One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies.

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6-20.7) and 32.3 (95% CI 27.3-38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58-5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.

Prevalence of asymptomatic bacteriuria in knee arthroplasty patients and subsequent risk of prosthesis infection.

INTRODUCTION: The risk of knee arthroplasty infection and appropriateness of antibiotic treatment are not clearly established in patients with preoperative asymptomatic bacteriuria. It has been the purpose to analyze the prevalence of preoperative asymptomatic bacteriuria in knee arthroplasty patients, as well as the incidence of prosthetic joint infection in those with asymptomatic bacteriuria treated and not with specific antibiotics. PATIENTS AND METHODS: This prospective study included 215 consecutive knee arthroplasty patients (73 ± 6 years, 168 females) with neither urinary symptoms nor perioperative urethral catheterization. A "clean-catch" urinalysis was obtained from all patients before surgery and an urine culture if urinalysis was abnormal. Asymptomatic bacteriuria was diagnosed if >100,000 colony-forming units/ml were cultured. Patients were treated (Group A) or not (Group B) with additional specific antibiotics for urine bacteria according to surgeon criteria. Minimum follow-up reached 48 months. No patient was lost to follow-up. RESULTS: Asymptomatic bacteriuria was diagnosed in 11/215 patients (5.1 %) (11/11 females), and four of these 11 were treated with specific antibiotics (Group A). Only one patient in Group A suffered a prosthesis infection along the first 3 months (1/125, 0.5 %), but bacteria cultured from the wound were absolutely different to those in urine culture. No patient in Group B suffered a prosthesis infection. CONCLUSIONS: Asymptomatic bacteriuria presents a low prevalence. We have not found any case of arthroplasty infection from urinary focus in patients with asymptomatic bacteriuria whether they received or not specific antibiotics.

Are antibiotics necessary in hip arthroplasty with asymptomatic bacteriuria? Seeding risk with/without treatment.

BACKGROUND: In patients with asymptomatic bacteriuria undergoing hip arthroplasty, the risk of prosthetic joint infection (PJI) and appropriateness of specific antibiotics are unclear. QUESTIONS/PURPOSES: We determined (1) the prevalence of asymptomatic bacteriuria; and (2) the incidence of PJI in patients with asymptomatic bacteriuria managed with or without specific antibiotics. METHODS: We conducted a prospective, randomized study of all 471 patients without urinary symptoms receiving a total hip arthroplasty (THA; n = 228; average age 68 years; 122 female) or hemiarthroplasty (HA; n = 243; average age 85 years; 170 female) between April 2009 and November 2010. No patients were catheterized in the perioperative period and all received intravenous cefazolin (allergy, vancomycin) for 48 hours postoperatively. Urinalysis was conducted on all patients; if abnormal, a urine culture was performed. Patients with bacteriuria (> 100,000 colonies/mL cultured) were randomly assigned to receive specific antibiotics (Group A) or not (Group B). Minimum followup was 1 month including those six who died or were lost to followup (average, 10.4 months; range, 1-12 months). RESULTS: Asymptomatic bacteriuria occurred in eight of 228 patients undergoing THAs (three of eight with specific antibiotics) and 38 of 243 patients undergoing HAs (23 of 38 with specific antibiotics). Arthroplasty infection after 3 months occurred in one of 228 patients undergoing THAs and 12 of 243 patients undergoing HAs (six of 117 in Group A and six of 126 in Group B); bacteria cultured from the wound were dissimilar to those cultured in urine samples in any case. No patient presented signs of PJI by 1 year after the index surgery. CONCLUSIONS: We identified no case of PJI from urinary origin in patients with asymptomatic bacteriuria whether or not they had been treated with specific antibiotics.

PCR-hybridization after sonication improves diagnosis of implant-related infection.

PURPOSE: We wanted to improve the diagnosis of implant-related infection using molecular biological techniques after sonication. METHODS: We studied 258 retrieved implant components (185 prosthetic implants and 73 osteosynthesis implants) from 126 patients. 47 patients had a clinical diagnosis of infection (108 components) and 79 patients did not (150 components). The fluids from sonication of retrieved implants were tested in culture and were also analyzed using a modified commercial PCR kit for detection of Gram-positive and Gram-negative bacteria (GenoType BC; Hain Lifescience) after extraction of the DNA. RESULTS: 38 of 47 patients with a clinical diagnosis of infection were also diagnosed as being infected using culture and/or PCR (35 by culture alone). Also, 24 patients of the 79 cases with no clinical diagnosis of infection were identified microbiologically as being infected (4 by culture, 16 by PCR, and 4 by both culture and PCR). Comparing culture and PCR, positive culture results were obtained in 28 of the 79 patients and positive PCR results were obtained in 35. There were 21 discordant results in patients who were originally clinically diagnosed as being infected and 28 discordant results in patients who had no clinical diagnosis of infection. INTERPRETATION: For prosthetic joint infections and relative to culture, molecular detection can increase (by one tenth) the number of patients diagnosed as having an infection. Positive results from patients who have no clinical diagnosis of infection must be interpreted carefully.

Influence of surgical quality (according to postoperative radiography) on mortality, complications and recovery of walking ability in 1425 hip fracture patients.

PURPOSE: To evaluate the influence of surgical quality (as evaluated in the post-surgical radiographic control) on mortality, complications and recovery of walking ability in patients older than 64 years with hip fracture. PATIENTS AND METHODS: Retrospective observational study of a single-center, consecutive cohort of 1425 patients operated from December/2012 to March/2018. Average age was 85.66±7.13 (65-108) years and 966 (67.86%) were female. Extracapsular fractures (811 cases, 56.91%) were fixed with trochanteric nails (Affixus-DePuy / PFNA-Synthes) (795 cases) or sliding-hip-screw-plates (Biomet) (16 patients). Intracapsular fractures (614, 43.09%) were treated with cannulated screws (Smith-Nephew) (134 cases) or with arthroplasty (472 bipolar and 8 total hip, Furlong-JRI or Exeter-Stryker). Postoperative radiographs were used to determine surgical quality (reduction, compression, screw position, tip-apex, stem position, Voss, intraoperative fracture). Patients were followed clinically and radiographically in outpatient clinic after 1, 3, 6, and 12 months. STATISTICAL ANALYSIS: Bivariate analysis (Pearson, Fischer, Mann-Whitney, Wilcoxon) was applied to study statistically significant relations, and Relative Risks (RR) were calculated. RESULTS: 196 patients (13.75%) died along follow-up, and poor reduction was found to be a risk factor for mortality both in trochanteric nail group (p=0.0495) (RR 1.510, 1.01-2.26) and in cannulated screw group (p=0.0023) (RR 6.48, 2.40-17.53); this is a previously non-published risk factor. Surgical complications included 33 infections (2.36%), 12 non-unions (1.27%), 12 cut-outs (1.47%), 7 broken nails (0.86%), 21 hemiarthroplasty dislocations (4.37%), and 8 ischemic necrosis of the femoral head (5.97%). The significant risk factors were: poor reduction for trochanteric nail breakage (p=0.041) (RR 4.47, 1.13-17.67), poor reduction for non-union in cannulated screws (p=0.035) (RR 10.91, 1.70-70.09), as well as "tip-apex distance" over 25mm in trochanteric fractures for "cut-out" type of fixation failure (p=0.0159) (RR 3.84, 1.19-12.40). Previous walking ability was restored in 564 patients (39.58%) and worsened in 581 (40.77%), but statistical relationships were not found, although follow-up data were inadequate in 212 cases (14.88%). CONCLUSIONS: Appropriate reduction of hip fractures is a significant step to reduce mortality, nail breakage and non-union. Adequate position of sliding screw (avoiding tip-apex distances over 25mm) is important to reduce "cut-out" in trochanteric fractures.

Results after late polymicrobial, gram-negative, and methicillin-resistant infections in knee arthroplasty.

BACKGROUND: Previous studies of knee arthroplasty infections caused by high-virulence organisms suggest poor outcomes. Polymicrobial and Gram-negative infections are less studied. QUESTIONS/PURPOSES: This study compared the results of treatment of knee arthroplasty infections by single versus polymicrobial isolates, Gram-positive versus Gram-negative, and methicillin-resistant versus -sensitive Staphylococci. METHODS: We prospectively followed 47 patients with late knee arthroplasty infections. The mean age was 72 years (range, 20-87 years). The treatment protocol included two-stage exchange and a combination of two oral antibiotics given for 6 months. Minimum followup was 1 year (average, 4.8 +/- 3 years; range, 1-12 years). Control of the infection was judged by absence of clinical, serologic, and radiologic signs of infection. The functional outcome was evaluated by Knee Society score at the last followup. RESULTS: Infection was controlled in all 15 patients with polymicrobial and in 28 of 32 (88%) with monomicrobial infections, in eight of nine patients with Gram-negative and in 35 of 38 (92%) with Gram-positive isolates. Control was also achieved in 22 of 25 patients (88%) infected by methicillin-resistant Staphylococci and in 14 of 14 by methicillin-sensitive Staphylococci. The Knee Society scores averaged 81-63 in patients with polymicrobial infections and were higher than in monomicrobial infections (75-52). The mean KSS was 85-59 in Gram-negative infections compared to 75-55 in Gram-positive infections. The mean KSS was similar in methicillin-resistant (78-54) and methicillin-sensitive Staphylococci (73-56) infections. CONCLUSIONS: Polymicrobial and Gram-negative infections can be controlled in late knee arthroplasty infections. On the other hand, infections by methicillin-resistant Staphylococci are less likely to be controlled by the regimens we used. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

What are the risk factors for infection in hemiarthroplasties and total hip arthroplasties?

BACKGROUND: Late infection is the second most frequent early complication after total hip arthroplasty (THA) and the most frequent after hemiarthroplasty. Known risk factors for infection after THA include posttraumatic osteoarthritis, previous surgery, chronic liver disease, corticoid therapy, and excessive surgical time. However, risk factors for hemiarthroplasty are not clearly established. QUESTIONS/PURPOSES: We therefore determined the preoperative and intraoperative risk factors for late infection (more than 3 months after surgery) in patients with hemiarthroplasties and THAs. METHODS: We retrospectively compared 47 patients with a hip arthroplasty (23 hemiarthroplasties, 24 total hip arthroplasties) and late infection with 200 randomly-selected patients with primary arthroplasty (100 hemiarthroplasties, 100 total hip arthroplasties) during the same time period of time without any infection during followup. Potential risk factors were identified from medical records. Minimum followup was 12 months (mean, 27 months; range, 12-112 months) for the study group and 18 months (mean, 84 months; range, 18-144 months) for the control group. RESULTS: The following factors were more frequent in late infected hemiarthroplasties: female gender; previous surgery; obesity (body mass index greater than 30 kg/m(2)); glucocorticoid and immunosuppressant treatments; prolonged surgical time; inadequate antibiotic prophylaxis; prolonged wound drainage; hematoma; dislocation; and cutaneous, urinary, and/or abdominal infections. The following were more frequent in infected total hip arthroplasties: posttraumatic osteoarthritis; previous surgery; glucocorticoids; chronic liver disease; alcohol and intravenous drug abuse; prolonged surgical time; prolonged wound drainage; dislocation; subsequent surgery; and cutaneous, urinary, respiratory and abdominal infections. Diabetes did not appear to be a risk factor. CONCLUSIONS: Our data suggest there are specific risk factors for infection in hemiarthroplasties. The major risk factors for late infection in hip arthroplasty must be recognized so they can be minimized or controlled if not possible to employ prophylactic measures.

Biofilm development by clinical isolates of Staphylococcus spp. from retrieved orthopedic prostheses.

BACKGROUND: Biofilms are considered the key factor in the development of implant-related infections. However, only a few reports have dealt with the ability of organisms isolated from such infections to develop biofilms in vitro. METHODS: We evaluated different phenotypic techniques (2 microtiter plate assays and confocal laser scanning microscopy (CLSM) and genotypic techniques (detection of the ica operon) related to biofilm development by clinical isolates of Staphylococcus spp. RESULTS: All 26 strains tested (from 23 specimens) were biofilm producers. Stepanovic test detected biofilm formation in 85% of the strains, microtiter plate assay in 65%, and CLSM in 39%. The ica operon was detected in 73% of all strains (all 13 S. aureus strains and 6 of the 13 coagulase-negative Staphylococcus strains). 7 ica-negative strains were biofilm-positive by phenotypic methods. INTERPRETATION: The detection of ica genes could not be related to the phenotypic ability of the strains to develop a biofilm in vitro, so both studies (genetic and phenotypic) are required for a better evaluation of the biofilm-producing ability of clinical strains of Staphylococcus isolated from orthopedic infections.

Editorial. The Challenges of Orthopaedic Trauma in Spain.

Spain is considered the healthiest nation in the world, due to lifepromoting aspects such as good diet, care facilities and a favourable family environment. However, although increased life expectancy is an indicator of development, it may have a negative impact on the other two variables of health service efficiency, namely health expenditure per capita and its relative weight in Gross Domestic Product.

Diagnostic Accuracy of Magnetic Resonance Images and Weight-Bearing Radiographs in Patients With Arthroscopic-Proven Medial Osteoarthritis of the Knee.

AIMS: The aim of this study is to analyze the diagnostic value of weight-bearing radiographs, magnetic resonance images (MRI), and the combination of both in osteoarthritic knees when using arthroscopic findings as the "gold standard" to compare with. METHODS: A total of 59 patients were studied because of chronic pain in 1 of their knees. Radiographs were classified according to Kellgren-Lawrence scale. Magnetic resonance images were classified according to Vallotton, and arthroscopic findings according to Outerbridge criteria. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were, respectively, 75.0%, 60.0%, 56.2%, 77.8%, and 66.1% for weight-bearing radiographs, and 70.8%, 88.6%, 81.0%, 81.6%, and 81.4% for MRI. Logistic regression analysis showed that a weight-bearing radiograph added to MRI offered no additional diagnostic value compared with MRI alone (P < .001). CONCLUSIONS: Magnetic resonance images presented higher specificity, positive and negative predictive values, and accuracy than weight-bearing radiographs for knee osteoarthritis. The combination of radiographs and MRI did not improve the diagnostic accuracy, compared with MRI alone.

Validation of a long bone fracture non-union healing score after treatment with mesenchymal stromal cells combined to biomaterials.

The available scores to clinically evaluate fracture consolidation encounter difficulties to interpret progression towards consolidation in long-bone non-union, particularly when incorporating biomaterials in the surgical treatment. The aims of this study were to validate the REBORNE bone healing scale in tibia, humerus and femur non-unions treated by a combination of mesenchymal stromal cells (MSCs) and biomaterials, through the interclass correlation (ICC) among raters, and to define reliability and concordance in anteroposterior and lateral radiographs, compared to computed tomography (CT). METHODS: Twenty-six cases from the EudraCT 2011-005441-13 clinical trial underwent bone healing evaluation, if at least 3 out of 4 cortical views clearly identified. Three senior orthopaedic surgeons evaluated radiographs and CTs at 3 and 6 months FU. All cases included preoperative imaging and radiographs at 12 months. The 4-stage scale score was obtained from each cortical view in orthogonal radiographs or CTs. A score of 0.6875 (11/16) was set as a threshold for bone healing. Statistically, ICC evaluated agreement among raters. Cronbach's alpha coefficient tested reliability. Lin's concordance correlation coefficients (CCC) were estimated between mean CT scores and mean radiographic scores. Bland and Altman graphs provided the limits of agreement between both imaging techniques. Sensitivity and specificity were assessed in radiographs (against CT), and the Area Under the Receiver Operating Characteristics (ROC) Curve was estimated. The probability to predict bone consolidation with REBORNE scores obtained from radiographs was modelled. RESULTS: An ICC of 0.88 and 0.91 (CT and radiographs) confirmed agreement in the REBORNE score for non-union bone healing, with an inter-rater reliability of 0.92 and 0.95. Scores through the radiographic evaluation were found equivalent to the CTs at 6 months FU. A CCC of 0.79 was detected against CT. The radiographic scores in the REBORNE bone healing scale correctly classified bone consolidation in 77%, with an accuracy of 83% based on ROC curves. CONCLUSIONS: The REBORNE score measured with CT or radiographic images was reliable among raters at a follow-up time above 6 months for long bone non-union fractures. The REBORNE scale measured with radiographs proved valid to assess consolidation against CT measurements.

Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine- and Phosphorus-Doped Nanostructured Ti-6Al-4V Alloy Loaded With Gentamicin and Vancomycin.

Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine- and phosphorus-doped, bottle-shaped, nanostructured (bNT) Ti-6Al-4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti-6Al-4V loading with a mixture of GV, measuring the release of these antibiotics using high-performance liquid chromatography. Further, we describe bNT Ti-6Al-4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti-6Al-4V following a Boltzmann non-linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti-6Al-4V GV compared with control. In vivo study results show that bNT Ti-6Al-4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti-6Al-4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588-597, 2020.

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions.

BACKGROUND AND STUDY AIM: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture. PATIENTS AND METHODS: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in VAS scale), and by radiological consolidation with a REBORNE score over 11/16 points (value of or above 0.6875). Means were statistically compared and mixed models for repeated measurements estimated the mean and confidence intervals (95%) of the REBORNE Bone Healing scale. Clinical and radiological consolidation were analyzed in the subgroups with Spearman correlation tests (adjusted by Bonferroni). RESULTS: Clinical consolidation was earlier confirmed, while radiological consolidation at 3 months was 25.0% (7/28 cases), at 6 months 67.8% (19/28 cases), and at 12 months, 92.8% (26/28 cases including the drop-out extrapolation of two failures). Bone biopsies confirmed bone formation surrounding the bioceramic granules. All locations showed similar consolidation, although this was delayed in tibial non-unions. No significant gender difference was found in 12-month consolidation (95% confidence). Higher consolidation scale values were seen in non-smoking patients at 6 (p = 0.012, t-test) and 12 months (p = 0.011, t-test). Longer time elapsed after the initial fracture did not preclude the occurrence of consolidation. CONCLUSION: Bone consolidation was efficaciously obtained with the studied expanded hBM-MSCs combined to biomaterials, by clinical and radiological evaluation, and confirmed by bone biopsies, with lower consolidation scores in smokers.

Oral antibiotics are effective for highly resistant hip arthroplasty infections.

Infected arthroplasties reportedly have a lower eradication rate when caused by highly resistant and/or polymicrobial isolates and in these patients most authors recommend intravenous antibiotics. We asked whether two-stage revision with interim oral antibiotics could eradicate these infections. We prospectively followed 36 patients (mean age, 71.8 years) with late hip arthroplasty infections. Combinations of oral antibiotics were prescribed according to cultures, biofilm, and intracellular effectiveness. The minimum followup was 1 year (mean, 4.4 years; range, 1-12 years). We presumed eradication in the absence of clinical, serologic, and radiographic signs of infection. Infection was eradicated in all 13 patients with highly resistant bacteria who completed a two-stage protocol (10 with methicillin-resistant Staphylococci) and in eight of 11 patients treated with only the first stage (and six of nine with methicillin-resistant Staphylococci). Infection was eradicated in six of six patients with polymicrobial isolates (of sensitive and/or resistant bacteria) who completed a two-stage protocol and in five of seven with polymicrobial isolates treated with only the first surgery. The Harris hip score averaged 88.1 (range, 70-98) in patients who underwent reimplantation and 56.8 (range, 32-76) in patients who underwent resection arthroplasty. Long cycles of combined oral antibiotics plus a two-stage surgical exchange appear a promising alternative for infections by highly resistant bacteria, methicillin-resistant Staphylococci, and polymicrobial infections.

Urine Aluminum Concentration as a Possible Implant Biomarker of Pseudomonas aeruginosa Infection Using a Fluorine- and Phosphorus-Doped Ti-6Al-4V Alloy with Osseointegration Capacity.

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both associated with high morbidity and a substantial cost burden for patients and health systems. The development of a biomaterial capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. Using an in vivo rabbit model, this study evaluates the osseointegration effect of the fluorine (F)- and phosphorus (P)-doped bottle-shaped nanostructured (bNT) Ti-6Al-4V alloy and effectiveness of monitoring urine aluminum concentration to determine the presence of Pseudomonas aeruginosa infection in Ti-6Al-4V implants. Unlike chemically polished (CP) Ti-6Al-4V alloy implants, bNT Ti-6Al-4V alloy implants promoted osseointegration and showed effectiveness as a biomaterial marker. The bNT Ti-6Al-4V alloy implants were associated with a twofold increase in bone thickness and up to 15% greater bone density compared to the CP alloy. Additionally, bNT Ti-6Al-4V alloy implants allowed for discrimination between P. aeruginosa-infected and noninfected animals for 15 days postoperatively, as indicated by the decrease of aluminum concentration in urine, while this difference was only appreciable over the first 7 days when CP Ti-6Al-4V alloy implants were used. Therefore, bNT Ti-6Al-4V alloys could have clinical applications by detecting the infection and by avoiding aseptic loosening.