2,218 research outputs found

    Limited progression of subclinical Dupuytren's disease:results from a prospective cohort study

    Get PDF
    AIMS: With novel promising therapies potentially limiting progression of Dupuytren's disease (DD), better patient stratification is needed. We aimed to quantify DD development and progression after seven years in a population-based cohort, and to identify factors predictive of disease development or progression. METHODS: All surviving participants from our previous prevalence study were invited to participate in the current prospective cohort study. Participants were examined for presence of DD and Iselin's classification was applied. They were asked to complete comprehensive questionnaires. Disease progression was defined as advancement to a further Iselin stage or surgery. Potential predictive factors were assessed using multivariable regression analyses. Of 763 participants in our original study, 398 were available for further investigation seven years later. RESULTS: We identified 143/398 (35.9%) participants with DD, of whom 56 (39.2%) were newly diagnosed. Overall, 20/93 (21.5%) previously affected participants had disease progression, while 6/93 (6.5%) patients showed disease regression. Disease progression occurred more often in patients who initially had advanced disease. Multivariable regression analyses revealed that both ectopic lesions and a positive family history of DD are independent predictors of disease progression. Previous hand injury predicts development of DD. CONCLUSION: Disease progression occurred in 21.5% of DD patients in our study. The higher the initial disease stage, the greater the proportion of participants who had disease progression at follow-up. Both ectopic lesions and a positive family history of DD predict disease progression. These patient-specific factors may be used to identify patients who might benefit from treatment that prevents progression. Cite this article: Bone Joint J 2021;103-B(4):704-710

    Understanding the role of long-acting muscarinic antagonists in asthma treatment

    Get PDF
    Objective: Long-acting muscarinic antagonists (LAMAs) have been used in the treatment of obstructive pulmonary diseases for years. Long-acting muscarinic antagonists were previously mainly used as bronchodilators in chronic obstructive pulmonary disease, but the use of LAMAs in the treatment of asthma has gained great interest. There is now ample evidence of the efficacy and safety of LAMAs as add-on therapy to inhaled corticosteroid (ICS) plus long-acting β 2-agonist (LABA) combinations in patients with moderate to severe uncontrolled asthma. Long-acting muscarinic antagonists have subsequently been included in asthma guidelines. This review summarizes the scientific evidence on the use of LAMAs in asthma and aims to provide a better understanding of the role of LAMAs in the asthma treatment care algorithm and the current gaps in our knowledge. Data sources: PubMed review using the following words: long-acting muscarinic antagonists, asthma, muscarinic receptors, tiotropium, glycopyrronium, umeclidinium. Study selections: This review focused on the key trials that led to the inclusion of LAMAs in asthma guidelines. In addition, we highlighted a number of studies with other study designs and populations. Results: We identified 6 major studies that led to inclusion in asthma guidelines and 3 studies with other study designs and populations. Conclusion: Long-acting muscarinic antagonists add-on therapy to ICS-LABA improves lung function, reduces exacerbations, and modestly improves asthma control in patients with moderate to severe asthma who are uncontrolled despite the use of ICS-LABA. Long-acting muscarinic antagonists are effective in all asthma phenotypes and endotypes

    Dementia in Parkinson's Disease Correlates with α-Synuclein Pathology but Not with Cortical Astrogliosis

    Get PDF
    Dementia is a common feature in Parkinson's disease (PD) and is considered to be the result of limbic and cortical Lewy bodies and/or Alzheimer changes. Astrogliosis may also affect the development of dementia, since it correlates well with declining cognition in Alzheimer patients. Thus, we determined whether cortical astrogliosis occurs in PD, whether it is related to dementia, and whether this is reflected by the presence of glial fibrillary acidic protein (GFAP) and vimentin in cerebrospinal fluid (CSF). We have examined these proteins by immunohistochemistry in the frontal cortex and by Western blot in CSF of cases with PD, PD with dementia (PDD), dementia with Lewy bodies (DLB) and nondemented controls. We were neither able to detect an increase in cortical astrogliosis in PD, PDD, or DLB nor could we observe a correlation between the extent of astrogliosis and the degree of dementia. The levels of GFAP and vimentin in CSF did not correlate to the extent of astrogliosis or dementia. We did confirm the previously identified positive correlation between the presence of cortical Lewy bodies and dementia in PD. In conclusion, we have shown that cortical astrogliosis is not associated with the cognitive decline in Lewy body-related dementia

    Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts

    Get PDF
    © 2019, The Author(s). COPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-β-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD

    Patient-perceived hand function measured can predict treatment for Dupuytren's disease

    Get PDF
    BACKGROUND: Web based patient-reported outcome measures (PROMs) could aid surgeons to remotely assess the need for examination and subsequent treatment of Dupuytren's disease (DD) patients. We studied whether the Unité Rhumatologique des affections de la Main (URAM) and the Michigan Hand Questionnaire (MHQ) could predict DD treatment.METHODS: In this prospective cohort study, we compared MHQ and URAM scores of treated patients with untreated patients. For the treatment group, we selected a score closest to one year before treatment. For controls we randomly selected a score. Additionally, we tested the predictive value of a one-year change score between 15 months and 6 weeks before treatment. The primary outcome measure was DD treatment.The predictive value was determined using the Area Under the Curve (AUC). An AUC &gt;0.70 was considered as good predictive ability, 0.70-0.50 as poor predictive ability and &lt;0.50 as no predictive ability.RESULTS: We included 141 patients for the MHQ analysis and 145 patients for the URAM analysis. The AUC of the MHQ and URAM scores measured one year before treatment were 0.80 (95% CI 0.71-0.88) and 0.75 (95% CI 0.68-0.82), respectively. The one-year change score resulted in an AUC of &lt;0.60 for both questionnaires.CONCLUSIONS: Our results show that both the MHQ and URAM score measured around one year before treatment can predict treatment for DD. If future studies show that telemonitoring of DD patients with PROMs is also cost-effective, web-based PROMs could optimise patient care and treatment effectiveness of DD.</p

    Single-nucleotide polymorphism rs2070600 regulates AGER splicing and the sputum levels of the COPD biomarker soluble receptor for advanced glycation end-products.

    Full text link
    The COPD susceptibility SNP rs2070600 affects the levels of the COPD biomarker sRAGE in sputum as well as splicing of AGER. Moreover, @PouwelsScience et al. demonstrate large differences in sRAGE levels between serum and sputum. https://bit.ly/3t0pJtK
    corecore