Fracture of the tibial baseplate in bicompartmental knee arthroplasty

Introduction. Bicompartmental knee arthroplasty (BKA) addresses combined medial and patellofemoral compartment osteoarthritis, which is relatively common, and has been proposed as a bridge between unicompartmental and total knee arthroplasty (TKA). Case Presentation. We present the case report of a young active man treated with BKA after unsuccessful conservative therapy. Four years later, loosening with fracture of the tibial baseplate was identified and the patient was revised to TKA. Discussion. Although our case is only the second fractured tibial baseplate to be reported, we believe that the modular titanium design, with two fixation pegs, is too thin to withstand daily cyclic loading powers. Light daily routine use, rather than high-impact sports, is therefore advised. Failures may also be related to the implant being an early generation and known to be technically complex, with too few implant sizes. We currently use TKA for the treatment of medial and patellofemoral compartment osteoarthritis

Diagnostic pitfalls in the differentiation between pyoderma gangrenosum and necrotizing fasciitis

Pyoderma gangrenosum and necrotizing fasciitis are two rare pathologic entities with a similar clinical  image, but a who require a very different management. In general physicians, orthopedics, dermatologists, plastic surgeons will hardly ever see it, but when they do it is very important to distinguish between both. In this paper with the focus on the practical approach ,we expose the diagnostic pitfalls in the differential diagnosis, explain how to prevent them and summarize the evidence on therapeutic management. To achieve this we use a case where the diagnosis was rather difficult and utilize reviews where the clinical features, early diagnostic tools and treatment options are explained

Safety and efficacy of a single intraarticular injection of a novel enhanced protein solution (JTA-004) compared to hylan G-F 20 in symptomatic knee osteoarthritis: a randomized, double-blind, controlled phase II/ III study

peer reviewedBackground: New minimally invasive treatments are vital to delay joint replacement surgery in patients with knee osteoarthritis. This study was designed to select the most effective among three formulations of an enhanced protein solution containing clonidine, hyaluronic acid, and human plasma (JTA-004), and compare the safety and efficacy of intra-articular administration of the selected formulation with a reference treatment (hyaluronic acid) in symptomatic knee osteoarthritis patients. Methods: In this two-stage, double-blind, phase II/III study conducted in 12 Belgian centers, 50–79 year-old patients with primary knee osteoarthritis were randomized (1:1:1:1) to receive one dose of one of three JTA 004 formulations (differing in clonidine concentration [50 or 100 μg/ml] and volume [2 or 4 ml]) or the reference treatment (hylan G-F 20). Patients were evaluated using Western Ontario McMaster Universities (WOMAC®) Scores and the Short-Form health survey up to 6 months post-injection (Month 6). Drug consumption and safety were evaluated. Results: Among 164 treated patients, 147 completed the study. The JTA-004 formulation containing 200 μg clonidine and 20 mg hyaluronic acid in 2 ml (JTA-200/2) was selected based on interim results at Month 6. The difference in adjusted mean change in WOMAC Pain Subscale Score from baseline (JTA-200/2 minus reference group) at Month 6 was − 9.49 mm; statistical superiority of JTA-200/2 over the reference was not demonstrated. No statistically significant differences in adjusted mean changes from baseline between JTA-200/2 and reference groups were observed for Pain, Physical Function and Stiffness Subscales WOMAC Scores, Total WOMAC Score, and Well being Score at any timepoint, although JTA-200/2 induced larger improvements in WOMAC Scores than the reference. Statistically significantly larger improvements in WOMAC Pain Subscale Scores for JTA-004 versus the reference were observed in post-hoc analyses on pooled data from all JTA-004 formulations at Month 6 (p = 0.030) and Month 3 (p = 0.014). All JTA-004 formulations had clinically acceptable safety profiles. Conclusions: This study provided preliminary evidence of the safety of intra-articular injection of JTA 004 in knee osteoarthritis patients. Phase III randomized controlled trials with larger sample sizes are needed to evaluate the efficacy of JTA-004 in knee osteoarthritis

Safety and efficacy of a single intra-articular injection of a novel enhanced protein solution (JTA-004) compared to hylan G-F 20 in symptomatic knee osteoarthritis: a randomized, double-blind, controlled phase II/III study

Background: New minimally invasive treatments are vital to delay joint replacement surgery in patients with knee osteoarthritis. This study was designed to select the most effective among three formulations of an enhanced protein solution containing clonidine, hyaluronic acid, and human plasma (JTA-004), and compare the safety and efficacy of intra-articular administration of the selected formulation with a reference treatment (hyaluronic acid) in symptomatic knee osteoarthritis patients. Methods: In this two-stage, double-blind, phase II/III study conducted in 12 Belgian centers, 50–79-year-old patients with primary knee osteoarthritis were randomized (1:1:1:1) to receive one dose of one of three JTA-004 formulations (differing in clonidine concentration [50 or 100 μg/ml] and volume [2 or 4 ml]) or the reference treatment (hylan G-F 20). Patients were evaluated using Western Ontario McMaster Universities (WOMAC®) Scores and the Short-Form health survey up to 6 months post-injection (Month 6). Drug consumption and safety were evaluated. Results: Among 164 treated patients, 147 completed the study. The JTA-004 formulation containing 200 μg clonidine and 20 mg hyaluronic acid in 2 ml (JTA-200/2) was selected based on interim results at Month 6. The difference in adjusted mean change in WOMAC Pain Subscale Score from baseline (JTA-200/2 minus reference group) at Month 6 was − 9.49 mm; statistical superiority of JTA-200/2 over the reference was not demonstrated. No statistically significant differences in adjusted mean changes from baseline between JTA-200/2 and reference groups were observed for Pain, Physical Function and Stiffness Subscales WOMAC Scores, Total WOMAC Score, and Well-being Score at any timepoint, although JTA-200/2 induced larger improvements in WOMAC Scores than the reference. Statistically significantly larger improvements in WOMAC Pain Subscale Scores for JTA-004 versus the reference were observed in post-hoc analyses on pooled data from all JTA-004 formulations at Month 6 (p = 0.030) and Month 3 (p = 0.014). All JTA-004 formulations had clinically acceptable safety profiles. Conclusions: This study provided preliminary evidence of the safety of intra-articular injection of JTA-004 in knee osteoarthritis patients. Phase III randomized controlled trials with larger sample sizes are needed to evaluate the efficacy of JTA-004 in knee osteoarthritis. Trial registration: Clinicaltrials.gov/identifier NCT02740231; clinicaltrialsregister.eu/identifier 2015–002117-30. Retrospectively registered 13/4/2016.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Clinical outcomes of characterized chondrocyte implantation

OBJECTIVE: To assess the clinical outcome of patients treated with autologous chondrocyte implantation using ChondroCelect in daily practice. METHODS: The study is a cross-sectional analysis of an open-label, noninterventional cohort. The setting was a compassionate use program, involving 43 orthopaedic centers in 7 European countries. The participants were patients treated with ChondroCelect between October 13, 2004 and July 2, 2008. The measurements used were Clinical Global Impression–Improvement and –Efficacy and solicited adverse event reports. RESULTS: Safety data were collected from 334 patients (90.3%), and effectiveness data were from 282 (76.2%) of the 370 patients treated. Mean age at baseline was 33.6 years (range, 12-57 years), 57% were male, and mean body mass index was 25 kg/m(2). Mean follow-up was 2.2 years (range, 0.4-4.1 years). A femoral condyle lesion was reported in 66% (288/379) and a patellar lesion in 19% (84/379). Mean lesion size was 3.5 cm(2); a collagen membrane was used in 92.4% (328/355). A therapeutic effect was reported in 89% (234/264) of patients overall and in 87% (40/46) of patellar lesion patients. Rates of much or very much improved patients were similar in patients with short- (<18 months: 71% [115/163]) and long-term follow-up (>18 months: 68% [70/103]) (P = 0.68) and were independent of lesion size (>4 cm(2): 75.5% [37/49]; ≤4 cm(2): 67.7% [111/164]) (P = 0.38). Adverse events were similar to those reported in the randomized trial with the same product, with more arthrofibrosis, more reduced joint mobility, and more crepitations reported in patellar lesions. Overall, less cartilage hypertrophy was noted, probably due to the use of a biological membrane cover. CONCLUSIONS: Implantation of ChondroCelect appeared to result in a positive benefit/risk ratio when used in an unselected heterogenous population, irrespective of the follow-up period, lesion size, and type of lesion treated

Aerosol and ozone changes as forcing for climate evolution between 1850 and 2100

International audienceGlobal aerosol and ozone distributions and their associated radiative forcings were simulated between 1850 and 2100 following a recent historical emission dataset and under the representative concentration pathways (RCP) for the future. These simulations were used in an Earth System Model to account for the changes in both radiatively and chemically active compounds, when simulating the climate evolution. The past negative stratospheric ozone trends result in a negative climate forcing culminating at −0.15 W m−2 in the 1990s. In the meantime, the tropospheric ozone burden increase generates a positive climate forcing peaking at 0.41 W m−2. The future evolution of ozone strongly depends on the RCP scenario considered. In RCP4.5 and RCP6.0, the evolution of both stratospheric and tropospheric ozone generate relatively weak radiative forcing changes until 2060-2070 followed by a relative 30 % decrease in radiative forcing by 2100. In contrast, RCP8.5 and RCP2.6 model projections exhibit strongly different ozone radiative forcing trajectories. In the RCP2.6 scenario, both effects (stratospheric ozone, a negative forcing, and tropospheric ozone, a positive forcing) decline towards 1950s values while they both get stronger in the RCP8.5 scenario. Over the twentieth century, the evolution of the total aerosol burden is characterized by a strong increase after World War II until the middle of the 1980s followed by a stabilization during the last decade due to the strong decrease in sulfates in OECD countries since the 1970s. The cooling effects reach their maximal values in 1980, with −0.34 and −0.28 W m−2 respectively for direct and indirect total radiative forcings. According to the RCP scenarios, the aerosol content, after peaking around 2010, is projected to decline strongly and monotonically during the twenty-first century for the RCP8.5, 4.5 and 2.6 scenarios. While for RCP6.0 the decline occurs later, after peaking around 2050. As a consequence the relative importance of the total cooling effect of aerosols becomes weaker throughout the twenty-first century compared with the positive forcing of greenhouse gases. Nevertheless, both surface ozone and aerosol content show very different regional features depending on the future scenario considered. Hence, in 2050, surface ozone changes vary between −12 and +12 ppbv over Asia depending on the RCP projection, whereas the regional direct aerosol radiative forcing can locally exceed −3 W m−2

Safety and efficacy of intra-articular injection of JTA-004, a novel viscosupplement, in symptomatic knee osteoarthritis: a randomized, double-blind controlled phase II/III study

Objective: The objective was to assess the safety and efficacy of a single intra-articular administration of JTA-004, a novel viscosupplement, in patients suffering from symptomatic knee osteoarthritis (OA) at 6 months. Design and methods: In this prospective, multicenter, double-blind phase II/III trial (NCT02740231), 164 patients with primary OA knee pain were randomly assigned to one of the three JTA-004 strengths or the comparator treatment (Hylan G-F 20) in a 1:1:1:1 ratio. Safety was assessed by monitoring and reporting vital signs, physical examination, adverse events and concomitant medications. The primary efficacy endpoint was the change from baseline at 6 months in WOMAC® VA3.1 pain subscale. Results: JTA-004 was shown to be well tolerated at all strengths evaluated. At 6 months, patients in the three JTA-004 groups showed a better improvement in pain compared to patients in the comparator group although statistical significance was not achieved. As the three JTA-004 strengths had a similar efficacy, a post hoc analysis was subsequently performed between the pooled JTA-004 treated patients and the comparator group. The exploratory analysis showed a 26.1±2.4 (adjusted mean±SE) mm improvement in pain in the pooled JTA-004 group vs. 15.6±4.1 mm in the comparator group at 6 months, demonstrating a statistically significant superiority of JTA-004 over the comparator (p = 0.030). Conclusions: This study provides first evidences of safety and efficacy of JTA-004 in the treatment of symptomatic knee OA. Efficacy will be further confirmed in a subsequent pivotal Phase III study

Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture

Background: As the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo. Purpose: To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometry and (2) evaluation of overall histological components of structural repair. Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score. Adverse events were recorded throughout the study. Results: Characterized chondrocyte implantation resulted in better structural repair, as assessed by histomorphometry (P =.003) and overall histologic evaluation (P =.012). Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation. Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage. Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score (56.30 +/- 13.61 and 59.53 +/- 14.95 for microfracture and characterized chondrocyte implantation, respectively), which increased in both groups to 70.56 +/- 12.39 and 72.63 +/- 15.55 at 6 months, 73.26 +/- 14.66 and 73.10 +/- 16.01 at 12 months, and 74.73 +/- 17.01 and 75.04 +/- 14.50 at 18 months, respectively. Both techniques were generally well tolerated; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture. Conclusion: One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings

Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture

BACKGROUND: As the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo. PURPOSE: To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometry and (2) evaluation of overall histological components of structural repair. Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score. Adverse events were recorded throughout the study. RESULTS: Characterized chondrocyte implantation resulted in better structural repair, as assessed by histomorphometry (P = .003) and overall histologic evaluation (P = .012). Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation. Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage. Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score (56.30 +/- 13.61 and 59.53 +/- 14.95 for microfracture and characterized chondrocyte implantation, respectively), which increased in both groups to 70.56 +/- 12.39 and 72.63 +/- 15.55 at 6 months, 73.26 +/- 14.66 and 73.10 +/- 16.01 at 12 months, and 74.73 +/- 17.01 and 75.04 +/- 14.50 at 18 months, respectively. Both techniques were generally well tolerated; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture. CONCLUSION: One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings.status: publishe