Charles-Henri Flouzat-Lachaniette

Induction of an inflammatory and prodegradative phenotype in autologous fibroblast-like synoviocytes by the infrapatellar fat pad from patients with knee osteoarthritis.

The infrapatellar fat pad (IFP) of the knee joint has an inflammatory phenotype in osteoarthritis (OA). Its close proximity to the synovial membrane suggests that the IFP could be involved in the induction of OA synovitis. This study was undertaken to investigate the response of fibroblast‐like synoviocytes (FLS) to autologous IFP and subcutaneous adipose tissue (SCAT) from patients with severe knee OA.

Cancer Risk Is Not Increased in Patients Treated for Orthopaedic Diseases with Autologous Bone Marrow Cell Concentrate

BACKGROUND There is concern that regenerative cell-based therapies could result in increased risk of tumor formation. We investigated the long-term risks for systemic and site-specific cancers in patients who had received autologous bone marrow-derived stromal progenitor cells to treat orthopaedic lesions. METHODS A total of 1873 patients were treated from 1990 to 2006 with bone marrow-derived concentrated cells. Patients were monitored for cancer incidence from the date of the first operation (1990) until death, or until December 31, 2011. The mean follow-up time was 12.5 years (range, five to twenty-two years). The average number of colony-forming unit fibroblasts returned to the patients was 483,000 fibroblasts (range, 62,000 to 2,095,000 fibroblasts). The primary outcome was to evaluate with radiographs and/or magnetic resonance imaging the risk of tumorigenesis at the cell therapy treatment sites. The secondary outcome was to evaluate the risk of cancer diagnosed in areas other than the treatment site during the follow-up period. The relative risk of cancer was expressed as the ratio of observed and expected number of cases, that is, the standardized incidence ratio, according to the cancer incidence in the French population. RESULTS No tumor formation was found at the treatment sites on the 7306 magnetic resonance images and 52,430 radiographs among the 1873 patients. Fifty-three cancers were diagnosed in areas other than the treatment site. On the basis of cancer incidence in the general population during the same period, the expected number of cancers was between ninety-seven and 108 for the same age and sex distribution. The range of the standardized incidence ratio for the follow-up period was between 0.49 and 0.54 (95% confidence interval, 0.30 to 0.80). CONCLUSIONS This study found no increased cancer risk in patients after application of autologous cell-based therapy using bone marrow-derived stromal progenitor cells either at the treatment site or elsewhere in the patients after an average follow-up period of 12.5 years.

The Natural Progression of Symptomatic Humeral Head Osteonecrosis in Adults with Sickle Cell Disease

BACKGROUND Osteonecrosis of the humeral head is a frequent complication in adults with sickle cell disease. However, little is known about the rate of, and the factors influencing, progression of symptomatic shoulder osteonecrosis in patients with this disease. METHODS Eighty-two adult patients with sickle cell disease and symptomatic osteonecrosis of the humeral head (104 shoulders) were identified with magnetic resonance imaging (MRI) between 1985 and 1993. Nineteen of the eighty-two patients were homozygous for hemoglobin S (S/S genotype), thirty-seven had hemoglobin S/hemoglobin C (S/C), and twenty-six had hemoglobin S/beta-thalassemia (S/T). Shoulder osteonecrosis was graded with the method of Cruess with an adaptation for MRI as proposed by Steinberg et al. for hip osteonecrosis. Annual radiographs were obtained. At the initial evaluation, thirty-eight symptomatic shoulders were designated as stage I (with osteonecrosis seen only on MRI), forty-two symptomatic shoulders were designated as stage II (radiographic evidence without collapse), and twenty-four symptomatic shoulders were designated as stage III or IV (a crescent line or collapse). RESULTS Partial or total repair with a decrease in the size of the osteonecrotic lesion or in the stage was never observed on MRI. At the time of the most recent follow-up (average, twenty years; range, fifteen to twenty-four years), collapse had occurred in eighty-nine shoulders (86%). The mean interval between the onset of pain and collapse was six years (range, six months to seventeen years; median, eight years). Of the 104 symptomatic shoulders, sixty-three (61%) with collapse worsened clinically until surgical treatment was needed. The principal risk factors for development of shoulder osteonecrosis in adults with sickle cell disease were the presence of hip osteonecrosis and the S/T or S/C genotype. The rate and risk of progression of the lesion until collapse occurred were significantly related to the S/S genotype, to a stage of II, to a large size of the osteonecrotic lesion, and to a medial or posterior location of the lesion. CONCLUSION Untreated symptomatic shoulder osteonecrosis related to sickle cell disease has a high likelihood of progressing to humeral head collapse, and the natural evolution in the long term requires surgical treatment for many of these patients.

Influence of soft tissue in the assessment of the primary stability of acetabular cup implants using impact analyses

Background: The acetabular cup (AC) implant primary stability is an important determinant for the success of cementless hip surgery but it remains difficult to assess the AC implant fixation in the clinic. A method based on the analysis of the impact produced by an instrumented hammer on the ancillary has been developed by our group (Michel et al., 2016a). However, the soft tissue thickness present around the acetabulum may affect the impact response, which may hamper the robustness of the method. The aim of this study is to evaluate the influence of the soft tissue thickness (STT) on the acetabular cup implant primary fixation evaluation using impact analyses. Methods: To do so, different AC implants were inserted in five bovine bone samples. For each sample, different stability conditions were obtained by changing the cavity diameter. For each configuration, the AC implant was impacted 25 times with 10 and 30 mm of soft tissues positioned underneath the sample. The averaged indicator Im was determined based on the amplitude of the signal for each configuration and each STT and the pull‐out force was measured. Findings: The results show that the resonance frequency of the system increases when the value of the soft tissue thickness decreases. Moreover, an ANOVA analysis shows that there was no significant effect of the value of soft tissue thickness on the values of the indicator Im (F = 2.33; p‐value = 0.13). Interpretation: This study shows that soft tissue thickness does not appear to alter the prediction of the acetabular cup implant primary fixation obtained using the impact analysis approach, opening the path towards future clinical trials. HighlightsNo effect of the tissue thickness is observed on the indicator of implant stabilityThe resonance frequency decreases when soft tissue thickness increasesThe indicator derived from impacts measurements can be used to assess the acetabular cup stability in vitro

Particularities of anterior fusion in L4-L5 isthmic spondylolisthesis.

PURPOSE L4-L5 isthmic spondylolisthesis may be associated with lumbosacral transitional vertebrae (LSTV) and altered venous vascular anatomy. The objectives of this study were to describe the anatomical characteristics of L4-L5 ISPL and the intraoperative difficulties encountered during the approach for anterior lumbar interbody fusion (ALIF). METHODS This is a retrospective review of 20 ALIFs for L4-L5 ISPL. The anatomy of the common iliac veins confluence and the position of L4-L5 with respect to the projection of the iliac crest were analysed on CT-scan. Intraoperative difficulties were noted. RESULTS A LSTV was present in 60% of cases, associated with abnormally distal positioning of L4-L5 below the projection of the iliac crest. The common iliac veins confluence was abnormally proximal compared to L4-L5. No complication was noted, even if the approach was unusually difficult in 11 cases. DISCUSSION Anterior lumbotomies are difficult because the left common iliac vein courses transversely across the left anterolateral aspect of the L4-L5 disc and L5 vertebral body, increasing the risk of vascular injury. Those difficulties have led us to abandon lumbotomies to treat L4-L5 ISPL to favour a pure anterior approach (midline) or an exclusive posterior approach. LEVEL OF EVIDENCE IV (retrospective study).

Ex Vivo Evaluation of Cementless Acetabular Cup Stability Using Impact Analyses with a Hammer Instrumented with Strain Sensors

The acetabular cup (AC) implant stability is determinant for the success of cementless hip arthroplasty. A method based on the analysis of the impact force applied during the press-fit insertion of the AC implant using a hammer instrumented with a force sensor was developed to assess the AC implant stability. The aim of the present study was to investigate the performance of a method using a hammer equipped with strain sensors to retrieve the AC implant stability. Different AC implants were inserted in five bovine samples with different stability conditions leading to 57 configurations. The AC implant was impacted 16 times by the two hammers consecutively. For each impact; an indicator IS (respectively IF) determined by analyzing the time variation of the signal corresponding to the averaged strain (respectively force) obtained with the stress (respectively strain) hammer was calculated. The pull-out force F was measured for each configuration. F was significantly correlated with IS (R2 = 0.79) and IF (R2 = 0.80). The present method has the advantage of not modifying the shape of the hammer that can be sterilized easily. This study opens new paths towards the development of a decision support system to assess the AC implant stability.

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

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 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 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.

Monitoring cementless femoral stem insertion by impact analyses: An in vitro study

The primary stability of the femoral stem (FS) implant determines the surgical success of cementless hip arthroplasty. During the insertion, a compromise must be found for the number and energy of impacts that should be sufficiently large to obtain an adapted primary stability of the FS and not too high to decrease fracture risk. The aim of this study is to determine whether a hammer instrumented with a force sensor can be used to monitor the insertion of FS. Cementless FS of different sizes were impacted in four artificial femurs with an instrumented hammer, leading to 72 configurations. The impact number when the surgeon empirically felt that the FS was fully inserted was noted Nsurg. The insertion depth E was assessed using video motion tracking and the impact number Nvid corresponding to the end of the insertion was estimated. For each impact, two indicators noted I and D were determined based on the analysis of the variation of the force as a function of time. The pull-out force F was significantly correlated with the indicator I (R2 = 0.67). The variation of D was analyzed using a threshold to determine an impact number Nd, which is shown to be closely related to Nsurg and Nvid, with an average difference of around 0.2. This approach allows to determine i) the moment when the surgeon should stop the impaction procedure in order to obtain an optimal insertion of the FS and ii) the FS implant primary stability. This study paves the way towards the development of a decision support system to assist the surgeon in hip arthroplasty.

Return to sports and quality of life after high tibial osteotomy in patients under 60 years of age.

INTRODUCTION Since knee osteoarthritis is unicompartmental in most cases, a knee osteotomy is the most logical solution to limit degeneration of the arthritic compartment, thereby delaying knee arthroplasty. Younger patients have high functional demands. The purpose of this study was to evaluate the return to sports and quality of life after high tibial osteotomy (HTO) in athletic patients less than 60 years of age. The hypothesis was that patients can return to sports within 1 year of HTO. MATERIALS AND METHODS A single-centre, retrospective study was performed of 30 patients under 60 years of age with medial tibiofemoral osteoarthritis and no history of surgery or trauma who underwent HTO between January 2014 and August 2015. The primary endpoint was the return to sport at 1 year based on the Tegner score. Secondary endpoints were the subjective IKDC score, Lysholm score and SF-36. RESULTS The mean follow-up was 1.3 years [1-1.5] and no patients were lost to follow-up. All the patients had returned to sports at 1 year: 73.3% at their pre-surgery level (before the pain started) and 23.3% at a higher level. Their quality of life was significantly improved according to the SF-36 questionnaire: 65.3% pre-operatively compared with 72.5% postoperatively (P=0.01). The preoperative and 1-year postoperative scores were comparable for the Tegner (P=0.167), IKDC (P=0.093) and Lysholm (P=0.061). CONCLUSION HTO allows patients to resume their sports activities within 1 year of surgery and significantly improves their quality of life. LEVEL OF EVIDENCE Level IV - Retrospective cohort study.

SPEED OF SOUND MEASUREMENT IN PORCINE INTERVERTEBRAL DISCS: AN IN VITRO STUDY

Disc degeneration is associated with premature ageing of intervertebral discs (IVD) and a gradual degradation of the nucleus pulposus (NP) biomechanical properties. The objective of this study is to investigate whether quantitative ultrasound (QUS) technique can be used to determine the speed of sound (SOS) in the NP and to correlate SOS with histological measurements. The ultrasonic measurements are realized with a 3.5MHz focused monoelement transducer used in echographic mode. The value of the interspecimen variability of SOS is significantly superior than the reproducibility of the measurements, which indicates that the technique is sensitive to variations of the material properties of the NP. A significant correlation between SOS values and the percentage of physaliphorous cells ratios is obtained (R2=0.68) when considering all samples. QUS can be useful to assess the biomechanical properties of the IVD, which may be useful in the context of tissue engineering applications.