Discrepancies in Sagittal Alignment of the Lower Extremity Among Different Brands of Robotic Total Knee Arthroplasty Systems.

BACKGROUND: There is an increasing number of different brands of robotic total knee arthroplasty (TKA) systems. Most robotic TKA systems share the same coronal alignment, while the definitions of sagittal alignment vary. The purpose of this study was to investigate whether these discrepancies impact the sagittal alignment of the lower extremity. METHODS: A total of 72 lower extremity computed tomography scans were included in our study, and 3-dimensional models were obtained using software. A total of 7 brands of robotic TKA systems were included in the study. The lower extremity axes were defined based on the surgical guide for each implant. We also set the intramedullary axis as a reference to evaluate the discrepancies in sagittal alignment of each brand of robotic system. RESULTS: On the femoral side, the axis definition was the same for all 7 robotic TKA systems. The robotic TKA axes showed a 2.41° (1.58°, 3.38°) deviation from the intramedullary axis. On the tibial side, the 7 robots had different axis definitions. The tibial mechanical axis of 6 of the TKA systems was more flexed than that of the intramedullary axis, which means the posterior tibial slope was decreased while the tibial mechanical axis of the remaining system was more extended. CONCLUSIONS: The sagittal alignment of the lower extremity for 7 different brands of robotic TKA systems differed from each other and all deviated from the intramedullary axis. Surgeons should be aware of this discrepancy when using different brands of robotic TKA systems to avoid unexpected sagittal alignment and corresponding adverse clinical outcomes. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

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.

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.

Surfactin induces ER stress-mediated apoptosis via IRE1-ASK1-JNK signaling in human osteosarcoma.

Osteosarcoma, one of primary bone tumor in children and young adults, has poor prognosis and drug resistances to chemotherapy. In order to reinforce the conventional therapies and antagonize the osteosarcoma in patients, a novel strategy is required for developing a new treatment. In this study, surfactin, a natural product from Bacillus subtilis, showed the efficiency of cell death in osteosarcoma, but not in normal cells. Surfactin triggers ER stress mechanism by promoting the aberrant Ca2+ release from ER lumen and ER-signaling to mitochondrial dysfunction following caspases activation mediating cell apoptosis. Surfactin-induced ER stress not only upregulated of glucose-regulated protein 78/94 and IRE1-ASK1-JNK pathway but also leading to calpains and Bcl-2 proteins family involving the release of cytochrome c. The releases into cytosol trigger the cleavage of caspase-9 and caspase-3 to induce cell apoptosis. In this study, surfactin demonstrated the potential functions to trigger the ER stress, ER stress-associated IRE1-ASK1-JNK signaling pathway, mitochondrial dysfunction, and caspase activations leading to programmed cell apoptosis. Importantly, implicating the signaling pathway that regulates the connection between ER stress and mitochondrial dysfunction causing apoptosis associated with surfactin. These results indicated a potential application of surfactin strengthen current conventional therapies.

The association between depression and chronic lower back pain from disc degeneration and herniation of the lumbar spine.

OBJECTIVE: Chronic lower back pain induced by lumbar disc degeneration or herniation exerts a great impact on patients' daily lives. Depression and anxiety often exist among patients with lower back pain. Some studies mentioned about mechanisms, such as inflammatory biomarkers, which are commonly seen in herniated intervertebral disc (HIVD) and major depressive disorder (MDD). Method: Our study used a large database from the National Health Insurance to explore the incidence rate of MDD in patients with HIVD and correlated risk factors. A total of 41,874 patients with HIVD were included in this work. The control group was matched by using propensity scores. Results: The results showed a temporal association between prior HIVD and subsequent MDD after adjusting for potential confounding factors. Patients with HIVD were at high risk of developing MDD (hazard ratio, HR: 9.00, 95% confidence interval, CI: 7.196-11.257) even after adjusting for demographic characteristics and comorbidities (HR: 8.47, 95% CI: 6.84-10.49, p < 0.0001). Conclusions: The combination of HIVD and MDD represents an important health problem that is associated with higher disability rates, socioeconomic disadvantage, and greater utilization of health care resources. Early detection and combined treatment of depressive symptoms may benefit patients with HIVD.

Does robotic-assisted computer navigation improve acetabular cup positioning in total hip arthroplasty for Crowe III/IV hip dysplasia? A propensity score case-match analysis.

AIMS: Total hip arthroplasty (THA) in patients with hip-dislocation dysplasia remains challenging. This study aims to evaluate whether these patients may benefit from robotic-assisted techniques. METHODS: We reviewed 135 THAs (108 conventional THAs and 27 robotic-assisted THAs) for Crowe type III or IV from January 2017 to August 2019 in our institution. Robotic-assisted THAs were matched with conventional THAs at a 1:1 ratio (27 hips each group) using propensity score matching. The accuracy of cup positioning and clinical outcomes were compared between groups. RESULTS: The inclination of the cup for conventional THAs and robotic THAs was 42.1 ± 5.7 and 41.3 ± 4.6 (p = 0.574), respectively. The anteversion of the cup for conventional THAs was significantly greater than that of robotic THAs (29.5 ± 8.1 and 18.0 ± 4.6; p < 0.001), respectively. The ratio of the acetabular cup in the Lewinnek safe zone was 37% (10/27) in conventional THAs and 96.3% (26/27) in robotic THAs (p < 0.001). Robotic THAs did not achieve better leg length discrepancy than that of conventional THAs (- 0.4 ± 10.9 mm vs. 0.4 ± 8.8 mm, p = 0.774). There was no difference in Harris Hip Score and WOMAC Osteoarthritis index between groups at the 2-year follow-up. No dislocation occurred in all cases at the final follow-up. CONCLUSION: Robotic-assisted THA for patients with high dislocation improves the accuracy of the implantation of the acetabular component with respect to safe zone.

The Efficacy and Safety of Disease-Modifying Osteoarthritis Drugs for Knee and Hip Osteoarthritis-a Systematic Review and Network Meta-Analysis.

BACKGROUND: Osteoarthritis (OA) is common and burdensome for patients and health care systems. Our study purpose was to evaluate the long-term efficacy and safety of DMOADs in adults with knee and hip osteoarthritis. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Knowledge without language, publication, or date restrictions from inception through November 2018 for randomized controlled trials assessing 12 classes of DMOADs with at least 12 months of follow-up. Therapeutic effects were evaluated with pairwise and network meta-analysis. Outcomes included pain, function, minimum joint space width or cartilage volume, radiographic progression, and total joint replacement. Analyses were also performed for drug safety. RESULTS: Twenty-eight randomized controlled trials with 11,890 patients were included. Glucosamine and chondroitin minimally improved both structure (minimum joint width or cartilage volume: network results: glucosamine: SMD 0.16; 95% CI [0.04, 0.28], chondroitin: SMD 0.21 [0.10, 0.32]) and symptoms (glucosamine: pain: - 0.15 [- 0.25, - 0.05]; function: - 0.17 [- 0.28, - 0.07], chondroitin: pain: - 0.06 [- 0.15, 0.03], and function: - 0.15 [- 0.26, - 0.03]). Strontium demonstrated improvement in structure (minimum joint width or cartilage volume: 0.20 [0.02, 0.38]), and vitamin D on symptoms (pain: - 0.15 [- 0.27, -0.03]; function: - 0.18 [- 0.31, - 0.06]). Although doxycycline also demonstrated a favorable efficacy ranking, its safety profile was poor (withdrawal: network relative risk 1.69 [1.03, 2.75]). The therapeutic effects of other medications were not ranked as highly. DISCUSSION: Glucosamine and chondroitin yielded statistically significant but clinically questionable long-term benefit on structure and symptoms, though both had favorable safety profiles. Strontium improved structure, and vitamin D improved symptoms. Although doxycycline had a favorable efficacy ranking, its safety profile was poor. None of the 12 classes of drugs appears to have long-term clinically significant benefit.

CTRP9 induces macrophages polarization into M1 phenotype through activating JNK pathway and enhances VSMCs apoptosis in macrophages and VSMCs co-culture system.

Inflammation plays a critical role in the development of atherosclerosis (AS), which has been identified as a major predisposing factor for stroke. Macrophages and VSMCs are associated with plaque formation and progression. Macrophages can dynamically change into two main functional phenotypes, namely M1 and M2, they can produce either pro-inflammatory or anti-inflammatory factors which may affect the outcome of inflammation. As a member of CTRPs family, CTRP9 has been reported play important protective roles in the cardiovascular system. However, whether CTRP9 can regulate macrophage activation status in inflammatory responses and have effect on VSMCs behaviors in co-culture system have not been fully investigated. In the present study, using peritoneal macrophages treated with CTRP9, we found that CTRP9 facilitated macrophages towards M1 phenotype, promoted TNF-α secretion and MMPs expression. CTRP9 showed synergistic effect with LPS in inducing M1 macrophages. In macrophages-VSMCs co-culture system, apoptosis and down-regulated proliferation of VSMCs were accelerated with CTRP9-treated macrophages. Then we attempted to explore the underlying molecular mechanisms of CTRP9 resulting in M1 activation. The c-Jun NH2-terminal kinases (JNK) are members of the mitogen activated protein kinases (MAPK) family, plays a central role in the cell stress response, with outcomes ranging from cell death to cell proliferation and survival. We found JNK expression was upregulated following CTRP9 stimulation, and inhibiting JNK phosphorylation level was associated with decreased expression of M1 markers and TNF-α concentration. Moreover, VSMCs apoptosis were ameliorated after inhibition of JNK. These results suggested that CTRP9 may promote macrophage towards M1 activation status through JNK signaling pathway activation.

What Is the Optimal Timing for Reading the Leukocyte Esterase Strip for the Diagnosis of Periprosthetic Joint Infection?

BACKGROUND: The leucocyte esterase (LE) strip test often is used to diagnose periprosthetic joint infection (PJI). In accordance with the manufacturer's directions, the LE strip test result is read 3 minutes after exposing it to joint fluid, but this has not been supported by robust research. Moreover, we have noted that the results of the LE strip test might change over time, and our previous studies have found that centrifugation causes the results of the LE strip test to degrade. Still, there is no evidence-based recommendation as to when to read the LE strip test to maximize diagnostic accuracy, in general, and the best reading times for the LE strip test before and after centrifugation need to be determined separately, in particular. QUESTIONS/PURPOSES: (1) What is the optimal timing for reading LE strip test results before centrifugation to diagnose PJI? (2) What is the optimal timing for reading LE strip test results after centrifugation to diagnose PJI? METHODS: This study was a prospective diagnostic trial. In all, 120 patients who were scheduled for revision arthroplasty and had signs of infection underwent joint aspiration in the outpatient operating room between July 2018 and July 2019 and were enrolled in this single-center study. For inclusion, patients must have had a diagnosis of PJI or nonPJI, valid synovial fluid samples, and must not have received antibiotics within 2 weeks before arthrocentesis. As such, 36 patients were excluded; 84 patients were included for analysis, and all 84 patients agreed to participate. The 2018 International Consensus Meeting Criteria (ICM 2018) was used for the classification of 49 patients with PJI (score ≥ 6) and 35 without PJI (score ≤ 2). The classification was used as the standard against which the different timings for reading LE strips were compared. All patients without PJI were followed for more than 1 year, during which they did not report the occurrence of PJI. All patients were graded against the diagnostic criteria regardless of their LE strip test results. In 83 patients, one drop of synovial fluid (50 µL) was applied to LE strips before and after centrifugation, and in one patient (without PJI), the sample was not centrifuged because the sample volume was less than 1.5 mL. The results of the strip test were read on an automated colorimeter. Starting from 1 minute after centrifugation, these strips were automatically read once every minute, 15 times (over a period of 16 minutes), and the results were independently recorded by two observers. Results were rated as negative, ±, 1+, and 2+ upon the machine reading. Grade 2+ (dark purple) was used as the threshold for a positive result. An investigator who was blinded to the study performed the statistics. Optimal timing for reading the LE strip before and after centrifugation was determined by using receiver operative characteristic (ROC) analysis. The specificity, sensitivity, and positive predictive and negative predictive values were calculated for key timepoints. RESULTS: Before centrifugation, the area under the curve was the highest when the results were read at 5 minutes (0.90 [95% CI 0.83 to 0.98]; sensitivity 0.88 [95% CI 0.75 to 0.95]; specificity 0.89 [95% CI 0.72 to 0.96]). After centrifugation, the area under the curve was the highest when the results were read at 10 minutes (0.92 [95% CI 0.86 to 0.98]; sensitivity 0.65 [95% CI 0.50 to 0.78]; specificity 0.97 [95% CI 0.83 to 1.00]). CONCLUSION: The LE strip test results are affected by time and centrifugation. For samples without centrifugation, we found that 5 minutes after application was the best time to read LE strips. We cannot deny the use of centrifuges because this is an effective way to solve the sample-mingling problem at present. We recommend 10 minutes postapplication as the most appropriate time to read LE strips after centrifugation. Multicenter and large-sample size studies are warranted to further verify our conclusion. LEVEL OF EVIDENCE: Level II, diagnostic study.

Comparison of three treatment methods for simple bone cyst in children.

BACKGROUND: The unicameral bone cyst (UBC) is a kind of benign tumor whose clinical treatments and efficacy are controversial. The purpose of this study was to evaluate the efficacy of the elastic stable intramedullary nail (ESIN), the injection of autologous bone marrow (ABM), and the combination of ESIN and ABM in the treatment of bone cyst in children. METHODS: Eighty-three cases with simple bone cyst were analyzed retrospectively. Twenty-eight cases were treated with ABM. Twenty-eight cases were treated with ESIN. Twenty-seven cases were treated with ABM and ESIN. All cases were diagnosed through X-ray, CT, or MRI scans. For the suspicious ones, the pathological biopsy was performed for an accurate diagnosis. X-ray examinations were carried out for the postoperative follow-up. Capanna criteria for bone cyst was used for postoperative evaluation of three methods. RESULTS: All cases accomplished the follow-up. The effective rate of the ABM + ESIN group was significantly higher than that of the ABM group (P < 0.05), and the cure rates of the ESIN group and the ABM + ESIN group were higher than that of the ABM group (P < 0.05, respectively). The cure time in the ESIN group was lower than that of the other two groups (P < 0.05, respectively). The times for admission were 2.0 ± 0.0 in the ESIN group, 5.7 ± 1.9 in the ABM group, and 4.7 ± 2.4 in the ABM + ESIN group (P < 0.05 when compared with each other). CONCLUSIONS: The method of ABM combined with ESIN for children's bone cyst has the highest effective rate and curative rate. For the individual method, ESIN has a higher effective rate and curative rate than that of ABM. Meanwhile, it has the fewest time of hospitalization.

The 2018 New Definition of Periprosthetic Joint Infection is Valuable for Diagnosis of Persistent Infection at Reimplantation in Patients without Synovial Fluid.

BACKGROUND: Diagnosis of persistent infection at reimplantation of 2-stage exchange revision is a challenging problem. The aim of our study is to evaluate the performance of the 2018 new definition and Musculoskeletal Infection Society (MSIS) criteria in determining the persistent infection at reimplantation in patients without synovial fluid. METHODS: We retrospectively reviewed 150 patients who underwent 2-stage exchange revision from 2014 to 2018. Two models were used to define persistent infection-model 1: identical major criteria of the MSIS criteria and new definition and model 2: identical major criteria of 2 criteria and/or subsequent infection after reimplantation. The predictive accuracy of the new definition and MSIS criteria was compared by using receiver operating characteristic curves. RESULTS: The receiver operating characteristic curves showed that the new definition had good performance in determining the persistent infection, with the area under the curve (AUC) of 0.871 in model 1 and 0.835 in model 2. The optimal threshold for aggregate scores in new definition was 4. The MSIS criteria had limited diagnostic value in both model 1 (AUC = 0.708) and model 2 (AUC = 0.664). In model 1, the sensitivity and specificity were 86.96% and 84.25% in new definition, and 47.83% and 93.70% in MSIS criteria in patients without synovial fluid. In model 2, the sensitivity and specificity were 78.57% and 85.25% in new definition, and 39.29% and 93.44% in MSIS criteria. CONCLUSION: The 2018 new definition of PJI is valuable in the diagnosis of persistent infection, which can improve diagnostic accuracy compared with the MSIS criteria in patients without synovial fluid.

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.

Correcting severe flexion contracture with fusiform capsulectomy of posterior capsule during total knee arthroplasty.

PURPOSE: This study aimed to evaluate the safety and efficacy of fusiform capsulectomy of posterior capsule in correcting severe flexion contracture during total knee arthroplasty (TKA). METHODS: A retrospective analysis was performed in the patients who had preoperative severe flexion contracture (> 30 degrees) prior to TKA and received fusiform capsulectomy of posterior capsule during TKA between December 2013 and November 2018. Range of motion (ROM), knee functional score, forgotten joint score (FJS), post-operative complications, and radiographic results were collected and evaluated. RESULT: Twenty patients (32 knees) were enrolled in this study. The mean duration of follow-up was 27.19 ± 15.92 months. The flexion contracture improved from pre-operative 37.69 ± 11.79° to post-operative 5.78 ± 4.44° (p < 0.001), and ROM increased from pre-operative 63.50 ± 21.74° to post-operative 97.88 ± 13.20° (p < 0.001). KSS clinical score increased from pre-operative 32.94 ± 11.03 to post-operative 82.34 ± 10.73 (p < 0.001), and KSS function score increased from pre-operative 28.97 ± 18.43 to post-operative 68.75 ± 15.96 (p < 0.001). The post-operative FJS was 76.08 ± 2.14. There was no implant loosening, infection, obvious haematoma formation, resultant instability, neurovascular complications, or revision for any reasons in the cohort until the last follow-up. CONCLUSIONS: The technique of fusiform capsulectomy of posterior capsule to correct the severe flexion contracture during primary TKA is safe and effective and could provide good short-term results.

CTRP9 induces iNOS expression through JAK2/STAT3 pathway in Raw 264.7 and peritoneal macrophages.

The C1q tumor necrosis factor (TNF)-related proteins 9 (CTRP9), an adipocyte-derived cytokine, affects a number of physiological processes, including immune function and inflammation. We investigated whether CTRP9 affects the expression of inflammation-related genes in Raw 264.7 and peritoneal macrophages. The CTRP9-induced expression of iNOS increased in a time- and dose-dependent manner. LPS and CTRP9 promote the expression of iNOS jointly in Raw 264.7 and peritoneal macrophages. CTRP9 induced the phosphorylation of JAK2 and STAT3 in Raw 264.7 and peritoneal macrophages. VX509 (JAK2 inhibitor) reduced the CTRP9-induced iNOS protein production. In addition, the CTRP9-induced phosphorylation of JAK2 and STAT3 was dramatically reduced by VX509. Collectively, these results suggest that JAK2/STAT3 signaling is involved in the CTRP9-induced expression of iNOS.

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.

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.

Outcomes and predictors of treatment failure following two-stage total joint arthroplasty with articulating spacers for evolutive septic arthritis.

BACKGROUND: The treatment strategy for evolutive septic arthritis (SA) with coexistent degenerative joint disease is not well established. The purposes of this study were to 1) investigate treatment outcome and potential risk factors of treatment failure in patients with evolutive SA following two-stage procedure, including insertion of an antibiotic-loaded spacer at the first stage and subsequent implantation of a new prosthesis; and 2) determine the performance of serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Interleukin-6 (IL-6) in predicting persisting infection at second-stage procedure. METHODS: We retrospectively reviewed 74 patients with evolutive SA of hips and knees who underwent a two-stage TJA between 2008 and 2015. The treatment success was defined according to the modified Delphi criteria and Kaplan-Meier survivorship curves were constructed to determine treatment success. A Cox regression model was performed to identify risk factors for treatment failure. Receiver operating characteristic (ROC) curves were generated to determine the prognostic value of ESR, CRP, and IL-6 in predicting persistent infection before second-stage prostheses implantation. RESULTS: Overall, the treatment success rate was 93% for hips and 100% for knees after the first-stage surgery. The treatment success rate was 89% for hips and 84% for knees after second-stage prosthesis implantation with a mean follow-up of 4.7 (range, 2.2 to 10.8) years. Older age (Hazard ratio [HR] [per 10-year increase], 1.20; 95% confidential interval [CI], 1.11 to 1.62), higher preoperative CRP level (HR [per 1-mg/dL increase], 1.15; 95% CI, 1.04 to 1.28) and resistant organism (HR, 13.96; 95% CI, 3.29 to 19.20) were associated with an increased risk of treatment failure. All serologic tests presented limited values in predicting persisting infection, with the area under ROC curve of ESR, CRP, IL-6 and combination of the three markers was 57.8, 61.6, 60.3, and 62.1%, respectively. CONCLUSIONS: Two-stage TJA is an adequate management of infection control in patients with evolutive SA. The three potential risk factors (old age, high preoperative CRP, and resistant organism profile) may predict treatment failure following a two-stage procedure for evolutive SA. Additionally, serum ESR, CRP, and IL-6 had no benefit in predicting persisting infection before second-stage prostheses implantation. These findings may be useful when treating patients with evolutive SA.

Does the use of a closed-suction drain reduce the effectiveness of an antibiotic-loaded spacer in two-stage exchange Arthroplasty for Periprosthetic hip infection? A prospective, randomized, controlled study.

BACKGROUND: There is a concern regarding the use of a closed-suction drain (CSD) in two-stage exchange arthroplasty for periprosthetic joint infection as it may decrease the antibiotic concentrations in the joint fluids. The purpose of this study was to identify whether the use of a CSD could reduce local antibiotic concentrations following spacer implantation. METHODS: A prospective, randomized, controlled trial was conducted at our institution between January 2018 and November 2018. We enrolled 32 patients undergoing two-stage exchange arthroplasty for periprosthetic hip infection with an interim cement spacer containing 4-g vancomycin and 2-g meropenem per 40-g methyl-methacrylate cement polymer. Patients were randomized and evenly divided into the study group (non-CSD) and control group (CSD group) by sealed envelopes. Drainage samples of joint fluids (n = 160) were collected every 24 h for the first five days following spacer implantation. The antibiotic concentrations of drainage samples were measured by high-performance liquid chromatography, and the bioactivities of the drainage samples against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) and E. coli were assessed. RESULTS: There was no significant difference in the decrease of vancomycin (study group vs. control group: 163.20 ± 77.05 vs. 162.39 ± 36.31; p = 0.917) and meropenem concentration (123.78 ± 21.04 vs. 117.27 ± 19.38; P = 0.548) between the two groups during the first five days following spacer implantation. All joint drainage samples in each group exhibited antibacterial activity against MSSA, MRSA and E. coli. CONCLUSIONS: The use of CSD following the implantation of an antibiotic-loaded cement spacer does not reduce the effectiveness of such a spacer in two-stage exchange arthroplasty. (Chinese Clinical Trial Registry, ChiCTR-INR-17014162. Registered 26 December 2017.).

Positive Culture During Reimplantation Increases the Risk of Reinfection in Two-Stage Exchange Arthroplasty Despite Administrating Prolonged Antibiotics: A Retrospective Cohort Study and Meta-Analysis.

BACKGROUND: The significance of a positive culture at reimplantation remains an important topic of consideration given the lack of clear metrics for when reimplantation can be performed. The purpose of this study is thus to investigate the (1) association between a positive culture during reimplantation and failure following 2-stage exchange arthroplasty and the (2) influence of prolonged antibiotics on these patients. METHODS: We retrospectively reviewed 117 patients undergoing 2-stage exchange hip arthroplasty from 2012 to 2016. Of them, 23 had positive culture during reimplantation and were treated with 2 weeks of intravenous and 4 weeks of oral antibiotics following reimplantation. All patients had a minimum follow-up of 1 year. Logistic regression models were performed to identify association between positive culture and subsequent treatment failure. A meta-analysis was also performed to validate findings. A subgroup analysis was performed to explore whether 6-week antibiotics (oral, intravenous, or both) after reimplantation improved outcomes. RESULTS: A total of 11 studies, which included 141 cases with a positive culture at reimplantation and 784 with negative cultures, were included in the meta-analysis. The pooled data showed a higher risk of failure in patients with a positive culture than those with a negative culture (41.1% vs 14.8%, odds ratio 4.58). The subgroup analysis revealed that 6 weeks of antibiotic administration following reimplantation decreased the odds of reinfection from 9.35 to 3.12. The findings in the retrospective cohort were consistent with those of the meta-analysis; the failure rate was significantly higher in patients with a positive culture than those with negative cultures (26.1% vs 6.4%, P < .001). CONCLUSION: Six weeks of antibiotics appear to decrease the odds of reinfection after reimplantation. However, despite patients receiving 6 weeks of antibiotics after reimplantation, the risk of reinfection in patients with a positive culture at reimplantation is still more than 3 times higher than those with negative cultures. Further studies are needed to investigate optimal management for such patients.

Intra-operative diagnosis of periprosthetic joint infection can rely on frozen sections in patients without synovial fluid analyses.

BACKGROUND: The purpose of this study was to determine whether frozen sections can increase diagnostic values of serological tests for the assessment of periprosthetic joint infection (PJI) in patients without synovial fluid analyses. METHODS: A retrospective review of 128 revision arthroplasties (79 hips and 49 knees) from January 2016 to December 2017 was performed. Diagnosis of PJI was based on the Musculoskeletal Infection Society criteria for infection. Three diagnostic models for PJI, with model 1 including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), model 2 including model 1 plus frozen sections > 5 polymorphonuclear neutrophil (PMN)s per high-power field (HPF), and model 3 including model 1 plus frozen sections > 10 PMNs per HPF, were developed. Then receiver operating characteristic (ROC) curves were generated, and the areas under the ROC curves (AUCs) were compared. RESULTS: The AUC of model 1, model 2, and model 3 was 79.40% [95% confidence interval (CI), 69.84 to 86.64%], 89.30% (95% CI, 82.93 to 93.92%), and 85.52% (95% CI, 78.44 to 91.4%), respectively. The AUC of model 1 was significantly lower than that of model 2 (p = 0.002) and model 3 (p = 0.039). Although the result was not significant (p = 0.132), there was a trend toward a higher AUC of model 2 than model 3. CONCLUSIONS: This study reveals that intra-operative frozen sections significantly increased the performance of serum ESR and CRP in the diagnosis of PJI. The combination of serological tests and frozen sections for the assessment of PJI may be reliable in patients without synovial fluid analyses.