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
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
To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
Methods
This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival.Aims
Methods
We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton. We conducted a retrospective study on a population-based cohort of all adult patients treated surgically for bony metastases of the appendicular skeleton between January 2014 and December 2019. We excluded patients in whom the status of bone metastases and resection margin was unknown. Patients were followed until the end of the study or to their death. We had no loss to follow-up. We used Kaplan-Meier analysis (with log-rank test) to evaluate patient survival. We identified 506 operations in 459 patients. A total of 120 operations (in 116 patients) were for solitary metastases and 386 (in 345 patients) for multiple metastases. Of the 120 operations, 70 (in 69 patients) had no/an unknown status of visceral metastases (solitary group) and 50 (in 49 patients) had visceral metastases. In the solitary group, 45 operations (in 44 patients) were R0 (resections for cure or complete remission) and 25 (in 25 patients) were R1/R2 (resections leaving microscopic or macroscopic tumour, respectively). The most common types of cancer in the solitary group were kidney (n = 27), lung (n = 25), and breast (n = 20).Aims
Methods
Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion.Aims
Methods
Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP. Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.Aims
Methods
The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset.Aims
Methods
The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied.Aims
Methods
Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture. This single tertiary-institutional, retrospectively matched case-control study included 72 patients who underwent prophylactic or therapeutic fixation for pathological fracture of the humerus, femur, or tibia with either a titanium (control group, n = 36) or carbon fibre (case group, n = 36) intramedullary nail between 2016 to 2020. Patients were excluded if intramedullary fixation was combined with any other surgical procedure/fixation method. Outcomes included operating time, blood loss, fluoroscopic time, and complications. Fisher’s exact test and Mann-Whitney U test were used for categorical and continuous outcomes, respectively.Aims
Methods
Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS).Aims
Methods
A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined.Aims
Methods
The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls.Aims
Methods
The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this. This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression.Aims
Methods
Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).Aims
Methods
In recent years, machine learning (ML) and artificial neural networks (ANNs), a particular subset of ML, have been adopted by various areas of healthcare. A number of diagnostic and prognostic algorithms have been designed and implemented across a range of orthopaedic sub-specialties to date, with many positive results. However, the methodology of many of these studies is flawed, and few compare the use of ML with the current approach in clinical practice. Spinal surgery has advanced rapidly over the past three decades, particularly in the areas of implant technology, advanced surgical techniques, biologics, and enhanced recovery protocols. It is therefore regarded an innovative field. Inevitably, spinal surgeons will wish to incorporate ML into their practice should models prove effective in diagnostic or prognostic terms. The purpose of this article is to review published studies that describe the application of neural networks to spinal surgery and which actively compare ANN models to contemporary clinical standards allowing evaluation of their efficacy, accuracy, and relatability. It also explores some of the limitations of the technology, which act to constrain the widespread adoption of neural networks for diagnostic and prognostic use in spinal care. Finally, it describes the necessary considerations should institutions wish to incorporate ANNs into their practices. In doing so, the aim of this review is to provide a practical approach for spinal surgeons to understand the relevant aspects of neural networks. Cite this article:
Open discectomy (OD) is the standard operation for lumbar disc herniation (LDH). Percutaneous endoscopic lumbar discectomy (PELD), however, has shown similar outcomes to OD and there is increasing interest in this procedure. However despite improved surgical techniques and instrumentation, reoperation and infection rates continue and are reported to be between 6% and 24% and 0.7% and 16%, respectively. The objective of this study was to compare the rate of reoperation and infection within six months of patients being treated for LDH either by OD or PELD. In this retrospective, nationwide cohort study, the Korean National Health Insurance database from 1 January 2007 to 31 December 2018 was reviewed. Data were extracted for patients who underwent OD or PELD for LDH without a history of having undergone either procedure during the preceding year. Individual patients were followed for six months through their encrypted unique resident registration number. The primary endpoints were rates of reoperation and infection during the follow-up period. Other risk factors for reoperation and infection were also evalulated.Aims
Methods
Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA. The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype.Aims
Methods
We aimed to investigate if the use of the largest possible cobalt-chromium head articulating with polyethylene acetabular inserts would increase the in vivo wear rate in total hip arthroplasty. In a single-blinded randomized controlled trial, 96 patients (43 females), at a median age of 63 years (interquartile range (IQR) 57 to 69), were allocated to receive either the largest possible modular femoral head (36 mm to 44 mm) in the thinnest possible insert or a standard 32 mm head. All patients received a vitamin E-doped cross-linked polyethylene insert and a cobalt-chromium head. The primary outcome was proximal head penetration measured with radiostereometric analysis (RSA) at two years. Secondary outcomes were volumetric wear, periacetabular radiolucencies, and patient-reported outcomes.Aims
Methods
Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI.Aims
Methods
Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in
Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article:
With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values. We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected.Aims
Methods
Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.Aims
Methods
Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between Aims
Methods
As the peak of the COVID-19 pandemic passes, the challenge shifts to safe resumption of routine medical services, including elective orthopaedic surgery. Protocols including pre-operative self-isolation, COVID-19 testing, and surgery at a non-COVID-19 site have been developed to minimize risk of transmission. Despite this, it is likely that many patients will want to delay surgery for fear of contracting COVID-19. The aim of this study is to identify the number of patients who still want to proceed with planned elective orthopaedic surgery in this current environment. This is a prospective, single surgeon study of 102 patients who were on the waiting list for an elective hip or knee procedure during the COVID-19 pandemic. Baseline characteristics including age, ASA grade, COVID-19 risk, procedure type, surgical priority, and admission type were recorded. The primary outcome was patient consent to continue with planned surgical care after resumption of elective orthopaedic services. Subgroup analysis was also performed to determine if any specific patient factors influenced the decision to proceed with surgery.Aims
Methods
Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing. The present study provides an update of a previously published prospective randomized controlled study, evaluating the serum cobalt levels of a consecutive cohort of 100 patients following THA with a MoM or a CoP articulation. A total of 31 patients were available for clinical and radiological follow-up examination. After exclusion of 11 patients because of other cobalt-containing implants, 20 patients (MoM (n = 11); CoP (n = 9)) with a mean age of 69 years (42 to 97) were analyzed. Serum cobalt levels were compared to serum cobalt levels five years out of surgery.Aims
Methods
To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity.Aims
Methods
This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs.Aims
Methods
Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.
Aims. Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells. Methods. We investigated the specific role of GNAQ using GNAQ wild-type cell lines (non-small-cell
The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death. This was a retrospective cohort study of consecutive patients referred to the orthopaedic department at a UK trauma centre with a proximal femoral metastasis (PFM) over a seven-year period (2010 to 2016). The study group were compared to a matched control group of non-metastatic hip fractures. Minimum follow-up was one year.Aims
Methods
MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.Objectives
Methods
Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment. This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded.Aims
Patients and Methods
This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM). We retrospectively reviewed the electronic medical records of 338 patients who underwent surgical treatment for metastatic spinal disease. The enrolled patients were divided into two groups. The SM-IMM group included patients with no history of malignancy whose site of primary malignancy was diagnosed after the identification of spinal metastasis. The other group included patients with a history of treatment for primary malignancy who then developed spinal metastasis (SM-DTM). The incidence of SM-IMM by site of primary malignancy was calculated. The difference between prognoses after surgical treatment for SM-IMM and SM-DTM was established.Aims
Patients and Methods
The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression. The medical records of 135 patients with complete paralysis due to neoplastic cord compression were retrospectively reviewed. Potential factors including the timing of surgery, muscular tone, and tumour characteristics were analyzed in relation to neurological recovery using logistical regression analysis. The association between neurological recovery and survival was analyzed using a Cox model. A nomogram was formulated to predict recovery.Aims
Patients and Methods
The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular. English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.Objectives
Methods
Pelvic reconstruction after the resection of a tumour around
the acetabulum is a challenging procedure due to the complex anatomy
and biomechanics. Several pelvic endoprostheses have been introduced,
but the rates of complication remain high. Our aim was to review
the use of a stemmed acetabular pedestal cup in the management of
these patients. The study involved 48 patients who underwent periacetabular reconstruction
using a stemmed pedestal cup (Schoellner cup; Zimmer Biomet Inc.,
Warsaw, Indiana) between 2000 and 2013. The indications for treatment included
a primary bone tumour in 27 patients and metastatic disease in 21
patients. The mean age of the patients at the time of surgery was
52 years (16 to 83).Aims
Patients and Methods
This study aims to assess first, whether mutations in the epidermal
growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes
are associated with overall survival (OS) in patients who present
with symptomatic bone metastases from non-small cell lung cancer
(NSCLC) and secondly, whether mutation status should be incorporated into
prognostic models that are used when deciding on the appropriate
palliative treatment for symptomatic bone metastases. We studied 139 patients with NSCLC treated between 2007 and 2014
for symptomatic bone metastases and whose mutation status was known.
The association between mutation status and overall survival was
analysed and the results applied to a recently published prognostic
model to determine whether including the mutation status would improve
its discriminatory power.Aims
Patients and Methods
To explore the of age of onset distribution for Perthes’ disease
of the hip, with particular reference to gender, laterality and
conformity to the lognormal distribution. A total of 1082 patients were identified from the Liverpool Perthes’
Disease Register between 1976 and 2010, of which 992 had the date
of diagnosis recorded. In total, 682 patients came from the geographical
area exclusively served by Alder Hey Hospital, of which 673 had
a date of diagnosis. Age of onset curves were analysed, with respect to
the predefined subgroups.Aims
Patients and Methods
Surgical intervention in patients with bone metastases from breast
cancer is dependent on the estimated survival of the patient. The
purpose of this paper was to identify factors that would predict
survival so that specific decisions could be made in terms of surgical
(or non-surgical) management. The records of 113 consecutive patients (112 women) with metastatic
breast cancer were analysed for clinical, radiological, serological
and surgical outcomes. Their median age was 61 years (interquartile
range 29 to 90) and the median duration of follow-up was 1.6 years
(standard deviation (Aims
Methods
Recently, the use of metal-on-metal articulations
in total hip arthroplasty (THA) has led to an increase in adverse
events owing to local soft-tissue reactions from metal ions and
wear debris. While the majority of these implants perform well,
it has been increasingly recognised that a small proportion of patients
may develop complications secondary to systemic cobalt toxicity
when these implants fail. However, distinguishing true toxicity
from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt
alloys in THA and to highlight the following related topics of interest:
mechanisms of cobalt ion release and their measurement, definitions
of pathological cobalt ion levels, and the pathophysiology, risk factors
and treatment of cobalt toxicity. Historically, these metal-on-metal
arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative
stresses placed on the prosthetic joint. It exerts its pathological
effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt
toxicity in patients with metal-on-metal hip arthroplasties. Take home message: Patients with new or evolving hip symptoms
with a prior history of THA warrant orthopaedic surgical evaluation.
Increased awareness of the range of systemic symptoms associated
with cobalt toxicity, coupled with prompt orthopaedic intervention, may
forestall the development of further complications. Cite this article:
The December 2015 Trauma Roundup360 looks at: Delay to surgery in hip fracture; Hexapod fixators in the management of hypertrophic tibial nonunions; Thromboembolism after nailing pathological fractures; Tibial plateau fracture patterns under the spotlight; The health economic effects of long bone nonunion; Adverse outcomes in trauma; The sacral screw in children; Treating the contralateral SUFE
This study investigates and defines the topographic
anatomy of the medial femoral circumflex artery (MFCA) terminal
branches supplying the femoral head (FH). Gross dissection of 14
fresh–frozen cadaveric hips was undertaken to determine the extra
and intracapsular course of the MFCA’s terminal branches. A constant
branch arising from the transverse MFCA (inferior retinacular artery;
IRA) penetrates the capsule at the level of the anteroinferior neck,
then courses obliquely within the fibrous prolongation of the capsule
wall (inferior retinacula of Weitbrecht), elevated from the neck,
to the posteroinferior femoral head–neck junction. This vessel has
a mean of five (three to nine) terminal branches, of which the majority
penetrate posteriorly. Branches from the ascending MFCA entered
the femoral capsular attachment posteriorly, running deep to the
synovium, through the neck, and terminating in two branches. The
deep MFCA penetrates the posterosuperior femoral capsular. Once
intracapsular, it divides into a mean of six (four to nine) terminal
branches running deep to the synovium, within the superior retinacula
of Weitbrecht of which 80% are posterior. Our study defines the
exact anatomical location of the vessels, arising from the MFCA
and supplying the FH. The IRA is in an elevated position from the
femoral neck and may be protected from injury during fracture of
the femoral neck. We present vascular ‘danger zones’ that may help
avoid iatrogenic vascular injury during surgical interventions about
the hip. Cite this article:
Total Of the 54 patients who underwent TES for a primary tumour between
1993 and 2010, 19 died and four were lost to follow-up. In January
2012, a questionnaire was sent to the 31 surviving patients. This
included the short form-36 to assess HRQoL and questions about the
current condition of their disease, activities of daily living (ADL)
and surgery. The response rate was high at 83.9% (26/31 patients).
We found that most patients were satisfied and maintained good performance
of their ADLs. The mental health status and social roles of the HRQoL scores
were nearly equivalent to those of healthy individuals, regardless
of the time since surgery. There was significant impairment of physical
health in the early post-operative years, but this usually returned
to normal approximately three years after surgery. Cite this article:
The December 2014 Oncology Roundup360 looks at: metaphyseal and diaphyseal osteosarcoma subtly different beasts; sports and endoprosthetic reconstruction of the knee; is curettage without tissue diagnosis sensible in cartilaginous tumours?; autoclaved autograft in bone tumour reconstruction; vascularised graft a step too far in bone defects?; interdigitated neoadjuvant chemoradiotherapy in high-grade sarcoma; predicting life expectancy in patients with painful metastasis; and osteolytic lesions of the hands and feet.
In 1999, we developed a technique for biological
reconstruction after excision of a bone tumour, which involved using
autografts of the bone containing the tumour treated with liquid
nitrogen. We have previously reported the use of this technique
in 28 patients at a mean follow up of 27 months (10 to 54). In this study, we included 72 patients who underwent reconstruction
using this technique. A total of 33 patients died and three were
lost to follow-up, at a mean of 23Â months (2 to 56) post-operatively,
leaving 36 patients available for a assessment at a mean of 101
months 16 to 163) post-operatively. The methods of reconstruction included
an osteo-articular graft in 16, an intercalary in 13 and, a composite
graft with prosthesis in seven. Post-operative function was excellent in 26 patients (72.2%),
good in seven (19.4%), and fair in three (8.3%) according to the
functional evaluation system of Enneking. No recurrent tumour occurred
within the grafts. The autografts survived in 29 patients (80.6%),
and the rates of survival at five and ten years were 86.1% and 80.6
%, respectively. Seven of 16Â osteo-articular grafts (44%) failed
because of fracture or infection, but all the composite and intercalary
grafts survived. The long-term outcomes of frozen autografting, particularly using
composite and intercalary grafts, are satisfactory and thus represent
a good method of treatment for patients with a sarcoma of bone or
soft tissue. Cite this article:
Patient-centred medicine is an approach to medical care that emphasises the patient experience. Treatment outcome measures reflect this experience, and outcomes are measured by obtaining patient feedback. Central to this type of care is the patient-physician relationship. Communication, physician empathy, and shared decision making are key components of this relationship. Patient-centred care is correlated with better patient outcomes across medical specialties and higher patient perceived quality of care. Payors are now using patient-centred quality measures in their physician reimbursement schedules.
The February 2014 Oncology Roundup360 looks at: suspicious lesions; limb salvage in pelvic sarcomas; does infection affect oncological survival?; cancer patient pathways; radiological arthritis with cement augmentation in GCT; and post-chemotherapy increase in tumour volume as a predictor of poor prognosis.
The revised Tokuhashi, Tomita and modified Bauer
scores are commonly used to make difficult decisions in the management
of patients presenting with spinal metastases. A prospective cohort
study of 199 consecutive patients presenting with spinal metastases,
treated with either surgery and/or radiotherapy, was used to compare
the three systems. Cox regression, Nagelkerke’s R2 and
Harrell’s concordance were used to compare the systems and find their
best predictive items. The three systems were equally good in terms
of overall prognostic performance. Their most predictive items were
used to develop the Oswestry Spinal Risk Index (OSRI), which has
a similar concordance, but a larger coefficient of determination
than any of these three scores. A bootstrap procedure was used to
internally validate this score and determine its prediction optimism. The OSRI is a simple summation of two elements: primary tumour
pathology (PTP) and general condition (GC): OSRI = PTP + (2 – GC). This simple score can predict life expectancy accurately in patients
presenting with spinal metastases. It will be helpful in making
difficult clinical decisions without the delay of extensive investigations. Cite this article:
We set out to determine the impact of surgery on quality of life and function in patients who had undergone surgery for symptomatic peri-acetabular metastases. From a prospective database we retrospectively reviewed 46 consecutive patients who had been treated operatively between June 2003 and June 2009. The mean age of the patients was 56.4 years (20 to 73) and the mean post-operative follow-up was 19.2 months (4 to 70). Functional evaluation and quality-of-life assessments were performed. At the most recent follow-up, 26 patients (56.5%) were alive. Their median survival time was 25.0 months. Ten major postoperative complications had occurred in eight patients (17.4%). The mean post-operative Musculoskeletal Tumor Society score (MSTS 93) was 56.3% (6.7% to 90.0%). Improvement in the Eastern Cooperative Oncology Group (ECOG) performance status was seen in 32 patients (69.6%). On the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire (QLQ-C30) measure of global health status there was a statistically significant improvement from the patients’ pre-operative status (42.8 ( Surgery for patients with peri-acetabular metastases reduces pain and improves their quality of life, and has a low rate of surgical complications.
Lately, concerns have arisen following the use of large metal-on-metal bearings in hip replacements owing to reports of catastrophic soft-tissue reactions resulting in implant failure and associated complications. This review examines the literature and contemporary presentations on current clinical dilemmas in metal-on-metal hip replacement.
In a systematic review, reports from national registers and clinical studies were identified and analysed with respect to revision rates after joint replacement, which were calculated as revisions per 100 observed component years. After primary hip replacement, a mean of 1.29 revisions per 100 observed component years was seen. The results after primary total knee replacement are 1.26 revisions per 100 observed component years, and 1.53 after medial unicompartmental replacement. After total ankle replacement a mean of 3.29 revisions per 100 observed component years was seen. The outcomes of total hip and knee replacement are almost identical. Revision rates of about 6% after five years and 12% after ten years are to be expected.
We present two cases of metastatic
In our database of 7935 patients referred for investigation of a soft-tissue mass, only 100 were found to have a soft-tissue metastasis (1.3%). Our aim was to define the clinical features of such patients and to identify the site of their primary tumour. The most common presentation was a painful lump, deep to the fascia, ranging between 2 cm and 35 cm (mean 8.3 cm) with 78% of the lumps located deep to the fascia. The mean age of the patients at presentation was 64 years (22 to 84) and there were almost equal numbers of men and women. Of 53 patients with a history of malignancy, 52 had metastases from the same primary (lung in 12, melanoma in ten, kidney in nine, gastrointestinal track in four, breast in five, bladder in four, and others in eight). The other 47 had no history of malignancy and the metastasis was the first presentation. The primary sites in these cases were the lung in 19, gastro-intestinal track in four, kidney in two, melanoma in nine, other in three, and unknown (despite investigations) in ten. There was no correlation between the site of the metastases and the primary tumour. Of the 7935 patients, 516 had a history of malignancy. Of these, only 10% had a soft-tissue metastasis, 29% had a benign diagnosis, 55% a soft-tissue sarcoma and 6% another malignancy. Patients with soft-tissue metastases have similar clinical features to those with soft-tissue sarcomas and should be considered for assessment at appropriate diagnostic centres for patients with suspicious soft-tissue lumps.
We have developed a hollow perforated cannulated screw. One or more of these was implanted percutaneously in 11 patients with an osteolytic metastasis in the femoral neck and multiple metastases elsewhere. They were supplemented by one or two additional standard 6.5 mm cannulated screws in nine patients. Polymethylmethacrylate bone cement was injected through the screw into the neck of the femur using small syringes, as in vertebroplasty. The mean amount of cement injected was 23.2 ml (17 to 30). Radiotherapy was started on the fourth post-operative day and chemotherapy, on average, was resumed a day later. Good structural stability and satisfactory relief from pain were achieved in all the patients. This technique may be useful in the palliation of metastases in the femoral neck.
In a prospective randomised study we compared the results of arthroscopic subacromial bursectomy alone with debridement of the subacromial bursa followed by acromioplasty. A total of 57 patients with a mean age of 47 years (31 to 60) suffering from primary subacromial impingement without a rupture of the rotator cuff who had failed previous conservative treatment were entered into the trial. The type of acromion was classified according to Bigliani. Patients were assessed at follow-up using the Constant score, the simple shoulder test and visual analogue scores for pain and functional impairment. One patient was lost to follow-up. At a mean follow-up of 2.5 years (1 to 5) both bursectomy and acromioplasty gave good clinical results. No statistically significant differences were found between the two treatments. The type of acromion and severity of symptoms had a greater influence on the clinical outcome than the type of treatment. As a result, we believe that primary subacromial impingement syndrome is largely an intrinsic degenerative condition rather than an extrinsic mechanical disorder.
We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value.
We report our early experience with a new peri-acetabular reconstruction endoprosthesis used for pelvic reconstruction after tumour resection. The outcome of 21 patients who underwent limb salvage following type II pelvic resection and reconstruction using the peri-acetabular reconstruction prosthesis between 2000 and 2006 was retrospectively reviewed. This prosthesis was designed to use the remaining part of the ilium to support a horizontally placed acetabular component secured with internal fixation and bone cement. Into this device a constrained acetabular liner is positioned which is articulates with a conventional femoral component to which a modular extension and modular head are attached. The mean follow-up was 20.5 months (1 to 77). The most common complications were deep infection, superficial wound infections, and dislocation. The mean musculoskeletal tumor society functional outcome score for the survivors was 20.1(11 to 27). We recommend the use of the peri-acetabular reconstruction prosthesis for reconstruction of large defects after type II pelvic resection, as this design has a greater inherent stability over other available prostheses.
While primary squamous-cell carcinoma of the hand is common, metastasis of a squamous-cell carcinoma to the hand is very rare. It has been reported to arise from carcinoma of the lung and oesophagus and, rarely, from other tumours. We describe a patient with metastatic squamous-cell carcinoma occurring in the first web space of the hand from primary
Peri- and sub-prosthetic fractures, or pathological fractures below an existing well-fixed femoral component, with or without an ipsilateral knee replacement, present a difficult surgical challenge. We describe a simple solution, in which a custom-made prosthesis with a cylindrical design is cemented proximally to the stem of an existing, well-fixed femoral component. This effectively treats the fracture without sacrificing the good hip. We describe five patients with a mean age of 73 years (60 to 81) and a mean follow-up of 47 months (6 to 108). The mean overlap of the prosthesis over the femoral component was 7.5 cm (5.5 to 10). There have been no mechanical failures, no new infections and no re-operations. We suggest that in highly selected cases, in which conventional fixation is not feasible, this technique offers a durable option and avoids the morbidity of a total femoral replacement.
We reviewed 20 patients who had undergone a Coonrad-Morrey total elbow arthroplasty after resection of a primary or metastatic tumour from the elbow or distal humerus between 1980 and 2002. Eighteen patients underwent reconstruction for palliative treatment with restoration of function after intralesional surgery and two after excision of a primary bone tumour. The mean follow-up was 30 months (1 to 192). Five patients (25%) were alive at the final follow-up; 14 (70%) had died of their disease and one of unrelated causes. Local control was achieved in 15 patients (75%). The mean Mayo Elbow Performance Score improved from 22 (5 to 45) to 75 points (55 to 95). Four reconstructions (20%) failed and required revision. Seven patients (35%) had early complications, the most frequent being nerve injury (25%). There were no infections or wound complications although 18 patients (90%) had radiotherapy, chemotherapy or both. The Coonrad-Morrey total elbow arthroplasty provides good relief from pain and a good functional outcome after resection of tumours of the elbow. The rates of complications involving local recurrence of tumour (25%) and nerve injury (25%) are of concern.
Between 1992 and 1999, we treated 350 patients with skeletal metastases. A multivariable analysis of the patients was conducted using the Cox proportional hazards model. We identified five significant prognostic factors for survival, namely, the site of the primary lesion, the performance status (Eastern Cooperative Oncology Group status 3 or 4), the presence of visceral or cerebral metastases, any previous chemotherapy, and multiple skeletal metastases. The score for each significant factor was derived from the corresponding estimated regression coefficients (natural logarithm of the hazard ratio). The prognostic score was calculated by adding all the scores for individual factors. The rate of survival was 31% at six months and 11% at one year for the patients with a prognostic score of 6 or more. By contrast, patients with a prognostic score of 2 or less had a rate of survival of 98% at six months and 89% at one year. This scoring system can be used to determine the optimal treatment for patients with pathological fractures or epidural compression.
The management of spinal metastases is palliative and aimed at improving quality of life at an acceptable risk. This population study uses administrative databases and measures survivorship and complication rates after surgery for spinal metastases. The effects of various potential predictor variables were evaluated. We identified 987 patients with a median survival for all types of cancer of 227 days. The one and three-month mortality was 9% and 29%, respectively. Increasing age, male gender and primary