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Background: The aim of this study was to describe the evolution of kinematic and clinical outcomes of a large patient cohort with knee osteoarthritis from before surgery (V1) to 3 months (V2) and 1 year (V3) after a total knee arthroplasty (TKA)., Methods: The patients were evaluated at each visit (118 patients at V1, 93 patients at V2, and 79 patients at V3) during a clinical gait analysis and were compared with a matched control group of healthy adults (CG). The kinematic parameters, the Western Ontario and MacMaster Osteoarthritis Index (WOMAC), quality of life, and patient satisfaction were assessed. Gait velocity and knee range of motion (ROM) as well as clinical parameters were compared at each visit with CG was based on the unpaired samples t-test. To determine changes in the data at baseline, 3 months, and 1 year after surgery in the patient groups, repeated-measure analysis of variance was conducted (P < .05). Pearson correlation was used to examine relationships between clinical and biomechanical outcomes., Results: One year after TKA (V3) compared to V1 and V2, the ROM of the operated knee during gait was significantly improved (V1: 44.2 ± 8.8° vs V3: 47.5 ± 7.1°, P < .001, and V2: 42.2 ± 9.3° vs V3: 47.5 ± 7.1°, P = .001), as was the gait velocity (V1: 1.0 ± 0.2 and V2: 1.1 ± 0.2 m/s vs V3: 1.3 ± 0.2 m/s, P < .001). The WOMAC and knee pain were significantly better 1 year after TKA. No strong relationships have been found between clinical parameters and knee kinematics., Conclusion: This study showed that 1 year after TKA, patients exhibited improved gait velocity and ROM and experienced a significant decrease in the level of pain and an increased clinical score (although different from CG)., (Copyright © 2016. Published by Elsevier Inc.)

Objective: In this study, we assess interdisciplinary surgical and medical parameters associated to recurrences of infected pressure ulcers., Background: There is a little in the published literature regarding factors associated with the outcome of treatment of infected pressure ulcers., Methods: We undertook a single-center review of spinal injured adults hospitalized for an infected pressure ulcer or implant-free osteomyelitis and reviewed the literature on this topic from 1990-2015., Results: We found 70 lesions in 31 patients (52 with osteomyelitis) who had a median follow-up of 2.7 years (range, 4 months to 19 years). The median duration of antibiotic therapy was 6 weeks, of which 1 week was parenteral. Clinical recurrence after treatment was noted in 44 infected ulcers (63%), after a median interval of 1 year. In 86% of these recurrences, cultures yielded a different organism than the preceding episode. By multivariate analyses, the following factors were not significantly related to recurrence: number of surgical interventions (hazard ratio 0.9, 95% confidence interval 0.5-1.5); osteomyelitis (hazard ratio 1.5; 0.7-3.1); immune suppression; prior sacral infections, and duration of total (or just parenteral) antibiotic sue. Patients with antibiotic treatment for <6 weeks had the same failure rate as those with as >12 weeks (χ test; P = 0.90)., Conclusions: In patients with infected pressure ulcers, clinical recurrence occurs in almost two-thirds of lesions, but in only 14% with the same pathogen(s). The number of surgical debridements, flap use, or duration of antibiotic therapy was not associated with recurrence, suggesting recurrences are caused by reinfections caused by other extrahospital factors.

In patients with artificial joints, the need for antimicrobial prophylaxis during dental procedures is often raised. The present document describes the pathogenic mechanisms and epidemiological data on the subject of periprosthetic joint infections (PJI) after dental procedures. The document reflects the opinion and recommendations of the expert group 'Infection' of Swiss Orthopaedics. Microorganisms belonging to oral flora can seed haematogenously to an artificial joint. The proof of a causative relation with dental procedures is not possible, because the responsible bacteraemia can originate from the oral cavity at any time, irrespective of when the dental procedure occurs. Good oral hygiene is associated with a lower risk for PJI. Transient bacteraemia occurs during daily oral hygiene activity (e.g., tooth brushing) and thus the cumulative risk for a haematogenous PJI from tooth brushing is higher than that from a dental procedure. PJI after a dental procedure are rarely reported. On the basis of an epidemiological model, several thousand patients with artificial joints must receive antimicrobial prophylaxis to prevent a single PJI. Considering this ratio, the number of adverse events due to the antimicrobial compound exceeds the benefit of administering it by a large magnitude. Therefore, as a rule for the vast majority of cases, antimicrobial prophylaxis during dental procedures is not recommended. It is important that a patient has a good oral health status before joint implantation and that good oral hygiene is continuously maintained in patients with artificial joints., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: There is few medical literature regarding factors associated with remission after surgical and medical treatment of postoperative spine infections., Methods: Single-centre case-control study 2007-2014. Cluster-controlled Cox regression model with emphasis on surgical and antibiotic-related parameters., Results: Overall, we found 66 episodes in 48 patients (49 episodes with metalwork) who had a median follow-up of 2.6 years (range, 0.5 to 6.8 years). The patients had a median of two surgical debridements. The median duration of antibiotic therapy was 8 weeks, of which 2 weeks parenteral. Clinical recurrence after treatment was noted in 13 episodes (20%), after a median interval of 2 months. In 53 cases (80%), the episodes were considered as in remission. By multivariate analyses, no variable was associated with remission. Especially, the following factors were not significantly related to remission: number of surgical interventions [hazard ratio (HR) 0.9; 95% confidence interval (CI), 0.8-1.1]; infection due to Staphylococcus aureus (HR 0.9; 0.8-1.1), local antibiotic therapy (HR 1.2; 0.6-2.4), and, duration of total (HR 1.0; 0.99-1.01) (or just parenteral) (HR 1.0; 0.99-1.01) antibiotic use., Conclusions: In patients with post-operative spine infections, remission is achieved in 80%. The number of surgical debridement or duration of antibiotic therapy shows no association with recurrence, suggesting that individual risk factors might be more important than the duration of antibiotic administration., Competing Interests: Parts of the manuscript have been presented as a poster at the Swiss National Meeting of Orthopedic Surgery, in Basel, June 2015.

Purpose of Review: Diabetes mellitus has reached pandemic levels and will continue to increase worldwide. Physicians and surgeons should know to manage one of its most prevalent complications, the diabetic foot infection (DFI), in a scientifically based and resource-sparing way. We performed a nonsystematic review of recent scientific literature to provide guidance on management of DFIs., Recent Findings: Studies in the past couple of years provide data on which recommendations for diagnosing and treating DFI are based, especially with validated guidelines and reviews of the microbiology and selected aspects of the complex DFI problem. Recent literature provides approaches to prevention and studies support more conservative surgical treatment. Unfortunately, there have been virtually no new therapeutic molecules, antibiotic regimens, randomized trials, or surgical techniques introduced in the recent past; we briefly discuss how this may change in the future., Summary: Recent scientific evidence on DFI strongly supports the value of multidisciplinary and some new care models, guideline-based management, more preventive approaches, and confirms several established therapeutic concepts. In contrast, there has been almost no new substantial information regarding the optimal antibiotic or surgical management in recent literature.

Background: Previous studies have demonstrated balance impairment in patients with knee osteoarthritis (OA). Although it is currently accepted that postural control depends on multi-joint coordination, no study has previously considered this postural strategy in patients suffering from knee OA. The objectives of this study were to investigate the multi-joint postural behavior in patients with knee OA and to evaluate the association with clinical outcomes., Methods: Eighty-seven patients with knee OA and twenty-five healthy elderly were recruited to the study. A motion analysis system and two force plates were used to investigate the joint kinematics (trunk and lower body segments), the lower body joint moments, the vertical ground reaction force ratio and the center of pressure (COP) during a quiet standing task. Pain, functional capacity and quality of life status were also recorded., Results: Patients with symptomatic and severe knee OA adopt a more flexed posture at all joint levels in comparison with the control group. A significant difference in the mean ratio was found between groups, showing an asymmetric weight distribution in patients with knee OA. A significant decrease in the COP range in the anterior-posterior direction was also observed in the group of patients. Only small associations were observed between postural impairments and clinical outcomes., Conclusion: This study brings new insights regarding the postural behavior of patients with severe knee OA during a quiet standing task. The results confirm the multi-joint asymmetric posture adopted by this population., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Unlabelled: Many physicians and surgeons think that prescribing antibiotics before intraoperative sampling does not alter the microbiological results., Methods: Case-control study of adult patients hospitalized with orthopedic infections., Results: Among 2740 episodes of orthopedic infections, 1167 (43%) had received antibiotic therapy before surgical sampling. Among these, 220 (19%) grew no pathogens while the proportion of culture-negative results in the 2573 who had no preoperative antibiotic therapy was only 6%. By multivariate analyses, pre-operative antibiotic exposure was associated with significantly more culture-negative results (odds ratio 2.8, 95% confidence interval 2.1-3.7), more non-fermenting rods and skin commensals (odds ratio 2.8 and 3.0, respectively). Even a single pre-operative dose of antibiotic was significantly associated with subsequent culture-negative results (19/93 vs. 297/2350; χ²-test, p = 0.01) and skin commensals (17/74 vs. 274/2350; p = 0.01) compared to episodes without preceding prophylaxis., Conclusions: Prior antibiotic use, including single-dose prophylactic administrations, is three-fold associated with culture-negative results, non-fermenting rods and resistant skin commensals., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: The debridement, antibiotic and implant retention (DAIR) procedure is an option for patients with prosthetic hip joint infections for whom arthroplasty removal is problematic. Unfortunately, some of the guidelines proposed for deciding on DAIR management of arthroplasty infections fail to take into consideration the role of the infecting pathogen. While Staphylococcus aureus and streptococci are major contributors to infected hip arthroplasties, their respective contributions to treatment success or failure rates with the DAIR procedure have not been thoroughly analysed from a microbiological perspective., Methods: This retrospective study included all patients who were hospitalised in Geneva University Hospitals between 1996 and 2012 and were initially treated with DAIR for prosthetic hip joint monomicrobial infection due to S. aureus or Streptococcus spp. The outcome of DAIR treatment was evaluated after a minimal follow-up of two years. A literature search was also performed to retrieve data from additional DAIR-treated cases in other institutions., Results: In our institution, 38 DAIR-treated patients with hip arthroplasty monomicrobial infections underwent at least one surgical debridement (median two, range one to five), exchange of mobile parts and concomitant targeted antibiotic therapy for several weeks or months. A literature search identified outcome data in other institutions from 52 additional DAIR-treated cases according to our study criteria. After merging our own data with those retrieved from other reports, we found a failure rate of 21 % instead of 24 % for S. aureus-infected, DAIR-treated patients, but no failure in 14 streptococcal-infected patients. In the pooled data, the failure rate linked with S. aureus infections was significantly higher than that with Streptococcus ssp. (19/90 vs 0/14 episodes; Fisher's exact test, P = 0.07)., Conclusions: DAIR-treated patients with prosthetic hip joint infections due to S. aureus tended to have worse outcomes than those infected with Streptococcus spp. The specific influence of the infecting pathogen should be considered in future guidelines and recommendations.

Purpose: In Gustilo grade III open fractures, it remains unknown which demographic or clinical features may be associated with an infection resistant to the administered prophylactic agent, compared to one that is susceptible., Methods: This was a retrospective case-control study on patients hospitalized from 2004 to 2009., Results: We identified 310 patients with Gustilo-III open fractures, 36 (12%) of which became infected after a median of ten days. In 26 (72%) of the episodes the pathogen was susceptible to the prophylactic antibiotic agent prescribed upon admission, while in the other ten it was resistant. All antibiotic prophylaxis was intravenous; the median duration of treatment was three days and the median delay between trauma and surgery was one day. In multivariate analysis adjusting for case-mix, only Gustilo-grade-IIIc fractures (vascular lesions) showed tendency to be infected with resistant pathogens (odds ratio 10; 95% confidence interval 1.0-10; p = 0.058). There were no significant differences between cases caused by antibiotic resistant and susceptible pathogen cases in patient's sex, presence of immune suppression, duration and choice of antibiotic prophylaxis, choice of surgical technique or materials, time delay until surgery, use of bone reaming, fracture localization, or presence of compartment syndrome., Conclusion: We were unable to identify any specific clinical parameters associated with infection with antibiotic resistant pathogens in Gustilo-grade III open fractures, other than the severity of the fracture itself. More research is needed to identify patients who might benefit from a broader-spectrum antibiotic prophylaxis.

Background: Increased antibiotic resistance against Staphylococcus aureus and low penetration into bone requires regimen optimization of available drugs., Methods: We evaluate pharmoacokinetic and pharmacodynamic parameters (PK/PD) as well as in vivo interactions of continuous flucloxacillin 12 g/d administration combined with high dose oral rifampicin 600 mg bid in the serum of 15 adult patients with bone and soft tissue infections. We use the patient's own serum directed against his own isolated S. aureus strain to reproduce in vivo conditions as closely as possible., Results: The continuous flucloxacillin infusion constantly generated plasma free drug levels largely exceeding the serum minimal inhibitory concentrations (mean 74-fold). Combination with rifampicin significantly increased flucloxacillin levels by 44.5%. Such an increase following rifampicin introduction was documented in 10/15 patients, whereas a decrease was observed in 1/15 patients. Finally, all infections were cured and the combination was well tolerated., Conclusions: In this in vivo methodological pilot study among adult patients with orthopaedic infections due to S. aureus, we describe a new method and reveal substantial but inconsistent interactions between flucloxacillin and rifampicin, of which the clinical significance remains unclear.

The clinical presentations of deep soft tissue infections can, initially, mimicry superficial skin infections such as erysipelas. However, a rapidly deteriorating health status, the spreading of the lesions and the lack of clear visual limitation of the infection on the skin are hallmarks of a more severe underlying infection, which may endanger patients' life. An immediate adequate multidisciplinary approach to therapy within a few hours is mandatory. The first step is surgical exploration with debridement of all infected tissues, accompanied by antibiotic therapy and additional supportive measures. Despite progress in the understanding of the physiopathology, the delay between suspicion of diagnosis and surgical exploration remains critical. Because of the low incidence of such severe infections, only multicenter studies might reveal deeper insights of optimal therapeutic strategies in the future and for possible improved patients' survival.

Purpose: In contrast to a large amount of epidemiological data regarding the incidence of implant infections after fracture management, surprisingly few have been published concerning the success of their treatment., Methods: This was a single-centre cohort study at Geneva University Hospitals from 2000 to 2012 investigating the remission rates of orthopaedic implant infections after fracture repair and associated variables., Results: A total of 139 episodes were included: There were 51 women (37%) and 28 immunosuppressed (20%) patients with a median age and American Society of Anaesthesiologists (ASA) score of 51 years and 2 points, respectively. The infected implants were plates (n = 75, 54 %), nails (24, 17%), wires (20), screws (10), cerclage cables or wires (3), hip screws (4) or material for spondylodesis (3). A pathogen was identified in 135 (97%) cases, including Staphylococcus aureus (73, 52%), coagulase-negative staphylococci (20), streptococci (7) and 19 Gram-negative rods. All patients underwent antibiotic treatment, and 128 (92%) remained in remission at a median follow-up time of 2.6 years (range one to 13 years). In multivariate logistic regression analysis, the plate infections were significantly associated with lower remission rates [65/75, 87%, odds ratio (OR) 0.1, 95% confidence interval (CI) 0.01-0.90]. No associations were found for gender, age, immune status, ASA score, additional surgical interventions (OR 0.4, 95% CI 0.1-4.1) or duration of antibiotic treatment (OR 1.0, 95% CI 0.98-1.01)., Conclusions: Among all infected and removed orthopaedic implants, plates were associated with slightly lower remission rates, while the overall treatment success exceeded 90%. The duration of antibiotic therapy did not alter the outcome.

The objective of this study was to investigate how gait and clinical outcomes contribute to patients' satisfaction three months following a total knee arthroplasty (TKA). Seventy-eight patients with knee osteoarthritis (OA) and a control group of twenty-nine subjects were evaluated. The gait parameters, Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and functional levels, quality of life and patients' satisfaction following TKA were assessed. A multiple linear regression model shows that the WOMAC functional score explained 39% of the global satisfaction and 37% of the satisfaction related to pain relief following TKA. Finally, the model shows that 65% of the satisfaction related to the functional improvement was explained by a combination of clinical and gait parameters. This study demonstrated the contribution of both gait and clinical outcomes to patients' satisfaction following TKA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To assess the risk factors for recurrence of septic arthritis with an emphasis on the duration of antibiotic treatment, to gather data for a prospective study on an optimized antibiotic treatment in adults with septic arthritis., Methods: This was a retrospective single-center study conducted for the period 1996-2008., Results: A total of 169 episodes of septic arthritis in 157 adult patients (median age 63 years; 65 females) were included. In 21 episodes (21/169, 12%), arthritis recurred after the end of antibiotic treatment. Multivariate analysis showed that Gram-negative infection (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.4-25.3), immune suppression (OR 5.3, 95% CI 1.3-22.0), and lack of surgical intervention were associated with recurrence. The size of the infected joint, the number of surgical drainages (OR 1.3, 95% CI 1.0-1.7), arthrotomy vs. arthroscopic drainage (OR 0.5, 95% CI 0.2-1.8), duration of antibiotic therapy (OR 1.0, 95% CI 0.95-1.05), and duration of intravenous antibiotic therapy (OR 1.0, 95% CI 1.0-1.0) were not. Seven days of intravenous therapy had the same success rate as 8-21 days (OR 0.4, 95% CI 0.1-1.7) and >21 days (OR 1.1, 95% CI 0.4-3.1). Fourteen days or less of total antibiotic treatment had the same outcome as 15-28 days (OR 0.4, 95% CI 0.1-2.3) or >28 days (OR 0.4, 95% CI 0.1-1.6)., Conclusions: In this retrospective study of adults with septic arthritis, the duration of antibiotic therapy, or an early switch from intravenous to oral administration, did not statistically influence the risk of recurrence. Due to study limitations, the data cannot be used directly for antibiotic therapy recommendations for septic arthritis. Prospective randomized trials are warranted to optimize the antibiotic treatment of septic arthritis., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with knee osteoarthritis present an altered gait pattern. Amongst many factors, the lower limb alignment (varus, valgus) has been identified as an important risk factor for the progression of knee osteoarthritis. Among the large number of studies on knee osteoarthritis gait, only a few have included patients with a valgus deformity. The aims of this study were to determine how knee alignment influences full-body gait in patients with knee osteoarthritis and if knee malalignment is associated with pain and functional capacity., Methods: Sixty patients with severe knee osteoarthritis scheduled for a total knee arthroplasty were included in this study. Twenty-six subjects were recruited as the control group. The spatio-temporal parameters, three-dimensional full-body kinematics, and lower body kinetics were evaluated during a comfortable gait and compared between the groups. Pain and function were assessed with the WOMAC questionnaire., Findings: The full-body gait analysis demonstrated substantially different gait patterns and compensation mechanisms between the three groups. Patients with varus knee alignment significantly augmented their trunk movements in sagittal and frontal planes compared to patients with a valgus knee. In addition, patients with a valgus knee reported lower pain and lower functional deficits compared to patients with a varus knee., Interpretation: We found that gait compensations were significantly influenced by lower limb alignment. These new insights related to different knee osteoarthritis gait patterns might help in the understanding of gait compensation behaviours prior to total knee arthroplasty and better manage the strategies of rehabilitation following surgery., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This study investigated the full-body strategies utilized during a sit-to-stand (STS) task in patients with knee osteoarthritis (OA) and the association between STS alterations and clinical measurements. Twenty-five patients with advanced knee OA and twenty healthy elderly adults were recruited to participate in this study. Patients were asked to stand up from a chair four times without using their arms. A 3D motion analysis system was used to capture the full-body kinematics during the task. Two force plates were used to capture the forces under each leg. The following parameters were investigated in the knee OA group and compared with the control group: the time to realize STS, the force ratio between both limbs, the knee and hip kinetics and the trunk kinematics. The pain and functional capacity were obtained from the WOMAC. The results showed that patients with knee OA put 10% additional weight on the contralateral side when compared with the symmetrical strategy of the control group. Patients with knee OA showed a significantly lower knee flexion moment (0.51 Nm/kg vs. 0.72 Nm/kg), a higher maximal trunk flexion (46.4° vs. 37.5°), and a higher lateral trunk lean on the contralateral side (2.4° vs. 0.9°) when compared with the control group. The main correlations were found between pain and the averaged time to complete the STS task (r=0.55). With the quantification of the full-body mechanisms utilized during the STS task, which includes both distal and proximal compensations, our study brings new insights, leading to a better understanding of the functional alterations in patients with advanced knee OA., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the mechanisms that underlie ESFT CSC development. We show that the EWS-FLI-1 fusion gene, associated with 85%-90% of ESFTs and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2, and NANOG in human pediatric MSCs (hpMSCs) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSCs expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWS-FLI-1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene, SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype.

Objective: Dislocation is a well-known complication after total hip arthroplasty (THA), and is the second-highest cause of revision surgery. Our objective was to assess the effect of preoperative patient education on the occurrence of hip dislocation within 6 months after primary THA., Methods: Between 1998 and 2007, we conducted a prospective cohort study at the Geneva University Hospital Department of Orthopaedic Surgery, including all primary THAs performed via an anterolateral transgluteal approach with the use of a 28-mm diameter head. The preoperative education session was introduced in June 2002 and included advice on muscle strengthening exercises and postoperative restrictions of range of motion as a means of preventing dislocation. The main outcome was the incidence of dislocation within 6 months of surgery., Results: A total of 597 patients who underwent 656 THAs between June 2002 and June 2007 participated in the education session, whereas 1,641 patients who underwent 1,945 procedures did not. Forty-six dislocations occurred over the study period, 5 (0.8%) in participants and 41 (2.1%) in nonparticipants (absolute risk reduction 1.3%; 95% confidence interval [95% CI] 0.4, 2.3), with the time interval between surgery and dislocation being significantly shorter among participants (0.2 versus 1.2 months). Nonparticipants had a 2.8 times higher risk of dislocation than participants (unadjusted odds ratio [OR] 2.80; 95% CI 1.10, 7.13). Adjustment for age, sex, comorbidities, and prior surgery did not change the results (adjusted OR 2.79; 95% CI 1.09, 7.15)., Conclusion: Our findings suggest that participation in a preoperative patient education session may reduce the risk of dislocation within 6 months after THA.

Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESFT), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in nonobese diabetic/severe combined immunodeficiency mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic, and chondrogenic lineages. Quantitative real-time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133- counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells and demonstration of their MSC properties, a critical step towards a better biological understanding and rational therapeutic targeting of these tumors.

Background: The EWS-FLI-1 fusion protein is associated with 85-90% of Ewing's sarcoma family tumors (ESFT), the remaining 10-15% of cases expressing chimeric genes encoding EWS or FUS fused to one of several ets transcription factor family members, including ERG-1, FEV, ETV1 and ETV6. ESFT are dependent on insulin-like growth factor-1 (IGF-1) for growth and survival and recent evidence suggests that mesenchymal progenitor/stem cells constitute a candidate ESFT origin., Methodology/principal Findings: To address the functional relatedness between ESFT-associated fusion proteins, we compared mouse progenitor cell (MPC) permissiveness for EWS-FLI-1, EWS-ERG and FUS-ERG expression and assessed the corresponding expression profile changes. Whereas all MPC isolates tested could stably express EWS-FLI-1, only some sustained stable EWS-ERG expression and none could express FUS-ERG for more than 3-5 days. Only 14% and 4% of the total number of genes that were respectively induced and repressed in MPCs by the three fusion proteins were shared. However, all three fusion proteins, but neither FLI-1 nor ERG-1 alone, activated the IGF1 promoter and induced IGF1 expression., Conclusion/significance: Whereas expression of different ESFT-associated fusion proteins may require distinct cellular microenvironments and induce transcriptome changes of limited similarity, IGF1 induction may provide one common mechanism for their implication in ESFT pathogenesis.

Ewing's sarcoma family tumors (ESFT) express the EWS-FLI-1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI-1 induces growth arrest or apoptosis in differentiated primary cells, and the identity of permissive primary human cells that can support its expression and function has until now remained elusive. Here we show that expression of EWS-FLI-1 in human mesenchymal stem cells (hMSC) is not only stably maintained without inhibiting proliferation but also induces a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWS-FLI-1 in hMSCs may recapitulate the initial steps of Ewing's sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. Among relevant candidate transcripts induced by EWS-FLI-1 in hMSCs, we found the polycomb group gene EZH2, which we show to play a critical role in Ewing's sarcoma growth. These observations are consistent with our recent findings using mouse mesenchymal progenitor cells and provide compelling evidence that hMSCs are candidate cells of origin of ESFT.

Comprehensive information before total hip replacement (THR) allows patients to better understand the benefits and risks of THR. Unfortunately there is an important gap between what surgeons say and what patient understand. Preoperative group sessions were introduced in order to improve patient information before THR. Between 2003 and 2005, 56% (n = 180) of all THR patients participated to this session. 74% of patients reported that the session was reassuring, 96% found that their questions had been answered, and 100% would recommend this seminar to others. Patients were mostly concerned about the prosthesis, the recovery period and the anaesthesia. In conclusion, such a patient-centered approach efficiently complements the usual medical interview.

Osteoarthritis of the hip is frequent in older individuals and almost one out of five patients undergoing total hip arthroplasty at the Orthopaedic surgery service of the HUG is 80 years or older. A review of the literature indicates that the intervention provides excellent pain relief, improved functional outcome and high satisfaction in patients over 80 years. However, postoperative confusion and minor urological problems are more frequent. Moreover, the risk of myocardial infarction and pulmonary embolism and the 90-day-mortality rate are higher in these patients than in patients aged 60-79 years. The incidence of orthopaedic complications seems similar to the incidence in younger patients. Finally, revision due to aseptic loosening, the most important problem in young and active individuals, is uncommon in patients over 80 years.

In Alzheimer disease (AD) the involvement of entorhinal cortex, hippocampus, and associative cortical areas is well established. Regarding the involvement of the primary motor cortex the reported data are contradictory. In order to determine whether the primary motor cortex is involved in AD, the brains of 29 autopsy cases were studied, including, 17 cases with severe cortical AD-type changes with definite diagnoses of AD, 7 age-matched cases with discrete to moderate cortical AD-type changes, and 5 control cases without any AD-type cortical changes. Morphometric analysis of the cortical surface occupied by senile plaques (SPs) on beta-amyloid-immunostained sections and quantitative analysis of neurofibrillary tangles (NFTs) on Gallyas-stained sections was performed in 5 different cortical areas including the primary motor cortex. The percentage of cortical surface occupied by SPs was similar in all cortical areas, without significant difference and corresponded to 16.7% in entorhinal cortex, 21.3% in frontal associative, 16% in parietal associative, and 15.8% in primary motor cortex. The number of NFTs in the entorhinal cortex was significantly higher (41 per 0.4 mm2), compared with those in other cortical areas (20.5 in frontal, 17.9 in parietal and 11.5 in the primary motor cortex). Our findings indicate that the primary motor cortex is significantly involved in AD and suggest the appearance of motor dysfunction in late and terminal stages of the disease.