Ninety-day postoperative mortality and complications in continuous and unselected single-stage revisions for chronic periprosthetic joint infection.

PURPOSE: Single-stage revision has gained significant attention as a major surgical approach for periprosthetic joint infection (PJI). However, the 90-day mortality and complication profile of single-stage revision is poorly characterized. The purposes of this study were to determine the incidence rates of and identify the risk factors for 90-day postoperative mortality and complications of single-stage revision for chronic PJI. METHODS: A retrospective review was conducted on patients who underwent single-stage revision for PJI between August 2000 and May 2022. Patient demographics, 90-day mortality, and postoperative complications were recorded. Complications were categorized into systemic and local complications. Patients in this study were further categorized into knee and hip revision groups. Univariate and multivariate logistic regression analyses were performed to identify significant independent predictors of the outcome measures. RESULTS: 348 patients (144 knees and 204 hips) were included in this study. The 90-day mortality rate was 0.9%. The incidence rates of postoperative complications in knee and hip surgeries were 31.3% and 19.6%, respectively. The most common complication was deep-vein thrombosis (DVT). Rheumatoid arthritis (RA) was the independent predictor of mortality. In the knee revision group, fungal infection was identified as the independent predictor of recurrent PJI; regular alcohol use was predictive of wound dehiscence. Among hip PJI patients, age ≥ 80 years was independently associated with DVT; RA was found to be a predictor of dislocation and wound dehiscence. CONCLUSION: For continuous and unselected patients with chronic PJI, single-stage revision demonstrated a satisfactory 90-day mortality. Nevertheless, the 90-day postoperative complication rates after single-stage revision in both knee and hip groups were relatively high.

Diagnosis of periprosthetic joint infections in patients who have rheumatoid arthritis.

Aims: To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods: The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results: For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/µl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/µl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion: Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI.

Efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism after revision hip arthroplasty: a retrospective cohort study.

PURPOSE: The purpose of the study is to determine the efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism (VTE) after revision THA, in comparison with a multiple-dose chemoprophylaxis protocol. METHODS: We retrospectively compared 295 patients undergoing revision THA who received multiple-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once and oral rivaroxaban for 10 days) or single-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once) for VTE. The patients in both groups performed active lower limb exercises. Each group was further stratified into subgroups based on the aetiology of revision. The incidence of VTE, wound complications within three months, hidden blood loss (HBL), transfusion rate, and surgical drainage duration were recorded. RESULTS: The incidence rates of VTE (P = 0.870) did not differ between the two prophylaxis protocols. However, significant differences were observed in wound complications within three months (P = 0.002), HBL (P = 0.015), transfusion rate (P = 0.028). Surgical drainage duration was also shorter in the single-dose chemoprophylaxis group (P = 0.0023). In the subgroup analysis, the use of single-dose chemoprophylaxis protocol cannot significantly reduce HBL and transfusion rate after septic revision THA. The use of multiple-dose chemoprophylaxis protocol (OR = 2.89, P = 0.002) and high BMI (OR = 1.09, P = 0.037) were independent risk factors of wound complications. CONCLUSIONS: Single-dose chemoprophylaxis protocol effectively and safely prevented VTE after revision THA compared with multiple-dose chemoprophylaxis protocol. The effect in reducing HBL and postoperative transfusion rate was limited in septic revision.

Intraoperative Direct Sonication of Implants and Soft Tissue for the Diagnosis of Periprosthetic Joint Infection.

BACKGROUND: Sonication is very efficacious for the microbiological diagnosis of periprosthetic joint infection (PJI), but it involves many steps and multiple workplaces and personnel and therefore carries a potential contamination risk. We present an innovative version of the sonication culture method that involves direct sonication of the retrieved implant and soft tissue, without a sonication tube, intraoperatively and incubation using a BACT/ALERT 3D blood culture system to enhance the efficacy of microbiological diagnosis of PJI. METHODS: We performed a prospective study of consecutive patients requiring implant removal and classified them as having PJI or aseptic failure according to standard criteria. The removed prosthetic components and adjacent soft tissue were directly sonicated in a small metal container, without a sonication tube, during the operation. The sonication fluid was immediately incubated in blood culture bottles in the operating room and cultured in the BACT/ALERT 3D blood culture system. The synovial fluid was also cultured in the BACT/ALERT 3D system to serve as a comparison. RESULTS: Of the 64 included patients, 36 had PJI and 28 had aseptic failure. Fluid from direct sonication and conventional synovial fluid showed sensitivities of 91.7% and 55.6% (p < 0.001) and specificities of 82.1% and 92.9%, respectively. Fourteen cases of PJI were detected by culture of fluid from direct sonication but not by culture of synovial fluid. Higher sensitivity was obtained by direct sonication of only tissue than by direct sonication of only the implant (88.9% versus 75.0%). No significant difference in detection time was found between Staphylococcus aureus and coagulase-negative Staphylococcus. CONCLUSIONS: When combined with incubation in BACT/ALERT bottles, direct intraoperative sonication of implants and soft tissues without a sonication tube was more sensitive than conventional synovial fluid culture and could reliably and rapidly detect the bacteria commonly found in PJI. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Comparison of clinical outcomes between the olecranon osteotomy approach and the Bryan-Morrey approach for total elbow arthroplasty.

BACKGROUND: This study aims to investigate the clinical efficacy of the olecranon osteotomy approach and the Bryan-Morrey approach in total elbow arthroplasty (TEA). METHODS: In this retrospective study, 49 patients with elbow disease were treated with TEA. A total of 22 patients with TEA by olecranon osteotomy approach were designated as group A, and 27 patients with TEA by Bryan-Morrey approach were designated as group B. There were 22 males and 27 females, aged 32-82 years with a mean age of 62 years. There were 44 cases of unilateral elbow joint, including 27 cases on the left elbow and 17 cases on the right elbow, and 5 cases of the bilateral elbow joint. There were 6 cases of osteoarthritis (7 elbows), 18 cases of rheumatoid arthritis (22 elbows), 14 cases of traumatic arthritis (14 elbows), 7 cases of distal humeral fractures (7 elbows), and 4 cases of elbow tuberculosis (4 elbows). For each group, we recorded the operative time, intraoperative bleeding, elbow flexion, extension, pronation, supination, postoperative complication rates, and Mayo Elbow Performance Score after surgery. RESULTS: Operative time and intraoperative bleeding were less in group A than in group B (53-120 min [70 (62.5, 78) min] vs. 64-105 min [77 (73, 87) min], and 10-200 ml [50 (20, 90) ml] vs. 5-250 ml [100 (50, 150) ml], P < .028). The elbow flexion, pronation activity, and Mayo Elbow Performance Score were higher in group A than in group B, [(121 ± 12)° vs. (112 ± 10)°, 85 (85,85)° vs. 80 (77,85)°, and (94 ± 3) points vs. (91 ± 4) points, P < .036], while elbow extension and supination activity and complication rates were not statistically significant in either group. CONCLUSION: Compared to Bryan-Morrey approach, the olecranon osteotomy approach to TEA provides adequate visualization, saves operative time and reduces bleeding, provides better flexion activity, effectively improves elbow function, and achieves satisfactory clinical outcomes.

[Effectiveness of total elbow arthroplasty via olecranon osteotomy approach].

Objective: To investigate the effectiveness of total elbow arthroplasty (TEA) via olecranon osteotomy approach. Methods: Between January 2011 and December 2021, 22 patients (25 sides) with elbow joint disease were treated with TEA via olecranon osteotomy approach. There were 9 males and 13 females with an average age of 52.0 years (range, 32-80 years). The disease involved unilateral elbow joint in 19 cases, including 12 cases on the left side and 7 cases on the right side, and 3 cases with bilateral elbow joints. There were 3 cases (3 sides) of osteoarthritis, 7 cases (9 sides) of rheumatoid arthritis, 6 cases (7 sides) of traumatic arthritis, 4 cases (4 sides) of distal humeral fracture, and 2 cases (2 sides) of elbow tuberculosis. The operation time, intraoperative blood loss, and postoperative complications were recorded. The Mayo Elbow Performance Score (MEPS) and range of motion (ROM) were used to evaluate the elbow joint function, and imaging was used to review the position of the prosthesis and the healing of the osteotomy. Results: The operation time ranged from 53 to 120 minutes (mean, 90.6 minutes); intraoperative blood loss ranged from 10 to 200 mL (mean, 68.4 mL). All incisions healed by first intention. All patients were followed up 3.9-126.7 months, with a median time of 47.6 months. At last follow-up, the MEPS scores of 22 patients ranged from 72 to 100 (mean, 91.6); the elbow joint function was rated as excellent in 17 sides, good in 7 sides, and fair in 1 side, with an excellent and good rate of 96%. Elbow joint ROM was 98°-140° in flexion (mean, 119.7°), 5°-23° in extension (mean, 13.9°), 70°-90° in anterior rotation (mean, 83.3°), and 63°-90° in posterior rotation (mean, 79.4°). The follow-up time of 17 patients (20 sides) without fracture and joint stiffness before operation was 3.9-126.7 months, with a median time of 53.9 months; at last follow-up, the MEPS score and the elbow joint ROM were significantly better than those before operation ( P<0.05). The follow-up time of 5 patients (5 sides) with fracture and joint stiffness before operation was 12.0-124.2 months, with a median time of 40.1 months. At last follow-up, MEPS scores ranged from 89 to 100 (mean, 91.2), and elbow joint ROM restored. Two cases (2 sides) developed ulnar nerve symptoms after operation, and 1 case (1 side) suffered from periprosthetic fracture and periprosthetic infection after revision, and the elbow prosthesis was removed. The prosthesis survival rate was 96%. During follow-up, no prosthesis loosening occurred. Conclusion: The intraoperative visual field exposure of TEA via the olecranon osteotomy approach is sufficient, which can reduce the incidence of complications such as triceps weakness and ulnar nerve injury, effectively improve the function of the elbow joint, and obtain satisfactory effectiveness.

Effective single-stage revision using intra-articular antibiotic infusion after multiple failed surgery for periprosthetic joint infection : a mean seven years' follow-up.

AIMS: Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition. METHODS: A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. RESULTS: A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months (24 to 133). The seven-year infection-free survival was 87.6% (95% confidence interval (CI) 79.4 to 95.8). No significant difference in infection-free survival was observed between hip and knee PJIs (91.5% (95% CI 79.9 to 100) vs 84.7% (95% CI 73.1 to 96.3); p = 0.648). The mean postoperative Harris Hip Score was 76.1 points (63.2 to 92.4) and Hospital for Special Surgery score was 78. 2 (63.2 to 92.4) at the most recent assessment. Polymicrobial and fungal infections accounted for 14.1% (11/78) and 9.0% (7/78) of all cases, respectively. CONCLUSION: Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid, thereby overcoming reduced vascular supply and biofilm formation. This supplementary route of administration may be a viable option in treating PJI after multiple failed prior surgeries for reinfection. Cite this article: Bone Joint J 2022;104-B(7):867-874.

[Comparison of effectiveness of total knee arthroplasty with tantalum monoblock tibial component and cemented tibial plateau prosthesis in patients of different ages].

OBJECTIVE: To investigate the difference of total knee arthroplasty (TKA) with tantalum monoblock tibial component (TMT) and cemented tibial plateau prosthesis in patients of different ages. METHODS: The clinical data of 248 patients (392 knees) who underwent primary TKA between May 2014 and May 2019 and met the selection criteria were retrospectively analyzed. There were 54 males (98 knees) and 194 females (294 knees). Of the 122 patients (183 knees), less than 65 years old, 52 (75 knees, group A1) were treated with TMT and 70 (108 knees, group B1) were treated with cemented tibial plateau prosthesis; of the 126 patients (209 knees), more than 65 years old, 57 (82 knees, group A2) were treated with TMT and 69 (127 knees, group B2) were treated with cemented tibial plateau prosthesis. The baseline data of patients, perioperative indicators [hemoglobin (Hb), hematocrit (Hct), total blood loss, unilateral operation time], effectiveness evaluation indicators [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analogue scale (VAS) score, Knee Society Scoring System (KSS) score, active flexion and extension range of motion (ROM) of the knee joint], complications, and imaging indicators [tibial prosthesis varus angle (ß angle), tibial prosthesis posterior slope angle (δ angle), tibio-femoral angle, occurrence of radiolucent line, prosthesis survival rate] were recorded and compared. RESULTS: There was no significant difference in gender, age, height, weight, body mass index, Kellgren-Lawrence grading, the length of hospital stay, and follow-up time between groups A1, B1 and groups A2, B2 ( P>0.05). The unilateral operation time in groups A1 and A2 was significantly shorter than that in the corresponding groups B1 and B2 ( P<0.05). There was no significant difference in differences of pre- and post-operative Hb and Hct and total blood loss between groups A1, B1 and groups A2, B2 ( P>0.05). There was no significant difference in preoperative effectiveness evaluation indicators between groups A1, B1 and groups A2, B2 ( P>0.05). There were significant differences in the differences of pre- and post-operative WOMAC activity and pain scores, KSS function and pain scores, and VAS scores between groups A1 and B1 ( P<0.05); there was no significant difference in WOMAC stiffness score and ROM ( P>0.05). There was no significant difference in the above indicators between groups A2 and B2 ( P>0.05). There was no significant difference in the incidence of complications (2.7% vs 6.5%, 3.7% vs 3.1%) and prosthesis survival rate (100% vs 97.2%, 100% vs 99.2%) between groups A1, B1 and groups A2, B2 ( P>0.05). During follow-up, there was no significant difference in ß angle, δ angle, and tibio-femoral angle between groups A1, B1 and groups A2, B2 ( P>0.05). In the evaluation of knee X-ray radiolucent line, 2 knees of group A1 and 2 knees of group A2 had radiolucent line at prosthesis-bone interface immediately after operation, and the radiolucent line was gradually filled by new bone, without new radiolucent line. During follow-up, 1 knee of group B1 and 1 knee of group B2 had prosthesis-bone interface radiolucent line, without radiolucent line widening or prosthesis loosening. CONCLUSION: TMT is recommended in patients less than 65 years old, and the two types of prostheses are available for patients nore than 65 years old. However, the long-term effectiveness of the two types of prosthesis in patients of different ages needs further follow-up.

Serum and Synovial Vancomycin Concentrations in Patients with Prosthetic Joint Infection after Intra-articular Infusion.

BACKGROUND AND OBJECTIVES: Vancomycin is one of the most commonly used antibiotics for intra-articular (IA) infusion in the treatment of prosthetic joint infection (PJI). This study aimed to preliminarily investigate the serum and synovial vancomycin concentrations in patients with PJI after IA infusion. METHODS: In total, 16 patients who developed PJI were enrolled in this study; 14 of the patients were treated with IA infusion of vancomycin postoperatively, while the other 2 patients received intravenous (IV) infusion of vancomycin alone. Chemiluminescent immunoassay assay (CLIA) and high-performance liquid chromatography (HPLC) were used to determine the serum and synovial vancomycin concentrations, respectively. RESULTS: Administration of vancomycin 0.5 g once daily (qd) IA maintained a high vancomycin trough concentration in synovial fluid before the next IA dose, regardless of whether it was given in combination with IV administration. The combination vancomycin 0.5 g qd IA + vancomycin 1 g every 12 h (q12h) IV yielded relatively good trough concentrations of vancomycin in both serum and synovial fluid. The mean trough serum vancomycin concentration of patients who used vancomycin 1 g q12h IV therapy was above 10 µg/mL; however, no vancomycin was detected in their synovial fluid. CONCLUSIONS: The rational use of IA vancomycin infusion may help to achieve effective therapeutic concentrations of vancomycin in the serum and synovial fluid of patients with PJI.

Mid-Term Outcomes of Cementless Total Hip Arthroplasty in Adult Patients with Childhood Hip Infection.

BACKGROUND Patients with hip joint infections in childhood often have many aftereffects of different degrees, regardless of the kind of treatment or natural course. Total hip arthroplasty is currently the most effective treatment for sequelae of childhood hip septic or tuberculous infection. This is a mid-term follow-up study of treatment results of patients who had undergone total hip arthroplasty (THA) with cementless prostheses. MATERIAL AND METHODS We retrospectively analyzed and followed 45 patients (45 hips) who underwent THA with cementless prostheses between 2010 and 2017. There were 45 patients, including 17 men and 28 women. The average age of the patients was 46 years (range, 18-67 years). All hip infections occurred in early childhood or adolescence, and the mean interval between initial infection and THA was 38.2 years (range, 15-60 years). The mean follow-up was 6.1 years (range, 2.7-9.5 years). RESULTS Two patients underwent revision surgery because of loosening of the prosthesis, and 1 patient underwent revision surgery because of a new infection with no relationship with childhood infection during the follow-up. The average Harris hip scores significantly increased from 43.1 to 86.4 (P<0.01), and the average visual analog scale significantly increased from 4.6 to 1.7 (P<0.01). The hip dysfunction and osteoarthritis outcome scores were also significantly changed (P<0.01) at the final follow-up. There were 2 cases of transient sciatic nerve palsy and intraoperative periprosthetic fractures in 3 cases. During follow-up, single revision was performed after 6 years of primary arthroplasty because of aseptic loosening in 2 cases and prosthesis infection in 1 case, which was not related to childhood pathogens. CONCLUSIONS THA for patients with sequelae of hip joint infection has a satisfactory effect that can effectively relieve joint pain and improve hip function. The recurrence rate of infection after either pyogenic infection or tuberculous is very low. The mid-term outcomes of THA in this setting were satisfactory, with high prosthesis survivorship and hip function scores.

Outcome of Irrigation and Debridement With Topical Antibiotics Delivery for the Management of Periprosthetic Joint Infection Occurring Within 3 Months Since the Primary Total Joint Arthroplasty.

BACKGROUND: Irrigation and debridement with modular component exchange is appealing for surgeons to treat early-stage periprosthetic joint infection (PJI). However, the indication, perioperative protocol, and success rate remain controversial. This study is the first one to present results of debridement, antibiotics, and implant retention (DAIR) with integrated MIT (modular component exchange, povidone-iodine and topical antibiotics delivery) protocol for treating PJI occurring within 3 months since the primary total joint arthroplasty. METHODS: We retrospectively analyzed patients who received DAIR with MIT protocol in our department between January 2011 and May 2018. Topical antibiotics were delivered in all cases. Topical antibiotics infusion was applied for those infected with multidrug-resistant bacteria, fungus, polymicrobial infection, and culture negative one. Failure was defined as additional surgical intervention for infection after DAIR; persistent sinus tract, drainage or excessive joint pain; need for suppressive antibiotics therapy due to the infection; infection relapse with the same pathogen; reinfection with different microorganism; and infection-related death. RESULTS: A total of 73 patients with a mean age of 63.30 ± 10.97 years were included in this study, including 43 men and 30 women. There are 41 knees and 32 hips. Thirty patients had sinus tract. With a mean follow-up of 63.79 ± 18.57 months, there were 9 failures in total with an overall success rate of 87.67%. The success rate was 88.57% and 86.84% for those receiving topical antibiotics infusion postoperatively and those without. CONCLUSIONS: DAIR with a standard MIT protocol is a viable and safe option for PJI occurring within 3 months since the primary total joint arthroplasty. LEVEL OF EVIDENCE: Level 4, therapeutic study.

Gr/TiO2 Films with Light-Controlled Positive/Negative Charge for Cell Harvesting Application.

Light-induced cell harvest shows much potential in in vitro cell culture. In this work, a light-responsive monolayer graphene (Gr)/titanium dioxide nanodot (TN) film is designed and used for light-induced cell harvest. It is found that after 20 min of 365 nm UV or 450 nm visible light illumination, different types of cells could be detached from the surface effectively. The highest cell detachment ratio reaches about 95%. The mechanism of such a cell detachment is contributed to light illumination generates charge accumulation, which, in turn, changes the conformation of the extracellular matrix protein molecules adsorbed to a more disordered state, and eventually leads to the cells detachment. Such UV and visible light responsive Gr/TiO2 film could be a good candidate for a surface with light-induced cell detachment property.

Artesunate, an Anti-Malaria Agent, Attenuates Experimental Osteoarthritis by Inhibiting Bone Resorption and CD31hiEmcnhi Vessel Formation in Subchondral Bone.

Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-ß/Smad2/3 signaling. Additionally, ART abrogated CD31hiEmcnhi vessel formation via downregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31hiEmcnhi vessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA.

Halofuginone Attenuates Osteoarthritis by Rescuing Bone Remodeling in Subchondral Bone Through Oral Gavage.

Osteoarthritis (OA) is a common debilitating joint disorder worldwide without effective medical therapy. Articular cartilage and subchondral bone act in concert as a functional unit with the onset of OA. Halofuginone is an analog of the alkaloid febrifugine extracted from the plant Dichroa febrifuga, which has been demonstrated to exert inhibition of SMAD 2/3 phosphorylation downstream of the TGF-ß signaling pathway and osteoclastogenesis. To investigate whether halofuginone (HF) alleviates OA after administration by oral gavage, 3-month-old male mice were allocated to the Sham group, vehicle-treated anterior cruciate ligament transection (ACLT) group, and HF-treated ACLT group. The immunostaining analysis indicated that HF reduced the number of matrix metalloproteinase 13 (MMP-13) and collagen X (Col X) positive cells in the articular cartilage. Moreover, HF lowered histologic OA score and prevented articular cartilage degeneration. The micro-computed tomography (µCT) scan showed that HF maintained the subchondral bone microarchitecture, demonstrated by the restoration of bone volume fraction (BV/TV), subchondral bone plate thickness (SBP.Th.), and trabecular pattern factor (Tb.Pf) to a level comparable to that of the Sham group. Immunostaining for CD31 and µCT based angiography showed that the number and volume of vessels in subchondral bone was restored by HF. HF administered by oral gavage recoupled bone remodeling and inhibited aberrant angiogenesis in the subchondral bone, further slowed the progression of OA. Therefore, HF administered by oral gavage could be a potential therapy for OA.

The fate of immunocompromised patients in the treatment of chronic periprosthetic joint infection: a single-centre experience.

PURPOSE: Immunocompromised patients with periprosthetic joint infection (PJI) are rare and currently there are no reliable guidelines according to which these infections can be successfully managed. The purpose of this study was to report the clinical course of different strategies for treatment of PJI in frail patients. METHODS: A retrospective analysis between 2004 and 2015 included 29 immunocompromised patients (13 hips and 16 knees) with chronic PJI who underwent one-stage revision or debridement, antibiotics and implant retention (DAIR). Patients were stratified according to the Musculoskeletal Infection Society (MSIS) staging system and the clinical course included recurrence of infection and functional outcomes which were extracted from patients' charts. The average follow-up was 68 months (range, 26-149 months). RESULTS: Sixteen of the 29 patients had recurrent infections. At last follow-up, 13 patients were on chronic suppressive antibiotic therapy, three patients died but not one death was considered to be related to the infection. A recurrent infection was observed in 13 of the 24 medically compromised hosts (MSIS type B). Sixteen of the 24 patients underwent one-stage revision; another eight of them underwent DAIR. The infection recurred in three of the five patients (60%) with the worst host grades (MSIS type C). One-stage revision was performed in one of the five patients and the remaining four patients received DAIR. CONCLUSION: Our results show that we should compromise our expectation and intemperate treatment for such a population. The goals of PJI treatment in these patients should take into account their preferences and may pay more attention to the concept of disease control rather than cure, especially for patients with severe comorbidities (MSIS C). LEVEL OF EVIDENCE: Therapeutic Level IV.

Isoliquiritigenin blunts osteoarthritis by inhibition of bone resorption and angiogenesis in subchondral bone.

Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been demonstrated to exert attenuation of osteoclastogenesis and anti-angiogenesis activity in a wide variety of cells. Here, we first evaluated the effects of ISL on pathogenesis of osteoarthritis in a mouse model of OA. The data showed that ISL blunted progression of OA and lowered the Osteoarthritis Research Society International (OARSI)-Modified Making Score and protected the articular cartilage. The thickness of calcified cartilage zone was significantly decreased in ISL-treated ACLT mice compared with vehicle group. ISL increased expression level of lubricin and decreased collagen X (Col X), matrix metalloproteinase-13 (MMP-13). Moreover, ISL reduced aberrant active subchondral bone remodelling, including lowered trabecular pattern factor (Tb.pf) and increased bone volume/tissue volume (BV/TV, %) and thickness of subchondral bone plate (SBP) compared with vehicle-treated group. The results of immunostaining further revealed that ISL directly reduced RANKL-RANK-TRAF6 singling pathway induced osteoclastogenesis, prevented abnormal bone formation through indirect inhibition of TGF-ß release. Additionally, ISL exerts anti-angiogenesis effects in subchondral bone through direct suppression of MMP-2. These results indicated that ISL attenuates progression of OA by inhibition of bone resorption and angiogenesis in subchondral bone, indicating that this may be a potential preventive therapy for OA.

Isoliquiritigenin suppresses IL-1ß induced apoptosis and inflammation in chondrocyte-like ATDC5 cells by inhibiting NF-κB and exerts chondroprotective effects on a mouse model of anterior cruciate ligament transection.

Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been demonstrated to exert attenuation of the nuclear factor-κB (NF-κB) signaling pathway and anti-inflammatory activity in a wide variety of cells. In the present study, the authors first evaluated the effects of ISL on cartilage degeneration in interleukin-1ß (IL-1ß)-stimulated chondrocyte-like ATDC5 cells and in a mouse model of osteoarthritis (OA). The data of a cell counting kit-8 and flow cytometry assay indicated that ISL suppressed the inhibitory effect of IL-1ß on cell viability. The mRNA and protein expression levels of cyclooxygenase-2 and matrix metalloproteinase-13 were significantly decreased, while the expression of collagen II was increased, as indicated by RT-qPCR and western blot analysis following the chondrocyte-like ATDC5 cells were co-intervened with IL-1ß and ISL for 48 h. Also, ISL attenuated protein expressions level of pro-apoptotic Bax, cleaved-caspase-3 and cleaved-caspase-9 and promoted expression of anti-apoptotic Bcl-2. Moreover, ISL inhibited NF-κB p65 phosphorylation induced by IL-1ß. In addition, ISL also increased improved the thickness of hyaline cartilage and the production of proteoglycans in the cartilage matrix in a mouse OA model. These results indicated that ISL exerted anti-inflammatory and anti-apoptotic effects on IL-1ß-stimulated chondrocyte-like ATDC5 cells, which may be associated with the downregulation of the NF-κB signaling pathway. In this way, the data supported the conclusion that ISL may be a novel potential preventive agent suitable for use in OA therapy.

Halofuginone attenuates articular cartilage degeneration by inhibition of elevated TGF­ß1 signaling in articular cartilage in a rodent osteoarthritis model.

Osteoarthritis (OA) is the most common degenerative condition of the weight­bearing joints worldwide without effective medical therapy. In order to investigate whether administration of halofuginone (HF) may attenuate OA, the present study allocated 3­month­old male mice into Sham group, vehicle­treated anterior cruciate ligament transection (ACLT) group and HF­treated ACLT group. The present study determined that HF treatment reduced the expression of matrix metallopeptidase­13 and collagen X in articular cartilage. Additionally, it lowered the Osteoarthritis Research Society International­Modified Mankin score and prevented the loss of articular cartilage from Safranin O and Fast Green staining. HF reduced the progression of osteoarthritis by downregulating abnormally elevated TGF­ß1 activity in articular cartilage. Administration of HF may be a potential preventive therapy for OA.

Single-Stage Revision for Chronic Fungal Periprosthetic Joint Infection: An Average of 5 Years of Follow-Up.

BACKGROUND: Periprosthetic infections caused by fungal pathogens are a rare entity, and there exist no definite guidelines according to which these infections can be successfully managed. In these situations, we wondered whether patients could be treated successfully for their fungal infections with single-stage revision. METHODS: A retrospective analysis between January 2004 and October 2014 included 11 patients (4 hips and 7 knees) with chronic fungal periprosthetic joint infection who underwent single-stage revision, including aggressive soft-tissue debridement, thorough removal of infected components and cement, pouring powdered vancomycin into the medullary cavity and direct intra-articular injection of fungus-sensitive antibiotics, and a reasonable combination of antifungal agents and antibacterial medications. Recurrence of infection and clinical outcomes were evaluated. The average follow-up was 5 years (range, 2-10 years). RESULTS: There were 3 failures during the study period; 1 patient died during the perioperative period because of acute heart failure on the eighth postoperative day. Of the 11 patients, 7 patients had satisfactory outcomes and required no additional surgical or medical treatment for recurrence of infection. The mean postoperative Harris hip score and Hospital for Special Surgery knee score was 77 points (67-88 points; P < .05) and 78 points (73-84 points; P < .05), respectively, at the most recent assessment. CONCLUSION: Treatment of chronic fungal periprosthetic joint infection with single-stage revision can be fairly effective for achieving acceptable functional outcomes, which indicated that this may be a feasible alternative strategy in selected patients.

Retention of the well-fixed implant in the single-stage exchange for chronic infected total hip arthroplasty: an average of five years of follow-up.

PURPOSE: Removal of an infected prosthesis was considered the gold standard for eradication of infection. However, removal of well-fixed components can result in structural bone damage and compromised reconstruction. In these situations we questioned whether the infection after the total hip arthroplasty could be treated effectively and retain the well-fixed implant in a single-stage exchange. METHODS: A retrospective analysis which included 31 patients with chronic infected THA who underwent major partial single-stage revision, including routinely exchanged femoral head and liner components, aggressive soft tissue debridement, removal of the femoral stem or acetabular cup and retention of the well-fixed component, thorough exposed component brushing, and adequate surgical soaking. Powdered Vancomycin was poured into the surgical area and the infection control rate and clinical outcomes were evaluated. The failure to treat the infection was defined as a recurrence of infection in the same hip. The average follow-up was five years (2-15 years). RESULT: There were four (12.9 %) failures during the study period at an average of 15 months (9-21 months) after partial single-stage revision. Of the 31 patients, 27 (87.1 %) patients had a satisfactory outcome and required no additional surgical or medical treatment for recurrence of infection. Acetabular cups were revised in 22 patients and femoral stems in nine patients. The mean post-operative Harris hip score at the most recent assessment was 74.6 (68-82). CONCLUSIONS: Treatment of chronic infected THA with retention of the well-fixed implant in a single-stage exchange can be fairly effective in the treatment of infection and achieving acceptable functional outcomes, which indicated that this may be an attractive alternative in highly selected patients. LEVEL OF EVIDENCE: Level IV, therapeutic study.