Objective:To investigate the effects of high-concentration of vancomycin and meropenem on the viability and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs), and to provide experimental evidence for local antibiotic treatment of periprosthetic joint infection (PJI). Methods:Rat BMSCs were cultured with vancomycin and meropenem at different concentrations (10-10 000 μg/mL). A cell counting kit 8 assay was used to assess the effects of the antibiotics on cell viability. The antibiotic concentration at which cell viability began to decrease by more than 50% compared to the control group (cells cultured without antibiotics) after 7 days was selected as the upper concentration limit for subsequent experiments. The lowest concentration at which cell viability significantly decreased compared to the control group after 7 days ( P<0.05) was selected as the lower concentration limit. The cells were then further cultured in osteogenic induction medium. After 7 days, the proportion of late apoptotic cells was measured by flow cytometry, and the protein expression of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and Osterix (Osx) was detected by Western blot. After 21 days, Alizarin red staining was performed to evaluate the effects of the antibiotics on BMSCs mineralization and osteogenic differentiation. Results:The inhibitory effects of vancomycin and meropenem on BMSCs viability gradually increased with prolonged intervention. After 7 days, the threshold concentration for a significant decrease in BMSCs viability was 500 μg/mL for both antibiotics ( P<0.05). Concentrations of 500, 1 000, and 3 000 μg/mL were selected for subsequent experiments. After 7 days of osteogenic induction, flow cytometry showed that the proportions of late apoptotic cells were significantly higher in the all antibiotics groups than in the control group ( P<0.05). Western blot showed that low-concentration vancomycin (500 μg/mL) promoted Runx2 expression but inhibited OPN and Osx expressions ( P<0.05), whereas high-concentration vancomycin (3 000 μg/mL) inhibited Runx2, OPN, and Osx expressions ( P<0.05). Low-concentration meropenem (500 μg/mL) promoted Runx2, OPN, and Osx expressions ( P<0.05), whereas high-concentration meropenem (3 000 μg/mL) inhibited the expressions of these osteogenesis-related proteins ( P<0.05). After 21 days, the percentage of mineralized area in the 3 000 μg/mL vancomycin and meropenem groups was significantly lower than that in the control group ( P<0.05). Conclusion:High-concentration (3 000 μg/mL) of vancomycin and meropenem administered for more than 7 days may inhibit the viability and osteogenic differentiation of rat BMSCs.
Background: Although cellularity is traditionally evaluated morphologically, an emerging transcriptome-sequencing-based algorithm enables simultaneous inference of cellular information. We studied whether cellularity profiles predicted using CIBERSORTx would (1) depict immune cell-type abundances in periprosthetic tissues across arthroplasty failure etiologies, and (2) provide prognostic value for identifying cases of periprosthetic joint infection (PJI). Methods: CIBERSORTx-derived cellularity profiles were evaluated in 185 periprosthetic tissue samples, including 135 from patients with PJI (64 males; median age, 66 years) and 50 from those with aseptic failure (AF) (36 males; median age, 62.5 years), that had been subjected to bulk RNA sequencing. Kaplan-Meier survival analysis was performed to assess prognostic outcomes in PJI. Results: Of the 22 evaluated cell types, 5 were significantly elevated in PJI cases: plasma cells, resting memory CD4 + T cells, CD8 + T cells, activated mast cells, and M1 macrophages (all p < 0.05 after Benjamini-Hochberg [BH] correction). Conversely, 3 cell types were significantly elevated in AF cases: gamma delta T cells, M0 macrophages, and M2 macrophages (all p < 0.05 after BH correction). Of the combined immune cell populations, total B cells, total T cells, and natural killer cells were significantly elevated in PJI cases, while total macrophages/monocytes were significantly elevated in AF cases (all p < 0.05 after BH correction). Patients with PJI who had a CD8 + /regulatory T cell (Treg) ratio above the median had a significantly lower rate of infection recurrence than those below the median (log-rank p = 0.0252). Conclusions: CIBERSORTx analysis of samples from periprosthetic tissues predicted distinct immune cell profiles that differed between PJI and aseptic arthroplasty failure modes, and also identified a high CD8 + /Treg ratio as a potential prognostic marker. This transcriptomic approach provides a novel, single-assay strategy for evaluating local immune cell responses across arthroplasty failure etiologies. Clinical Relevance: The comparative analysis of immune cell-type abundances in periprosthetic tissues across arthroplasty failure etiologies revealed distinct immune microenvironment signatures that differentiate PJI from AF. Additionally, the finding that a higher CD8 + /Treg cell ratio is associated with a lower rate of infection recurrence offers a potential prognostic marker to help identify patients with PJI who are at a lower risk for treatment failure.
Abstract Background Robotic-assisted total joint arthroplasty (rTJA) has witnessed rapid adoption across the Asia-Pacific region. However, practice heterogeneity and conflicting evidence regarding its clinical value necessitate standardized guidance. Therefore, this expert consensus aims to establish consensus-based recommendations to guide and standardize the clinical application of rTJA. Methods The Arthroplasty Society in Asia (ASIA) convened a panel of 45 experts. A modified Delphi technique was employed across three rounds. A systematic literature review informed the generation of consensus statements, which were finalized through anonymous voting. Consensus was defined as ≥ 75% agreement. Results The panel reached consensus on 18 critical clinical questions spanning general principles, total hip arthroplasty, and total knee arthroplasty. Key consensus points include: (1) rTJA demonstrates superior accuracy in implant positioning and alignment restoration compared to manual techniques (98%); (2) current evidence does not yet support a definitive superiority in long-term survivorship or PROMs (77%); (3) robotic platforms are enabling technologies that make personalized alignment philosophies technically reproducible (100%); and (4) soft-tissue balancing should take precedence over rigid mechanical alignment targets in rTKA when conflicts arise(91%). Conclusion This consensus statement provides a comprehensive framework for the application of robotic technology in hip and knee arthroplasty, emphasizing safety, precision, and the need for rigorous training.
Aims Three-phase bone scintigraphy (TPBS) is a simple, reliable, and straightforward imaging modality for diagnosing periprosthetic joint infection (PJI). This study aimed to evaluate the diagnostic efficacy of the combined diagnostic method of TPBS and CRP in the detection of PJI. Methods A retrospective analysis was performed on 317 patients undergoing revision surgery (211 hips and 106 knees) between January 2017 and January 2024, with TPBS obtained prior to surgical intervention. PJI was diagnosed according to the 2013 Musculoskeletal Infection Society (MSIS) criteria. The diagnostic performance of TPBS, CRP, and TPBS-CRP combined method was evaluated. Results In the total knee arthroplasty (TKA) cohort, TPBS-CRP achieved maximal sensitivity (100%) and negative predictive value (100%), enabling definitive exclusion of PJI, albeit with reduced specificity (50.0%). Antibiotic therapy significantly reduced CRP accuracy (79.1% vs 97.1%, p = 0.020) but minimally impacted TPBS (100% vs 88.6%, p = 0.037). For total hip arthroplasty (THA), the TPBS-CRP demonstrated a superior diagnostic efficacy (AUC = 0.846, 0.834, and 0.795) and demonstrated a more balanced sensitivity (81.6%, 67.3%, and 64.3%) and specificity (87.6%, 91.2%, and 94.7%) compared to CRP and TPBS. Antibiotic-treated patients exhibited significantly higher diagnostic accuracy for TPBS (81.5% vs 57.7%, p = 0.028), CRP (88.9% vs 59.2%, p = 0.005), and TPBS-CRP (96.3% vs 76.1%, p = 0.020) compared to untreated patients. False-positive TPBS cases in both cohorts exhibited severe bone loss and prolonged symptoms compared to true negatives (p < 0.05). Conclusion TPBS demonstrates limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP synergizes localized bone metabolic profiles with systemic inflammatory biomarkers, achieving superior diagnostic accuracy. Caution is warranted in patients with severe bone loss and prolonged symptoms. Cite this article: Bone Joint Res 2026;15(4):354–362.
This study aimed to determine whether robotic-assisted total knee arthroplasty (RATKA) provides superior patient-reported outcomes compared to conventional manual total knee arthroplasty (MTKA), with particular emphasis on the forgotten joint score (FJS) and postoperative satisfaction levels. In this prospective longitudinal observational study, we enrolled 157 consecutive patients who underwent primary TKA between May and July 2023. The participants were assigned to either the RATKA or MTKA groups based on the surgical technique utilized. Following exclusions for periprosthetic joint infection (n = 2) and inadequate follow-up compliance (defined as > 5 missed visits, n = 26), the final analytic cohort comprised 129 participants. The RATKA group (n = 55) demonstrated significantly higher preoperative expectations (P = 0.011) and longer operative duration (P < 0.001) compared to the MTKA group (n = 74), while all other baseline characteristics were comparable between the groups. The mean FJS increased from preoperative values of 21.07 and 20.06 to 73.46 and 72.08 in the RATKA and MTKA groups, respectively (P < 0.001). During follow-up from 2 to 12 months, the RATKA group consistently showed higher FJS than the MTKA group at all time points; however, the differences neither reached the minimal clinically important difference (MCID) nor attained statistical significance (P = 0.458). At 12 months, satisfaction was numerically higher in the RATKA group but was not statistically significant (94.5
The Forgotten Joint Score (FJS) has emerged as a vital metric for assessing the outcomes of total knee arthroplasty (TKA). However, its post-TKA trajectory patterns and predictive factors remain controversial. This study aimed to elucidate the evolution trajectory of the FJS within the first year following TKA and identify its predictive factors. This was an longitudinal, prospective, observational, single-center study. A total of 157 patients who underwent primary TKA from May 2023 to July 2023 were included. Preoperatively, patient demographics and comorbidities were collected, and composite scores (Knee Society Score, FJS, Hospital Anxiety and Depression Scale, ASA) were assessed. FJS assessments were obtained monthly using standardized protocols during the 2–12 month postoperative follow-up period. Latent growth modeling techniques were employed to characterize FJS trajectory patterns. Multivariable logistic regression analysis was performed to identify predictors associated with trajectory membership. A total of 129 patients completed postoperative FJS assessments. The FJS trajectory following TKA exhibited a triphasic progression: rapid improvement (2–5 months), decelerated growth rate (5–10 months), and functional plateau from 10 to 12 months. The predictors were body mass index (BMI) (OR = 1.278, 95
Objective:To explore the differences in gut microbiota diversity and structural characteristics among patients with periprosthetic joint infection (PJI), aseptic failure (AF), and osteoarthritis (OA), and to analyze the association between gut microbiota dysbiosis and the occurrence of PJI, thereby providing a new theoretical basis for elucidating the pathogenesis and treatment strategies of PJI in clinical practice. Methods:The study enrolled patients with PJI and AF admitted between February 2024 and December 2024, as well as OA patients admitted in February 2024. A total of 52 PJI patients, 19 AF patients, and 29 OA patients who met the selection criteria were included in the analysis. Significant differences were observed among the three groups in terms of gender, age, surgical site, preoperative C-reactive protein levels, and erythrocyte sedimentation rate ( P<0.05), while no significant difference was found in American Society of Anesthesiologists (ASA) classification and body mass index ( P>0.05). Among the PJI patients, infection staging was as follows: 9 cases in the acute phase, 28 cases in the delayed phase, and 15 cases in the chronic phase; 23 cases were accompanied by sinus tract formation. Fecal samples were collected at different time points: for the PJI group, samples were obtained preoperatively and on postoperative days (7±1) and (14±1); for the AF group, preoperatively and on postoperative day (7±1); and for the OA group, preoperatively only. Metagenomics next-generation sequencing were employed to analyze gut microbiota α-diversity indices (ACE index, Chao1 index, Shannon index, Simpson index, and observed_species index) and differential bacterial genera (screened using the LEfSe algorithm). Results:Analysis of gut microbiota diversity showed that the preoperative α-diversity indices (ACE index, Chao1 index, Shannon index, Simpson index, and observed_species index) in the PJI group were significantly lower than those in AF group and OA group ( P<0.05). Compared with the AF group on postoperative day (7±1), the α-diversity indices in the PJI group on postoperative day (7±1) were lower, but the difference was not significant ( P>0.05); by postoperative day (14±1), these indices further decreased, and the difference was significant ( P<0.05). In the PJI group, no significant difference was observed in any of the indices across different time points postoperatively ( P>0.05). Analysis of gut microbiota structural characteristics revealed that the PJI group exhibited characteristic dysbiosis both before and after operation. Preoperatively, the PJI group was characterized by enrichment of Pseudomonadota (relative abundance 13.19%), Enterobacteriaceae ( Escherichia 3.26%, Klebsiella 1.90%), and opportunistic pathogens such as Enterococcus faecium (0.43%), while the relative abundances of Firmicutes (51.83%) and Bifidobacterium (0.24%) decreased. Postoperatively, the α-diversity in the PJI group further declined, with increased relative abundances of Escherichia and Klebsiella, and the relative abundance of Firmicutes decreased to 40.24%. LEfSe analysis of preoperative gut microbiota composition between the PJI group and AF group indicated that the AF group was predominated by Firmicutes, Bifidobacterium, and Roseburia preoperatively, with greater postoperative microbial stability compared to the PJI group. Conclusion:Patients with PJI exhibited a gut microbiota profile characterized by reduced diversity and enrichment of opportunistic pathogens. Postoperative antibiotic treatment further aggravated this dysbiosis, providing new clinical insights into the role of gut microbiota imbalance in the pathogenesis and progression of PJI.
Periprosthetic joint infection (PJI), sustained by antibiotic-tolerant biofilms, hinders infection control and impairs bone healing. To address this, we developed a dual-action strategy combining low-intensity pulsed ultrasound (LIPUS) with vancomycin-loaded microbubbles (MBs@V) designed to concurrently eliminate methicillin-resistant Staphylococcus aureus (MRSA) biofilms and enhance bone regeneration. In vitro, LIPUS activation of MBs@V generated cavitation that effectively disrupted mature biofilm architecture, significantly enhancing intrabiofilm vancomycin penetration and bactericidal efficacy. In vivo, using a rat model of PJI with infected titanium implants, the MBs@V + LIPUS therapy demonstrated synergistic effects: it markedly reduced bacterial burden and inflammation while remodeling the immune microenvironment through polarization of macrophages toward the reparative M2 phenotype and enhancing osteogenic activity. This immunomodulation and pro-osteogenic transition fostered a reparative environment, which simultaneously enhanced peri-implant bone mineralization and improved trabecular quality. Collectively, this integrated ultrasound-mediated approach provides a multifunctional platform for effective PJI management by synergistically targeting biofilm elimination and promoting bone regeneration.
Aims:Preoperative anaemia is common in patients undergoing revision total joint replacement (TJR), yet its effects on inflammatory markers for diagnosing chronic periprosthetic joint infection (PJI) are poorly understood. This study aimed to investigate how preoperative anaemia impacts inflammatory biomarkers, and to establish anaemia-adjusted diagnostic thresholds for PJI. Methods:This retrospective cohort study was conducted at a tertiary referral centre, evaluating 886 revision arthroplasty cases (396 PJI and 490 aseptic failures) between January 2008 and October 2023. Serum biomarkers (CRP, ESR, D-dimer, fibrinogen, fibrin degradation products (FDP), procalcitonin, and interleukin-6 (IL-6)) and synovial fluid markers (white blood cell count (SF-WBC) and polymorphonuclear percentage (SF-PMN)) were analyzed. The diagnostic performance of these markers was assessed using receiver operating characteristic (ROC) curve analysis, with patients stratified by anaemia status. Results:Preoperative anaemia was present in 55.1% (218/396) of patients with chronic PJI. In anaemic patients, serum biomarker levels were significantly higher than those of non-anaemic patients: CRP (28.35 vs 14.75 mg/l; p < 0.001), ESR (58 vs 40 mm/h; p < 0.001), D-dimer (615 vs 415 ng/ml; p < 0.001), and IL-6 (22.19 vs 10.74 pg/ml; p < 0.001). After adjusting diagnostic thresholds for anaemia, the area under the curve (AUC) for CRP improved from 0.838 to 0.927. Similar improvements were observed for ESR and IL-6. Fibrinogen and FDP demonstrated moderate diagnostic utility, while procalcitonin showed limited diagnostic value in both anaemic and non-anaemic patients. Conclusion:Preoperative anaemia is associated with statistically significant increases in most inflammatory biomarker levels and with higher diagnostic thresholds in chronic PJI. Anaemia-adjusted cut-off values for CRP, ESR, and IL-6 may enhance diagnostic accuracy for PJI in this patient population.
BACKGROUND:Tranexamic acid (TXA) reduces blood loss and transfusion requirements in patients who underwent primary total hip arthroplasty. However, the optimal route of TXA administration remains unclear. This randomized controlled trial evaluated whether intraosseous (IO) TXA administration was noninferior to intravenous (IV) or topical administration. METHODS:In this equal-proportion, noninferior randomized controlled trial, 126 patients undergoing primary total hip arthroplasty from October 2024 to April 2025 were randomized to IO (20 mg/kg TXA applied in the cancellous bone of the femur and ilium), IV (20 mg/kg TXA applied five minutes before incision), or topical (20 mg/kg TXA applied before suture) group. The primary outcome was hemoglobin reduction on the day of surgery (DOS) and postoperative days one to three (POD one to three). The secondary outcomes included blood loss, transfusion rate, and adverse events. Demographics were similar among the groups. RESULTS:The mean hemoglobin reduction was comparable on the DOS, POD one, POD two, and POD three (P = 0.431, 0.532, 0.479, and 0.443, respectively). Exploratory analyses showed lower mean calculated total blood loss in the IO group on the DOS and POD one than in the other groups (DOS and POD one: P = 0.005 and 0.016, respectively), although the clinical relevance of this finding remains uncertain. Transfusion rates were 2.3, 7.1, and 2.3% in the IO, IV, and topical groups, respectively (P = 0.434). There was one patient in the topical group who developed deep vein thrombosis; no pulmonary embolism or infections were reported. CONCLUSIONS:The blood-sparing efficacy of IO TXA administration is noninferior to that of IV and topical administration, with potential benefit in early postoperative blood loss control. Further high-quality studies are needed to confirm its superiority and establish its clinical value.
Aims Currently, fungal periprosthetic joint infection (FPJI) following joint arthroplasty remains a major therapeutic challenge worldwide. Therefore, this study aims to investigate a novel and promising therapeutic approach. Methods In the in vitro experiment, ultrasound and voriconazole (VOR) were used alone or in combination against Candida albicans. In the in vivo experiment, 100 male Sprague-Dawleyrats were randomly divided into ten groups, with ten rats in each group: control group(underwent sham surgery), prosthesis group (uninfected prosthesis implanted), model group(prosthesis implanted and infected with C. albicans); the remaining seven groups weretreated using separate therapeutic methods for infections: ultrasound, intra-articular (IA) (IAVOR injection), IA + ultrasound, intravenous (IV) (IV VOR injection), IV + ultrasound, IA +IV, and IA + IV + ultrasound groups. Relevant tests and examinations were performed duringand after the 14-day treatment. Results In vitro, the combination of ultrasound and VOR showed the most pronounced antifungaleffect. In vivo, IA VOR injection is better for maintaining high local VOR concentrations. Basedon this, the combination of ultrasound and IA VOR demonstrated superior outcomes acrossmultiple endpoints, including serum biochemical markers, weightbearing scores, reactivebone changes, inflammation, and local knee skin temperature, as well as reduced colonycounts on soft tissues, bone, and implants. In contrast, IV VOR showed minimal improvement across these parameters. Moreover, in rats subjected to any VOR and ultrasound treatment, no pathological changes in major metabolic organs or abnormal serum markers were observed. Additionally, no skin pathological changes were found after ultrasound exposure. Conclusion The combination of ultrasound and IA injection of VOR represents a novel and promising therapeutic strategy for C. albicans-induced FPJI.
Aims:Three-phase bone scintigraphy (TPBS) is a simple, reliable, and straightforward imaging modality for diagnosing periprosthetic joint infection (PJI). This study aimed to evaluate the diagnostic efficacy of the combined diagnostic method of TPBS and CRP in the detection of PJI. Methods:A retrospective analysis was performed on 317 patients undergoing revision surgery (211 hips and 106 knees) between January 2017 and January 2024, with TPBS obtained prior to surgical intervention. PJI was diagnosed according to the 2013 Musculoskeletal Infection Society (MSIS) criteria. The diagnostic performance of TPBS, CRP, and TPBS-CRP combined method was evaluated. Results:In the total knee arthroplasty (TKA) cohort, TPBS-CRP achieved maximal sensitivity (100%) and negative predictive value (100%), enabling definitive exclusion of PJI, albeit with reduced specificity (50.0%). Antibiotic therapy significantly reduced CRP accuracy (79.1% vs 97.1%, p = 0.020) but minimally impacted TPBS (100% vs 88.6%, p = 0.037). For total hip arthroplasty (THA), the TPBS-CRP demonstrated a superior diagnostic efficacy (AUC = 0.846, 0.834, and 0.795) and demonstrated a more balanced sensitivity (81.6%, 67.3%, and 64.3%) and specificity (87.6%, 91.2%, and 94.7%) compared to CRP and TPBS. Antibiotic-treated patients exhibited significantly higher diagnostic accuracy for TPBS (81.5% vs 57.7%, p = 0.028), CRP (88.9% vs 59.2%, p = 0.005), and TPBS-CRP (96.3% vs 76.1%, p = 0.020) compared to untreated patients. False-positive TPBS cases in both cohorts exhibited severe bone loss and prolonged symptoms compared to true negatives (p < 0.05). Conclusion:TPBS demonstrates limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP synergizes localized bone metabolic profiles with systemic inflammatory biomarkers, achieving superior diagnostic accuracy. Caution is warranted in patients with severe bone loss and prolonged symptoms.
Aims: This study aimed to develop voriconazole-loaded microbubbles (MBs@VRC) combined with ultrasound-targeted microbubble destruction (UTMD) as a novel strategy to disrupt Candida albicans biofilms and enhance antifungal efficacy, addressing the critical challenge of biofilm-associated resistance in fungal periprosthetic joint infections (PJIs). Methods: MBs@VRC were produced using a thin-film hydration method, and their physicochemical properties were evaluated, including size, zeta potential, and drug loading efficiency. The penetration of DiI-labelled MBs@VRC into C. albicans biofilms was visualized via confocal laser scanning microscopy (CLSM). The antibiofilm activity of the UTMD + MBs@VRC treatment was comprehensively assessed on polystyrene, glass, and titanium surfaces using crystal violet staining (biomass quantification), live/dead staining (viability and thickness analysis), scanning electron microscopy (SEM, morphological evaluation), and colony-forming unit (CFU) counting. Furthermore, the cytocompatibility of MBs@VRC was evaluated in RAW 264.7 macrophages. Results: The synthesized MBs@VRC exhibited a uniform spherical morphology with a mean diameter of 500.87 nm (SD 6.94) and an encapsulation efficiency of 35.33% (SD 2.52%). While C. albicans biofilms showed a notable increase in tolerance, with a minimum biofilm eradication concentration (MBEC50) (1,966.08 μg/ml) approximately 66,000-fold higher than the planktonic minimum inhibitory concentration (MIC) (0.03 μg/ml), MBs@VRC successfully penetrated deep into the 3D biofilm architecture. Compared to monotherapies, the UTMD + MBs@VRC markedly reduced biofilm biomass (by approximately 63% on glass and 73% on titanium), reduced biofilm thickness (as quantified on glass, by approximately 68%), and reduced the viability of C. albicans (by approximately 66% on glass; by approximately 84% on titanium). SEM imaging confirmed extensive hyphal rupture and structural collapse in the combination group. No significant cytotoxicity was observed, with cell viability remaining above 90%. Conclusion: MBs@VRC combined with UTMD effectively disrupts C. albicans biofilms, enhances targeted drug delivery and release, and significantly improves antifungal activity without detectable cytotoxicity. This approach represents a promising adjunctive therapy for combating recalcitrant fungal biofilm infections. Cite this article: Bone Joint Res 2026;15(5):537–548.
BACKGROUND:Although cellularity is traditionally evaluated morphologically, an emerging transcriptome-sequencing-based algorithm enables simultaneous inference of cellular information. We studied whether cellularity profiles predicted using CIBERSORTx would (1) depict immune cell-type abundances in periprosthetic tissues across arthroplasty failure etiologies, and (2) provide prognostic value for identifying cases of periprosthetic joint infection (PJI). METHODS:CIBERSORTx-derived cellularity profiles were evaluated in 185 periprosthetic tissue samples, including 135 from patients with PJI (64 males; median age, 66 years) and 50 from those with aseptic failure (AF) (36 males; median age, 62.5 years), that had been subjected to bulk RNA sequencing. Kaplan-Meier survival analysis was performed to assess prognostic outcomes in PJI. RESULTS:Of the 22 evaluated cell types, 5 were significantly elevated in PJI cases: plasma cells, resting memory CD4+ T cells, CD8+ T cells, activated mast cells, and M1 macrophages (all p < 0.05 after Benjamini-Hochberg [BH] correction). Conversely, 3 cell types were significantly elevated in AF cases: gamma delta T cells, M0 macrophages, and M2 macrophages (all p < 0.05 after BH correction). Of the combined immune cell populations, total B cells, total T cells, and natural killer cells were significantly elevated in PJI cases, while total macrophages/monocytes were significantly elevated in AF cases (all p < 0.05 after BH correction). Patients with PJI who had a CD8+/regulatory T cell (Treg) ratio above the median had a significantly lower rate of infection recurrence than those below the median (log-rank p = 0.0252). CONCLUSIONS:CIBERSORTx analysis of samples from periprosthetic tissues predicted distinct immune cell profiles that differed between PJI and aseptic arthroplasty failure modes, and also identified a high CD8+/Treg ratio as a potential prognostic marker. This transcriptomic approach provides a novel, single-assay strategy for evaluating local immune cell responses across arthroplasty failure etiologies. CLINICAL RELEVANCE:The comparative analysis of immune cell-type abundances in periprosthetic tissues across arthroplasty failure etiologies revealed distinct immune microenvironment signatures that differentiate PJI from AF. Additionally, the finding that a higher CD8+/Treg cell ratio is associated with a lower rate of infection recurrence offers a potential prognostic marker to help identify patients with PJI who are at a lower risk for treatment failure.
Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants. We conducted a retrospective, multicenter cohort study involving 226 patients who underwent cementless single-stage exchange hip arthroplasty for PJI between 1 October 2013 and 31 July 2022. Patients were divided into partial revision (n = 61) and full revision (n = 165) groups. The primary outcome was treatment success, defined as the absence of clinical symptoms and signs of infection at a minimum follow-up of 2 years. The success rates were 77.0
Abstract Background Fungal periprosthetic joint infection remains a challenging complication in revision arthroplasty. Candida albicans ( C. albicans ) is among the most frequently reported fungal pathogens, and biofilm formation further limits antifungal efficacy. Tranexamic acid (TXA) is routinely used to reduce perioperative blood loss in arthroplasty and may come into direct contact with antifungal agents within the joint environment. However, whether TXA modifies antifungal activity against C. albicans remains unclear. This study aimed to evaluate the effect of TXA on the in vitro activity of representative antifungal agents against C. albicans under planktonic and established biofilm conditions. Results Baseline planktonic MICs for FLC, VRC, CAS, and AMB were 0.75, 0.5, 1, and 0.75 µg/mL, respectively. In the presence of TXA, susceptibility shifts were class-dependent: MICs for VRC and CAS decreased four-fold and two-fold, respectively, while AMB exhibited a two-fold increase and FLC remained unchanged. Established biofilms showed markedly reduced antifungal susceptibility, and TXA further altered the XTT-derived biofilm metabolic inhibition profiles. For FLC, TXA increased peak metabolic inhibition from approximately 50–55% in saline to 85–90%, with an XTT-derived MBEC₉₀ of 192 µg/mL. In contrast, TXA attenuated VRC-mediated biofilm metabolic inhibition, producing a right-shifted dose-response profile relative to saline conditions. For CAS, TXA lowered the XTT-derived activity threshold from 256 to 128 µg/mL, although the response curves converged at higher concentrations. For AMB, TXA reduced apparent biofilm activity, increasing the XTT-derived minimum biofilm eradication concentrations (MBECs) threshold from 1.5 to 12 µg/mL. Conclusions TXA differentially modulated the apparent in vitro activity of representative antifungal agents against C. albicans in an antifungal class- and growth-state-dependent manner. The discordance between planktonic and antibiofilm responses under TXA co-exposure supports further mechanistic and translational validation in clinically relevant Candida biofilm models.
BACKGROUND:Limited evidence exists on risk factors for failure after one-stage revision for periprosthetic joint infection (PJI). This study aimed to characterize patients who failed one-stage revision for chronic knee PJI under broad inclusion criteria and to identify associated risk factors. METHODS:We identified 44 patients who experienced failure after one-stage revision for chronic knee PJI between June 18, 2004, and August 23, 2025. Failure was defined as the need for any subsequent surgeries. During the same period, a 1:2 matched control group comprising 88 patients who did not have failure was selected, matched by age (± five years), sex, and surgery year (± five years). Conditional logistic regression analyses were performed to identify factors associated with failure and reinfection. RESULTS:In the failure group, 52.3% (23 of 44) had sinus tracts, and 84.1% (37) failed within two years after one-stage revision. Reinfection occurred in 31 patients (70.4%). A history of multiple failed surgeries was significantly associated with failure (odds ratio [OR], 13.27; 95% confidence interval [CI], 1.43 to 123.48; P = 0.023), with the wide CI suggesting considerable imprecision. Operative time greater than 150 minutes was also significantly associated with failure (OR, 5.11; 95% CI, 1.83 to 14.27; P = 0.002). For reinfection, the same two factors remained significant, and polymicrobial infection was additionally identified as a risk factor (OR, 3.16; 95% CI, 1.12 to 9.40; P = 0.029). CONCLUSIONS:We reported that most failures after one-stage revision occur within two years postoperatively. A history of multiple failed surgeries and operative time greater than 150 minutes were independent risk factors for failure. These factors also remained significant for reinfection, with polymicrobial infection additionally identified as a risk factor. These findings highlight the importance of identifying and managing these risk factors in patients undergoing one-stage revision.
Background Standard 14-day incubation protocols for periprosthetic joint infections (PJIs) lack specificity.The optimal culture duration for distinct acute and chronic PJI remains undefined. This study aimed to define the microbial time-to-positivity (TTP) and distribution in different PJI categories to evaluate the feasibility of a stratified culture strategy. Methods This retrospective study analysed the medical records of patients from 1 June 2016 to 1 July 2024. Patients who met the Musculoskeletal Infection Society (MSIS) criteria and had positive intraoperative synovial-fluid cultures were classified into Early acute PJI, Late acute PJI, and Late chronic PJI based on clinical symptoms. The microbial spectrum and TTP of synovial-fluid specimens were recorded. The microbial profiles and detection rates of different PJI subtypes were compared across different time stages. Results We included 181 patients (mean age 65 years). Among them, 41 cases were Early acute PJI; 35 cases, Late acute PJI; and 105 Late chronic PJI. All pathogens recovered within 12 days. In Early acute PJI and Late acute PJI, 90.3 and 94.3% of pathogens, respectively, grew by day 7, whereas 96.2% of Late chronic PJI isolates required up to 10 days. The rate of new microbial detection decreased sharply after day 5 of incubation. After 7 days, delayed microbial growth was predominantly seen in the Late chronic PJI cohort. Previous antibiotic exposure did not significantly affect the growth of microorganisms in acute PJI (OR = 2.52, 95% CI 0.43–14.65; P = 0.31). Conclusion Previous use of antibiotics prolongs the incubation time of microorganisms but has a limited effect on the incubation time of microorganisms in acute PJI. A 7-day incubation period is sufficient to reliably detect pathogen in acute PJI. For chronic PJI, considering the delayed growth of some pathogen, at least 10 days of culture are required.
Aims:Conventional mechanical debridement may be insufficient to fully eradicate biofilms adherent to prosthetic and surrounding tissue surfaces in cases of periprosthetic joint infection (PJI). This study aimed to evaluate the eradication efficacy and safety of non-contact low-frequency ultrasonic debridement (NLFUD) combined with antiseptic solutions against Staphylococcus aureus biofilms. Methods:Ex vivo, sequential NLFUD was followed by one of four antiseptic protocols (0.9% saline, 3% H2O2, 0.5% povidone-iodine (PI), or 3% H2O2 then 0.5% PI) to eliminate S. aureus biofilms on titanium discs, and evaluated eradication efficacy by live/dead staining and scanning electron microscopy (SEM). In vivo, the approach was subsequently evaluated in a S. aureus-infected PJI rat model comprising four groups: mechanical debridement alone, mechanical and chemical debridement, mechanical and NLFUD debridement, and combined mechanical, NLFUD, and chemical debridement. In vivo, biofilm disruption was assessed by SEM, and safety by haematology, hepatorenal function, major-organ histology, local angiogenic/inflammatory markers, and periprosthetic bone integration. Results:NLFUD combined with each antiseptic produced residual live and dead biofilm areas of < 1%. NLFUD + PI and NLFUD + H2O2 + PI groups exhibited no bacterial regrowth. SEM analysis confirmed effective biofilm disruption using NLFUD on titanium discs ex vivo and on titanium alloy prosthesis in vivo. NLFUD treatment significantly increased bacterial counts in surgical fluid (median 2,665 vs 195 CFU/ml, p = 0.002). Biofilms were reformed in all groups at two weeks after debridement surgery. No significant between-group differences were seen in local immunohistochemical markers (including periprosthetic bone integration and angiogenic markers), or systemic inflammatory indicators, and haematoxylin and eosin staining revealed no structural abnormalities in major organs. Conclusion:As an intraoperative adjunct to debridement in PJI, sequential NLFUD and antiseptic irrigation enhance immediate biofilm disruption while maintaining a favourable systemic and local safety profile, warranting clinical evaluation to reduce residual biofilm burden.