Publications by authors named "Philippe Rosset"

58 Publications

Osteonecrosis of the Femoral Head Safely Healed with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells in a Multicentric Trial with Minimum 5 Years Follow-Up.

J Clin Med 2021 Feb 1;10(3). Epub 2021 Feb 1.

INSERM U957, Lab. Pathophysiology of Bone Resorption, Faculty of Medicine, University of Nantes, 44035 Nantes, France.

: Osteonecrosis (ON) of the femoral head represents a potentially severe disease of the hip where the lack of bone regeneration may lead to femoral head collapse and secondary osteoarthritis, with serious pain and disability. The aim of this European, multicentric clinical trial was to prove safety and early efficacy to heal early femoral head ON in patients through minimally invasive surgical implantation of autologous mesenchymal stromal cells (MSC) expanded from bone marrow (BM) under good manufacturing practices (GMP). : Twenty-two patients with femoral head ON (up to ARCO 2C) were recruited and surgically treated in France, Germany, Italy and Spain with BM-derived, expanded autologous MSC (total dose 140 million MSC in 7 mL). The investigational advanced therapy medicinal product (ATMP) was expanded from BM under the same protocol in all four countries and approved by each National Competent Authority. Patients were followed during two years for safety, based on adverse events, and for efficacy, based on clinical assessment (pain and hip score) and imaging (X-rays and MRIs). Patients were also reviewed after 5 to 6 years at latest follow-up for final outcome. : No severe adverse event was recalled as related to the ATMP. At 12 months, 16/20 per protocol and 16/22 under intention-to-treat (2 drop-out at 3 and 5 months) maintained head sphericity and showed bone regeneration. Of the 4 hips with ON progression, 3 required total hip replacement (THR). At 5 years, one patient (healed at 2 years visit) was not located, and 16/21 showed no progression or THR, 4/21 had received THR (all in the first year) and 1 had progressed one stage without THR. : Expanded MSCs implantation was safe. Early efficacy was confirmed in 80% of cases under protocol at 2 years. At 5 years, the overall results were maintained and 19% converted to THR, all in the first year.
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http://dx.doi.org/10.3390/jcm10030508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867148PMC
February 2021

Soft tissue reconstruction after pelvic amputation: The efficacy and reliability of free fillet flap reconstruction.

J Plast Reconstr Aesthet Surg 2020 Nov 8. Epub 2020 Nov 8.

Royal Orthopaedic Hospital, Birmingham, UK.

Background: The majority of hindquarter amputation defects can be reconstructed with local anterior or posterior thigh flaps. Less than 5% of soft tissue defects require free flap reconstruction after tumour resection. Lower extremity fillet flap is described for reconstructing such defects, but the majority of publications are case reports or short single institutional series. There is a lack of data regarding the oncological outcomes of this highly selected patient group.

Methods: Three tertiary sarcoma units treated twelve patients with hindquarter amputation or hip disarticulation for oncological indications with a free flap reconstruction of the soft tissue defect.

Results: The median age of patients was 60 (range 12-76) years. Bone resection was carried out through the SI-joint in six patients and through the sacrum in five patients, with one patient undergoing hip disarticulation. Nine patients had R0 resection margin and three had R1 resection. The median surgical time and flap ischaemia time was 420 (249-650) and 89 (64-210) min, respectively. Median hospital and ICU stay was 18 (10-42) and 3 (1-8) days, respectively. Median blood loss was 2400 (950-10000) ml. There were three returns to theatre due to vascular compromise, with one total flap loss due to arterial thrombosis. Overall survival was 58% (95%CI 28-91%) both at 1-year and at 3-years.

Discussion: Carefully selected patients requiring hindquarter amputation with extensive soft tissue defect necessitating free flap reconstruction can be reconstructed with a lower extremity free fillet flap with low rate of local wound complications. Survival of these patients is similar to that in patients requiring less extensive resection.
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http://dx.doi.org/10.1016/j.bjps.2020.10.070DOI Listing
November 2020

Frontiers in non-union research.

EFORT Open Rev 2020 Oct 26;5(10):574-583. Epub 2020 Oct 26.

Service de Chirurgie Orthopédique et Traumatologie, CHU Tours, Université de Tours, Tours, France.

Multifactorial aetiology defines non-unions, with a biological and a mechanical distortion of the timeline of bone healing.Research on new advances to increase osteogenesis and promote non-union healing is strongly directed towards new forms of cell products.Basic science and research on non-union treatments is needed to compile preclinical data on new treatments.Bone marrow concentration and expanded mesenchymal stromal cells still require extensive clinical research to confirm efficacy in non-union treatment.Solid preclinical studies, precise cell product definition and preparation, and appropriate ethical and regulatory approvals are needed to assess new advanced therapy medicinal products. Cite this article: 2020;5:574-583. DOI: 10.1302/2058-5241.5.190062.
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http://dx.doi.org/10.1302/2058-5241.5.190062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608578PMC
October 2020

In situ production of pre-vascularized synthetic bone grafts for regenerating critical-sized defects in rabbits.

Acta Biomater 2020 09 18;114:384-394. Epub 2020 Jul 18.

Inserm, UMR 1238, PHY-OS, Bone sarcomas and remodeling of calcified tissues, Faculty of Medicine, University of Nantes, 1 rue Gaston Veil, Nantes 44035, France. Electronic address:

Reconstructing large bone defects caused by severe trauma or resection of tumors remains a challenge for surgeons. A fibula free flap and its vascularized bed can be transplanted to the reconstruction site to achieve healing. However, this technique adds morbidity, and requires microsurgery and sculpting of the bone tissue to adapt the graft to both the vasculature and the anatomy of the defect. The aim of the current study was to evaluate an alternative approach consisting of the in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a critical-sized bone defect. 3D printed chambers containing biphasic calcium phosphate (BCP) granules, perfused by a local vascular pedicle, with or without the addition of stromal vascular fraction (SVF), were subcutaneously implanted into New Zealand White female rabbits. SVF was prepared extemporaneously from autologous adipose tissue, the vascular pedicle was isolated from the inguinal site, while BCP granules alone served as a control group. After 8 weeks, the constructs containing a vascular pedicle exhibited abundant neovascularization with blood vessels sprouting from the pedicle, leading to significantly increased vascularization compared to BCP controls. Pre-vascularized synthetic bone grafts were then transplanted into 15 mm critical-sized segmental ulnar defects for a further 8 weeks. Micro-CT and decalcified histology revealed that pre-vascularization of synthetic bone grafts led to enhanced bone regeneration. This pre-clinical study demonstrates the feasibility and efficacy of the in situ production of pre-vascularized synthetic bone grafts for regenerating large bone defects, thereby addressing an important clinical need. STATEMENT OF SIGNIFICANCE: The current gold standard in large bone defect regeneration is vascularized fibula grafting. An alternative approach consisting of in situ production of a pre-vascularized synthetic bone graft and its subsequent transplantation to a bone defect is presented here. 3D printed chambers were filled with biphasic calcium phosphate granules, supplemented with autologous stromal vascular fraction and an axial vascular pedicle and subcutaneously implanted in inguinal sites. These pre-vascularized synthetic grafts were then transplanted into critical-sized segmental ulnar defects. Micro-CT and decalcified histology revealed that the pre-vascularized synthetic bone grafts led to higher bone regeneration than non-vascularized constructs. An alternative to vascularized fibula grafting is provided and may address an important clinical need for large bone defect reconstruction.
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http://dx.doi.org/10.1016/j.actbio.2020.07.030DOI Listing
September 2020

Regeneration of segmental defects in metatarsus of sheep with vascularized and customized 3D-printed calcium phosphate scaffolds.

Sci Rep 2020 04 27;10(1):7068. Epub 2020 Apr 27.

Inserm, UMR 1238, PHY-OS, Bone sarcomas and remodelling of calcified tissues, Faculty of Medicine, University of Nantes, Nantes, 44035, France.

Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months post-implantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. The presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds.
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http://dx.doi.org/10.1038/s41598-020-63742-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184564PMC
April 2020

Survival and complications in hinged knee reconstruction prostheses after distal femoral or proximal tibial tumor resection: A retrospective study of 161 cases.

Orthop Traumatol Surg Res 2020 05 8;106(3):403-407. Epub 2020 Apr 8.

SoFCOT, 56, rue Boissonade, 75014 Paris, France.

Introduction: Hinged knee megaprostheses are mainly used for reconstruction after tumor resection. They may incur complications, but this has not been assessed in the French literature, except in small series at short follow-up. We therefore conducted a large-scale nationwide multicenter retrospective study with a minimum 5 years' follow-up. The objectives were (1) to compare survival between distal femoral and proximal tibial reconstruction prostheses, and (2) to analyze complications and failure.

Hypothesis: Distal femoral hinged reconstruction prostheses show longer survival with fewer complications than proximal tibial prostheses.

Material And Methods: One hundred sixty-one patients were included: 118 in the distal femoral group, and 43 in the proximal tibial group. Tumors were mostly osteosarcomas (90 cases) or chondrosarcomas (31 cases). Mean age was 37 years (range, 12-86 years). Complications were assessed on the Henderson classification. Failure was defined by prosthesis anchor exchange or amputation.

Results: At a mean 9 years' follow-up (range, 5-23 years), implant survival was longer in the distal femoral group: 5- and 10-year survival, 84% [95% CI, 75-89] and 70% [95% CI, 59-79] versus 74% [95% CI, 69-85] and 43% [95% CI, 23-61] (p=0.02). Revision surgery for complications mainly concerned aseptic loosening (19%, 30 cases) or deep infection (16%, 25 cases) and more often involved the proximal tibia (65% vs. 43%, 28 vs. 51 cases; OR 2.4 [95% CI, 1.2-5.1]; p=0.02).

Discussion: Hinged knee reconstruction prosthesis is a solution in tumoral pathology, but with a high risk of complications (loosening and infection) and a higher failure rate in the proximal tibial reconstruction prosthesis.

Level Of Evidence: IV, case series.
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http://dx.doi.org/10.1016/j.otsr.2019.11.027DOI Listing
May 2020

Fixed-hinge cemented modular implants: An effective reconstruction technique following primary distal femoral bone tumor resection. A 136-case multicenter series.

Orthop Traumatol Surg Res 2020 05 20;106(3):397-402. Epub 2020 Mar 20.

Service d'orthopédie et traumatologie 3A, Aix-Marseille université, hôpital Nord, AP-HM, chemin des Bourrély, 13015 Marseille, France.

Background: Reconstruction by endoprosthesis is widespread after bone tumor resection. The design and type of fixation and of hinge remain a matter of debate. The aim of the present study was to assess survival, complications and functional results in a homogeneous series of adult patients undergoing bone defect reconstruction following distal femoral tumor resection, using a single model of fixed-hinge cemented endoprosthesis, at a minimum 5 years' follow-up.

Hypothesis: The study hypotheses were that loosening and infection are the main causes of failure, and that this type of reconstruction is reliable following distal femoral resection.

Patients And Methods: All patients aged over 17 years undergoing reconstruction using the Stanmore Mets® fixed-hinge cemented modular endoprosthesis following distal femoral resection for primary bone tumor in 4 French reference centers between 2004 and 2013 were included. Epidemiological data, MSTS functional score, clinical and radiological examination results, complications and survival with types of failure according to the Henderson classification were assessed.

Results: One hundred and thirty-six patients (68 male, 68 female; mean age, 41.2 years [range, 17-77 years]) were included. Mean follow-up was 81 months [range, 61-134 months]. Thirty-two patients (38%) experienced a total 67 complications requiring surgical revision: mainly infection (n=28) or mechanical failure (n=26). Overall implant survival was 78% at 5 years. There were 30 implant failures on the Henderson classification. Mean MSTS score was 82%.

Discussion: The present results are comparable to those of the literature and for other types of reconstruction. Recent meta-analyses suggest that type of hinge and of stem fixation have little effect on implant survival. International comparative studies are needed to determine the exact role of each type of reconstruction according to the patient profile.

Level Of Evidence: IV, multicenter retrospective series.
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http://dx.doi.org/10.1016/j.otsr.2019.10.029DOI Listing
May 2020

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions.

Injury 2020 Apr 26;51 Suppl 1:S63-S73. Epub 2020 Feb 26.

INSERM U957, Lab. Pathophysiology of bone resorption, Faculty of Medicine, University of Nantes, Nantes, France.

Background And Study Aim: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture.

Patients And Methods: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in VAS scale), and by radiological consolidation with a REBORNE score over 11/16 points (value of or above 0.6875). Means were statistically compared and mixed models for repeated measurements estimated the mean and confidence intervals (95%) of the REBORNE Bone Healing scale. Clinical and radiological consolidation were analyzed in the subgroups with Spearman correlation tests (adjusted by Bonferroni).

Results: Clinical consolidation was earlier confirmed, while radiological consolidation at 3 months was 25.0% (7/28 cases), at 6 months 67.8% (19/28 cases), and at 12 months, 92.8% (26/28 cases including the drop-out extrapolation of two failures). Bone biopsies confirmed bone formation surrounding the bioceramic granules. All locations showed similar consolidation, although this was delayed in tibial non-unions. No significant gender difference was found in 12-month consolidation (95% confidence). Higher consolidation scale values were seen in non-smoking patients at 6 (p = 0.012, t-test) and 12 months (p = 0.011, t-test). Longer time elapsed after the initial fracture did not preclude the occurrence of consolidation.

Conclusion: Bone consolidation was efficaciously obtained with the studied expanded hBM-MSCs combined to biomaterials, by clinical and radiological evaluation, and confirmed by bone biopsies, with lower consolidation scores in smokers.
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http://dx.doi.org/10.1016/j.injury.2020.02.070DOI Listing
April 2020

Epidemiological, clinical and histological features of adipose tumors in the hand and wrist: Findings from a continuous series of 37 cases.

Orthop Traumatol Surg Res 2020 Apr 6;106(2):329-334. Epub 2020 Feb 6.

Unité de chirurgie de la main, Hôpital Trousseau, CHRU de Tours, Tours, France; UMR 1253 Imagerie et Cerveau (iBrain), Faculté de Médecine, Université de Tours, Tours, France. Electronic address:

Introduction: Adipose tumors are the most common soft tissue tumor in adults; however, their epidemiology and histology in the hand and wrist are not well-defined. The aim of this study was to describe the histology and treatment strategy for this type of tumor at a specialized cancer center.

Hypothesis: The frequency of these tumors is underestimated, and their histology signature varies.

Materials And Methods: The clinical and paraclinical data of adults treated for an adipose tumor lesion in the hand or wrist were analyzed retrospectively: age, clinical history, time elapsed between discovery and treatment, type of treatment. The dimensions, location and histology of the tumor were collected. The patients were contacted to inquire about persistent symptoms and sequelae.

Results: Thirty-seven tumors (37 patients) were included between January 2003 and December 2018, thus making up 7.5% of all the soft tissue tumors in the hand or wrist. The mean patient age was 59years (28-84years). Except for one fortuitous discovery, the tumors were discovered because the patient had an unusual lump. The lump was associated with distal paresthesia in six cases. The mean time to treatment was 47.5months (1-240months). The lesion was a conventional lipoma (31 cases) or one of its benign variants (6 cases). The mean size was 3.76cm in the long axis (1-11.5cm) and the mean weight was 9.8g (3-60g). The mean follow-up was 73.5months (2-177months). Tumors in the fingers were smaller and lighter than those in the wrist (p=0.004 and p=0.034).

Discussion: The prevalence of adipose tumors is underestimated within hand and wrist tumors. The most common way these tumors are discovered is due to compressive neuropathy with paresthesia and/or dysesthesia. While these tumors are nearly always benign, this does not justify ignoring the opinion of the multidisciplinary tumor board or underestimating the small possibility of the lesion being a liposarcoma.

Level Of Evidence: IV, retrospective, single-center study.
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http://dx.doi.org/10.1016/j.otsr.2019.12.011DOI Listing
April 2020

Clinical and dynamometric results of hip abductor system repair by trochanteric hydroxyapatite plate with modular implant after resection of proximal femoral tumors.

Orthop Traumatol Surg Res 2019 11 3;105(7):1319-1325. Epub 2019 Oct 3.

Orthopedics and Trauma Department, University Hospital Hôtel-Dieu, CHU de Nantes, 1, place Alexis-Ricordeau, 44093 Nantes Cedex 1, France; Inserm UMR 1238, Bone sarcomas and remodeling of calcified tissues, faculté de médecine, 1, rue Gaston-Veil, 44035 Nantes cedex 1, France.

Introduction: The capacity of the hydroxyapatite-coated trochanteric screwed plates used with modular hip implants to restore abductor system efficacy after proximal femoral tumor resection has never been assessed. We therefore conducted a retrospective study aiming to: (1) quantitatively evaluate abduction conservation on dynamometry according to use of digastric reinsertion, conserving continuity between the gluteus medius and vastus lateralis muscles, or not, and of standard versus small-offset; (2) assess radiographic trochanteric plate fixation; (3) assess functional scores; and (4) assess complications.

Hypothesis: Trochanteric reinsertion better conserves abduction strength when reinsertion is digastric.

Patients And Methods: Thirty-one patients undergoing proximal femoral tumor resection between 2006 and 2016 with reconstruction by Stanmore METS™ modular implant with trochanteric plate were included. Twenty-one had digastric fixation between the gluteus medius and vastus lateralis and 10 had simple trochanteric fixation without digastric continuity. Abduction strength was compared between sides on dynamometer. Sixteen patients had full assessment of muscle strength, by a single observer; there were 8 deaths, 5 patients lost to follow-up, and 2 cases of material removal.

Results: Abduction strength conservation versus the contralateral side was 55.2±23.3% (range, 5.8-86.1%): 66.6±13.0% (46.4-86.1) with versus 36.0±24.7% (5.8-63.2%) without digastric continuity (p=0.01); severe limp rate was 4/21 when digastric continuity was preserved (19%) versus 6/10 (60%) (p=0.04), and radiologic trochanteric reinsertion stability rate was 19/21 (90%) versus 4/10 (40%) (p=0.005). Standard femoral offset conserved greater abduction strength: 64.9±20.0% versus small-offset 45.4±23.2% (p=0.05). Toronto Extremity Salvage Score (TESS) was 89±9.4%, and Musculoskeletal Tumor Society (MSTS) score 75.4±5.4%. There were 6 complications (19%): 4 infections, 1 dislocation, and 1 plate removal; the single dislocation (3%) was in the digastric conservation group. TESS (90.7±7.8% vs 88.3±4) and MSTS score (75.6±4.0% vs 75.1±3.7) and complications [4/21 (19%) vs 2/10 (20%)] did not differ according to digastric or non-digastric reinsertion (p=1).

Conclusions: Abduction strength with a modular implant using a hydroxyapatite-coated trochanteric plate was better conserved by digastric trochanteric reinsertion, resulting in less limping, although the complications rate and functional scores were unaffected. Longer term assessment is needed to confirm this conservation of abduction strength.

Level Of Evidence: IV, retrospective study without control group.
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http://dx.doi.org/10.1016/j.otsr.2019.08.011DOI Listing
November 2019

Early detection of multiple bone and extra-skeletal metastases by body magnetic resonance imaging (BMRI) after treatment of Myxoid/Round-Cell Liposarcoma (MRCLS).

Eur J Surg Oncol 2019 Dec 13;45(12):2431-2436. Epub 2019 Aug 13.

Service de Chirurgie Orthopédique 1&2, Hôpital Trousseau, CHRU de Tours, France Faculté de Médecine, Université de Tours, France; INSERM UMR1238. Bone Sarcoma and Remodeling of Calcified Tissues. Faculté de Médecine de Nantes, France.

Introduction: Myxoid Round cell containing myxoid liposarcomas (MRCLS) have a high propensity to metastasize to soft tissue and bone. Whole Body Magnetic Resonance Imaging (BMRI) has been reported as a critical modality to early detect disease spreading in asymptomatic patients. The purpose of this study is to describe metastatic patterns and outcomes in patients through annual BMRI surveillance after diagnosis of MRCLS of the extremities and trunk.

Materiel And Patients: This retrospective study included patients with histology confirmed MRCLS. Initial BMRI were done within 6 months following the first line treatment then once a year.

Results: Forty-five out of 51 consecutive MRCLS patients were included. At the last follow-up 10 patients (22.2%) had an extra-pulmonary soft-tissue or/and bone metastasis detected in a median delay of 22.7±16 months [0-49] from the diagnosis of the MRCLS. Nine patients were asymptomatic. Finally, 5-years metastatic free survival was 72±8%. All metastatic patients had multiple lesion within the year following the first lesion diagnosis.

Conclusion: Systematic BMRI in MRCLS patients following treatment frequently identify extra-pulmonary metastasis in asymptomatic patients within the first 5 years of follow-up. Despite a long survival can be expected after diagnosis, extra-skeletal metastasis was a signal of disseminated disease.
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http://dx.doi.org/10.1016/j.ejso.2019.08.014DOI Listing
December 2019

Poor prognosis for infectious complications of surgery for ankle and hindfoot fracture and dislocation. A 34-case series.

Orthop Traumatol Surg Res 2019 10 30;105(6):1119-1124. Epub 2019 Jul 30.

Services d'orthopédie et traumatologie 1 et 2, faculté de médecine, université de Tours, CHU de Trousseau, avenue de la République, 37170 Chambray-les-Tours, France.

Introduction: Ankle and hindfoot fractures are associated with high rates of complications, and of infection in particular, for which rates of 1% to 48% are reported.

Hypothesis: Treatment of bone and joint infection (BJI) secondary to surgery for ankle or hindfoot fracture is at high risk of failure. We analyzed results of treatment of BJI in this context.

Material And Methods: 33 patients (34 cases) were treated for ankle or hindfoot BJI between 2010 and 2015. Cure was defined by absence of fistula and of local or general inflammatory signs and by normal C-reactive protein level, at a minimum 2 years' follow-up. Fusion without infection was counted as success; recurrent infection and amputation were counted as failure. Mean age at trauma was 52 years (range, 16-85 years). Median time to diagnosis of BJI was 44 days (range, 2-830 days).

Results: Mean follow-up was 20 months (range, 3-59 months). Twenty-two patients were cured (65%). Seven cases required joint fusion (21%). The failure rate was 15%, including 5 transtibial amputations. Skin cover flap was required for 15 patients (44%), at a median 33 days (range, 0-167 days).

Discussion: Despite its retrospective design and small numbers, the present study confirmed the poor prognosis of BJI following surgery for ankle and/or hindfoot fracture. Patients need to be informed of this.

Type Of Study And Level Of Evidence: IV, retrospective observational.
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http://dx.doi.org/10.1016/j.otsr.2019.06.006DOI Listing
October 2019

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate.

Ann Surg Oncol 2019 Oct 23;26(11):3526-3534. Epub 2019 Jul 23.

Department of Medical Oncology and Surgery, Gustave Roussy Institute, Villejuif, France.

Background: The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown.

Objective: The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation.

Methods: Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C).

Results: Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01).

Conclusion: Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.
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http://dx.doi.org/10.1245/s10434-019-07494-6DOI Listing
October 2019

Biomarkers of bone healing induced by a regenerative approach based on expanded bone marrow-derived mesenchymal stromal cells.

Cytotherapy 2019 08 1;21(8):870-885. Epub 2019 Jul 1.

SSD Fisiopatologia Ortopedica e Medicina Rigenerativa, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università degli Studi di Bologna, Bologna, Italy.

Background: Safety and feasibility of a regenerative strategy based on the use of culture-expanded mesenchymal stromal cells (MSCs) have been investigated in phase 2 trials for the treatment of nonunion and osteonecrosis of the femoral head (ONFH). As part of the clinical study, we aimed to evaluate if bone turnover markers (BTMs) could be useful for predicting the regenerative ability of the cell therapy product.

Materials And Methods: The bone defects of 39 patients (nonunion: n = 26; ONFH: n = 13) were treated with bone marrow-derived MSCs, expanded using a clinical-grade protocol and combined with biphasic calcium phosphate before implantation. Bone formation markers, bone-resorption markers and osteoclast regulatory proteins were measured before treatment (baseline) and after 12 and 24 weeks from surgery. At the same time-points, clinical and radiological controls were performed to evaluate the bone-healing progression.

Results: We found that C-Propeptide of Type I Procollagen (CICP) and C-terminal telopeptide of type-I collagen (CTX) varied significantly, not only over time, but also according to clinical results. In patients with a good outcome, CICP increased and CTX decreased, and this trend was observed in both nonunion and ONFH. Moreover, collagen biomarkers were able to discriminate healed patients from non-responsive patients with a good diagnostic accuracy.

Discussion: CICP and CTX could be valuable biomarkers for monitoring and predicting the regenerative ability of cell products used to stimulate the repair of refractory bone diseases. To be translated in a clinical setting, these results are under validation in a currently ongoing phase 3 clinical trial.
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http://dx.doi.org/10.1016/j.jcyt.2019.06.002DOI Listing
August 2019

Preclinical safety study of a combined therapeutic bone wound dressing for osteoarticular regeneration.

Nat Commun 2019 05 14;10(1):2156. Epub 2019 May 14.

INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, 11 Rue Humann, 67000, Strasbourg, France.

The extended life expectancy and the raise of accidental trauma call for an increase of osteoarticular surgical procedures. Arthroplasty, the main clinical option to treat osteoarticular lesions, has limitations and drawbacks. In this manuscript, we test the preclinical safety of the innovative implant ARTiCAR for the treatment of osteoarticular lesions. Thanks to the combination of two advanced therapy medicinal products, a polymeric nanofibrous bone wound dressing and bone marrow-derived mesenchymal stem cells, the ARTiCAR promotes both subchondral bone and cartilage regeneration. In this work, the ARTiCAR shows 1) the feasibility in treating osteochondral defects in a large animal model, 2) the possibility to monitor non-invasively the healing process and 3) the overall safety in two animal models under GLP preclinical standards. Our data indicate the preclinical safety of ARTiCAR according to the international regulatory guidelines; the ARTiCAR could therefore undergo phase I clinical trial.
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http://dx.doi.org/10.1038/s41467-019-10165-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517440PMC
May 2019

Immune Modulation by Transplanted Calcium Phosphate Biomaterials and Human Mesenchymal Stromal Cells in Bone Regeneration.

Front Immunol 2019 2;10:663. Epub 2019 Apr 2.

Laboratory Phy-Os, Inserm UMR1238, University of Nantes, Nantes, France.

A wide variety of biomaterials have been developed as both stabilizing structures for the injured bone and inducers of bone neoformation. They differ in chemical composition, shape, porosity, and mechanical properties. The most extensively employed and studied subset of bioceramics are calcium phosphate materials (CaPs). These materials, when transplanted alongside mesenchymal stem cells (MSCs), lead to ectopic (intramuscular and subcutaneous) and orthotopic bone formation in preclinical studies, and effective fracture healing in clinical trials. Human MSC transplantation in pre-clinical and clinical trials reveals very low engraftment in spite of successful clinical outcomes and their therapeutic actions are thought to be primarily through paracrine mechanisms. The beneficial role of transplanted MSC could rely on their strong immunomodulatory effect since, even without long-term engraftment, they have the ability to alter both the innate and adaptive immune response which is critical to facilitate new bone formation. This study presents the current knowledge of the immune response to the implantation of CaP biomaterials alone or in combination with MSC. In particular the central role of monocyte-derived cells, both macrophages and osteoclasts, in MSC-CaP mediated bone formation is emphasized. Biomaterial properties, such as macroporosity and surface microstructure, dictate the host response, and the ultimate bone healing cascade. Understanding intercellular communications throughout the inflammation, its resolution and the bone regeneration phase, is crucial to improve the current therapeutic strategies or develop new approaches.
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http://dx.doi.org/10.3389/fimmu.2019.00663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455214PMC
July 2020

Sarcomas in patients over 90: Natural history and treatment-A nationwide study over 6 years.

Int J Cancer 2019 10 15;145(8):2135-2143. Epub 2019 Apr 15.

Centre Léon Bérard, University Claude Bernard Lyon I, Lyon, France.

Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow-up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs. 66.3%), are less frequently metastatic (5.3% vs. 14·7%) at diagnosis, have more often superficial tumors (39.8% vs. 14.7%), as well as limbs and head and neck sites (75.2% vs. 38.7%) (all p < 0.001). Optimal diagnostic procedures and surgery were less frequently performed in patients over 90 (p < 0.001). These patients were less frequently operated in NETSARC centers, as compared to those of younger age groups including aged 80-90. However, local relapse-free survival, metastatic relapse-free survival and relapse-free survival were not significantly different from those of younger patients, in the whole cohort, as well as in the subgroup of operated patients. As expected overall survival was worse in patients over 90 (p < 0.001). Patients over 90 who were not operated had worse overall survival than younger patients (9.9 vs. 27.3 months, p < 0.001). Patients with STS diagnosed after 90 have distinct clinicopathological features, but comparable relapse-free survival, unless clinical practice guidelines recommendations are not applied. Standard management should be proposed to these patients if oncogeriatric status allows.
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http://dx.doi.org/10.1002/ijc.32307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767526PMC
October 2019

Distal extremities soft tissue sarcomas: Are they so different from other limb localizations?

J Surg Oncol 2019 Mar 4;119(4):479-488. Epub 2019 Jan 4.

Faculté de Médecine de la Timone, Génétique Médicale et génomique fonctionnelle, UMR S910 Inserm, Université Aix-Marseille 2, Marseille, France.

Background And Objectives: Soft tissue sarcoma localization in distal extremities (DESTS) of the limbs (hand/fingers, and foot/toes) is unusual. The literature is scarce about their behavior and this study was designed to assess their epidemiological characteristics, outcomes, and prognosis compared to other limb localizations (OLSTS).

Methods: From 1980 to 2010, adult DESTS and OLSTS in 22 centers were included. Demographics, tumor type, treatment modalities, and latest follow-up status were collected. Primary endpoints were overall survival and local/metastatic recurrence incidences.

Results: Two hundred five DESTS and 3001 OLSTS were included. The patients were younger, with more female and smaller tumors in DESTS. There were more clear cell/epithelioid sarcomas, synovial sarcomas, and myxoid liposarcomas vs more dedifferentiated liposarcomas in OLSTS. DESTS tumors were less irradiated and more often amputated (24.3% vs 3.4%). The five-year survival rate was 78.2% compared to 68.6% in OLSTS and after multivariate analysis, STS localization did not impact survival or local/metastatic recurrence.

Conclusion: Though rare and smaller than other limb localizations, DESTS are to be considered as aggressive. Despite a higher amputation rate, the prognosis remains the same as in OLSTS. Limb sparing vs amputation should be carefully assessed in DESTS, especially if grade 3 or of a poor prognosis histological subtype.
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http://dx.doi.org/10.1002/jso.25359DOI Listing
March 2019

Free fillet lower leg flap for coverage after hemipelvectomy or hip disarticulation.

Orthop Traumatol Surg Res 2019 02 27;105(1):47-54. Epub 2018 Dec 27.

Département de chirurgie orthopédique 2, centre hospitalo-universitaire Tours - faculté de medecine, université de Tours, 37000 Tours, France; Inserm UN UMR 1238, PhyOs, bone sarcomas and remodeling of calcified tissues, faculté de médecine de Nantes, 44000 Nantes, France.

Introduction: Tumor resection is the gold standard treatment for soft tissue and bone sarcomas. In the pelvis, this may require a hemipelvectomy that can compromise primary skin closure. Flaps are essential in this context; however the vascularization of potential pedicled flaps may have been removed during tumor excision. Using healthy tissue from the amputated limb as a free flap is an excellent coverage option.

Hypothesis: The free fillet flap from an amputated lower limb is a simple and reliable coverage technique after hemipelvectomy or hip disarticulation.

Material And Methods: Seven patients were operated on at three specialty centers: six transpelvic amputations (external hemipelvectomy) and one hip disarticulation. In three cases, the flap consisted of the superficial posterior compartment of the calf area and in the three other cases, the lower leg compartments with the fibula and its intact periosteum. Complications were documented.

Results: Clear resection margins were achieved in all patients. The mean follow-up at the final visit was 13 months (range, 6.5 to 21 months). Six patients had complications but only one resulted in loss of the flap. Four patients were able to be fitted with a hip prosthesis.

Discussion: The free fillet flap from an amputated lower limb is a reliable coverage technique (86%) after hemipelvectomy or hip disarticulation. In the 16 cases previously reported in the literature, there were no wound-healing failures. Local flaps are often too fragile with insufficient muscular padding. This free flap is the preferred first-line technique as it spares other potential free flaps in case of failure without increasing the morbidity of a procedure that is already extensive. This coverage technique should be one the options considered after external hemipelvectomy.

Level Of Evidence: IV, retrospective study.
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http://dx.doi.org/10.1016/j.otsr.2018.10.018DOI Listing
February 2019

Three-dimensional orientation of the femoral curvature. How well does it match with the sagittal curvature of femoral implants?

Orthop Traumatol Surg Res 2019 02 24;105(1):11-16. Epub 2018 Dec 24.

Service de chirurgie orthopédique et traumatologique, CHRU hopitaux de Tours-Trousseau, avenue de la République, 37170 Chambray-lès-Tours, France; Faculté de médecine, université François-Rabelais, 10, boulevard Tonnellé, 37000 Tours, France.

Background: The curvature of the femoral shaft is generally considered as residing in the sagittal plane. While many studies have measured the femur's radius of curvature, very few have studied the orientation of the plane in which it resides. The orientation of this plane may affect the rotation of intramedullary nails or revision stems with diaphyseal locking. This led us to conduct a three-dimensional (3D) anatomical study to: 1) analyze the 3D curvature of the femoral diaphysis by specifying the orientation of the plane in which it resides, 2) look for relationships between the curvature's orientation and anatomical parameters of the femur.

Hypothesis: We hypothesized that the femoral curvature resides in the anterolateral plane, not the sagittal plane.

Materials And Methods: A computed tomography scan was performed on 45 dry femur bones provided by a cadaver laboratory. The 3D reconstructions were analyzed to characterize the curvature of the diaphyseal shaft, radius of its various portions and to determine the plane in which it resides relative to the standard coronal reference plane defined by three points: posterior side of both condyles and the greater trochanter. The following parameters were measured: length, neck-shaft angle, femoral valgus (between anatomical and mechanical axis) and neck anteversion.

Results: The largest curvature was in a plane oriented on average of 78.3°±14.9° (35.2° to 106.7°) anterolateral. The correlation between femoral curvature and neck-shaft angle (R=0.172), size (R=0.095), valgus (R=0.104) and overall curvature (R=0.60) was low.

Discussion: Implants with diaphyseal fixation are designed such that the femoral curvature resides in a strict sagittal plane. Long revision stems with diaphyseal fixation may have a tendency to rotate laterally (externally) during insertion. Correcting this external rotation to prevent anteversion may result in a less than satisfactory press-fit. The femoral curvature must be taken into account when designing intramedullary implants.

Level Of Evidence: IV, Cadaver study without control group.
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http://dx.doi.org/10.1016/j.otsr.2018.09.018DOI Listing
February 2019

Acute Tibial osteomyelitis caused by intraosseous access during initial resuscitation: a case report and literature review.

BMC Infect Dis 2018 Dec 17;18(1):665. Epub 2018 Dec 17.

Department of Internal Medicine and Infectious Diseases, University Hospital of Tours, Hospital Bretonneau, Tours, France.

Background: Intra-osseous (IO) access is recommended in cases of pre-hospital emergency or resuscitation when intravascular (IV) route is difficult or impossible. Despite recent improvement in IO devices and increasing indications, it remains rarely used in practice. Various complications have been reported but are uncommon.

Case Presentation: We report a case of massive acute tibial osteomyelitis in an adult male three months after an IO catheter insertion for emergency drug infusion. We review the literature on association between IO access and acute osteomyelitis in children and adults.

Conclusions: Emergency-care givers and radiologists should be informed about this infrequent complication in order to make early diagnosis and initiate adequate antibiotic therapy.
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http://dx.doi.org/10.1186/s12879-018-3577-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296120PMC
December 2018

Impact of setting up a bone and joint infection referral center on arthroscopic treatment of septic arthritis of the knee and shoulder: Retrospective study.

Orthop Traumatol Surg Res 2018 12 17;104(8):1265-1269. Epub 2018 Oct 17.

Société orthopédique de L'Ouest, 18, rue de Bellinière, 49800 Trélazé, France.

Introduction: Referral Centers for Bone and Joint Infection (BJI) were set up to optimize BJI management thanks to multidisciplinary teamwork. The main aim of the present study was to assess the impact of setting up the Western France Bone and Joint Infection Referral Center on arthroscopic treatment of septic arthritis of the shoulder and knee. The secondary aim was to identify other risk factors for failure of this treatment. The null hypothesis was that there was no difference between the "success group" and the "failure group".

Material And Methods: This single-center retrospective study included 52 patients treated for septic arthritis between January 1, 2000 and December 31, 2013 by arthroscopic joint lavage associated to at least 4 weeks' antibiotic therapy. Exclusion criteria comprised: retrospective diagnosis of rheumatoid arthritis after negative bacteriological analysis, early cessation of antibiotic treatment, and follow-up less than 4 weeks. Failure was defined as non-healing after first-line treatment. The primary endpoint was date of treatment compared to the launch date of the Center in the first quarter of 2010. The influence of pre- and intraoperative criteria related to patient, treatment and microorganism was assessed.

Results: At follow-up, 17 patients (32.9%) showed failure of first-line treatment and 5 (9.6%) were non-healed at end of treatment, whatever the re-intervention. The failure rate significantly decreased after setting up the Center, from 42.9% to 11.8% (p=0.03). In the failure group, 70.6% of patients showed immunosuppression, versus 37.2% in the success group (p=0.01). Neither time to surgery (p=1), type of microorganism, or performance of antiseptic lavage (p=0.25) or synovectomy (p=0.62) influenced outcome.

Conclusion: Multidisciplinary management of septic arthritis improved treatment success.

Level Of Evidence: III, Retrospective comparative study.
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http://dx.doi.org/10.1016/j.otsr.2018.08.006DOI Listing
December 2018

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.

Biomaterials 2019 03 19;196:100-108. Epub 2018 Mar 19.

INSERM U957, Lab. Pathophysiology of Bone Resorption, Faculty of Medicine, University of Nantes, Nantes, France.

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis.

Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority.

Findings: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging).

Interpretation: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic.

Funding: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).
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http://dx.doi.org/10.1016/j.biomaterials.2018.03.033DOI Listing
March 2019

A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

Stem Cells Int 2018 22;2018:6025918. Epub 2018 Feb 22.

Reparto di Ortopedia e Traumatologia, Azienda Ospedaliero-Universitaria di Modena, Largo del Pozzo 71, 41125 Modena, Italy.

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 10 hBM-MSCs is noninferior to that of 200 × 10 hBM-MSCs. The participants ( = 108) will be randomly assigned to either the experimental low dose ( = 36), the experimental high dose ( = 36), or the comparator arm ( = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.
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http://dx.doi.org/10.1155/2018/6025918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842679PMC
February 2018

Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma.

Int J Mol Sci 2018 Mar 1;19(3). Epub 2018 Mar 1.

Laboratoire d'étude des sarcomes osseux et remodelage des tissus calcifiés, INSERM UMR 1238, Université de Nantes, PhyOS, 44034 Nantes CEDEX 1, France.

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments.
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http://dx.doi.org/10.3390/ijms19030707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877568PMC
March 2018

Antibiotic therapy duration for prosthetic joint infections treated by Debridement and Implant Retention (DAIR): Similar long-term remission for 6 weeks as compared to 12 weeks.

Int J Infect Dis 2017 Oct 10;63:37-42. Epub 2017 Aug 10.

Tours University Hospital, France; Geneva University Hospitals, Switzerland.

Background: The required duration of antibiotic treatment for prosthetic joint infections (PJI) with debridement and retention of the implant (DAIR procedure) is unknown.

Methods: Multicenter retrospective study emphasizing the duration of antibiotic therapy in patients treated with by DAIR.

Results: We included 87 hip or knee PJI episodes in 87 patients from three university hospitals in France and Switzerland. All debridements were performed within 3 weeks of symptom onset. After a mean follow-up of 52.1 months, 60 patients with PJI (69%) remained in remission, with no significant difference between hip and knee cases (73.3% vs. 59.3%, 95% confidence interval (CI), 0.20-1.38), or between patients receiving 6 compared with 12 weeks of antibiotic treatment (70.5% vs.67.4%, 95%CI 0.27-2.10, p=0.60). Methicillin-resistant Staphylococcus aureus was isolated from 13.8% of infections and this was the only variable associated with a poorer outcome (remission in 41.7% vs. 73.3% for those with other pathogens, 95%CI 0.05-0.77, p=0.02).

Conclusions: In patients undergoing DAIR for hip or knee PJI, the likelihood of long-term remission was not significantly different for those receiving 6 versus 12 weeks of antibiotic therapy. Prospective randomized trials are required to confirm this observation.
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http://dx.doi.org/10.1016/j.ijid.2017.08.002DOI Listing
October 2017

Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach.

Stem Cells Int 2017 20;2017:3674045. Epub 2017 Jun 20.

Orthopedic Pathophysiology and Regenerative Medicine Unit, Rizzoli Orthopedic Institute, Bologna, Italy.

In this clinical trial, we investigated if biochemical bone turnover markers (BTM) changed according to the progression of bone healing induced by autologous expanded MSC combined with a biphasic calcium phosphate in patients with delayed union or nonunion of long bone fractures. Bone formation markers, bone resorption markers, and osteoclast regulatory proteins were measured by enzymatic immunoassay before surgery and after 6, 12, and 24 weeks. A satisfactory bone healing was obtained in 23 out of 24 patients. Nine subjects reached a good consolidation already at 12 weeks, and they were considered as the "early consolidation" group. We found that bone-specific alkaline phosphatase (BAP), C-terminal propeptide of type I procollagen (PICP), and beta crosslaps collagen (CTX) changed after the regenerative treatment, BAP and CTX correlated to the imaging results collected at 12 and 24 weeks, and BAP variation along the healing course differed in patients who had an "early consolidation." A remarkable decrease in BAP and PICP was observed at all time points in a single patient who experienced a treatment failure, but the predictive value of BTM changes cannot be determined. Our findings suggest that BTM are promising tools for monitoring cell therapy efficacy in bone nonunions, but studies with larger patient numbers are required to confirm these preliminary results.
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http://dx.doi.org/10.1155/2017/3674045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506673PMC
June 2017

Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status.

J Bone Oncol 2016 Mar 12;5(1):5-14. Epub 2015 Dec 12.

INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes F-44035, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, Nantes F-44035, France.

Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose-derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG-HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence.
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http://dx.doi.org/10.1016/j.jbo.2015.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782020PMC
March 2016

[Bone and joint infections in adults and children].

Rev Prat 2016 03;66(3):e121-e131

Service de médecine interne et maladies infectieuses, CHRU de Tours, 37000 Tours, France.

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March 2016