Predictors of fracture healing in patients with recalcitrant nonunions treated with autologous culture expanded bone marrow-derived mesenchymal stromal cells.

The study reports the prospective outcome of treating severe recalcitrant fracture nonunion in patients with autologous bone marrow-derived mesenchymal stromal cells (BMSC) from 2003 to 2010 and analyze predictors of union. Autologous BMSC were culture expanded and inserted at nonunion site with or without carriers in addition to surgical stabilization of the fracture. Radiological union was ascertained by musculoskeletal radiologists on plain radiographs and/or CT scans. A logistic regression analysis was performed with cell-expansion parameters (cell numbers, cell doubling time) and known clinical factors (e.g., smoking and diabetes) as independent variables and fracture union as the dependent variable to identify the factors that influence bony healing. An Eq5D index score assessed the effect of treatment on general quality of health. A total of 35 patients (mean age 51+/-13 years) with established nonunion (median 2.9 years, 1-33) and, at least one failed nonunion surgery (median 4,1-14) received treatment. Fracture union was achieved in 21 patients (60%; 95%CI 44-75) at 2.6 years. Multiple penalized logistic regression revealed faster cell doubling time (p = 0.07), absence of diabetes (p = 0.003), less previous surgeries (p = 0.008), and lower age at cell implantation (p = 0.02) were significant predictors for fracture union. A significant increase in Eq5D index (p = 0.01) was noted with a mean rise of the score by 0.34 units (95%CI 0.11-0.58) at 1 year following the study. In summary, the study revealed cell doubling time as a novel in vitro parameter in conjunction with age, multiple surgeries, and diabetes as being significant predictors of the fracture union. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res

Dual energy computed tomography in gout: our experience

© 2021 The Authors. Published by Radiance Research Academy. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.31782/IJCRR.2021.131432Introduction: Gout is a common medical problem, affecting at least 1% of men in Western countries, with a male: female ratio ranging from 7:1 to 9:1. For many patients, traditional investigations can be inconclusive. Dual Energy Computed Tomography (DECT) is emerging as a valuable tool for non-invasive confirmation of urate deposits in painful joints. Aim: To establish the effectiveness of the DECT in the identification of gout in patients with complex presentations where the diagnosis is not clear. Method: DECT at 140 kV and 80kV was used to image patients where the clinical diagnosis was unclear Results: Seven case studies are presented where an unclear clinical presentation was successfully diagnosed with the use of DECT. Conclusion: In a specialist tertiary referral centre, treating many patients whose presentation is atypical, DECT has become a valuable tool in confirming the presence or absence of gouty arthritis, in difficult cases with a diagnostic dilemmaPublished versio

Histological and Radiological Assessment of Endogenously Generated Repair Tissue In Vivo Following a Chondral Harvest.

OBJECTIVE: To examine repair tissue formed approximately 15 months after a chondral harvest in the human knee. DESIGN: Sixteen individuals (12 males, 4 females, mean age 36 ± 9 years) underwent a chondral harvest in the trochlea as a pre-requisite for autologous chondrocyte implantation (ACI) treatment. The harvest site was assessed via MRI at 14.3 ± 3.2 months and arthroscopy at 15 ± 3.5 months (using the Oswestry Arthroscopy Score [O-AS] and the International Cartilage Repair Society Arthroscopy Score [ICRS-AS]). Core biopsies (1.8 mm diameter, n = 16) of repair tissue obtained at arthroscopy were assessed histologically (using the ICRS II and OsScore histology scores) and examined via immunohistochemistry for the presence of collagen types I and II. RESULTS: The mean O-AS and ICRS-AS of the repaired harvest sites were 7.2 ± 3.2 and 10.1 ± 3.5, respectively, with 80.3% ± 26% repair fill depth on MRI. The histological quality of the repair tissue formed was variable, with some hyaline cartilage present in 50% of the biopsies; where this occurred, it was associated with a significantly higher ICRS-AS than those with no hyaline cartilage present (median 11 vs. 7.5, P = 0.049). Collagen types I and II were detected in 12/14 and 10/13 biopsies, respectively. CONCLUSIONS: We demonstrate good-quality structural repair tissue formed following cartilage harvest in ACI, suggesting this site can be useful to study endogenous cartilage repair in humans. The trochlea is less commonly affected by osteoarthritis; therefore, location may be critical for spontaneous repair. Understanding the mechanisms and factors influencing this could improve future treatments for cartilage defects

Migratory Loose Bodies from the Ankle Joint into the Flexor Hallucis Longus Tendon Sheath

Objective: Loose bodies resulting from any form of osteochondral insult can migrate out of their intra-articular position to adjacent compartments. This retrospective study aims to illustrate the phenomenon of loose bodies migration from the ankle joint into the flexor hallucis longus (FHL) tendon sheath. Materials and Methods: Cases of loose bodies in the FHL tendon sheath were identified from the authors' radiological database by way of keyword interrogation, covering the modalities of CT, MRI, and ultrasound over a period of 11 years. The imaging features of the loose bodies were recorded, together with the presence of ankle instability and osteoarthritis. Patient demographics and relevant history, including trauma and surgery, were collected. Results: Thirty-four cases including 33 patients, with a total of 125 loose bodies in the FHL tendon sheath, were identified. There were 58 loose bodies (46.4%) in Zone 1 of the FHL tendon sheath, 65 loose bodies (52%) in Zone 2, and 2 loose bodies (1.6%) in Zone 3. All patients had features of ankle osteoarthritis on imaging, 14 of which had imaging features of ankle instability, and 19 patients had previous ankle trauma. Conclusion: Osteochondral loose bodies originating from the ankle joint can migrate into the FHL tendon sheath. It is important to recognise this phenomenon as a distinct entity, different from primary tenosynovial chondromatosis of the FHL tendon sheath, which may have a different surgical management and clinical outcome. Detection of FHL tendon sheath loose bodies should also prompt closer examination for articular disease in the ankle joint

A Convolutional Approach to Vertebrae Detection and Labelling in Whole Spine MRI

We propose a novel convolutional method for the detection and identification of vertebrae in whole spine MRIs. This involves using a learnt vector field to group detected vertebrae corners together into individual vertebral bodies and convolutional image-to-image translation followed by beam search to label vertebral levels in a self-consistent manner. The method can be applied without modification to lumbar, cervical and thoracic-only scans across a range of different MR sequences. The resulting system achieves 98.1% detection rate and 96.5% identification rate on a challenging clinical dataset of whole spine scans and matches or exceeds the performance of previous systems on lumbar-only scans. Finally, we demonstrate the clinical applicability of this method, using it for automated scoliosis detection in both lumbar and whole spine MR scans.Comment: Accepted full paper to Medical Image Computing and Computer Assisted Intervention 2020. 11 pages plus appendi

Osteochondral Lesions of the Ankle Treated with Bone Marrow Concentrate with Hyaluronan and Fibrin: A Single-Centre Study.

Osteochondral defects of the ankle (OCD) are being increasingly identified as a clinically significant consequence of injury to the ankle, with the potential to lead to osteoarthritis if left untreated. The aim of this retrospective cohort study was to evaluate a single-stage treatment of OCD, based on bone marrow aspirate (BMA) centrifuged to produce bone marrow concentrate (BMC). In a dual syringe, the concentrate was mixed with thrombin in one syringe, whereas hyaluronan and fibrinogen were mixed in a second syringe. The two mixtures were then injected and combined into the prepared defect. Clinical outcome and quality of life scores (MOXFQ and EQ-5D) were collected at baseline and yearly thereafter. Multilevel models were used to analyse the pattern of scores over time. Ninety-four patients were treated between 2015 and 2020. The means of each of the three components of the MOXFQ significantly improved between baseline and 1 year (p < 0.001 for each component), with no further change from year 1 to year 3. The EQ-5D index also improved significantly from baseline to 1 year, with no evidence for further change. Our results strongly indicate that this BMC treatment is safe for, and well tolerated by, patients with OCD of the ankle as both primary treatment and those who have failed primary treatment. This technique provides a safe, efficacious alternative to currently employed cartilage repair techniques, with favourable outcomes and a low complication rate at 36 months

Combined Autologous Chondrocyte and Bone Marrow Mesenchymal Stromal Cell Implantation in the Knee: An 8-year Follow Up of Two First-In-Man Cases

Autologous chondrocyte implantation (ACI) has been used to treat cartilage defects for >20 years, with promising clinical outcomes. Here, we report two first-in-man cases (patient A and B) treated with combined autologous chondrocyte and bone marrow mesenchymal stromal cell implantation (CACAMI), with 8-year follow up. Two patients with International Cartilage Repair Society (ICRS) grade III-IV cartilage lesions underwent a co-implantation of autologous chondrocytes and bone marrow-derived mesenchymal stromal cells (BM-MSCs) between February 2008 and October 2009. In brief, chondrocytes and BM-MSCs were separately isolated and culture-expanded in a good manufacturing practice laboratory for a period of 2-4 weeks. Cells were then implanted in combination into cartilage defects and patients were clinically evaluated preoperatively and postoperatively, using the self-reported Lysholm knee score and magnetic resonance imaging (MRI). Postoperative Lysholm scores were compared with the Oswestry risk of knee arthroplasty (ORKA) scores. Patient A also had a second-look arthroscopy, at which time a biopsy of the repair site was taken. Both patients demonstrated a significant long-term improvement in knee function, with postoperative Lysholm scores being consistently higher than ORKA predictions. The most recent Lysholm scores, 8 years after surgery were 100/100 (Patient A) and 88/100 (Patient B), where 100 represents a fully functioning knee joint. Bone marrow lesion (BML) volume was shown to decrease on postoperative MRIs in both patients. Cartilage defect area increased in patient A, but declined initially for patient B, slightly increasing again 2 years after treatment. The repair site biopsy taken from patient A at 14 months postoperatively, demonstrated a thin layer of fibrocartilage covering the treated defect site. The use of a combination of cultured autologous chondrocytes and BM-MSCs appears to confer long-term benefit in this two-patient case study. Improvements in knee function perhaps relate to the observed reduction in the size of the BML

The synovial fluid from patients with focal cartilage defects contains mesenchymal stem/stromal cells and macrophages with pro- and anti-inflammatory phenotypes

Objective The synovial fluid (SF) of patients with focal cartilage defects contains a population of poorly characterised cells that could have pathophysiological implications in early osteoarthritis and joint tissue repair. We have examined the cells within SF of such joints by determining their chondrogenic capacity following culture expansion and establishing the phenotypes of the macrophage subsets in non-cultured cells. Design Knee SF cells were obtained from 21 patients receiving cell therapy to treat a focal cartilage defect. Cell surface immunoprofiling for stem cell and putative chondrogenic markers, and the expression analysis of key chondrogenic and hypertrophic genes were conducted on culture-expanded SF cells prior to chondrogenesis. Flow cytometry was also used to determine the macrophage subsets in freshly isolated SF cells. Results Immunoprofiling revealed positivity for the monocyte/macrophage marker (CD14), the haematopoietic/endothelial cell marker (CD34) and mesenchymal stem/stromal cell markers (CD73, CD90, CD105) on culture expanded cells. We found strong correlations between the presence of CD14 and the vascular cell adhesion marker, CD106 (r=0.81, p=0.003). Collagen type II expression after culture expansion positively correlated with GAG production (r=0.73, p=0.006), whereas CD90 (r=-0.6, p=0.03) and CD105 (r=-0.55, p=0.04) immunopositivity were inversely related to GAG production. Freshly isolated SF cells were positive for both pro- (CD86) and anti-inflammatory markers (CD163 and CD206). Conclusions The cellular content of the SF from patients with focal cartilage injuries is comprised of a heterogeneous population of reparative and inflammatory cells. Additional investigations are needed to understand the role played by these cells in the attempted repair and inflammatory process in diseased joints

The spine in Paget’s disease

Paget’s disease (PD) is a chronic metabolically active bone disease, characterized by a disturbance in bone modelling and remodelling due to an increase in osteoblastic and osteoclastic activity. The vertebra is the second most commonly affected site. This article reviews the various spinal pathomechanisms and osseous dynamics involved in producing the varied imaging appearances and their clinical relevance. Advanced imaging of osseous, articular and bone marrow manifestations of PD in all the vertebral components are presented. Pagetic changes often result in clinical symptoms including back pain, spinal stenosis and neural dysfunction. Various pathological complications due to PD involvement result in these clinical symptoms. Recognition of the imaging manifestations of spinal PD and the potential complications that cause the clinical symptoms enables accurate assessment of patients prior to appropriate management

Treatment of bone tumours by radiofrequency thermal ablation

Radiofrequency thermal ablation (RFTA) is considered the treatment of choice for osteoid osteomas, in which it has long been safely used. Other benign conditions (chondroblastoma, osteoblastoma, giant cell tumour, etc.) can also be treated by this technique, which is less invasive than traditional surgical procedures. RFTA ablation is also an option for the palliation of localized, painful osteolytic metastatic and myeloma lesions. The reduction in pain improves the quality of life of patients with cancer, who often have multiple morbidities and a limited life expectancy. In some cases, these patients are treated with RFTA because conventional therapies (surgery, radiotherapy, chemotherapy, etc.) have been exhausted. In other cases, it is combined with conventional therapies or other percutaneous treatments, e.g., cementoplasty, offering faster pain relief and bone strengthening. A multidisciplinary approach to the management of these patients is recommended to select the optimal treatment, including orthopaedic surgeons, neurosurgeons, medical and radiation oncologists and interventional radiologists