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Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 35 - 35
1 Apr 2017
Ciapetti G Fotia C Granchi D Rojewski M Rosset P Gómez-Barrena E Baldini N
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Background

Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. Within the REBORNE project, a multi-center orthopaedic clinical trial was focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union.

Methods

Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-ups (6, 12 and 24 weeks post-surgery).


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 39 - 39
1 Apr 2017
Gomez-Barrena E Rosset P Hernigou P Gebhard F Ehrnthaller C Baldini N Layrolle P
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Background

Definitive proof is lacking on mesenchymal stem cell (MSCs) cellular therapy to regenerate bone if biological potential is insufficient. High number of MSCs after GMP expansion may solve the progenitor insufficiency at the injury but clinical trials are pending.

Methods

A prospective, multicenter, multinational Phase I/IIa interventional clinical trial was designed under the EU-FP7 REBORNE Project to evaluate safety and early efficacy of autologous expanded MSCs loaded on biomaterial at the fracture site in diaphyseal and/or metaphysodiaphyseal fractures (femur, tibia, humerus) nonunions. The trial included 30 recruited patients among 5 European centres in France, Spain, Germany, and Italy. Safety endpoints (local and general complication rate) and secondary endpoints for early efficacy (number of patients with clinically and radiologically proven bone healing at 12 and 24 weeks) were established. Cultured MSCs from autologous bone marrow, expanded under GMP protocol was the Investigational Medicinal Product, standardised in the participating countries confirming equivalent cell production in all the contributing GMP facilities. Cells were mixed with CE-marked biphasic calcium phosphate biomaterial in the surgical setting, at an implanted dose of 20−106 cells per cc of biomaterial (total 10cc per case) in a single administration, after debridement of the nonunion.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 11 - 11
1 Jan 2017
Ciapetti G Granchi D Barrena EG Rojewski M Rosset P Layrolle P Donati D Spazzoli B Baldini N
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Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. The REBORNE project entailed a multi-center orthopaedic clinical trial focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial, to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union.

Peripheral blood was collected from patients at fixed time-endpoints, that is at 6,12 and 24 weeks post-surgery for implantation of expanded autologus MSC and bone-like particles. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-up visits.

A significant relationship with age was found only at 6 months, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the baseline value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with a negative outcome. The BTM profile apparently indicated a remarkable bone formation activity 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome.

Blood markers related to bone cell function are useful to measure the efficacy of a expanded MSC-regenerative approach applied to long bone non-unions. Changes of the markers may provide a support to radiological assessment of bone healing.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 49 - 49
1 Apr 2012
Mascard E Rosset P Beaudet P Missenard G Salles de Gauzy G Mathieu G Oberlin O Eid A Plantaz D Wicart P Glorion C Gouin F
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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.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 530 - 530
1 Nov 2011
Marty F Legouge A Rosset P Burdin P
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Purpose of the study: Osteosynthesis material adapted to a mini-invasive approach certainly reduces surgical trauma. The purpose of this work was to establish the osteosynthesis equivalence for pertrochanteric fractures using a dynamic hip screw, inserted according to the conventional technique versus a mini-invasive screw system (MISS), in terms of healing without loss of reduction.

Material and methods: This was a prospective pilot study in a single centre. From May 2006 to April 2007, 78 patients (mean age 83 years, 70% women) were included (38 MISS, 40 DHS). There was one exclusion criteria: poor reduction on the orthopaedic table before incision. Radiographic and clinical follow-up for six months. The main outcome was the quality of the reduction and healing at three months.

Results: Eight patients were lost to follow-up and two had died at three months. The two groups were comparable regarding mean age, ASA, fracture type, operator experience, and centring of the head screw. In the MISS group, there was a 20% reduction in blood loss, a shorter incision (9 cm) and shorter operative time (16 min). The differences were not significant. The healing rate without loss of reduction at three months was the same in both groups: 82%. There were three revisions in the MISS group: one infection and two material disassemblies. This problem disappeared with the addition of a locking screw on the nail. There were no revisions for haematoma.

Discussion: There were several biases. The series was not really randomised because the type of material used depended on the availability of the instrument sets. The MISS implant evolved during the course of the study. The operators were more familiar with the DHS. Inclusion criteria were too restrictive. Multiple-injury patients with bleeding had a false impact on blood loss data. None of the differences were statistically significant. Revision for infection was not directly attributable to the material. Nail locking never failed after use of the locking screw.

Conclusion: The main outcome was validated: the healing rate without reduction at three months is equivalent with the two methods (82%). A multicentric study should be conducted to confirm that the mini-incision and the MISS reduces blood loss. It could be expected that this mini-invasive approach will become the rule for osteosynthesis of these fractures with a dynamic hip screw.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 521 - 521
1 Nov 2011
Marty F Rosset P Faizon G Laulan J
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Purpose of the study: Available epidemiological data on hand and wrist tumours are scarce and sometimes discordant. In our unit, these tumours are managed conjointly by hand surgeons and tumour specialists. We conducted an epidemiological study of 624 tumours treated from 1980 to 2008.

Material and methods: The recruitment used three methods: diagnostic coding in the database, analysis of discharge letters, study of tumour registries. All hand and wrist tumours treated surgically in our unit were included retrospectively. Exclusion criteria were: patients aged less than 15 years and/or managed in the paediatric surgery unit; poorly identified cases; recurrences.

Results: The study population included 624 tumours (375 female and 249 male). Mean age was 48 years (range 16–94). Eight tumours were malignant: 4 skin, 3 soft tissue, 1 bone metastasis of a primary renal tumour. Soft tissue tumour concerned 525 patients (84.1% of the study population). Respectively, 71 tumours concerned bone and 28 skin. There were 221 synovial cysts. The bone tumours exhibited a harmonious distribution for age and gender with a peak from 35 to 50 years and a sex ratio of 1/1. There were 43 chondromas found at all ages, mainly in long bones.

Discussion: Our series is the third largest reported. A review of the literature identified the eight largest studies available. For 6452 tumours, 81.7% concerned soft tissues, 13% skin, 4.7% bone tissue. These lesions occurred at all ages with female predominance (60%). Malignant tumours were found in 4.4% of the cases. Exclusion of the paediatric cases and the retrospective nature of the data collection were the main biases of this work.

Conclusion: Data on 624 hand and wrist tumours were in agreement with published work. Tumours involved mainly soft tissues. Synovial cysts predominated. Chondromas accounted for 70% of the bone tumours. Malignant tumours were rare (2.9%). For suspect cases, we recommend referral to a specialised centre for the management of malignant tumours of the hand. A pluridisciplinary analysis is indicated to adapt the diagnostic and therapeutic strategy.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_II | Pages 138 - 138
1 Apr 2005
Synave J Rosset P Burdin P Favard L
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Purpose: The aim of this work was to assess retrospectively osteofixation and survival of a long custom-made femoral stem with complete hydroxyapatite coating and without locking for replacement of the femoral implant.

Material and methods: From 1990 to 1999, 89 stems were implanted for revision total hip arthroplasty. Seventy-five hips were reviewed at one to ten years (mean four years). Radiographic analysis searched for bone damage, osteofixation and implant migration. All measures were taken on the AP views postoperatively and at last follow-up.

Results: Revision was performed for aseptic loosening in 75%, for septic loosening in 12%, for fracture in 11% and for instability in 2%. Destruction was SOFCOT stage I in 36%, stage II in 44%, stage III in 17% and could not be assessed in 3%. The femorotomy approach was used in 60% and trochanterotomy in 32% and endofemoral assess in 8%. There were 18% intraoperative fractures, 4.8% postoperative infections and 2.4% dislocations. At last follow-up, the Postel Merle d’Aubigné score was 15.3 and the Harris Hip Score was 77.9. Thigh pain was present in 4%. Bone fixation was considered good in 48%, partial but better than 50% contact in 36% and could not be interpreted in 16%. Complete metaphyseal reconstruction was present in 8%. A piecemeal allograft was used in 89%. Between the postoperative and last follow-up films, 16% of the stems descended a mean 11 mm. Five percent of the stems were removed for infection and one (1.3%) for non-fixation. At five years, 95% of the stems was still in place and 80% at ten years, including removals for infection. All revisions for septic loosening had comparable clinical and radiological results in this series and did not develop secondary infection.

Discussion: These results demonstrate the usefulness of the uncemented stems for replacement compared with cemented stems which have a 10% revision rate at five years (SOFCOT 1999). The complete hydroxyapatite coating improves distal fixation of the stem in a healthy zone without compromising secondary proximal fixation and authorising spontaneous metaphyseal bone reconstructions. This may explain the low rate of painful thighs. Modularity and locking could improve the primary fixation and limit descent.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_I | Pages 46 - 46
1 Mar 2002
Lautman S Faizon G Roger R Rosset P
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Purpose: Classifications of fractures of the thoracolumbar spine are theoretically designed to help make therapeutic decisions. Three classifications (J. Laulan, F. Denis, F. Magerl) were compared to assess reproducibility for use by a surgery team.

Material and methods: The classifications were described during a SOFCOT symposium in 1995. Four observers examined 60 files reading them twice at a 1 month interval. The files included plain radiographs (AP and lateral view) and a scanner series and were read in random order. Intra- and interobserver concordance were measured with the kappa method.

Results: Intra- and interobserver reproducibility was good for the classification proposed by F. Denis (kappa = 0.6229 and 0.0795) for classification groups but was weak for subgroups (kappa = 0.028 and 0.571). Reproducibility was moderate for the classification proposed by J. Laulin (interob-server kappa = 0.460, intraobserver kappa = 0.541). The Magerl classification produced low to negligible reproducibility for classification groups and subgroups (intra- and interobserver kappa = 0.138 to 0.0343).

Discussion: Because of its low to negligible reproducibility, the Magerl classification would be difficult to use in clinical practice to make coherent therapeutic decisions or for scientific research to analyze series of fractures treated using this classification. The reproducibility of the F. Denis classification was good for groups but low for subgroups that include fractures resulting from different mechanisms requiring radically different treatment strategies. This is a good classification system for descriptive work but can lead to treatments poorly adapted to the causal mechanism of the fracture. The reproducibility of the J. Laulan classification is moderate but each group in this classification corresponds to fractures caused by the same mechanism. Therapeutic indications determined with this system would be more coherent.


The Journal of Bone & Joint Surgery British Volume
Vol. 72-B, Issue 1 | Pages 84 - 88
1 Jan 1990
Karray S Zlitni M Fowles J Zouari O Slimane N Kassab M Rosset P

We report the management of two children and 11 adults with paraplegia secondary to vertebral hydatidosis. Destruction of pedicles, posterior vertebral elements and discs as well as the vertebral bodies was common and all six patients with thoracic disease had involvement of adjacent ribs. The 13 patients had a total of 42 major surgical procedures; two patients died from postoperative complications and four from complications of the disease and paraplegia. All eight patients initially treated by laminectomy or anterior decompression alone relapsed within two years and seven required further surgery. Circumferential decompression and grafting gave the best results, six of nine patients being in remission an average of three years and six months later. The prognosis for such patients is poor; remission is the aim, rather than cure. Anthelminthic drugs may improve the prognosis, but radical surgery is likely to remain the keystone of treatment in the foreseeable future.