Synovial fluid from patients with various arthritides contains procoagulant, cell-derived microparticles. Here we studied whether synovial microparticles modulate the release of chemokines and ...cytokines by fibroblast-like synoviocytes (FLS). Microparticles, isolated from the synovial fluid of rheumatoid arthritis (RA) and arthritis control (AC) patients (n = 8 and n = 3, respectively), were identified and quantified by flow cytometry. Simultaneously, arthroscopically guided synovial biopsies were taken from the same knee joint as the synovial fluid. FLS were isolated, cultured, and incubated for 24 hours in the absence or presence of autologous microparticles. Subsequently, cell-free culture supernatants were collected and concentrations of monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1) were determined. Results were consistent with previous observations: synovial fluid from all RA as well as AC patients contained microparticles of monocytic and granulocytic origin. Incubation with autologous microparticles increased the levels of MCP-1, IL-8 and RANTES in 6 of 11 cultures of FLS, and IL-6, ICAM-1 and VEGF in 10 cultures. Total numbers of microparticles were correlated with the IL-8 (r = 0.91, P < 0.0001) and MCP-1 concentrations (r = 0.81, P < 0.0001), as did the numbers of granulocyte-derived microparticles (r = 0.89, P < 0.0001 and r = 0.93, P < 0.0001, respectively). In contrast, GM-CSF levels were decreased. These results demonstrate that microparticles might modulate the release of chemokines and cytokines by FLS and might therefore have a function in synovial inflammation and angiogenesis.
While millions of people drink arsenic-contaminated tube well water across Bangladesh, there is no recent scientific explanation which is able to either comprehensively explain arsenic mobilization ...or to predict the spatial distribution of affected wells. Rather, mitigation strategies have focused on the sinking of deep tube wells into the currently arsenic-free Pleistocene aquifer. In this study, Bangladesh shallow tube wells identified as contaminated and uncontaminated, as well as deep tube wells, were analyzed for geochemical and
in situ microbiological composition. Whereas arsenic was detected in all Holocene aquifer wells, no arsenic was found in wells accessing the Pleistocene aquifer. Bacterial genera, including Comamonadaceae,
Acidovorax,
Acinetobacter, and
Hydrogenophaga, associated with tolerance of high arsenic concentrations, rather than dissimilatory Fe(III) or As(V) reduction, were identified in shallow tube wells, indicating that mobilization may not occur at depth, but is rather due to drawdown of surface contaminated water. Deep tube wells contained microbes indicative of aerobic conditions, including the genera
Aquabacterium,
Limnobacter, and
Roseomonas. It is concluded that through drawdown of arsenic or organic matter, further utilization of the Pleistocene aquifer could result in contamination similar to that observed in the Holocene aquifer.
The aim of this study was to determine long-term survival and clinical outcomes of the surface replacement trapeziometacarpal joint prosthesis (SR™TMC) and to evaluate implant migration using ...radiostereometric analysis (RSA).
In this clinical long-term follow-up study outcomes of ten patients who received the SR™TMC joint prosthesis were evaluated using DASH and Nelson scores, Visual Analogue Scale (VAS) of pain, and key pinch strength. RSA-radiographs were obtained direct postoperatively and 6 months, 1, 5 and 10 years postoperatively and were analyzed using model-based RSA software.
During follow-up, two early revisions took place. Mean pre-operative DASH and Nelson scores were 54 (SD 15) and 54 (SD 17), improved significantly after 6 months (DASH 25 (SD 20), Nelson 75 (SD 18)) and remained excellent during long-term follow-up in all patients with a stable implant. At final follow-up, clinical scores deteriorated clearly in two patients with a loose implant in situ.
Long-term survival of the SR™TMC joint prosthesis is relatively poor. However, clinical outcomes improved significantly in the short-term and remained excellent in the long-term in those patients with a stable implant, but deteriorated clearly in case of loosening. The role of RSA in TMC joint arthroplasty is potentially valuable but needs to be further investigated. Several challenges of RSA in the TMC joint have been addressed by the authors and suggestions to optimize RSA-data are given.
This study was registered in the Netherlands Trial Register ( NL7126 ).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolic syndrome (MetS) is characterized by central obesity, insulin resistance, dysglycemia, and a pro-atherogenic plasma lipid profile. MetS creates a high risk for development of type 2 diabetes ...(T2DM) and cardiovascular disease (CVD), presumably by altering inflammatory responses. Presently, it is unknown how the chronic metabolic disturbances in acute hyperglycemia, MetS and T2DM affect the immune activity of peripheral blood cells.
We performed genome-wide expression analysis of peripheral blood cells obtained from patients with T2DM (n = 6) and age-, sex- , BMI- and blood pressure-matched obese individuals with MetS (n = 4) and lean healthy normoglycemic controls (n = 3), both under fasting conditions and after controlled induction of acute hyperglycemia during a 70 min hyperglycemic clamp. Differential gene expression during fasting conditions was confirmed by real-time PCR, for which we included additional age-, sex-, BMI-, and blood pressure-matched obese individuals with (n = 4) or without (n = 4) MetS.
Pathway and Gene ontology analysis applied to baseline expression profiles of peripheral blood cells from MetS and T2DM patients revealed metabolic changes, highly similar to a reoviral infection gene signature in T2DM patients. Transcription factor binding site analysis indicated that increased HIF-1α activity, a transcription factor induced by either hypoxia or oxidative stress, is responsible for this aberrant metabolic profile in peripheral blood cells from T2DM patients. Acute hyperglycemia in healthy controls resulted in reduced expression of cytotoxicity-related genes, representing NK- and CD8(+) cells. In obese controls, MetS and especially T2DM patients, baseline expression of genes involved in cytotoxicity was already low, compared to healthy controls and did not further decrease upon acute hyperglycemia.
The reduced activity of cytotoxic genes in T2DM is explained by chronic hyperglycemia, but its acute effects are restricted to healthy controls. Genome expression of circulating leukocytes from T2DM patients differs from MetS individuals by a specific reovirus signature. Our data thus suggest a role for suppressed anti-viral capacity in the etiology of diabetes.
Background: Synovial tissue (ST) from end stage destructive rheumatoid arthritis (RA) and arthroscopic biopsies obtained during active inflammation might exhibit different characteristics. Objective: ...To define the cell infiltrate and the expression of proinflammatory cytokines, angiogenic factors, and matrix metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from end stage RA. Methods: Synovial biopsy specimens were obtained from the actively inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared with ST from 10 patients with end stage, destructive RA. Immunohistological analysis was performed to detect T cells, plasma cells, macrophages, fibroblast-like synoviocytes (FLS), and the expression of interleukin (IL)1β, IL6, tumour necrosis factor α (TNFα), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF. Results: The expression of CD68+ macrophages was significantly higher in ST selected at arthroscopy than in samples obtained at surgery, both in the intimal lining layer and in the synovial sublining. The expression of CD3+ T cells also tended to be higher in arthroscopic samples. The expression of TNFα, IL6, MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at arthroscopy. In contrast, the expression of IL1β was on average higher in surgical samples. Conclusion: Active arthritis activity is associated with increased cell infiltration, expression of proinflammatory cytokines, MMPs, and angiogenic growth factors in synovial biopsy samples selected at arthroscopy. Increased expression of IL1β in the synovium of patients with destructive RA requiring joint replacement may well reflect the important role of IL1β in cartilage and bone destruction.
Transcription profiling of rheumatic diseases van Baarsen, Lisa G M; Bos, Carina L; van der Pouw Kraan, Tineke C T M ...
Arthritis research & therapy,
01/2009, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Rheumatic diseases are a diverse group of disorders. Most of these diseases are heterogeneous in nature and show varying responsiveness to treatment. Because our understanding of the molecular ...complexity of rheumatic diseases is incomplete and criteria for categorization are limited, we mainly refer to them in terms of group averages. The advent of DNA microarray technology has provided a powerful tool to gain insight into the molecular complexity of these diseases; this technology facilitates open-ended survey to identify comprehensively the genes and biological pathways that are associated with clinically defined conditions. During the past decade, encouraging results have been generated in the molecular description of complex rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome and systemic sclerosis. Here, we describe developments in genomics research during the past decade that have contributed to our knowledge of pathogenesis, and to the identification of biomarkers for diagnosis, patient stratification and prognostication.
We investigated the non-operative management of trapeziometacarpal osteoarthritis with a three-dimensional (3-D) printed patient-customized brace compared with a conventional plaster brace. Fifty-two ...patients with symptomatic trapeziometacarpal osteoarthritis were enrolled in a 9-week crossover study, which was designed as a randomized controlled trial of two periods of 4-week brace therapies. The primary outcome was patient satisfaction measured with the Dutch version of the Quebec User Evaluation of Satisfaction with Assistive Technology questionnaire survey. Secondary outcomes included pain, patient-reported function, functional hand strength measured by pinch and grip strength, and compliance assessed through a daily log of self-reported brace usage. The 3-D printed patient-customized brace had higher patient satisfaction and compliance than the conventional plaster brace. Patients preferred the 3-D printed customized brace (93%) rather than the conventional plaster brace (7%). This suggests that the 3-D printed patient-customized brace is effective in the non-operative management of trapeziometacarpal osteoarthritis.
Level of evidence: I
Abstract
Background
Patient decision aids (PtDAs) support patients and clinicians in shared decision-making (SDM). Real-world outcome information may improve patients’ risk perception, and help ...patients make decisions congruent with their expectations and values. Our aim was to develop an online PtDA to support kidney failure treatment modality decision-making, that: 1) provides patients with real-world outcome information, and 2) facilitates SDM in clinical practice.
Methods
The International Patient Decision Aids Standards (IPDAS) development process model was complemented with a user-centred and convergent mixed-methods approach. Rapid prototyping was used to develop the PtDA with a multidisciplinary steering group in an iterative process of co-creation. The results of an exploratory evidence review and a needs-assessment among patients, caregivers, and clinicians were used to develop the PtDA. Seven Dutch teaching hospitals and two national Dutch outcome registries provided real-world data on selected outcomes for all kidney failure treatment modalities. Alpha and beta testing were performed to assess the prototype and finalise development. An implementation strategy was developed to guide implementation of the PtDA in clinical practice.
Results
The ‘Kidney Failure Decision Aid’ consists of three components designed to help patients and clinicians engage in SDM: 1) a paper hand-out sheet, 2) an interactive website, and 3) a personal summary sheet. A ‘patients-like-me’ infographic was developed to visualise survival probabilities for each treatment modality on the website. Other treatment outcomes were incorporated as event rates (e.g. hospitalisation rates) or explained in text (e.g. the flexibility of each treatment modality). No major revisions were needed after alpha and beta testing. During beta testing, some patients ignored the survival probabilities because they considered these too confronting. Nonetheless, patients agreed that every patient has the right to choose whether they want to view this information. Patients and clinicians believed that the PtDA would help patients make informed decisions, and that it would support values- and preferences-based decision-making. Implementation of the PtDA has started in October 2020.
Conclusions
The ‘Kidney Failure Decision Aid’ was designed to facilitate SDM in clinical practice and contains real-world outcome information on all kidney failure treatment modalities. It is currently being investigated for its effects on SDM in a clinical trial.
CTC characterization by a 16-gene profile identified from previously published CTC-specific genes detected poor prognosis metastatic breast cancer (MBC) patients. In multivariate analysis, the CTC ...profile was the only factor significantly associated with outcome. While validation in an independent patient set did not reach significance, our profile underlines the potential of CTC characterization.
A circulating tumor cell (CTC) count is an established prognostic factor in metastatic breast cancer (MBC). Besides enumeration, CTC characterization promises to improve outcome prediction and treatment guidance. Having shown the feasibility of quantifying clinically relevant mRNA transcripts in CTCs, we determined the prognostic value of CTC gene expression in MBC.
CTCs were isolated and enumerated from blood of 197 MBC patients who were about to start first-line systemic therapy. Of these, 180 were assessable for quantification of mRNA expression by RT-qPCR in relation to time-to-treatment failure (TTF). A prognostic CTC gene profile was generated by leave-one-out cross validation in a 103 patient discovery set and validated in 77 patients. Additionally, all 180 patients were randomly divided into two equal sets to discover and validate a second prognostic profile.
CTC count predicted for TTF at baseline {≥5 versus <5 CTCs/7.5 ml blood, hazard ratio (HR) 2.92 95% confidence interval (CI) 1.71–4.95P < 0.0001}. A 16-gene CTC profile was generated in the first discovery set, which identified patients with death or TTF <9 months versus those with a better outcome. In multivariate analysis, the 16-gene profile was the only factor associated with TTF HR 3.15 (95% CI 1.35–7.33)P 0.008. Validation of this profile in the independent patient set pointed into the same direction, but was not statistically significant. A newly generated 8-gene profile showed similarly favorable test characteristics as the 16-gene profile, but did not significantly pass validation either.
A 16-gene CTC profile was identified, which provided prognostic value on top of CTC count in MBC patients. However, validation of this profile in an independent cohort, nor of a second profile, reached statistical significance, underscoring the need to further fine-tune the still promising approach of CTC characterization.
Background: Tumour necrosis factor α (TNFα) blockade using infliximab, a chimeric anti-TNFα antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA). Objective: To analyse ...the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples. Methods: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis. Results: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm2v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFα treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation. Conclusions: The effects of anti-TNFα therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.
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