Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity.

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.

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.

Non-Tuberculosis Mycobacterium Periprosthetic Joint Infections Following Total Hip and Knee Arthroplasty: Case Series and Review of the Literature.

OBJECTIVE: Periprosthetic joint infection (PJI) caused by non-tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are lacking. In this case series and systematic review, the clinical manifestations, diagnosis, and management of NTM PJI are summarized and analyzed. METHODS: From 2012 to 2020, we retrospectively analyzed consecutive PJI cases caused by NTM in our institution. A literature review was also conducted from January 2000 to December 2021, utilizing the PubMed, MEDLINE, Cochrane Library, and EMBASE databases to identify all reported NTM-induced PJI cases. The clinical characteristics, demographics, pathogen identification, treatment protocols, and prognosis of NTM PJI were summarized and analyzed. RESULTS: In this retrospective analysis, seven patients infected with NTM following total joint arthroplasty at our institution were included, including six cases of PJI caused by NTM and one case of septic arthritis (SA) caused by NTM. There were six men and one woman, and their average age was 62.3 years. The average interval between TJA and PJI onset was 4 months. The preoperative serological markers, including the mean ESR (51 mm/h), CRP (4.0 mg/dL), fibrinogen (5.7 g/L), and D-dimer (1.1 g/L), were increased. Six patients underwent staged revision surgery, and one patient with SA received antibiotic-loaded bone cement beads to treat the infection. After an average of 33 months of observation following surgical intervention, none of the patients showed any symptoms of infection recurrence. From 2000 to 2021, 68 patients with NTM PJI were found in 39 studies in the published literature. Reinfections occurred within 1 year after arthroplasty in more than half (53.2%) of the patients. M. fortuitum and M. abscesses were the most prevalent rapidly growing mycobacteria (RGM) in all PJI patients, whereas Mycobacterium avium intracellulare (MAC) was the most prevalent slowly growing mycobacterium (SGM). The corresponding antibiotics were amikacin and ethambutol. The rate of culture-negative without specific clinical symptoms was as high as 36.4% (12/33), while 45% (18/40) utilized additional diagnostic techniques such as NGS. A final clinical follow-up record was available for 59 patients (86.7%; mean follow-up period, 29 months), and 10.1% of patients failed to respond to treatment. CONCLUSION: Orthopaedic surgeons should consider NTM in patients with negative routine cultures who are at risk for Mycobacterium infection. Treatment options rely on the accurate result of microbiologic identification and drug sensitivity testing, and to achieve this, it may be necessary to send multiple culture specimens, extend the culture time, and change the culture medium. Every effort should be made to identify NTM and its various subtypes through modern diagnostic tools if necessary.

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.

Antimicrobial effect of methylene blue in microbiologic culture to diagnose periprosthetic joint infection: an in vitro study.

BACKGROUND: As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro. METHODS: Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud's agar plates at 35 â„ƒ. (Streptococci were cultured in a CO2-rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB. RESULTS: Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays. CONCLUSION: MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue.

Early Clinical and Radiographic Outcomes of Robot-Assisted Versus Conventional Manual Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: Robot-assisted surgery has been promoted worldwide in recent years. The development of a domestic orthopaedic robot and its clinical application are therefore of great significance. This study aimed to compare the early clinical and radiographic outcomes of domestic robot-assisted total knee arthroplasty (RA-TKA) with conventional manual total knee arthroplasty (CM-TKA). METHODS: A total of 77 patients who underwent primary single-sided TKA from June to December 2020 were prospectively enrolled; resulting in the inclusion of 72 patients. The patients were randomly divided into the RA-TKA group (37 cases, with TKA being assisted by the Yuanhua Orthopaedic Robotic System) and the CM-TKA group (35 cases, with TKA being performed using conventional tools). Knee function was evaluated by the knee range of motion (ROM), the American Knee Society Score (KSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Postoperative radiographic results were evaluated by full-length weight-bearing X-rays of the lower limb and anteroposterior and lateral X-rays of the knee were obtained preoperatively and at 90 days postoperative. The operative duration, blood loss, postoperative knee function, radiographic outcomes, and incidence of complications were compared by Student's t-test, Mann-Whitney U test, or chi-square test. Serum levels of inflammatory markers before the operation and 1, 3, and 30 days after the operation were recorded and compared between the two groups. RESULTS: The operation was significantly longer in the RA-TKA group than in the CM-TKA group (154.3 vs 115.2 min, p < 0.001). There was no significant difference in blood loss (933 vs 863 ml, p = 0.519) between the two groups. The knee ROM, KSS, and WOMAC were significantly improved in both groups 90 days after the operation compared with before the operation (p < 0.05), but there were no significant differences between the two groups (p > 0.05). The incidence of postoperative deep vein thrombosis was not statistically different between the two groups. In the radiographic findings at 90 days postoperatively we found the frequency of lateral tibial component (LTC) angle outliers was significantly lower in the RA-TKA group (3.0% vs 29.4%, p = 0.003). The neutrophil-to-lymphocyte ratio (NLR) was significantly lower in the RA-TKA group than in the CM-TKA group on day 1 after surgery (9.9 vs 12.7, p = 0.024). CONCLUSIONS: RA-TKA requires more time than CM-TKA, which may be related to the learning curve and intraoperative registration. The short-term postoperative knee functional outcomes had no differences between the two groups, and RA-TKA improved the accuracy of tibial component alignment. Further follow-up studies are required to investigate the long-term outcomes.

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.

Fourth-Generation Ceramic-on-Ceramic THA in Patients with Ankylosing Spondylitis: A Minimum 10-Year Follow-Up.

OBJECTIVE: To report the long-term outcomes of total hip arthroplasty (THA) with fourth-generation ceramic-on-ceramic (CoC) bearing in patients with ankylosing spondylitis (AS). METHODS: We retrospectively identified 180 primary THAs performed in 110 patients with AS, including 100 (90.9%) men and 10 women (9.1%), from 2009 to 2011.The mean age of the patients at surgery was 33 years (range, 16 to 65 years). Cementless prostheses with fourth-generation CoC bearings were used in all patients. Survivorship of the implants and postoperative complications were calculated. Functional improvement was assessed by the hip flexion-extension range of motion (ROM) and Harris hip score (HHS). A special noise assessment questionnaire was performed at the last follow-up. The cumulative incidence of noise was calculated by the Kaplan-Meier method with 95% confidence intervals (CIs). Clinical characteristics and functional outcomes were compared in the hips with noise to those without noise. RESULTS: The mean follow-up was 11 years (range, 10 to 12 years), and survivorship of the implants was 99.4% at the most recent follow-up. The complications included dislocation (one hip, 0.6%), periprosthetic joint infection (one hip, 0.6%), mild to moderate pain (five hips, 2.8%), heterotopic ossification (12 hips, 6.7%), and noise (52 hips, 28.9%). The flexion-extension ROM improved significantly with a median from 10° (range, 0 ~ 130°) to 100° (30 ~ 130°) after THA (p < 0.001), and the HHS increased significantly from 41 ± 20 to 90 ± 8 (p < 0.001). The cumulative incidence of noise at 0.5, 5, and 10 years was 6.1% (95% CI, 2.6 ~ 9.6), 16.7% (95% CI, 11.2 ~ 22.1), and 28.9% (95% CI, 22.2 ~ 35.5), respectively, and that of squeaking at 0.5, 5, and 10 years was 4.4% (95% CI, 1.4 ~ 7.4), 13.3% (95% CI, 8.4 ~ 18.3), and 23.9% (95% CI, 17.6 ~ 30.1), respectively. None of the patients with noise generation in the hip reported it affecting daily activities or causing dissatisfaction. No differences in age, sex, BMI, disease duration, bilateral THA, the frequency of bony ankylosis, the proportion of using a 36-mm-diameter femoral head, pre/postoperative flexion-extension ROM, or pre/postoperative HHS were found between hips with noise and those without noise (p > 0.05). CONCLUSION: THAs with fourth-generation CoC bearings exhibit excellent long-term survival and clinical outcomes in patients with AS, with a very low dislocation rate. The incidence of noise associated with CoC bearings in THA performed in patients increases over time, but it does not affect postoperative hip function or daily activities.

Reconstruction of Paprosky Type III Acetabular Defects by Three-Dimensional Printed Porous Augment: Techniques and Clinical Outcomes of 18 Consecutive Cases.

OBJECTIVE: To introduce the surgical technique of reconstruction of Paprosky type III acetabular defects by 3D printed porous augments. METHODS: First, CT scans of pelvis were obtained to establish the 3D reconstruction model of 3D printed porous augment. Then, a nylon pelvis model was printed to simulate operation with the surgeons. At this time, the augment was designed and modified according to the surgeon's suggestions and the 3D printing principles. Eighteen patients with Paprosky type III acetabular defects receiving reconstructive surgery by 3D printed porous augments were included in current study. Their data, including general information, intra-operative findings, imaging results, functional scores, and complications were retrospectively analyzed. RESULTS: The mean follow-up time lasted 33.3 ± 2.0 (24-56) months. The average limb-length discrepancy (LLD) was 31.7 ± 4.2 (3-59) mm preoperatively, 7.7 ± 1.4 (1-21) mm postoperatively (P < 0.0001), and 7.5 ± 1.2 (0-18) mm at the latest follow-up. The mean vertical position of hip center of rotation (HCOR) from the interteardrop line changed from preoperative 50.7 ± 3.9 (23.3-75.3) mm to postoperative 22.9 ± 1.9 (10.1-40.3) mm (P < 0.0001), with the latest follow-up revealing an HCOR of 22.3 ± 1.7 (11.0-40.5) mm. Follow-up study showed that no hip had radiolucencies and radiological loosening of the acetabular components and augment. The average Harris hip score (HHS) improved from 40.3 ± 4.5 (10.5-71) before operation to 88.4 ± 1.9 (75-97) at the last follow-up (P < 0.0001). Moreover, follow-up exhibited that no periprosthetic joint infection, hip dislocation, fracture, and re-revision occurred. CONCLUSION: Surgical treatment of Paprosky type III acetabular defect with 3D printed porous augment was simple, achieved good match between porous augment and the defect bone surface and the acetabular component, ideally restored LLD and HCOR after operation, significantly improved HHS and attained good early clinical outcomes. It is a promising personalized solution for patients with severe acetabular bone defect.

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.

Hip Replacement in Ankylosing Spondylitis Patients with Advanced Hip Involvement: Factors Associated with Bilateral Total Hip Arthroplasty.

BACKGROUND: This study aimed to compare the clinical data of ankylosing spondylitis (AS) patients who underwent unilateral and bilateral total hip arthroplasty (THA) due to advanced hip involvement. Furthermore, to determine the factors associated with bilateral THA. METHODS: Utilizing a single-institution database, we selected 373 consecutive AS patients undergoing primary THA from 2012 to 2017 and compared the clinical characteristics and anti-tumor necrosis factor (TNF) therapy of the patients who underwent unilateral and bilateral THA. Logistic regression was used to identify factors associated with bilateral THA. RESULTS: Bilateral THA was performed in 67.3% (n=251) of the patients. Male patients had a higher frequency of undergoing bilateral THA compared with female ones (P<0.05). The proportion of the patients who had bilateral onset in hips, administration of TNF inhibitors, flexion contracture in the hip, and a BASRI-hip score of 4 was significantly higher in patients with bilateral THA than that with unilateral THA (P<0.05). Patients with bilateral THA experienced longer disease duration than those with unilateral THA (P<0.05). The results of the logistic regression showed that factors related to bilateral THA were bilateral onset in hips, administration of TNF inhibitors, a BASRI-hip score of 4, and an erythrocyte sedimentation rate (ESR) level (P<0.05). CONCLUSION: Bilateral THA is more common in AS patients with advanced hip involvement. Bilateral onset in hips, a BASRI-hip score of 4, and a higher level of ESR are risk factors associated with bilateral THA, while anti-TNF therapy is a protective factor reducing the progression of hip involvement to bilateral THA.

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.

In Vivo Reconstruction of the Acetabular Bone Defect by the Individualized Three-Dimensional Printed Porous Augment in a Swine Model.

METHODS: As an acetabular bone defect model created in Bama miniswine, an augment individually fabricated by 3D print technique with Ti6Al4V powders was implanted to repair the defect. Nine swine were divided into three groups, including the immediate biomechanics group, 12-week biomechanics group, and 12-week histological group. The inner structural parameters of the 3D printed porous augment were measured by scanning electron microscopy (SEM), including porosity, pore size, and trabecular diameter. The matching degree between the postoperative augment and the designed augment was assessed by CT scanning and 3D reconstruction. In addition, biomechanical properties, such as stiffness, compressive strength, and the elastic modulus of the 3D printed porous augment, were measured by means of a mechanical testing machine. Moreover, bone ingrowth and implant osseointegration were histomorphometrically assessed. RESULTS: In terms of the inner structural parameters of the 3D printed porous augment, the porosity was 55.48 ± 0.61%, pore size 319.23 ± 25.05 µm, and trabecular diameter 240.10 ± 23.50 µm. Biomechanically, the stiffness was 21464.60 ± 1091.69 N/mm, compressive strength 231.10 ± 11.77 MPa, and elastic modulus 5.35 ± 0.23 GPa, respectively. Furthermore, the matching extent between the postoperative augment and the designed one was up to 91.40 ± 2.83%. Besides, the maximal shear strength of the 3D printed augment was 929.46 ± 295.99 N immediately after implantation, whereas the strength was 1521.93 ± 98.38 N 12 weeks after surgery (p = 0.0302). The bone mineral apposition rate (µm per day) 12 weeks post operation was 3.77 ± 0.93 µm/d. The percentage bone volume of new bone was 22.30 ± 4.51% 12 weeks after surgery. CONCLUSION: The 3D printed porous Ti6Al4V augment designed in this study was well biocompatible with bone tissue, possessed proper biomechanical features, and was anatomically well matched with the defect bone. Therefore, the 3D printed porous Ti6Al4V augment possesses great potential as an alternative for individualized treatment of severe acetabular bone defects.

Factors associated with blood loss in ankylosing spondylitis patients with hip involvement undergoing primary total hip arthroplasty: a cross-sectional retrospective study of 243 patients.

BACKGROUND: Total hip arthroplasty (THA) can cause considerable blood loss and perioperative transfusion in ankylosing spondylitis (AS) patients. This study aimed to identify the factors related to blood loss in AS patients with hip involvement undergoing THA. METHODS: We analyzed 243 AS patients with advanced hip involvement undergoing primary THA from 2012 to 2017. Bilateral THA was performed by a one-stage operation during one general anesthesia session. The patients were divided into three groups according to the grade of blood loss, as determined by the Advanced Trauma Life Support hypovolemic shock classification system. Ordinal logistic regression was used to identify factors associated with blood loss in the patients. RESULTS: The proportion of patients who were male, underwent bilateral THA, had a hip range of motion (ROM) = 0°, had a BASRI-hip score of 4, underwent iliopsoas and adductor release, and underwent autologous or allogenic transfusion increased significantly with the grade of blood loss, while that of the patients who received tranexamic acid (TXA) decreased significantly (P < 0.05). The preoperative hemoglobin (Hb) level, hematocrit level, and operating time also increased significantly with the grade of blood loss (P < 0.05). The ordinal logistic regression results identified the factors related to blood loss during THA in AS patients with hip involvement to be the male sex (odds ratio [OR] = 3.287; 95% confidence interval [CI] 1.022, 10.567), bilateral THA (OR = 13.896; 95% CI 4.950, 39.011), hip ROM = 0° (OR = 2.513; 95% CI 1.277, 4.946), an elevated erythrocyte sedimentation rate (ESR) level (OR = 3.042; 95% CI 1.320, 7.014), an elevated preoperative Hb level (OR = 1.043; 95% CI 1.017, 1.070), a long operating time (OR = 1.009; 95% CI 1.003, 1.016), and the administration of TXA (OR = 0.252; 95% CI 0.134, 0.472). CONCLUSIONS: The male sex, bilateral THA, a hip ROM = 0°, an elevated ESR level, a high preoperative Hb level, and a long operating time are risk factors associated with blood loss in AS patients with hip involvement undergoing THA, while the administration of TXA is a protective factor. These results might help determine the risk of bleeding in the perioperative assessment and develop more efficient blood management strategies for THA in AS patients with hip involvement.

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.

The use of augmented antibiotic-loaded cement spacer in periprosthetic joint infection patients with acetabular bone defect.

BACKGROUND: Spacer complications may affect final clinical outcome of the two-stage approach in periprosthetic joint infection (PJI) patients. This study aimed to investigate clinical outcomes and complications of augmented antibiotic-loaded cement spacer in PJI patients with acetabular bone defect. METHODS: Data on PJI patients with acetabular bone defect receiving two-stage revision from January 2009 to December 2016, in our hospital were retrospectively reviewed. Screw-cement-shell was used to improve the stability of the hip with acetabular wall defect. Handmade acetabular spacer could prevent femoral spacer entering into pelvis in patients with acetabular internal wall defect. A total of 26 patients (11 males and 15 females) were included in the current study. Their mean age was 46.7 ± 15.4 years old. Clinical outcomes and complications were measured. RESULTS: Twenty-one of total 26 hips (21/26, 80.8%) showed positive cultures and 15/26 (57.7%) samples were cultured with staphylococcus. Of enrolled patients, 5/26 (19.2%) developed mixed infection. There was one patient (3.8%) with spacer dislocation and two (7.7%) with spacer fracture. One patient developed acute PJI 5 years after the second-stage revision, so overall success rate among these patients was 96.2%. Differences in Paprosky classifications before the first and second stage did not reach significant level (p > 0.05). Hip Harris score was raised from 40.9 ± 14.0 to 81.2 ± 11.2 (p < 0.05). CONCLUSIONS: Augmented antibiotic-loaded cement spacer could achieve satisfactory clinical outcomes in PJI patients with acetabular bone defect. It provided joint mobility, increased additional joint stability, and decreased iatrogenic bone defect caused by acetabular wear.

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.

Correction to: The 2018 new definition of periprosthetic joint infection improves the diagnostic efficiency in the Chinese population.

In the original publication of this article, [1] the affiliation of the first author Haitao Guan needs to be revised.

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.