Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with
Introduction. Chondrocytes are enveloped within the pericellular matrix (PCM), a structurally intricate network primarily demarcated by the presence of collagen type VI microfibrils and perlecan, resembling a protective cocoon. The PCM serves pivotal functions in facilitating cell mechanoprotection and mechanotransduction. The progression of osteoarthritis (OA) is associated with alterations in the spatial arrangement of chondrocytes, transitioning from single strings to double strings, small clusters, and eventually coalescing into large clusters in advanced OA stages. Changes in cellular patters coincide with structural degradation of the PCM and loss of biomechanical properties. Here, we systematically studied matrix metalloproteinases (MMPs), their distribution, activity, and involvement in PCM destruction, utilizing chondrocyte arrangement as an OA biomarker. Methods. Cartilage specimens were obtained from 149 osteoarthritis (OA) patients, and selected based on the predominant spatial pattern of chondrocytes. Immunoassays were employed to screen for the presence of various MMPs (-1, -2, -3, -7, -8, -9, -10, -12, -13). Subsequently, the presence and activity of elevated MMPs were further investigated through immunolabeling, western blots and zymograms. Enzymatic assays were utilized to demonstrate the direct involvement of the targeted MMPs in the PCM destruction. Results. Screening revealed increased levels of MMP-1, -2, -3, -7, and -13, with their expression profile demonstrating a distinct dependency on the stage of degeneration. We found that MMP-2 and -3 can directly compromise the integrity of collagen type VI, whereas MMP-3 and MMP-7 disrupt perlecan. Conclusions. Presence of both pro- and active forms of MMP-2, -3, and -7 in OA-induced patterns, along with their direct involvement in collagen type VI and perlecan degradation, underscores their crucial role in early PCM destruction. Given the early stages of the disease already exhibit heightened MMP expression, this understanding could inform early
The burden of osteoporosis (OP), and its accompanied low energy fractures, is ever increasing. Targeted therapies are under development to stem the tide of the disease, with microRNAs identified as biomarkers and potential targets. Assessing the functional capacity of bone marrow mesenchymal stromal cells (BMSC) from patients with low energy neck of femur fractures (NOF) will identify the expected outcomes to be achieved from new,
Introduction. Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration, inflammation, and pain. Current treatments provide only symptomatic relief, necessitating novel molecular targets. The caspase family, known for its roles in apoptosis and inflammation regulation, may additionally influence crucial processes for cartilage homeostasis such as differentiation and proliferation. However, the specific roles of individual caspases in OA pathogenesis remain unclear. This study aims to investigate the involvement of the caspase family in OA and as potential
Mesoporous bioactive glasses (MBGs) have been widely studied as bone regeneration systems, due to their bioactivity and ability to store and release therapeutic agents with specific biological functions. The incorporation of these nanomaterials into a thermosensitive hydrogel (TSH), in which a solution undergoes a sol-gel transition under physiological conditions, represents a promising approach to design multifunctional devices able to deliver selected molecules to pathological sites. In fact, this system can perfectly fit the defect cavity shape prior to the complete gelation, and acts as a carrier for therapeutic agents prolonged release in situ. This challenging concept is the underlying idea of the MOZART project, whose objective was to develop a library of MBGs containing different therapeutic ions and drugs, to be used as a new, smart platform technology for highly
Aim. Decubitus ulcers are found in approximately 4.7% of hospitalized patients, with a higher prevalence (up to 30%) among those with spinal cord injuries. These ulcers are often associated with hip septic arthritis and/or osteomyelitis involving the femur. Girdlestone resection arthroplasty is a surgical technique used to remove affected proximal femur and acetabular tissues, resulting in a substantial defect. The vastus lateralis flap has been employed as an effective option for managing this dead space. The aim of this study was to evaluate the long-term outcomes of this procedure in a consecutive series of patients. Method. A retrospective single-center study was conducted from October 2012 to December 2022, involving 7 patients with spinal cord injuries affected by chronic severe septic hip arthritis and/or femoral head septic necrosis as a consequence of decubitus ulcers over trochanter area. All patients underwent treatment using a multidisciplinary approach by the same surgical team (orthopedic and plastic surgeons) along with infectious disease specialists. The treatment consisted of a one-stage procedure combining Girdlestone resection arthroplasty with unilateral vastus lateralis flap reconstruction, alongside
While STS as a group represent a significant portion of all solid tumors in childhood, individual histologic entities are rare due to their extreme heterogeneity. This represents the principal obstacle to clinical trials. A compromise between clinical vs. statistical precision has been necessary in the majority of clinical trials on STS resulting in contradictory conclusions. Clinical trials have to reduce uncertainty but trials, which overlook clinical heterogeneity can even contribute to it. An example is many clinical trials, which have been carried out in the recent decades to answer the question of the role of adjuvant chemotherapy in “Non-RMS-STS”. Majority of these trials have overlooked clinically relevant subgroups. The result is that we still do not have certainty whether and which adjuvant chemotherapy is beneficial. In addition, most clinical trials of treatments for STS rely on the endpoints of survival or event-free survival, so results have taken years to accrue and even longer to report. However, in STS with well defined genetic abnormalities and strong preclinical rationale for activity of a molecular
Infected non-unions of proximal femoral fractures are difficult to treat. If debridement and revision fixation is unsuccessful, staged revision arthroplasty may be required. Non-viable tissue must be resected, coupled with the introduction of an antibiotic-eluting temporary spacer prior to definitive reconstruction. Definitive tissue microbiological diagnosis and
Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Upregulation of specific microRNAs has been identified in-vivo in osteoporotic patients. It is hypothesized that modulation of specific mircoRNA expression may have a key role in future
Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity . 1,2,3. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Up-regulation of specific microRNAs has been identified in-vivo in osteoporotic patients . 4,5. It is hypothesized that modulation of specific microRNA expression may have a key role in future
Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve.Aims
Methods
This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.Aims
Methods
Multiple myeloma (MM) is a chronic, malignant B-cell disorder, with a less than 50% 5-year survival rate [1]. This disease is responsible for vertebral compression fractures (VCFs) in 34 to 64% of diagnosed patients [1], and at least 80% of MM patients experience pathological fractures [3]. Even though reduced DXA-derived bone mineral density (BMD) has been observed in MM patients with vertebral fractures [4], the current quantitative standard method is insufficient in MM due to the osteo-destructive bone changes. Finite-element (FE) analysis is a computational and non-destructive modeling and testing approach to determine bone strength using 3D bone models from CT images. Thus, this study aimed to assess the differences in FE-predicted critical fracture load in MM patients with and without VCFs in the thoracic and lumbar segments of the spine. Multi-detector CT (MDCT) images of two radiologically assessed MM patients (1 with VCFs and 1 without VCFs) were used to generate three-dimensional (3D) models of the whole spine. For each subject, the thoracic segments, 1 to 12 (T1-T12) and lumbar segments, 1 to 5 (L1-L5) were segmented and meshed. Heterogeneous, non-linear anisotropic material properties were applied by discretizing each vertebral segment into 10 distinct sets of materials. A compressive load was simulated by constraining the surface nodes on the inferior endplate in all directions, and a displacement load was applied on the surface nods on the superior endplate [2]. This analysis was performed using ABAQUS version 6.10 (Hibbitt, Karlsson, and Sorensen, Inc., Pawtucket, RI, USA). The MM subject with VCFs had originally experienced fractures in the T4, T5, T12, L1, and L5 segments whereas the MM subject without VCFs experienced none. The former displayed large and abrupt differences in fracture loads between adjacent vertebrae segments, unlike the latter, which exhibited progressive differences instead (no abrupt changes between adjacent vertebrae segments observed). Results from this preliminary study suggest that segments at high risk of fracture are collectively involved in an unstable network, which place the vertebral segments with high values of fracture loads (peaks) as well as the adjacent segments at risk of VCF. For instance, the high fracture load at T11 places T10, T11 and T12 at risk of fracture. Accordingly, T12 has already fractured, and T10 and T11 remain at risk. The relative changes between adjacent vertebrae segments that indicate instability (extremely high fracture load values) enables ease of identification of segments at high fracture risk. Clinicians would be able to work with pre-emptive treatment strategies in future as they can focus on more
The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures.Aims
Methods
Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan.Aims
Methods
This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.Aims
Methods
Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures.Aims
Methods
Introduction. Plantar fasciopathy is a common cause of heel pain, and is usually treated in primary practice with conservative measures. Intractable cases can prove very difficult to treat. Currently plantar fasciopathy is not routinely imaged and treatment is empirical. At the Royal Surrey County Hospital patients with intractable plantar fasciopathy are managed in a unique ‘one-stop’ Heel Pain clinic. Here they undergo clinical assessment, ultrasound scanning and
For rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis. We reviewed 15 patients over a five-year period (January 2017 to December 2022) who had undergone extra-articular resection of the hip joint due to malignant tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis. Each of the 15 patients had a single lesion, with six originating from the acetabulum side and nine from the proximal femur. All patients had their posterior column preserved according to the surgical plan.Aims
Methods
Beadmill processing combined with automated blood culture bottle methods (BACTEC™) has a greater sensitivity and specificity, and a shorter time to positivity compared with primary plates (PP) for prosthetic joint infection (PJI) diagnosis but the clinical impact of Bactec on antimicrobial therapy has not yet been evaluated. We compared time-to-positivity of Columbia agar with horse blood plates (BA) and chocolatized horse blood plates (CHOC) versus anaerobic (ANA) and aerobic blood culture bottles (02) in patients with PJI. We compared the contributions of the two methods to the commencement of effective and targeted antimicrobial therapy. Retrospective observational study from June 2013 to March 2014. Inclusion criteria were confirmed PJI (IDSA criteria) with at least 2 perioperative samples. After beadmill processing BA and CHOC plates were incubated for 2 days and discarded if negative, BactecTM bottles were incubated for 14 days and sub-cultured if positive. MALDI-TOF (Microflex, Brucker) was used for identification and all isolates had sensitivities performed (Phoenix, BD). Standard empirical antibiotic treatment was teicoplanin, piperacillin/tazobactam and amikacin. We defined time to switch as difference between date of sample collection and date of commencing targeted or effective therapy; prior antibiotic therapy was defined as the use of antibiotics within 14 days before samples collection. Fifty cases were identified during the study period. 330 microbiological isolates were included: 24 (7.3%) were considered contaminants; 153 isolates (50.0%) were detected both from BactecTM and PP; 152 (49.7%) from BactecTM only; 1 isolate (0.3%) from PP only. 17 (34%) diagnoses of PJI was made exclusively by BactecTM. The majority of isolates on BA and CHOC plates grew in the first 24 hours (81.2% and 77.5% respectively). 293/305 isolates from BactecTM (96.1%) grew in the first 2 days. Antibiograms were available after 2.5 days from PP versus 4 days from BACTEC (p<0.0001). When we compared time to switch from empiric to