder were treated with two-stage exchange. Of the 84 treated with one-stage exchange, eight patients died of unrelated causes and were therefore excluded, one patient declined to participate in the study, and another eight patients were lost before the minimum study follow-up of 2 years or had incomplete datasets, leaving 80% (67 of 84) for analysis in this study. The included study population consisted of 60% males (40 of 67) with a mean age of 64 ± 8 years and a mean (range) BMI of 30 ± 6 kg/m2 (21 to 40). The mean number of prior surgeries was 4 ± 2 (1 to 9) on the affected knee. Fifteen percent (10 of 67) of knees had a preoperative joint communicating sinus tract, and 66% (44 of 67) had experienced a prior PJI on the affected knee. The antimicrobial regimen was chosen based on the advice of our infectious disease consultant and individually adapted for the organism cultured. The mean follow-up duration was 6 ± 2 years. Kaplan-Meier survivorship analysis was performed using the endpoints of survivorship free from repeat revision for infection and survivorship free from all-cause revision. The functional outcome was assessed using the Oxford Knee Score (on a 12- to 60-point scale, with lower scores representing less pain and greater function), obtained by interviewing patients for this study at their most recent follow-up visit. Preoperative scores were not obtained. RESULTS: The Kaplan-Meier analysis demonstrated an overall survivorship free from reoperation for any cause of 75% (95% CI 64% to 87%) at the mean follow-up of 6 years postoperatively. Survivorship free from any repeat operative procedure for infection was 90% (95% CI 83% to 97%) at 6 years. The mean postoperative Oxford Knee Score was 37 ± 11 points. CONCLUSION: With an overall revision rate of about 25% at 6 years and the limited functional results based on the poor Oxford Knee Scores, patients should be counseled to have modest expectations concerning postoperative pain and function level after one-stage exchange of an infected rotating-hinge arthroplasty. Nevertheless, patients may be informed about a reasonable chance of PJI eradication and might opt for this approach as a means to try to avoid high transfemoral amputation or joint arthrodesis, which in this population often is associated with the inability to ambulate at all. Regarding the relatively high number of patients with aseptic loosening, future studies might focus on implant design of revision knee systems as well. A longer course of oral antibiotics after such procedures may also be warranted to limit the chance of reinfection but requires further study. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds.

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects.

Short-term mortality after primary and revision total joint arthroplasty: a single-center analysis of 103,560 patients.

INTRODUCTION: The demand for total joint arthroplasty (TJA) is increasing worldwide with excellent long-term results. In general, TJA provides several benefits to the patients but also causes possible complications. The aim of our study was to describe trends in mortality after TJA in a high-volume arthroplasty center, and to examine the potential risk factors. METHODS: From 1996 to 2018, a total of 103,560 patients (73,130 primary cases, 30,430 revision cases) underwent a TJA procedure in our institution. Anthropometric parameters, Charlson Comorbidity Index (CCI), pre- and postoperative hemoglobin (Hb), blood loss during surgery, postoperative complication (such as infection, deep vein thrombosis, pulmonary embolism, etc.) and cause of death from all patients who deceased during hospitalization were collected. The short-term mortality rate was analyzed between the primary and the revision groups. RESULTS: The short-term mortality rate within our investigated groups was low with 0.041% in primary THA, 0.299% in revision THA, 0.045% in primary TKA, 0.205% in revision TKA, 0.214% in TSA/RSA, 0.15 % in primary TAA and 0% after TEA. Significant differences were found for preoperative Hb-values in patients undergoing septic revision (10.7 g/dl) compared to patients undergoing aseptic revision (12.8 g/dl) or primary arthroplasty (13.6 g/dl) (p < 0.001). Furthermore, we found significant differences regarding CCI between the groups. The comparison between causes of death (COD) showed a significantly higher number for pulmonary embolisms in the aseptic groups, while septic shock was the leading COD in the septic group and myocardial infarction as COD was found significantly more often after primary TJA. CONCLUSION: This is the largest single-center study presenting the short-term mortality rate following TJA. Consequently, TJA is a safe procedure with a low short-term mortality rate. However, depending on the type of surgery, certain risk factors cannot be eliminated. In order to further reduce the mortality, procedures as such should continue to be performed at specialized centers under standardized conditions.

The 2018 International Consensus Meeting Minor Criteria for Chronic Hip and Knee Periprosthetic Joint Infection: Validation From a Single Center.

BACKGROUND: Recently, a revised definition of the minor criteria scoring system for diagnosing periprosthetic joint infection (PJI) was developed by the second International Consensus Meeting on musculoskeletal infection. The new system combines preoperative and intraoperative findings, reportedly achieving high sensitivity and specificity. We aimed to validate the modified scoring system at a high-volume center. METHODS: We retrospectively reviewed patients who underwent a revision total hip or knee arthroplasty at our institution from May 2015 to August 2018. Serum C-reactive protein, synovial white blood cell count and polymorphonuclear percentage, leukocyte esterase test, alpha-defensin, microbiological and histologic results, and documented existence of sinus tract and intraoperative purulence were available for all patients. Cases with at least 1 major criterion were considered as infected. Using the new minor criteria, a score of ≥6 reflects PJI, while a score <3 can be considered as noninfected. Sensitivity, specificity, mean accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were analyzed. RESULTS: A total of 345 cases were included. A cutoff score of ≥6 points had the following diagnostic performance: area under the curve (AUC) = 0.90; ACC = 0.88; sensitivity = 0.96; specificity = 0.84; PPV = 0.70; NPV = 0.98. Diagnostic performance was better for the hip (AUC = 0.92; ACC = 0.90; sensitivity = 0.96; specificity = 0.86; PPV = 0.81; NPV = 0.98) than the knee (AUC = 0.89; ACC = 0.85; sensitivity = 0.95; specificity = 0.83; PPV = 0.59; NPV = 0.98). CONCLUSION: The modified scoring system proposed by the 2018 International Consensus Meeting in diagnosing PJI showed high sensitivity and a good performance, especially as rule-out diagnostic criteria. The cutoff level seems to be different between the hip and knee. Further validation studies considering the acknowledged limitations are recommended.

What are the Factors Associated with Re-revision After One-stage Revision for Periprosthetic Joint Infection of the Hip? A Case-control Study.

BACKGROUND: Despite increased interest in one-stage revision arthroplasty for periprosthetic joint infection (PJI) of the hip, the reported infection-free proportions after the one-stage approach are still comparable to that of two-stage revision. However, we still lack studies that analyze factors associated with any re-revision after one-stage revision arthroplasty for PJI. QUESTIONS/PURPOSES: After one-stage revision arthroplasty for PJI of the hip, what factors were associated with an increased risk of re-revision, and what factors were associated with an increased risk of reinfection? METHODS: We performed a single-center retrospective case-control analysis. Patients who underwent one-stage revision arthroplasty for PJI of the hip in our hospital between 2009 and 2017, and who were subsequently re-revised due to any reason, including reinfection, were identified from our electronic medical records. A total of 121 patients who underwent repeat revision for any reason after one-stage exchange for PJI of the hip were identified. The re-revision procedures were performed after a mean of 407 days. The primary reasons for re-revision were repeated hip dislocation in 53 of 121 patients (44%), reinfection including both new and persistent infections in 40 of 121 patients (33%), and aseptic loosening in 16 patients (13%). Forty-three patients underwent another revision procedure after the re-revision procedure (43 of 121; 36%). More than 40 potential patient-, joint- and surgery-related risk factors were investigated and compared with a 1:1 matched control participants by age, sex and year of the one-stage revision. Similar to the re-revision patients, controls were treated for PJI with one-stage revision arthroplasty; however, they did not undergo subsequent revision for any reason by the latest followup examination. The mean followup of the control group was 66 months (range, 17-119 months). The mean length of hospital stay was 26 days in the re-revised group (SD, 11.6 days) compared with 22 days for the controls (SD, 6.6 days). All analyses were performed to identify factors associated with general re-revision and reinfection. RESULTS: The independent factors associated with repeat revision for any reason were persistent wound drainage for at least 1 week (odds ratio [OR], 7.4; 95% CI, 2.6-20.6; p < 0.001), isolation of enterococci (OR, 4.8; 95% CI, 1.4-15.7; p = 0.010), and prior surgery due to infection before the one-stage hip revision (OR, 3.6; 95% CI, 2.0-6.4; p < 0.001). The factors associated with reinfection including both new and persistent infections were prolonged wound drainage (OR, 6.9; 95% CI, 2.2-21.5; p = 0.001) and prior surgery due to infection (OR, 4.3; 95% CI, 1.9-9.5; p < 0.001). CONCLUSIONS: Prolonged wound drainage after the one-stage revision arthroplasty for PJI of the hip must be treated rigorously. Patients with a history of a prior surgical procedure due to hip infection should be informed about the risk of further re-revision when deciding for the one-stage exchange. In case of enterococcal isolation, surgeons may consider another treatment approach rather than the one-stage exchange. Furthermore, we recommend the use of dual mobility cups when performing the one-stage revision hip arthroplasty to reduce the risk of dislocation.Level of Evidence Level III, therapeutic study.

What Is the Diagnostic Accuracy of Alpha-Defensin and Leukocyte Esterase Test in Periprosthetic Shoulder Infection?

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) after total shoulder arthroplasty (TSA) is challenging, especially in patients with Cutibacterium (formerly Propionibacterium) acnes infection. Despite the increasing number of patients with PJI of the shoulder, there are still no robust data regarding diagnostic tests in detecting shoulder PJI. QUESTIONS/PURPOSES: (1) What are the sensitivity, specificity, and negative- and positive-predictive values for the alpha-defensin enzyme-linked immunosorbent assay test in detecting PJI after TSA? (2) What are the diagnostic accuracies in detecting shoulder PJI for synovial alpha-defensin, leukocyte esterase Test, and serum C-reactive protein (CRP)? METHODS: All patients with painful TSA, who underwent joint aspiration to validate or exclude a PJI, between July 2015 and February 2018 were enrolled in this single-center study. Further indications for aspiration were as follows: planned revision arthroplasty, early loosening and clinical signs of infections, especially serum CRP elevation. A total of 121 patients were aspirated to exclude or verify a PJI, and 16 patients were excluded. In all, 105 patients with a mean age of 68 years (± 12 years) were included for analysis. Patients who underwent TSA were considered aseptic or septic according to the Musculoskeletal Infection Society criteria. Twenty-four patients had a PJI, and the remaining 81 patients were in the aseptic group. The microbiologic evaluation including polymicrobial infection showed C. (formerly P.) acnes in 15 patients (63%). Synovial fluid was then analyzed using microbiology cultures, alpha-defensin immunoassay, and leukocyte esterase. The specificity, sensitivity, and positive-predictive and negative-predictive values were calculated for each test. RESULTS: The overall accuracy for alpha-defensin was 91% (95% confidence interval [CI], 84.4-96); sensitivity was 75% (95% CI, 53-90), specificity was 96% (95% CI, 90-99), negative predictive value was 93% (95% CI, 85-97), and positive predictive value was 86% (95% CI, 64-97). In contrast, the overall accuracy for leukocyte esterase was 76% (95% CI, 61-88), sensitivity was 50% (95% CI, 21-79), specificity was 87% (95% CI, 69-96), positive predictive value 60% (95% CI, 26-88) and negative predictive value was 81% (95% CI, 64-93). CONCLUSIONS: Summarizing the study results, the alpha-defensin ELISA and leukocyte esterase tests had less sensitivity in detecting shoulder PJI than previously reported TKA or THA results. The quality and low amount of joint fluid is the difficult part of the diagnostic. C. (formerly P.) acnes was the most common cause of PJI. Focusing on low-grade infections, alpha-defensin has shown its advantages in diagnosing PJI regardless pathogen virulence. Since the diagnostic of a PJI is always a synopsis of findings, the alpha-defensin and leukocyte esterase test can be used as adjunct diagnostic tool in patients with painful TSA. We propose further prospective studies to improve the diagnostic and confirm the results. LEVEL OF EVIDENCE: Level III, diagnostic study.

The Impact of α-Defensin Test in Diagnosing Periprosthetic Infection After Total Ankle Arthroplasty.

Periprosthetic joint infection (PJI) after total ankle arthroplasty (TAA) is a serious complication, and a reliable diagnostic test to identify PJI is needed. The purpose of this study was to investigate the use of synovial α-defensin levels in identifying PJI of the ankle. Data from 33 patients were retrospectively collected between September 2015 and May 2018. Patients who had pain or suspected loosening after TAA and who had undergone joint aspiration were included in the study. Aspiration was performed in a semisterile theatre. Synovial fluid was processed in descending order for microbiological cultures, α-defensin, leukocyte esterase strip test, and cell count. A periprosthetic infection was defined by Musculoskeletal Infection Society criteria. The sensitivity, specificity, and overall accuracy were calculated, and based on a receiver operating characteristic curve, the quality of the α-defensin test was determined. The calculated area under the curve was 0.97 ± 0.32. Two of 33 patients fulfilled the 2014 Musculoskeletal Infection Society criteria and were scheduled for septic revision arthroplasty. Sensitivity, specificity, and overall accuracy of the α-defensin test were 100% (95% confidence interval [CI], 15.8% to 100%), 93.5% (95% CI, 78.6% to 99.2%), and 93.9% (95% CI, 79.8% to 99.3%), respectively. The positive predictive value was 50% (95% CI, 20.7% to 79.3%), and the negative predictive value was 100%. The α-defensin test seems to be the best available synovial test to detect a late-onset PJI after total ankle arthroplasty. Further prospective studies with a larger number of patients are required.

Use of intra-operative fluorescence imaging in periprosthetic joint infection: State of the art and future perspectives.

BACKGROUND: In periprosthetic joint infections (PJIs), the surgeon's role becomes pivotal in addressing the infection locally, necessitating the surgical removal of infected and necrotic tissue. Opportunity to enhance the visualization of infected tissue during surgery could represent a game-changing innovation. OBJECTIVE: The aim of this narrative review is to delineate the application of intraoperative fluorescence imaging for targeting infected tissues in PJIs. METHODS: A systematic review, adhering to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was carried out. The search included multiple online database; MEDLINE, Scopus, and Web of Science. For data extraction the following were evaluated: (i) diagnosis of musculoskeletal infection; (ii) use of intraoperative fluorescence imaging; (iii) infected or necrotic tissues as target. RESULTS: Initially, 116 studies were identified through online database searches and reference investigations. The search was narrowed down to a final list of 5 papers for in-depth analysis at the full-text level. Subsequently, 2 studies were included in the review. The study included a total of 13 patients, focusing on cases of fracture-related infections of the lower limbs. CONCLUSION: The primary and crucial role for orthopedic surgeons in PJIs is the surgical debridement and precise removal of necrotic and infected tissue. Technologies that enable clear and accurate visualization of the tissue to be removed can enhance the eradication of infections, thereby promoting healing. A promising avenue for the future involves the potential application of intraoperative fluorescence imaging in pursuit of this objective.

Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis.

Introduction: Immune checkpoint inhibitors are used in the treatment of various cancers and have been extensively researched with regard to inflammatory and autoimmune diseases. However, this revolutionary therapeutic strategy often provokes critical auto-inflammatory adverse events, such as inflammatory reactions affecting the cardiovascular, gastrointestinal, nervous, and skeletal systems. Because the function of these immunomodulatory co-receptors is highly cell-type specific and the role of macrophages as osteoclast precursors is widely published, we aimed to analyze the effect of immune checkpoint inhibitors on these bone-resorbing cells. Methods: We established an in vitro model of osteoclastogenesis using human peripheral blood mononuclear cells, to which various immune checkpoints and corresponding antagonistic antibodies were administered. Formation of osteoclasts was quantified and cell morphology was analyzed via immunofluorescence staining, cell size measurements, and calculation of cell numbers in a multitude of samples. Results: These methodical approaches for osteoclast research achieved objective, comparable, and reproducible results despite the great heterogeneity in the form, size, and number of osteoclasts. In addition to the standardization of experimental analyses involving osteoclasts, our study has revealed the substantial effects of agonistic and antagonistic checkpoint modulation on osteoclastogenesis, confirming the importance of immune checkpoints in bone homeostasis. Discussion: Our work will enable more robust and reproducible investigations into the use of immune checkpoint inhibitors in conditions with diminished bone density such as osteoporosis, aseptic loosening of endoprostheses, cancer, as well as the side effects of cancer therapy, and might even pave the way for novel individualized diagnostic and therapeutic strategies.

Resection of the proximal femur during one-stage revision for infected hip arthroplasty : risk factors and effectiveness.

AIMS: One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions. METHODS: In this single-centre, case-control study, 57 patients who underwent one-stage revision arthroplasty for PJI of the hip and required resection of the proximal femur between 2009 and 2018 were identified. The control group consisted of 57 patients undergoing one-stage revision without bony resection. Logistic regression analysis was performed to identify any correlation with resection and the risk factors for re-revisions. Rates of all-causes re-revision, reinfection, and instability were compared between groups. RESULTS: Patients who required resection of the proximal femur were found to have a higher all-cause re-revision rate (29.8% vs 10.5%; p = 0.018), largely due to reinfection (15.8% vs 0%; p = 0.003), and dislocation (8.8% vs 10.5%; p = 0.762), and showed higher rate of in-hospital wound haematoma requiring aspiration or evacuation (p = 0.013), and wound revision (p = 0.008). The use of of dual mobility components/constrained liner in the resection group was higher than that of controls (94.7% vs 36.8%; p < 0.001). The presence and removal of additional metal hardware (odds ratio (OR) = 7.2), a sinus tract (OR 4), ten years' time interval between primary implantation and index infection (OR 3.3), and previous hip revision (OR 1.4) increased the risk of proximal femoral resection. A sinus tract (OR 9.2) and postoperative dislocation (OR 281.4) were associated with increased risk of subsequent re-revisions. CONCLUSION: Proximal femoral resection during one-stage revision hip arthroplasty for PJI may be required to reduce the risk of of recurrent or further infection. Patients with additional metalware needing removal or transcortical sinus tracts and chronic osteomyelitis are particularly at higher risk of needing proximal femoral excision. However, radical resection is associated with higher surgical complications and increased re-revision rates. The use of constrained acetabular liners and dual mobility components maintained an acceptable dislocation rate. These results, including identified risk factors, may aid in preoperative planning, patient consultation and consent, and intraoperative decision-making. Cite this article: Bone Joint J 2021;103-B(11):1678-1685.

In situ Forming Hyperbranched PEG-Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties.

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol-ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0-1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0-1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0-500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care.