From a large collection of 88 Aim
Method
Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. Aim of this study was to investigate P. acnes phylogeny and to screen for virulence factors among a large collection of clinical isolates involved in spine material infections, arthroplasty infections and acne lesions. 88 P. acnes clinical isolates were collected between January 2003 and December 2014 at Nantes University Hospital (France). Fifty-eight isolates came from spine infections, 14 from prosthetic infections (knee, hip or shoulder), 14 from acne lesions and two reference strains (ATCC11827 and ATCC6919). Implant associated infections were confirmed using Infectious Diseases Society of America criteria for bone and joint infections. Phylotypes and Multi-Locus Sequence Typing (MLST) was carried out on all isolates as described by Lomholt et al. All isolates were tested by established PCR-based assays for 21 putative virulence factor genes characteristic of P. acnes. MLST analysis revealed an association between clonal complexes (CCs) and origin of P. acnes isolates (p = 0,027). Regarding CCs distribution between different origins, CC36 and phylotype II P. acnes isolates are more frequently observed in prosthetic joint infections. On the other hand, CC18 (IA) and CC28 (IB) P. acnes isolates are more frequently involved in spine infections and acne lesions. Among all virulence factors screened, hyaluronate lyase gene was only present in CC36 and phylotype II P acnes isolates. Other virulence factors were present in all isolates, whatever their origin or CC. Regarding molecular typing results, P. acnes involved in spine infections seem to have a skin origin (same CC as isolates from acne lesion). Interestingly, the origin of prosthetic joint infection isolates seems different and they all carry one more virulence factor. Hyaluronate lyase (Hyl) is a major surface protein of P. acnes with potential antigenetically variable properties that might be essential for P. acnes virulence. Increased tissue permeability caused by the action of hyaluronidase on the extracellular matrix appears to play a role in wound infections, pneumonia, and other sepsis such as bacteremia and meningitis. It could be also take a prominent part in P. acnes prosthetic joint infection pathogenesis.
Staphylococcus aureus is a leading cause of implant-associated infections (IAI). The aim of this study was to identify bacterial and/or clinical features involved in the pathogenesis of S. aureus IAI. 57 IAI S. aureus and 31 nasal carriage (NC) S. aureus isolates were studied. S. aureus genetic background was obtained by microarray analysis. Multi-Locus Sequence Typing was performed to determine clonal complexes (CC). The ability of S. aureus isolates to produce biofilm was investigated by resazurin and crystal violet methods. Clinical data were retrospectively collected from the patient's medical records. Fifty-five IAI patients were included. Two of them had two different S. aureus IAI episodes. The median age was 73 years (range: 21–96 years) with 29 women (52.7%). The main diagnosis for arthroplasty was arthrosis (38%). Implants were hip prosthesis (n=35), knee prosthesis (n=18) and osteosynthesis (n=4). Infectious and nasal carriage isolates belonged respectively to 18 and 13 different sequence types (STs) without significant difference. Among IAI isolates, five strains were methicillin resistant. IAI isolates were classified as strong (14%), moderate (42.1%) and weak (43.9%) biofilm producers. For NC isolates, distribution was 12.9%, 25.8% and 61.3% for strong, moderate and weak, respectively. Staphylokinase gene was associated with the occurrence of S. aureus IAI (p<0.001). Patients’ ABO blood group phenotype was associated with IAI S. aureus genetic background (sasG, slpB, lukD and set12/ssl8) (p≤0.01). In vitro, CC8 S. aureus strains produce more biofilm than others (p≤0.0001). Two alleles of bbp gene were significantly associated with CC8 S. aureus strains (p≤0.0001). No specific CC involved in IAI compared to NC S. aureus isolates was revealed. Our results suggested that occurrence of IAI may depend on patients’ ABO blood group and staphylokinase gene detection. We also observed a strong biofilm producer phenotype in CC8 S. aureus. Further studies are needed to prove whether one bbp gene variant is correlated to this phenotype. This study was supported by a grant number WS1106649 from Pfizer, France and by the French “Ministère de l'Enseignement Supérieur et de la Recherche”.
Resecting bone tumours within the pelvis is highly challenging and requires good cutting accuracy to achieve sufficient margins. Computer-assisted technologies such as intraoperative navigation have been developed for pelvic bone tumour resection. Patient-specific instruments have been transposed to tumour surgery. The present study reports a series of 11 clinical cases of PSI-assisted bone tumour surgery within the pelvis, and assesses how accurately a preoperative resection strategy can be replicated intraoperatively with the PSI. The patient series consisted in 11 patients eligible for curative surgical resection of primary bone tumor of the pelvis. Eight patients had a bone sarcoma of iliac bone involving the acetabulum, two patients had a sacral tumor, and one patient had a chondrosarcoma of proximal femur with intra-articular hip extension. Resection planning was preoperatively defined including a safe margin defined by the surgeon from 3 up to 15 mm. PSI were designed using a computer-aided design software according to the desired resection strategy and produced by additive manufacturing technology. Intraoperatively, PSI were positioned freehand by the surgeon and fixed on the bone surface using K-wires. The standard surgical approach has been used for each patient. Dissection was in accordance with the routine technique. There was no additional bone exposure to position the PSI. Histopathological analysis of the resected tumor specimens was performed to evaluate the achieved resection margins. Postoperative CT were acquired and matched to the preoperative CT to assess the local control of the tumor. Two parameters were measured: achieved resection margin (minimum distance to the tumor) and location accuracy (maximum distance between achieved and planned cuttings; ISO1101 standard). PSI were quick and easy to use with a positioning onto the bone surface in less than 5 minutes for all cases. The positioning of the PSI was considered unambiguous for all patients. Histopathological analysis classified all achieved resection margins as R0 (tumor-free), except for two patients : R2 because of a morcelised tumour and R1 in soft tissues. The errors in safe margin averaged −0.8 mm (95% CI: −1.8 mm to 0.1 mm). The location accuracy of the achieved cut planes with respect to the desired cut planes averaged 2.5 mm (95% CI: 1.8 to 3.2 mm). Results in terms of safe margin or the location accuracy demonstrated how PSI enabled the surgeon to intraoperatively replicate the resection strategies with a very good cutting accuracy. These findings are consistent with the levels of bone-cutting accuracy published in the literature. PSI technology described in this study achieved clear bone margins for all patients. Longer follow-up period is required but it appears that PSI has the potential to provide clinically acceptable margins.
Cam type femoroacetabular impingement (FAI) is due to an aspheric femoral head, which is best quantified by the alpha angle described on MRI and CT-scan. Radiographic measurement of the alpha angle is not well codified and studies from the literature cannot conclude on the best view to measure it. Most authors also describe a mixed type FAI which associates an aspheric femoral head with an excessive anterior acetabular coverage of the femoral head. Anterior center edge (ACE) angle has been described on the false profile view to measure anterior acetabular coverage in hip dysplasia and has never been evaluated in FAI. In this study, we developed a new lateral hip view which associates a lateral view of the femoral neck and a false profile view of the acétabulum, which we called profile view in impingement position (PVIP). Twenty six patients operated for FAI had CT-scan, the PVIP and the false profile view of one or two hips according to pain. A control group of 19 patients who did not suffer from the hip had the PVIP. Alpha angles were measured twice on 17 CT scan of FAI patients by two observers and compared with the alpha angles measured on the corresponding hip PVIP by a correlation analysis. Alpha angles were measured twice on 45 PVIP in FAI patient and on 19 PVIP in the control group by three observers. ACE angles were measured once on 15 PVIP and on 15 false profile views. Means were compared by two tail paired t-tests, intra- and inter-observer reliability were measured by intraclass correlation coefficient. Mean alpha angle on CT scan was 65.8° and 65.6° for observers 1 and 2 respectively (p>0.05). It was 63.6° and 64.3° on the PVIP (p>0.05). No significant difference was found between CT scan and radiographic measurements, and Pearson's correlation coefficients were good at 0.74 and 0.8. ICC was 0.86 for inter-rater reliability, and 0.91 for intra-rater reliability for CT-scan alpha angle measures. ICC for PVIP measures varied from 0.82 to 0.9 for intra-rater reliability and from 0.6 to 0.9 for inter-rater reliability. Mean alpha angle measured on PVIP in FAI patients was 63.3° and was 44.9° in control subjects and the difference was significant (p<0.001) for the three observers. None of the FAI patients and 88% of the control subjects had an alpha angle < 50°. Mean ACE angle was 26.8° on PVIP and 32.8° on the false profile view, the difference was significant (p=0.015), and the Pearson's correlation coefficient was moderate (r=0.58). The PVIP is a reliable radiographic view to measure the alpha angle. It allows a good quantification of the alpha angle comparable to CT-scan measurements and permits to differentiate patients from control subjects. PVIP is not a good view to quantify anterior edge angle probably because of acetabular retroversion due to the hip flexion needed in this view. Mean ACE angle measured on the false profile view in FAI patient was comparable to ACE angle in general population reported in the literature.
To investigate the prognostic effect of surgical margins in soft tissue sarcoma on Local Recurrence (LRFS), Metastasis (MFS) and Disease Free Survival (DFS). This is a retrospective, single center study of 105 consecutive patients operated with curative intent. Quality of surgery was rated according to the International Union Against Cancer classification (R0/R1) and a modification of this classification (R0M/R1M) to take into account growth pattern and skip metastases in margins less than 1mm. Univariate and multivariate analysis was done to identify potential risk factors. Kaplan-Mayer estimated cumulative incidence for LRFS, MFS and DFS were calculated. Survival curves were compared using Log rank tests.Purpose
Patients and Methods
For many surgeons amputation is the usual treatment in sarcoma of the foot. The aim of our study was to report the functional and oncologic results of treatment in 54 sarcomas of the foot to assess if conservative treatment was acceptable We retrospectively reviewed the records of 54 patients with sarcomas of the foot, aged 6 to 50 (mean 17), 30 females and 26 males. At time of referral, 18 had a local recurrence of a previous inadequate treatment. There were 27 soft tissue sarcomas (STS: 10 synovial sarcomas, 6 rhadomyosarcomas, 1 liposarcomas and 10 others) and 27 bone tumours (16 Ewing's, 8 chondrosarcomas, 3 osteosarcomas). Toes tumours were excluded, 18 tumours involved the metatarsal, 12 the plantar soft tissues, 11 the calcaneum, 3 the talus, 2 the midtarsal bones. Surgery consisted in 19 resection without reconstruction, 21 resections with bone reconstruction, 9 partial amputations of the foot, and 6 trans tibial amputations. In 34 cases surgical margins were adequate (R0), in 13 patients resection was inadequate (9 R1 and 4 R2). In 7 cases the margins were not assessed. After a 5.5 years average follow-up (3m to 17y), 31 patients had no evidence of disease, 8 were in second remission, 4 had an evolutive disease and 11 were deceased. The mean MSTS score was 26/30 (31 cases). In conclusion, a conservative treatment is feasible in metatarsal bones with skin coverage by flap if necessary. In STS adequate margins are difficult to achieve with a high rate of local recurrence. In calcaneus and talus, a conservative treatment is possible in tumours limited to bone after good response to chemotherapy. In other cases conservative treatment is debatable because amputation gives excellent functional results.
The purpose of this study was to quantify and analyse these specific failure.
Kaplan-Meier survival curves were constructed for the outcomes of revision for any reasons and for ceramic liner fracture. Seven fractures (2%) of ceramic sandwich liner were found and occured at a mean of 4,3 years after surgery without trauma. Fractures (20%) were the third diagnosis leading to the liner revision after dislocation (43%) and sepsis (26%). Neither patient related factors nor X ray position of the implants could be isolated as risk factor of liner fracture.
Planning resection margins for soft tissue sarcomas is a compromise between functional sacrifice and therapeutic safety. In practice, the histological analysis of the resection margins often shows that the preoperative objective has not been achieved. We studied the prevalence and factors of risk of this surgical outcome. This was a prospective monocentric study of 133 patients. The resection objectives, pathological results and operative reports were examined. Margins were classified according to the UICC (R0, R1, R2). Data were included in a grid which also included patient related and tumour related preoperative information. Inadequate resection was noted as planned R0 with R1 or R2 outcome. Statistical analysis was performed with Statview 5.0. The prevalence of inadequate resection was 25.2%. Among the factors analysed, the aspect of tumor limits (badely or well defined) was significantly related to poor surgical results (odds ration 2.85 [1.47–5.52], p <
0.005). No other significant risk factor could be identified. Margins greater than two mm were associated with adequate surgery in every case. No preoperative risk factor predictive of inadequate resection margins was clearly identified in this study. Postoperatively, the microscopic aspect of the proliferation limits at the final pathology examination is for us significantly associated with inadequate resection. However the current classification for resection margins lacks precision, especially regarding R0 and R1 when margins are small, in defining the risk of inadequate resection. This appears to be the source of the difficulties encountered in interpreting pathology samples and therefore in choosing the right treatment. Further follow-up is needed to clarify such questions. We conclude that where resection margins are thin (less than two mm), the definition of R0 or R1 resections should be clarified to optimize patient care. To achieve this, potential risk factors for inadequate resection such as tumor limits should be taken into account and further studied.
Enchondromatosis is a non-hereditary disease, characterised by the presence of multiple enchondromas. While Ollier Disease is typified by multiple enchondromas, in Maffucci Syndrome they are combined with haemangioma. Due to the rarity of these diseases, systematic studies on clinical behaviour providing information how to treat patients are lacking. This study intends to answer the following questions: What are predictive factors for developing chondrosarcoma? When is extensive surgery necessary? How often patients die due to dedifferentiation or metastasis? Twelve institutes in eight countries participated in this descriptive retrospective EMSOS-study. 118 Patients with Ollier Disease and 15 patients with Maffucci Syndrome were included. Unilateral localization of disease was found in 60% of Ollier patients and 40% of patients with Maffucci Syndrome. One of the predictive factors for developing chondrosarcoma is the location of the enchondromas; the risk increases especially when enchondromas are located in the scapula (33%), humerus (18%), pelvis (26%) or femur (15%). For the phalanges, this risk is 14% in the hand and 16% in the feet. The decision whether or not to perform extensive surgery is difficult, especially in patients who suffer multiple chondrosarcomas. Malignant transformation was found in fourty-four patients with Ollier Disease (37%) and eight patients with Maffucci Syndrome (53%). Multiple synchronous or metachronous chondrosarcomas were found in 15 patients. Nine patients died (range 21–54 yrs). Seven of them died disease related due to pulmonary metastasis (2 humerus, 2 pelvis, 3 femur). Two patients died from glioma of the brain. In conclusion, one important predictive factor for developing chondrosarcoma is the location of the enchondromas; interestingly, only patients with chondrosarcoma outside the small bones died of their disease. In this series, no dedifferentiation of chondrosarcoma was seen. A first design flow-chart how to approach chondrosarcoma in patients with Ollier Disease and Maffucci Syndrome is in preparation.
The development of multidisciplinary therapy for Ewing’s sarcoma (ES) has increased current long-term survival rates to greater than 50%, but only 20% for patients with clinically detectable metastases at diagnosis, or not responding to therapy or with disease relapse. Anti-bone resorption bisphosphonates (BP) may represent promising adjuvant molecules to limit the osteolytic component of bone tumor. The combination of zoledronic acid (ZOL) and ifosfamide (IFOS) or mafosfamide (MAFOS) was studied in ES models and in 8 human cell lines all expressing the EWS-FLI1 fusion gene. Cell proliferation, viability, apoptosis and cell cycle distribution were analysed. The ES models were developed in immuno-deficient mice by inoculating the human tumor cells either intra-muscular (soft tissue tumor development) or intra-osseous (bone tumor development). Mice were then treated with ZOL (100 μg/kg twice or 4 times/week) and/or ifosfamide (IFOS 30 mg/kg, one to 3 sequences of 3 injections). All the cell lines studied were more or less sensitive to ZOL and MAFOS in terms of cell proliferation. Both drugs induced cell cycle arrest respectively in S and G2M phase and final apoptosis associated to caspase 3 activation. In vivo, ZOL had no effect on soft tumor progression although it dramatically inhibits ES development in bone site. When combined with IFOS, ZOL exerts synergistic effects in the soft tissue model leading to a similar quantitative inhibitory effect when associated with 1 sequence IFOS as compared to 3 sequences of IFOS alone. In the bone model, ZOL prevents tumor recurrence observed with a lonely sequence of IFOS. Combination of ZOL with conventional chemotherapy showed promising results in both ES models and could allow the clinicians to diminish the doses of chemotherapy. Moreover, as ZOL and MAFOS induce cell death by different pathways, respective resistance may be circumvented.
The fractures of the hip are a main problem of health care. These fractures will be multiply by 2 in 2025 and 3 in 2050. In the population of old people, 1/3 of the women and 1/9 of the men will have a fracture of their hip. Some authors used the name of “EPIDEMIC”. The aima of the INPECH project (Indicators of the Performance for the comparison between hospital) was to check if the comparison of performances of clinical teams, on the basis of indicators chosen by themselves, allowed to improve their performances. It was an experimentation of a volonteer processes of comparison of performance between 3 multidisciplinary teams. The study followed some stages:
in every hospital, description of the process of care of the hip fractures with a choice of indicators of performance (difficulties of the care percepted by the professionals, possibilities of improvement, feasibility of the record of the indicators during the whole process) a first meeting of concertation with the three hospitals where a common choice of 20 indicators was done: 5 factors of adjustement corresponding to the prefracture status, 10 factors of the processes and 5 factors recorded at 3 months postoperatively a first period of inclusion (433 patients of more than 65 years-old) a second meeting of confrontation in order to analyze the results of the first inclusion period and to have exchange between the different teams about the disparities - the age, the autonomy and the mobility of the patients did not differ between the hospitals - the preoperative time was significantly different: 0.7 to 3.6 days - the time of the first get up (2 to 4 days), of the first social demand 3 to 7 days), of the hospitalization in surgery (9 to 14 days) and the rate of transfert in rehabilitation centers varied significantly between the centers. - At three months, the mortality, the levels of dependance and of autonomy were not significantly different. Each team had a reflexion about the opportunities of improvement and the actions to begin A second period of inclusion was realized in order to objectivize if the proposed improvements allowed a real change of our professional practices. (423 patients) The analysis of this second inclusion authorized a real change in our professional practices and showed the efficacy of the indicators which were improved. This study had permitted to show qualitative differences of care of hip fractures between the hospitals. The confrontation between the teams had authorized a positive reflexion of some of our professional practices and the improvement was underlined by the second series of inclusion.
Since 1996, we have been filling bone defect at the time of revision with macroporous calcium phosphate ceramic. We reported our first experience between 1996 and 1999.
2 patients died of a cause unrelated to the procedure and 2 patients were lost of follow-up. Bone defect were classified into type I ( 4 hips), type IIA ( 8 hips ), type IIB ( 5 hips), type IIC ( 9 hips), IIIA ( 4 hips ), type IV ( 5 hips ) according to Paprosky classification. The functional status of the patients was evaluated according to the Merle d’Aubign ip rating.. The interfaces bioactive ceramics/bone base and bioactive ceramics/cementless component, as well as the homogeneity and the density of the graft were examined radiologically.
We saw no radiolucent lines or spaces at the interface between bioactive ceramics and the host bone. Morphological changes or a decreased in graft volume were not seen, except for the patient with the loose cup.