Identification of immune infiltration and immune-related biomarkers of periprosthetic joint infection.

Background: The immune response associated with periprosthetic joint infection (PJI) is an emerging but relatively unexplored topic. The aim of this study was to investigate immune cell infiltration in periprosthetic tissues and identify potential immune-related biomarkers. Methods: The GSE7103 dataset from the GEO database was selected as the data source. Differentially expressed genes (DEGs) and significant modular genes in weighted correlation network analysis (WGCNA) were identified. Functional enrichment analysis and transcription factor prediction were performed on the overlapping genes. Next, immune-related genes from the ImmPort database were matched. The protein-protein interaction (PPI) analysis was performed to identify hub genes. CIBERSORTx was used to evaluate the immune cell infiltration pattern. Spearman correlation analysis was used to evaluate the relationship between hub genes and immune cells. Results: A total of 667 DEGs were identified between PJI and control samples, and 1847 PJI-related module genes were obtained in WGCNA. Enrichment analysis revealed that the common genes were mainly enriched in immune and host defense-related terms. TFEC, SPI1, and TWIST2 were the top three transcription factors. Three hub genes, SDC1, MMP9, and IGF1, were identified in the immune-related PPI network. Higher levels of plasma cells, CD4+ memory resting T cells, follicular helper T cells, resting mast cells, and neutrophils were found in the PJI group, while levels of M0 macrophages were lower. Notably, the expression of all three hub genes correlated with the infiltration levels of seven types of immune cells. Conclusion: The present study revealed immune infiltration signatures in the periprosthetic tissues of PJI patients. SDC1, MMP9, and IGF1 were potential immune-related biomarkers for PJI.

Incidence, associated factors, and outcomes of acute kidney injury following placement of antibiotic bone cement spacers in two-stage exchange for periprosthetic joint infection: a comprehensive study.

Background: Two-stage exchange with placement of antibiotic cement spacer (ACS) is the gold standard for the treatment of chronic periprosthetic joint infection (PJI), but it could cause a high prevalence of acute kidney injury (AKI). However, the results of the current evidence on this topic are too mixed to effectively guide clinical practice. Methods: We retrospectively identified 340 chronic PJI patients who underwent the first-stage exchange with placement of ACS. The Kidney Disease Improving Global Outcomes guideline was used to define postoperative AKI. Multivariate logistic analysis was performed to determine the potential factors associated with AKI. Furthermore, a systematic review and meta-analysis on this topic were conducted to summarize the knowledge in the current literature further. Results: In our cohort, the incidence of AKI following first-stage exchange was 12.1%. Older age (per 10 years, OR= 1.509) and preoperative hypoalbuminemia (OR= 3.593) were independent predictors for postoperative AKI. Eight AKI patients progressed to chronic kidney disease after 90 days. A meta-analysis including a total of 2525 PJI patients showed the incidence of AKI was 16.6%, and AKI requiring acute dialysis was 1.4%. Besides, host characteristics, poor baseline liver function, factors contributing to acute renal blood flow injury, and the use of nephrotoxic drugs may be associated with the development of AKI. However, only a few studies supported an association between antibiotic dose and AKI. Conclusion: AKI occurs in approximately one out of every six PJI patients undergoing first-stage exchange. The pathogenesis of AKI is multifactorial, with hypoalbuminemia could be an overlooked associated factor. Although the need for acute dialysis is uncommon, the fact that some AKI patients will develop CKD still needs to be taken into consideration.

The superiority of immune-inflammation summary index for diagnosing periprosthetic joint infection.

BACKGROUND: Accurate and rapid diagnosis of periprosthetic joint infections (PJI) is particularly challenging. This study aimed to evaluate the diagnostic value of a newly developed immune-inflammation summary index (IISI) for PJI. METHODS: Our study enrolled 171 aseptic loosening (AL) and 172 PJI cases. Based on a biological-driven approach, the IISI was formulated as C-reaction protein (CRP) × globulin × neutrophil / [lymphocyte × albumin]. Receiver operating characteristic (ROC) curves were constructed to compare the diagnostic performance of IISI with other known serum markers. Subgroup analysis was also performed to explore the robustness of IISI. Restricted cubic splines were used to evaluate the dose-response association. Additionally, changes in IISI levels prior to reimplantation were investigated. RESULTS: The levels of all tested biomarkers were significantly different between the PJI and AL groups (all P < 0.05). ROC analysis revealed that IISI outperformed any other marker in diagnosing PJI with an area under the curve (AUC) value of 0.890. The diagnostic performance of IISI was also optimal in the hip (0.898), knee (0.903), low-grade infection (0.841), and culture-negative (0.919) subgroups. The optimal cut-off value is stabilized at around 1.6. The nonlinear association between IISI scores and PJI was also confirmed (P < 0.001). The levels of IISI before reimplantation demonstrated a significant decrease (P < 0.001) and were comparable to those of the AL group (P = 0.143). CONCLUSION: IISI can improve the utilization of serum indicators and is superior to other well-known biomarkers in diagnosing PJI. Further studies should evaluate its specific role in different infectious and inflammatory diseases.

Host Immune Regulation in Implant-Associated Infection (IAI): What Does the Current Evidence Provide Us to Prevent or Treat IAI?

The number of orthopedic implants for bone fixation and joint arthroplasty has been steadily increasing over the past few years. However, implant-associated infection (IAI), a major complication in orthopedic surgery, impacts the quality of life and causes a substantial economic burden on patients and societies. While research and study on IAI have received increasing attention in recent years, the failure rate of IAI has still not decreased significantly. This is related to microbial biofilms and their inherent antibiotic resistance, as well as the various mechanisms by which bacteria evade host immunity, resulting in difficulties in diagnosing and treating IAIs. Hence, a better understanding of the complex interactions between biofilms, implants, and host immunity is necessary to develop new strategies for preventing and controlling these infections. This review first discusses the challenges in diagnosing and treating IAI, followed by an extensive review of the direct effects of orthopedic implants, host immune function, pathogenic bacteria, and biofilms. Finally, several promising preventive or therapeutic alternatives are presented, with the hope of mitigating or eliminating the threat of antibiotic resistance and refractory biofilms in IAI.

A Nomogram That Characterizes a Patient's Odds of Developing Squeaking After Fourth-generation Ceramic-on-ceramic THA.

BACKGROUND: Although ceramic-on-ceramic (CoC) bearings result in the lowest wear rate of any bearing combination, postoperative squeaking remains worrisome. However, data concerning squeaking in long-term follow-up studies are still lacking, especially for fourth-generation CoC THA. QUESTIONS/PURPOSES: (1) After keeping the prosthesis in place for 10 years, what percentage of patients treated with fourth-generation CoC THA implants report squeaking, and are there points in time when squeaking occurs more frequently? (2) What are the characteristics, association with hip function, and factors associated with squeaking? (3) Can we create a nomogram that characterizes a patient's odds of experiencing squeaking based on the factors associated with it? METHODS: Between January 2009 and December 2011, 1050 patients received primary THAs at our institution, 97% (1017) of whom received fourth-generation CoC THAs because this was the preferred bearing during this period. Of the 1017 eligible patients, 5% (54) underwent THAs performed by low-volume surgeons, 3% (30) were implanted with cemented prostheses, 2% (22) died, 1% (10) were immobile, 1% (six) underwent revision surgery, and 17% (169) were lost to follow-up before 10 years, leaving 726 patients for analysis here at a mean of 11 ± 1 years. In the study cohort, 64% (464) were male and 36% (262) were female, with a mean age of 44 ± 13 years at primary THA. We extracted data about articular noise from follow-up records in our institutional database and used a newly developed questionnaire to ascertain the percentage of patients who reported squeaking at the latest follow-up interval. Although not validated, the questionnaire was modeled on previous studies on this topic. The longitudinal pattern for squeaking was explored to find timepoints when squeaking occurs more frequently. Based on the questionnaire data, we calculated the percentages of frequent, reproducible, and avoidable squeaking. Hip function was evaluated with the Harris Hip Score and WOMAC score and compared between the squeaking and nonsqueaking groups. Factors associated with squeaking, which were examined in a multivariate analysis, were used to develop a nomogram. RESULTS: At 10 years, 16% (116 of 726) of patients reported squeaking. Two squeaking peaks were determined, at 0 to 1 year and 8 to 10 years. Frequent, reproducible, and avoidable squeaking accounted for 42% (36 of 86), 20% (17 of 86), and 41% (35 of 86), respectively. The mean Harris Hip Score (93 ± 4 versus 94 ± 5; p = 0.81) and WOMAC score (16 ± 13 versus 15 ± 13; p = 0.23) did not differ between patients with squeaking and those without. After controlling for potential confounding variables such as etiology and head offset, we found that patients younger than 46 years (odds ratio 2.5 [95% confidence interval 1.5 to 5.0]; p < 0. 001), those who were male (OR 2.0 [95% CI 1.1 to 3.5]; p = 0.04), those having a total flexion and extension arc of less than 50° (OR 2.0 [95% CI 1.2 to 3.3]; p = 0.02), and those with the Corail hip implant (OR 4.1 [95% CI 2.1 to 7.7]; p < 0. 001) were more likely to report squeaking. We created a nomogram that can be used at the point of care that can help clinicians identify patients at a higher risk of experiencing squeaking; this nomogram had good performance (area under the receiver operating characteristic curve of 77%). CONCLUSION: As a potential late complication, squeaking after fourth-generation CoC THA is of concern and may be related to increased stripe wear. We recommend that surgeons use this nomogram to assess the odds of squeaking before selecting a bearing, especially in patients at high risk, to facilitate shared decision-making and improve patient satisfaction. Future external validation of the model is still needed to enhance its applicability.Level of Evidence Level III, therapeutic study.

Moderate-to-Severe Malnutrition Identified by the Controlling Nutritional Status (CONUT) Score Is Significantly Associated with Treatment Failure of Periprosthetic Joint Infection.

The prevalence and role of malnutrition in periprosthetic joint infection (PJI) remain unclear. This study aimed to use measurable nutritional screening tools to assess the prevalence of malnutrition in PJI patients during two-stage exchange arthroplasty and to explore the association between malnutrition and treatment failure. Our study retrospectively included 183 PJI cases who underwent 1st stage exchange arthroplasty and had available nutritional parameters, of which 167 proceeded with 2nd stage reimplantation. The recently proposed Musculoskeletal Infection Society (MSIS) Outcome Reporting Tool was used to determine clinical outcomes. The Controlling Nutritional Status (CONUT), Nutritional Risk Index (NRI), and Naples Prognostic Score (NPS) were used to identify malnutrition at 1st and 2nd stage exchange, respectively. Multivariate logistic regression analyses were performed to determine the association between malnutrition and treatment failure. Restricted cubic spline models were further used to explore the dose−response association. Additionally, risk factors for moderate-to-severe malnutrition were evaluated. Malnourished patients identified by CONUT, NPS, and NRI accounted for 48.1% (88/183), 98.9% (181/183), and 55.7% (102/183) of patients at 1st stage, and 9.0% (15/167), 41.9% (70/167), and 43.1% (72/167) at 2nd stage, indicating a significant improvement in nutritional status. We found that poorer nutritional status was a predictor of treatment failure, with CONUT performing best as a predictive tool. Moderate-to-severe malnutrition at 1st stage identified by CONUT was significantly related to treatment failure directly caused by PJI (odds ratio [OR] = 5.86), while the OR was raised to 12.15 at 2nd stage (OR = 12.15). The linear dose−response associations between them were also confirmed (P for nonlinearity at both 1st and 2nd stage > 0.05). As for total treatment failure, moderate-to-severe malnutrition as determined by CONUT was associated with a 1.96-fold and 8.99-fold elevated risk at the 1st and 2nd stages, respectively. Age ≥ 68 years (OR = 5.35) and an increased number of previous surgeries (OR = 2.04) may be risk factors for moderate-to-severe malnutrition. Overall, the prevalence of malnutrition in PJI patients is very high. Given the strong association between moderate-to-severe malnutrition identified by CONUT and PJI treatment failure, COUNT could be a promising tool to evaluate the nutritional status of PJI patients to optimize treatment outcomes.

Identification of PSMB9 and CXCL13 as Immune-related Diagnostic Markers for Rheumatoid Arthritis by Machine Learning.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes significant physical and psychological damage. Although researchers have gained a better understanding of the mechanisms of RA, there are still difficulties in diagnosing and treating RA. We applied a data mining approach based on machine learning algorithms to explore new RA biomarkers and local immune cell status. METHODS: We extracted six RA synovial microarray datasets from the GEO database and used bioinformatics to obtain differentially expressed genes (DEGs) and associated functional enrichment pathways. In addition, we identified potential RA diagnostic markers by machine learning strategies and validated their diagnostic ability for early RA and established RA, respectively. Next, CIBERSORT and ssGSEA analyses explored alterations in synovium-infiltrating immune cell subpopulations and immune cell functions in the RA synovium. Moreover, we examined the correlation between biomarkers and immune cells to understand their immune-related molecular mechanisms in the pathogenesis of RA. RESULTS: We obtained 373 DEGs (232 upregulated and 141 downregulated genes) between RA and healthy controls. Enrichment analysis revealed a robust correlation between RA and immune response. Comprehensive analysis indicated PSMB9, CXCL13, and LRRC15 were possible potential markers. PSMB9 (AUC: 0.908, 95% CI: 0.853-0.954) and CXCL13 (AUC: 0.890, 95% CI: 0.836-0.937) also showed great diagnostic ability in validation dataset. Infiltrations of 16 kinds of the immune cell were changed, with macrophages being the predominant infiltrating cell type. Most proinflammatory pathways in immune cell function were activated in RA. The correlation analysis found the strongest positive correlation between CXCL13 and plasma cells, PSMB9, and macrophage M1. CONCLUSION: There is a robust correlation between RA and local immune response. The immune-related CXCL13 and PSMB9 were identified as potential diagnostic markers for RA based on a machine learning approach. Further in-depth exploration of the target genes and associated immune cells can deepen the understanding of RA pathophysiological processes and provide new insights into diagnosing and treating RA.

Comparison of serum inflammatory indicators and radiographic results in MAKO robotic-assisted versus conventional total knee arthroplasty for knee osteoarthritis: a retrospective study of Chinese patients.

BACKGROUND: The purpose of this study was to compare the serum inflammatory indicators and radiographic results of conventional manual total knee arthroplasty (CM-TKA) with those of MAKO-robotic assisted total knee arthroplasty (MA-TKA). METHODS: We retrospectively analysed 65 patients with knee osteoarthritis who underwent unilateral TKA from December 2020 to November 2021 in our department, which included 34 patients who underwent MA-TKA and 31 patients who underwent CM-TKA. The tourniquet time and estimated blood loss (EBL) were compared between the two groups. Knee function was evaluated using range of motion (ROM), functional score and pain score. Leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), creatine kinase (CK), and neutrophil-to-lymphocyte ratio (NLR) were recorded at 3 time points (preoperative, and on the first and third postoperative days). The hip-knee-ankle angle (HKA) and the femoral and tibial component angles in the coronal and sagittal planes were used for postoperative radiographic evaluation. RESULTS: The postoperative MA-TKA group had less EBL (496.9 ± 257.8 vs. 773.0 ± 301.3 ml, p < 0.001). There was no significant difference in knee function scores at 6 weeks postoperatively (p > 0.05). IL-6 levels were significantly lower in the MA-TKA group on the 1st postoperative day (11.4 (5.2, 21.0) vs. 24.6 (86.3, 170.8), p = 0.031). This difference in inflammatory indices became more pronounced at 72 hours after the operation because CRP, ESR, IL-6, and CK values were significantly lower in the MA-TKA group on the 3rd postoperative day (72 h) (p < 0.05). Postoperative radiographic examinations performed 2 days after the MA-TKA group suggested that only 2 cases of HKA had outlier values, which was remarkably better than the 12 cases found in the CM-TKA group (5.9% vs. 38.7%, p < 0.001). The frontal femoral component was significantly closer to the expected value of 90° in the MA-TKA group (90.9 (90.5, 92.3) vs. 92.4 (91.3, 93.7), p = 0.031). The remaining imaging evaluation parameters were not significantly different between the two groups (p > 0.05). CONCLUSIONS: In Chinese patients with OA, there was a milder systemic inflammatory response in the early postoperative period after MA-TKA compared to that of CM-TKA, as well as better radiographic outcomes. However, the tourniquet time was prolonged, and no advantages were observed in terms of functional score or pain score in the short-term follow-up.

Gender Differences in Ankylosing Spondylitis Patients with Advanced Hip Involvement: Results from A Matched Retrospective Cohort Study.

OBJECTIVE: To determine the gender differences in ankylosing spondylitis (AS) patients with advanced hip involvement. METHODS: We retrospectively analyzed the 373 consecutive AS patients with advanced hip involvement from 2012 to 2017 and divided them into two groups by sex with 340 men and 33 women. Research data on hip involvement in the patients were obtained from medical records and radiographs. The severity of radiographic hip involvement was evaluated by the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-hip) scoring system. The data on clinical characteristics, radiographic hip involvement, and laboratory values were compared between the two groups. The comparison was performed again between the two groups after adjusting for the onset age and disease duration by propensity score matching (PSM). RESULTS: Men underwent total hip arthroplasty earlier than women in the patients, with a median age of 31 years (range, 19-67 years) vs 36 years (range, 23-67 years), respectively (P < 0.05). Hip involvement was found to be younger in men than that in women, with a median age of 18 years (range, 7-56 years) vs 23 years (range, 5-55 years) (P < 0.05), and men with bilateral onset in hips had a higher frequency than women with that (66.2% vs 39.4%) (P < 0.05). There was no gender difference in the proportion of bilateral advanced hip involvement (85.3% vs 72.7%) (P > 0.05). The proportion of the patients who had spinal involvement (89.1% vs 69.7%), flexion contracture in the hip (43.8% vs 24.2%), hip range of motion =0° (53.5% vs 30.3%), and an elevated level of C-reactive protein (CRP) (69.1% vs 51.5%) was significantly higher in men than that in women (P < 0.05). After adjusting for the onset age and disease duration by PSM (1:1), men with bilateral onset in hips still had a higher frequency than women with that (76.7% vs 40.0%), and the proportion of the patients who had spinal involvement (90.0% vs 66.7%) and an elevated level of CRP (80.0% vs 53.3%) was significantly higher in men than that in women (P < 0.05). CONCLUSIONS: The disease pattern of hip involvement in AS has gender differences, with bilateral onset being the dominant pattern in men and unilateral onset being more common in women. However, the frequency of bilateral advanced hip involvement has no gender difference eventually. The higher prevalence of spinal involvement in men with AS may be responsible for the more severe functional impairment compared with women.

The risk factors of polymicrobial periprosthetic joint infection: a single-center retrospective cohort study.

BACKGROUND: Periprosthetic joint infection is a serious complication after total joint arthroplasty and polymicrobial PJI which compose a subtype of PJI often indicate worse outcomes compared to monomicrobial periprosthetic joint infection. However, a literature review suggested that there were limited number studies evaluating the risk factors of polymicrobial PJI. MATERIALS AND METHODS: Between 2015 January and 2019 December, a total of 64 polymicrobial PJI patients and 158 monomicrobial PJI patients in a tertiary center were included in this study and corresponding medical records were scrutinized. The diagnosis of PJI was based on 2014 MSIS criteria. Logistic regression was used to identify the association between various variables and polymicrobial PJI and ROC curve was used to identify their efficiency. RESULTS: The prevalence of polymicrobial PJI is 28.3% in our cohorts. After adjusting for the presence of sinus, previous and knee infection, isolation of enterococci (OR, 3.025; 95%CI (1.277,7.164) p = 0.012), infection with atypical organisms (OR, 5.032;95%CI: (1.470,17.229) p = 0.01), infection with gram-negative organisms (OR, 2.255; 95%CI (1.011,5.031) p = 0.047), isolation of streptococcus spp. (OR, 6; 95%CI (2.094,17.194) p = 0.001), and infection with CNS (OfR, 2.183;95%CI (1.148,4.152) p = 0.017) were risk factors of polymicrobial PJI compared to monomicrobial PJI. However, knee infection is related to a decreased risk of polymicrobial PJI with an adjusted OR = 0.479 (p = 0.023). CONCLUSION: This study demonstrated that the prevalence of polymicrobial PJI is 28.3% in PJI patients. Moreover, the presence of sinus tract and previous joint revisions were risk factors for identifying different bacterial species in the intraoperative specimens. Therefore, in these PJI cases, it is necessary to examine multiple specimens of both intraoperative tissue and synovial fluid for increasing the detection rate and obtaining resistance information.

Positive frozen section during reimplantation increases the risk of treatment failure in two-stage exchange arthroplasty even in patients with normal ESR and CRP.

AIMS: It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. METHODS: We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure. RESULTS: Treatment failure occurred in eight (30.77%) of the 26 PJI patients with positive frozen sections at reimplantation, compared with 13 (9.49%) of 137 patients with negative results. In the multivariate analysis, positive frozen section increased the risk of failure (odds ratio 4.70; 95% confidence interval (CI) 1.64 to 13.45). The mean number of months to reinfection was lower in the positive frozen section group than in the control group (p = 0.041). While there were nine (34.62%) patients with positive frozen section and 25 (18.25%) patients with negative frozen section who had prolonged antibiotic use (p = 0.042), the mean duration of antibiotic use was comparable in two groups. Synovial white blood cell count (p = 0.137) and polymorphonuclear leucocyte percentage (p = 0.454) were not associated with treatment failure in logistic regression model. CONCLUSION: Positive frozen section at reimplantation was independently associated with subsequent failure and earlier reinfection, despite normal ESR and CRP levels pre-reimplantation. Surgeons should be aware of the risk of treatment failure in patients with positive frozen sections and carefully consider benefits of reimplantation. Cite this article: Bone Joint J 2021;103-B(5):916-922.

Leukocyte esterase test and alpha-defensin test have similar accuracy for the diagnosis of periprosthetic joint infection.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) after total joint replacement remains challenging. Synovial biomarkers are recommended as the major diagnostic criteria for PJI. The purpose of this study was to test the accuracy of the alpha-defensin test and compare it with that of the leukocyte esterase (LE) test for the diagnosis of PJI. METHODS: We obtained 130 hip or knee aspirates from May 2015 to September 2018. PJI was defined according to the European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid samples were tested with the alpha-defensin ELISA and a LE strip. For the LE strip test, besides using the traditional threshold 500 (equal to ++), we are also using an improved one, with 500 (equal to ++) serving as the threshold for the tests before centrifugation and both 250 and 500 indicating positive results after centrifugation. The receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value, negative predictive value, and Cohen's Kappa value were calculated for the LE and alpha-defensin tests. RESULTS: The area under the curve (AUC) of alpha-defensin, LE strip test with traditional, and improved interpretation strategy were 0.875, 0.854, and 0.877, respectively. The Cohen's Kappa value for the alpha-defensin tests was 0.826 with the traditional LE interpretation strategy and 0.875 with the improved strategy. CONCLUSION: The present study shows that the use of the LE strip to test synovial fluid yielded an accuracy similar to that of the alpha-defensin immunoassay for the diagnosis of PJI; this finding supports the 2018 ICM PJI definition, which considers positive alpha-defensin and LE test results to be equivalent.

Two-stage exchange Arthroplasty is a viable treatment for Periprosthetic joint infection in inflammatory diseases.

BACKGROUND: Inflammatory diseases are chronic autoimmune systemic autoimmune diseases, which may increase the risk of prosthetic joint infection (PJI) after total joint arthroplasty (TJA). However, to our best knowledge, few studies have studied the association between inflammatory diseases and subsequent failure after two-stage exchange reimplantation. The aims of this study were to identify the differences in (1) serum markers, synovial indicators and pathology results and (2) treatment outcomes following two-stage exchange arthroplasty between patients with or without inflammatory diseases. METHODS: A retrospective review of 184 patients with PJI who underwent two-stage revision from 2014 to 2018 was conducted. PJI was diagnosed by using the MSIS criteria. Serum biomarkers, synovial fluid, organism and pathology results at the time of the PJI diagnosis and reimplantation were compared between patients with or without inflammatory diseases. Treatment success was defined according to the Delphi-based consensus criteria; Kaplan-Meier survivorship curves of the patients were generated and compared. RESULTS: There was no difference in the biomarkers, pathology results or organism profile at the time of the PJI diagnosis. At reimplantation, the patients with inflammatory diseases generally had higher values of serum markers than those without inflammatory diseases. However, synovial white blood cell count was comparable in patients with inflammatory diseases (1142.8 ± 1385.3*109/mL) and group C (1315.8 ± 1849.3*109/mL, p = 0.841). The total treatment success rate was 91.3% (92% for individuals with inflammatory diseases and 91.2% for the controls). The survivorship of the inflammatory disease group was comparable with that of the control group. CONCLUSION: Two-stage exchange arthroplasty is a viable option for PJIs with inflammatory diseases. Synovial fluid analysis may be less affected by inflammatory diseases than serum markers did in the diagnosis persistent infection at reimplantation.

Neutrophil to lymphocyte ratio as a predictor for diagnosis of early Periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a catastrophic complication after total knee or hip arthroplasty. The diagnosis of PJI is very difficult, especially in the early postoperative period. The value of the neutrophil to lymphocyte ratio (NLR) is useful for diagnosing infectious diseases. The objective of this study was to investigate the accuracy of the NLR for the diagnosis of early PJI after total knee or hip arthroplasty. METHODS: We retrospectively evaluated consecutive primary total knee or hip arthroplasty and identified the patients who readmitted within the first 90 days postoperatively between January 2011 and October 2018.There were 20 cases diagnosed early PJI and 101 uninfected cases on the basis of the modified Musculoskeletal Infection Society (MSIS) criteria. The serum parameters including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood-cell (WBC) count, NLR and interleukin-6 (IL-6) were compared between the two groups. Receiver operating characteristic curves were generated to estimate the optimal cutoff values for each parameter. The sensitivity, specificity, positive predictive value and negative predictive value for each parameter were calculated. RESULTS: The CRP, ESR, WBC, NLR and IL-6 values were all significally higher in the infected group than the uninfected group. The median of CRP was 66.6 mg/l in the infected group and 8.6 mg/l in the uninfected group (p < 0.001). The median of ESR was 34.8 mm/hr. in the infected group and 17.4 mm/hr. in the uninfected group (p < 0.001). In the infected group and uninfected group, the median of WBC was 8.2X109 /L and 6.1 X109 /L (p = 0.002), respectively; while the median of NLR was 5.2 and 2.1 (p < 0.001). The median of IL-6 was 46 pg/ml and 6.4 pg/ml (p < 0.001),respectively. The best parameter for the diagnosis of early PJI was IL-6 (AUC = 0.814) followed by the NLR (AUC =0.802), CRP (AUC =0.793), ESR (AUC =0.744) and WBC (AUC = 0.632). CONCLUSIONS: This study is the first to show that NLR values are more accurate than CRP and may be considered as useful parameters for the diagnosis of early PJI because it is a cheap and convenient parameter to be calculated in daily practice without extra costs.

Changes in serum markers failed to predict persistent infection after two-stage exchange arthroplasty.

BACKGROUND: The proper timing of reimplantation is importation to treatment success in the two-stage exchange revision. The 2018 International Consensus Meeting suggested that a variation trend toward normalization in serum markers was useful for determining the proper timing of reimplantation. However, the opposite results were found by previous studies, and the normalization of serum markers was reported to fail to predict infection control. We investigated whether value changes and percent changes in four common serum markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen) can predict persistent infection. METHODS: A retrospective review of 141 patients treated with the two-stage revision from 2014 to 2018 was conducted. The variation trend in serum indicators was evaluated by the percent changes (using values of serum markers pre-reimplantation divided by values pre-resection) and value changes (using values of serum markers pre-resection minus values pre-reimplantation). Treatment success was defined according to the Delphi-based consensus criteria with a minimum follow-up of 1 year, and the receiver operator characteristic (ROC) was used to examine the usefulness of changes in serum markers. RESULTS: Twenty-two patients (15.60%) were persistently infected. No significant difference was found in either the value change or percent change in serum markers between reinfection and non-reinfection patients. When predicting persistent infection, the area under the curves (AUC) demonstrated that both percent changes and value changes in serum markers were poor indicators. The AUC of value changes was 0.533 for the CRP, 0.504 for the IL-6, 0.508 for the ESR, and 0.586 for fibrinogen when predicted persistent PJI. In addition, the AUC indicated that percent changes in the CRP (0.464), the IL-6 (0.534), the ESR (0.527), and fibrinogen (0.586) were all poor markers. CONCLUSIONS: We have shown that both value changes and percent changes in serum markers were not sufficiently rigorous to aid in persistent infection diagnosis. The proper timing of reimplantation must, therefore, take into account various clinical tests rather than the downward trend of serum markers only.

Saline Solution Lavage and Reaspiration for Culture with a Blood Culture System Is a Feasible Method for Diagnosing Periprosthetic Joint Infection in Patients with Insufficient Synovial Fluid.

BACKGROUND: Culture is a key step for detecting periprosthetic joint infection (PJI) before surgery. However, using saline solution lavage and reaspiration in patients with insufficient synovial fluid remains controversial. The objective of this study was to evaluate this technique. METHODS: This study included 286 aspirations performed by 1 surgeon in patients after total joint arthroplasty during the period of April 2015 to August 2018. If >1.0 mL of synovial fluid was obtained, then we directly used the fluid for culture. For cases in which ≤1.0 mL of synovial fluid was aspirated, 10 mL of saline solution was injected and the joint was reaspirated for culture. The samples were injected into 2 blood culture bottles for anaerobic bacterial culture and aerobic bacterial and fungal culture, and were inoculated for 14 days in a BACT/ALERT 3D blood culture system unless microorganisms were detected. A PJI diagnosis was determined on the basis of the modified Musculoskeletal Infection Society criteria. RESULTS: Saline solution lavage and reaspiration were used in 82 cases (47 PJI cases and 35 non-PJI cases), while direct aspiration was used in 204 cases (99 PJI cases and 105 non-PJI cases). The overall rate for the use of saline solution lavage was 28.7% (82 of 286). Among knee cases, the saline solution lavage rate was 15.0% (21 of 140), and among hip cases, the rate was 41.8% (61 of 146). The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of culture were 0.795 (95% confidence interval [CI], 0.720 to 0.857), 0.957 (95% CI, 0.909 to 0.984), 0.951 (95% CI, 0.896 to 0.982), and 0.817 (95% CI, 0.749 to 0.873); and for "dry tap" cases, they were 0.851 (95% CI, 0.717 to 0.938), 0.857 (95% CI, 0.697 to 0.952), 0.889 (95% CI, 0.760 to 0.963), and 0.811 (95% CI, 0.648 to 0.920), respectively. CONCLUSIONS: Saline solution lavage and reaspiration for culture in patients with insufficient synovial fluid before surgery may be a sound practice. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Plasma Fibrinogen Exhibits Better Performance Than Plasma D-Dimer in the Diagnosis of Periprosthetic Joint Infection: A Multicenter Retrospective Study.

BACKGROUND: The search for potential markers for a timely and accurate diagnosis of periprosthetic joint infection (PJI) is ongoing. Previous studies have focused on inflammatory markers and have rarely examined coagulation-related indicators. The purpose of this study was to evaluate the values of plasma fibrinogen, D-dimer, and other blood markers for the diagnosis of PJI through a multicenter retrospective study. METHODS: A total of 565 revision total hip and knee arthroplasty cases were enrolled in this study from January 2016 through December 2017, 126 of which had coagulation-related comorbidities and were analyzed separately. The remaining 439 cases included 76 PJI and 363 non-PJI patients. The definition of PJI was based on the International Consensus Meeting (ICM) on Periprosthetic Infection criteria. The diagnostic values of D-dimer, plasma fibrinogen, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood-cell (WBC) count were analyzed using receiver operating characteristic (ROC) curves. RESULTS: ROC curves showed that plasma fibrinogen had the highest area under the curve (AUC), 0.852, followed by 2 classical markers, the CRP level and ESR, which had an AUC of 0.810 and 0.808, respectively. D-dimer had an AUC of 0.657, which was the second lowest value and only slightly higher than that of the WBC count, 0.590. The optimal threshold for plasma D-dimer was 1.25 µg/mL, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.645, 0.650, 0.278, and 0.897, respectively. The optimal threshold for plasma fibrinogen was 4.01 g/L, which showed good sensitivity, specificity, PPV, and NPV, with values of 0.763, 0.862, 0.537, and 0.946, respectively. CONCLUSIONS: Plasma D-dimer may have a very limited diagnostic value for PJI, while plasma fibrinogen, another coagulation-related indicator, exhibits promising performance. Plasma fibrinogen has good sensitivity and specificity for diagnosing PJI, with values similar to those of classical markers, including CRP level and ESR. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

[Mechanical complications with self-made, antibiotic-loaded cement articulating spacers in the treatment of the infected hip replacement].

OBJECTIVE: To study the complications and efficacy of self-made, antibiotic-loaded cement articulating spacers in the treatment of the infected hip replacement. METHODS: Between January 2006 and July 2016, 265 patients (266 hips) received a self-made, antibiotic-loaded cement articulating spacer as part of a two-stage protocol. Among those patients, there were 143 males(144 hips) and 122 females(122 hips). The cement articulating spacers with vancomycin and two Steinman pins were made by a self-made mold system. Meanwhile, another antibiotic was added to the spacers according to the drug sensitivity test. Record if the infected prosthesis was removed, related complication with spacer(breakage and dislocation), Harris score, and control rate of infection. RESULTS: The mean age of two-stage revision operation was(57.4±14.2) years. Thirty-nine patients(14.7%) used extended trochanteric osteotomy(ETO) to remove the infected prosthesis. And 38 patients occurred mentioned complications(14.3%). Spacer breakage occurred in 28 cases(10.5%) and dislocation occurred in 10 cases(3.8%). The mean follow-up time was(83.4±14.6) months. The Harris hip score was from 47.56±14.23 preoperatively to 86.43±12.84 at final follow-up(P<0.05). The infection of 256 cases(96.6%) got control after revision operation. However, during postoperative follow-up, 4 cases occurred re-infection, and they were reoperated, and the infections obtained effective control after the operation. Thus total infection control rate was 95.1%(252/265). CONCLUSIONS: Antibiotic-loaded cement articulating spacer made by a self-made mold system is effective in controling infection caused by hip replacement. Related complication is less with spacer by a mould enclosing two Steinman pins. Using metallic internal fixation or allograft bone combined with spacer does not affect infection control.

[Clinical results of arthroscopic suture for meniscal tear in middle aged adults].

OBJECTIVE: To study the characteristics and clinical effect of total hip arthroplasty(THA) for osteoarthritis and (or) avascular necrosis of femoral head after failure of internal fixation of acetabular fracture. METHODS: From February 2009 to October 2014, 31 patients (31 hips) with hip traumatic osteoarthritis and (or) femoral head avascular necrosis after failure of internal fixation of acetabular fracture were treated with THA including 26 males and 5 females, who injured when the average age of(41±12) years. THA were performed, and the duration ranged from 3 to 132 months with a mean of(20.6±26.9) months secondary to traumatic osteoarthritis and(or) femoral head avascular necrosis. All THA were performed with posterior-lateral approach. The postoperative complications were observed. VAS and Harris hip scores were compared pre-operation and post-operation. RESULTS: Twenty-seven cases were followed up, and the duration ranged from 12 to 80 months with a mean of (43.2±11.7) months. One patient had infection around prosthesis. Aseptic loosening occurred in 1 patient, dislocation of prosthesis in 1 patient. No sciatic nerve injury occurred. Hip function and gaits were obviously improved. To the last follow-up, VAS score was decreased from 7.6±1.2 pre-operatively to 1.2±0.9 post-operatively, while the Harris score was improved from 45.5±13.6 pre-operatively to 88.5±7.8 post-operatively, both differences were statistically significant(P<0.01). The post-operative ROM of hip was significantly improved compared to pre-operative ROM(P<0.05), in addition to extension motion. X-ray showed all the acetabular cups were stable, one femur stem subsided 3 mm. Heterotopic ossification occurred in 2 cases. CONCLUSIONS: Correct dealing with of internal fixation implants, looking out potential infection and reasonable reconstruction of acetabular bone deficiency were the key to the success of THA for osteoarthritis and(or) avascular necrosis of femoral head after failure of internal fixation of acetabular fracture.

[Antibiotic-loaded cement articulating spacer made by a self-made mold system in the treatment of the infected hip replacement].

OBJECTIVES: To summarize the experience and lessons of the using of antibiotic-loaded cement articulating spacer made by a self-made mold system for the treatment of the infected hip replacement, and to evaluate its efficiency and role in the two-stage revision of infected total hip arthroplasty (THA). METHODS: The patients with infected THA treated with two-stage revision protocol from August 2005 to December 2009 were reviewed. All of the 127 patients were debridement thoroughly and followed by implantation of an antibiotic-loaded cement articulated spacer made by a self-made mold system; Two-stage revisions were not followed until the infection were controlled. Among of them, 106 patients, 107 hips were gotten fully followed up. Evaluations were made for the efficiency of infection control, convenience of making, implanting and removing of the spacers, occurrence of complications, the deal of the special circumstances, the function and satisfaction of the patients. RESULTS: The 107 hips were gotten an average of 34.3 months' (3 - 55 months) follow-up. The infection control rate was 96.3% after the first-stage surgery, the infection control rate was 94.4% at last follow-up after two-stage revisions. The breakage rate of the spacer was 4.7%, dislocation rate was 2.8%, removal of the spacers with difficulty were seen in 15 patients (14.0%). The satisfactory rate of the patients was 93.5%. CONCLUSIONS: Antibiotic-loaded cement articulating spacer made by a self-made mold system is an effective methods for the two-stage revision of the infected hip replacement, characterized by simple, good reproducible, high rates of infection control, better joint function after surgeries, high rate of patients satisfaction and other advantages. And it can decrease the complications, such as the breakage, spacer dislocation of hip joint and difficulty in removal of spacer at the second stage revision. Using of metallic internal fixation or allograft bone combined with spacer does not affect the results of infection controlling.