Search results
Found 30795 matches for
Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes.
Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis.
Proceedings of the GRAPPA 2022 Executive Retreat
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) leadership congregated for a strategic planning meeting before the 2022 GRAPPA annual meeting in New York, USA. Meeting aims were to review GRAPPA's performance in relation to its 2016 goals and identify successes and areas for further improvement, identify key GRAPPA priorities and activities for the next 5 years, and explore committee structures to best support these aims.
Diversity, Equity, and Inclusion: Sex and Gender and Intersectionality With Race and Ethnicity in Psoriatic Disease
Sex (biological attributes associated with being male or female) and gender (sociocultural-driven traits and behaviors related to being a man or a woman) are emerging as important determinants of disease course and response to therapy in patients with psoriasis and psoriatic arthritis (PsA). Although psoriatic disease (PsD) is equally prevalent in men and women, the condition affects them in different and unique ways, giving rise to sex- and gender-related differences in clinical presentation, including baseline disease activity, disease course, and response to treatment. Better understanding of the roles sex and gender play in the development and evolution of PsD has the potential to improve patient care. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) continues its effort to highlight issues related to diversity, equity, and inclusion in people with PsD by dedicating a session during the annual meeting to sex and gender and their intersectionality with race and ethnicity in individuals with PsA.
Demographic and geographical variability in physiotherapy provision following hip and knee replacement. An analysis from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.
BACKGROUND: Total hip (THR) and knee replacement (TKR) are two of the most common elective orthopaedic procedures worldwide. Physiotherapy is core to the recovery of people following joint replacement. However, there remains uncertainty as to physiotherapy provision at a national level. OBJECTIVES: To examine the relationship between patient impairment and geographical variation on the provision of physiotherapy among patients who undergo primary total hip or knee replacement (THR/TKR). DESIGN: Population-based observational cohort study. METHODS: Patients undergoing THR (n=17,338) or TKR (n=20,260) recorded in the National Joint Registry for England (NJR) between 2009 and 2010 and completed Patient Reported Outcome Measures (PROMs) questionnaires at Baseline and 12 months postoperatively. Data were analysed on the frequency of physiotherapy over the first postoperative year across England's Strategic Health Authorities (SHAs). Logistic regression analyses examined the relationship between a range of patient and geographical characteristics and physiotherapy provision. RESULTS: Following THR, patients were less likely to receive physiotherapy than following TKR patients ('some' treatment by a physiotherapist within 1st post operative year: 53% vs 79%). People with worse functional outcomes 12 months postoperatively, received more physiotherapy after THR and TKR. There was substantial variation in provision of physiotherapy according to age (younger people received more physiotherapy), gender (females received more physiotherapy) ethnicity (non-whites received more physiotherapy) and geographical location (40% of patients from South West received some physiotherapy compared to 40 73% in London after THR). CONCLUSIONS: There is substantial variation in the provision of physiotherapy nationally. This variation is not explained by differences in the patient's clinical presentation.
Meniscal Tear Outcome (METRO) review: a protocol for a systematic review summarising the clinical course and patient experiences of meniscal tears in the current literature.
INTRODUCTION: Meniscal tears are a common knee injury with an incidence of 60 per 100 000. Management of meniscal tears can include either non-operative measures or operative procedures such as arthroscopic partial meniscectomy (APM). Despite substantial research evaluating the effectiveness of APM in the recent past, little is known about the clinical course or the experiences of patients with a meniscal tear. AIM: To summarise the short to long-term patterns of variability in outcome in patients with a meniscal tear.To summarise the evidence on patient experiences of meniscal tears. In particular, we will focus on patient experiences of treatment options, treatment pathways and their views of the outcomes used in meniscal tear research. METHODS AND ANALYSIS: Two search strategies will be developed to identify citations from EMBASE, MEDLINE, AMED, CENTRAL, Web of Science and Sociofile. The date of our planned search is 14 August 2020. For the quantitative review we will identify studies reporting patient-reported outcome measures in patients after a meniscal tear. The standardised mean change will be used to assess the variation in size of response and summarise the overall response to each treatment option. All studies will undergo quality assessment using either the Cochrane risk of bias or the Newcastle-Ottawa tool.A qualitative systematic review will be used to identify studies reporting views and experiences of patients with a meniscal tear. All studies will be assessed using the Critical Appraisal Skills Programme tool and if sufficient data are present a meta-synthesis will be performed to identify first, second and third-order constructs. ETHICS AND DISSEMINATION: Given the nature of this study, no formal ethical approval will be sought. Results from the review will be disseminated at national conferences and will be submitted to a peer-reviewed journal for publication. Lay summaries will be freely available via the study Twitter page. PROSPERO REGISTRATION NUMBER: CRD42019122179.
Optimized medial unicompartmental knee arthroplasty outcome: learning from 20 years of propensity score matched registry data.
BACKGROUND AND PURPOSE: Unicompartmental knee arthroplasty (UKA) has increased in use. We investigated changes to UKA revision risk over the last 20 years compared with total knee arthroplasty (TKA), examined external and patient factors for correlation to UKA revision risk, and described the survival probability for current UKA and TKA practice. PATIENTS AND METHODS: All knee arthroplasties reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were linked to the National Patient Register and the Civil Registration System for comorbidity, emigration, and mortality information. All primary UKA and TKA patients with primary osteoarthritis were included and propensity score matched 4 TKAs to 1 UKA. Revision and mortality were analyzed using competing risk cox regression with a shared gamma frailty component. RESULTS: The matched cohort included 48,195 primary knee arthroplasties (9,639 UKAs). From 1997-2001 to 2012-2017 the 3-year hazard ratio decreased from 5.5 (95% CI 2.7-11) to 1.5 (CI 1.2-1.8) due to increased UKA survival. Cementless fixation, a high percentage usage of UKA, and increased surgical volume decreased UKA revision risk, and increased in occurrence parallel to the decreasing revision risks. Current UKA practice using cementless fixation at a high usage unit has a 3-year implant survival of 96% (CI 97-95), 1.1% lower than current TKA practice. INTERPRETATION: UKA revision risk has decreased over the last 20 years, nearing that of TKA surgery. High usage rates, surgical volume, and the use of cementless fixation have increased during the study and were associated with decreased UKA revision risks.
Alternative and complementary therapies in osteoarthritis and cartilage repair.
Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.
Extreme context specificity in differential allelic expression.
Variability in cis-regulation of gene expression has been implicated in the phenotypic manifestation of complex traits including common, multifactorial diseases. The differential expression of alleles due to polymorphism in cis-regulatory elements is common in the human genome, but there is a paucity of information about the context specificity of these control elements. In this study, we examined the differential allelic expression (DAE) of BMP5 in human mesenchymal tissues obtained from 16 donors undergoing joint replacement for treatment of osteoarthritis. We observed significant differences in BMP5 allelic output, with allelic ratios greater than 4:1 (P < 10(-20)) in the tissues of some donors. We also discovered a significant variability in allelic expression within the different tissues of donors. For 12 of our donors, we examined the allelic expression of BMP5 in two different regions of cartilage: cartilage adjacent to the site of the osteoarthritic lesion and cartilage distal from the lesion. Five of these 12 donors demonstrated highly significant differences (P < or = 10(-8)) in allelic expression between the different regions of their cartilage. Using DAE as a phenotype, we attempted to map tissue-specific cis-regulatory polymorphisms, and we identified a single nucleotide polymorphism located downstream of BMP5, which was significantly associated with DAE in some but not all of the examined tissues. These findings suggest that allelic expression can be highly context specific and that when interrogating the cis-regulatory control of a particular gene, one cannot necessarily assume that allelic expression is conserved across different tissues or even across different regions of the same tissue.
Shoulder hemiarthroplasty in patients with juvenile idiopathic arthritis.
Replacement of the shoulder in juvenile idiopathic arthritis is not often performed and there have been no published series to date. We present nine glenohumeral hemiarthroplasties in eight patients with systemic or polyarticular juvenile idiopathic arthritis. The mean follow-up was six years (59 to 89 months). The mean age at the time of surgery was 32 years. Surgery took place at a mean of 27 years after diagnosis. The results indicated excellent relief from pain. There was restoration of useful function which deteriorated with time, in part because of progression of the systemic disease in this severely affected group. No patient has required revision to date and there has been no radiological evidence of loosening or osteolysis around the implants. We discuss the pathoanatomical challenges unique to this group. There was very little space for a prosthetic joint and, in some cases, bony deformity and the small size necessitated the use of custom-made implants.
Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia.
Epigenetic therapies demonstrate significant clinical activity in acute myeloid leukemia (AML) and myelodysplasia (MDS) and constitute an important new class of therapeutic agents. However hematological responses are not durable and disease relapse appears inevitable. Experimentally, leukemic stem/progenitor cells (LSC) propagate disease in animal models of AML and it has been postulated that their relative chemo-resistance contributes to disease relapse. We serially measured LSC numbers in patients with high-risk AML and MDS treated with 5'-azacitidine and sodium valproate (VAL-AZA). Fifteen out of seventy-nine patients achieved a complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with VAL-AZA therapy. There was no significant reduction in the size of the LSC-containing population in non-responders. While the LSC-containing population was substantially reduced in all patients achieving a CR/CRi it was never eradicated and expansion of this population antedated morphological relapse. Similar studies were performed in seven patients with newly diagnosed AML treated with induction chemotherapy. Eradication of the LSC-containing population was observed in three patients all of whom achieved a durable CR in contrast to patients with resistant disease where LSC persistence was observed. LSC quantitation provides a novel biomarker of disease response and relapse in patients with AML treated with epigenetic therapies. New drugs that target this cellular population in vivo are required.
Modular endoprosthetic replacement for failed internal fixation of the proximal femur following trauma.
PURPOSE: Although originally designed for reconstruction after primary malignant bone tumour resection, modular endoprosthetic replacement (EPR) can be used in salvage surgery for complex periprosthetic fracture and failed internal fixation. The purpose of this study was to assess the functional outcome following EPR for failed internal fixation of the proximal femur. METHODS: We assessed clinical and functional outcomes of using a modular tumour endoprosthesis to reconstruct the proximal femur following failed internal fixation in eight consecutive patients between 2001 and 2008. RESULTS: There were four men and four women, with a mean age of 67.5 (range 50-79) years and a mean follow-up of 16.5 (6-36) months. All patients had failed internal fixation for traumatic proximal femoral fractures--four 31.A2.3, two 31.A3.1, two 31.A3.3 using the Arbeitsgemeinshaft für Osteosynthesefragen (AO) fracture classification. Mean time from the first attempted internal fixation to definitive EPR was 34 (6-102) months, and the median number of previous surgical procedures was two (1-11). Histology revealed infection (two cases), uninfected nonunion (five cases) and plasmocytoma (one case). The EPR was carried out as a one-stage procedure in six cases and a two-stage procedure in two cases. Mean postoperative Harris Hip Score was 71.4 (range 64-85). There were no surgical complications. One patient died as a result of systemic complications of myeloma several years following EPR. CONCLUSIONS: EPR is an effective salvage procedure for failed fixation of traumatic proximal femoral fractures. Immediate weightbearing and a good functional outcome can be expected in this difficult group of patients.
Meniscal tears with displaced fragments: common patterns on magnetic resonance imaging.
OBJECTIVE: To identify the commonly occurring patterns of small displaced tears of the menisci of the knee on magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective review of knee MRI scans over 16 months at two hospitals provided 70 studies with 73 displaced meniscal fragments for analysis. Fragment position was recorded. RESULTS: Two common positions were identified for medial fragments. For the medial meniscus, 93% of fragments were positioned medially or posterolaterally. The medially displaced fragments were positioned in either the superior or inferior recesses. Lateral meniscal fragments were more evenly dispersed. CONCLUSION: The pattern of small displaced tears of the medial meniscus is highly predictable. Awareness of the typical locations of these fragments should aid the reporter in identifying these lesions on MRI.
Oxford medial unicompartmental knee arthroplasty. A survival analysis of an independent series.
We describe the outcome of a series of 124 Oxford meniscal-bearing unicompartmental arthroplasties carried out for osteoarthritis of the medial compartment. They had been undertaken more than ten years ago in a non-teaching hospital in Sweden by three surgeons. All the knees had an intact anterior cruciate ligament, a correctable varus deformity and full-thickness cartilage in the lateral compartment. Thirty-seven patients had died; the mean time since operation for the remainder was 12.5 years (10.1 to 15.6). Using the endpoint of revision for any cause, the outcome for every knee was established. Six had been revised (4.8%). At ten years there were 94 knees still at risk and the cumulative survival rate was 95.0% (95% confidence interval 90.8 to 99.3). This figure is similar to that reported by the designers of the prosthesis and to the best published results for independent series of total knee replacement. If patients are selected appropriately, this implant is a reliable treatment for anteromedial osteoarthritis of the knee.