242 research outputs found
Pathogenicity of proteinase 3-anti-neutrophil cytoplasmic antibody in granulomatosis with polyangiitis: Implications as biomarker and future therapies
Granulomatosis with polyangiitis (GPA) is a rare but serious necrotizing auto-immune vasculitis. GPA is mostly associated with the presence of Anti-Neutrophil Cytoplasmic Antibody (ANCA) targeting proteinase 3 (PR3-ANCA), a serine protease contained in neutrophil granules but also exposed at the membrane. PR3-ANCAs have a proven fundamental role in GPA: they bind neutrophils allowing their auto-immune activation responsible for vasculitis lesions. PR3-ANCAs bind neutrophil surface on the one hand by their Fab binding PR3 and on the other by their Fc binding Fc gamma receptors. Despite current therapies, GPA is still a serious disease with an important mortality and a high risk of relapse. Furthermore, although PR3-ANCAs are a consistent biomarker for GPA diagnosis, relapse management currently based on their level is inconsistent. Indeed, PR3-ANCA level is not correlated with disease activity in 25% of patients suggesting that not all PR3-ANCAs are pathogenic. Therefore, the development of new biomarkers to evaluate disease activity and predict relapse and new therapies is necessary. Understanding factors influencing PR3-ANCA pathogenicity, i.e. their potential to induce auto-immune activation of neutrophils, offers interesting perspectives in order to improve GPA management. Most relevant factors influencing PR3-ANCA pathogenicity are involved in their interaction with neutrophils: level of PR3 autoantigen at neutrophil surface, epitope of PR3 recognized by PR3-ANCA, isotype and glycosylation of PR3-ANCA. We detailed in this review the advances in understanding these factors influencing PR3-ANCA pathogenicity in order to use them as biomarkers and develop new therapies in GPA as part of a personalized approach
The Patience of Film. Cavell, Nancy and a thought for the world
Despite considerable differences Stanley Cavell and Jean ÂLuc Nancy share the demand for a renewal of thinking produced through and with the concept of the world. Their articulation of the legacy bequeathed by Heidegger and Wittgenstein begins with an understanding of the world in excess of knowledge and insists on this impossible mastery as the most productive incentive for thinking. Inasmuch as philosophy has understood itself as producer of worldviews, systems and principle, philosophy has constantly suppressed the thinking of the world, for any worldview absorbs and dissolves the world in its vision. For both Cavell and Nancy an insistence on this suppression leads to an emphasis on film. Two gestures can be said to intertwine in their thinking of film: to recapture our relation to the world as one that is not based on knowing as certainty, but on the reception of the singular; to recapture thinking as that which is attracted and called for by the insurgence of the singular, by the seam(s) in experience. Nancy and Cavell reverse the idea of cinema as completing the regime of representation stressing how cinema produces a step away from thinking as representation in view of what the article names thinking as patience. The article concludes by asking: what does it mean for philosophy to understand itself as patience
Factors that influence bile fluid microbiology in cholecystectomized patients
Introducción y objetivo: Las vÃas biliares son normalmente estériles, aunque puede existir cultivo
positivo hasta en el 4.2% de las personas sanas. Existen ciertas circunstancias que lo
favorecen, como pueden ser las litiasis o la manipulación de la vÃa biliar. El objetivo del estudio
fue determinar los factores que influyen en la presencia de bacteriobilia, asà como su implicación
en la práctica clÃnica.
Material y métodos: Estudio prospectivo de los cultivos de bilis obtenidos de los pacientes
colecistectomizados en nuestro centro desde 2013 a 2015.
Resultados: Se recogieron un total de 196 pacientes (42.3% mujeres y 57.7% hombres) a los
que se habÃa realizado colecistectomÃa tanto abierta como laparoscópica tomando muestra
del lÃquido biliar. Se analizaron las caracterÃsticas clÃnicas, epidemiológicas y analÃticas de los
pacientes, asà como la indicación quirúrgica (cirugÃa urgente o programada). Respecto a la
microbiologÃa, en el 47% los cultivos de bilis recogidos fueron positivos: 56.5% con un microorganismo,
25% con dos y 18.5% con tres o más. También se incluyeron los antibióticos empleados
tanto para tratamiento como para profilaxis.
Conclusión: El análisis de la microbiologÃa de la bilis no deberÃa realizarse de forma sistemática,
ya que solamente en casos en los que se demuestren los factores de riesgo estudiados su
resultado puede llegar a ser relevante. En estos mismos casos también resulta imprescindible
para establecer un tratamiento antibiótico adecuado tanto en lo referente al espectro como a
la duración del mismo, con el fin de evitar complicaciones y el aumento de resistencias.Introduction and aim: Normally, the bile ducts are sterile, but up to 4.2% of healthy persons can
present with positive cultures. Certain circumstances favor that situation, such as gallstones
or biliary tree manipulation. The aim of the present study was to determine the factors that
influence the presence of bacteriobilia, as well as its implications for clinical practice.
Materials and methods: A prospective study was conducted on bile cultures from patients that
underwent cholecystectomy at our hospital center within the time frame of 2013 to 2015.
Results: The study included 196 patients (42.3% women and 57.7% men) that underwent either
open or laparoscopic cholecystectomy and in whom bile fluid samples were taken. The clinical,
epidemiologic, and laboratory test characteristics of the patients were analyzed, as well as the
surgical indication (urgent surgery or programmed surgery). With respect to microbiology, 47%
of the bile cultures were positive: 56.5% presented with one microorganism, 25% with two, and
18.5% with three or more.
Conclusion: Microbiologic bile analysis should not be systematically performed, given that its
result is relevant only in cases that present with demonstrated risk factors. However, in those
cases, said analysis is essential to establish adequate antibiotic treatment, in relation to activity
spectrum and duration, to prevent complications and an increase in microbial resistance
Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: A multi-centre all-case analysis
Aims Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine.
Methods and results One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among mate patients after colchicine treatment (36 vs. 17%, P = 0.046), and those with previous corticosteroid treatment (43 vs. 13%, P = 0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% Cl: 1.65-27.02) and mate gender (OR 4.20, 95% Cl: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy.
Conclusion Treatment with colchicine is highly effective in preventing recurrent pericarditis, white pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis
Handedness of children determines preferential facial and eye movements related to hemispheric specialization
Comparing HLA Shared Epitopes in French Caucasian Patients with Scleroderma
Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, 67FLEDR71, shared by HLA-DRB susceptibility alleles, or 71TRAELDT77, shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient’s clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ2 = 28.4, p<10−6) and with anti-topoisomerase antibody (ATA) production (χ2 = 43.9, p<10−9) whereas TRAELDT association is weaker in both subgroups (χ2 = 7.2, p = 0.027 and χ2 = 14.6, p = 0.0007 respectively). Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes
Evaluation of Measurement Properties and Differential Item Functioning in the English and French Versions of the University of California, Los Angeles, Loneliness Scale-6: A Scleroderma Patient-Centered Intervention Network (SPIN) Study
Objective: Loneliness has been associated with poorer health-related quality of life but has not been studied in patients with systemic sclerosis (SSc). The current study was undertaken to examine and compare the psychometric properties of the English and French versions of the University of California, Los Angeles, Loneliness Scale-6 (ULS-6) in patients with SSc during the COVID-19 pandemic. Methods: This study used baseline cross-sectional data from 775 adults enrolled in the Scleroderma Patient-Centered Intervention Network (SPIN) COVID-19 Cohort. Reliability and validity of ULS-6 scores overall and between languages were evaluated using confirmatory factor analysis (CFA), differential item functioning (DIF) through the multiple-indicator multiple-cause (MIMIC) model, omega/alpha calculation, and correlations of hypothesized convergent relationships. Results: CFA for the total sample supported the single-factor structure (comparative fit index [CFI] 0.96, standardized root mean residual [SRMR] 0.03), and all standardized factor loadings for items were large (0.60–0.86). The overall MIMIC model with language as a covariate fit well (CFI 0.94, SRMR 0.04, root mean square error of approximation 0.11). Statistically significant DIF was found for 3 items across language (βitem2 = 0.14, P < 0.001; βitem4 = –0.07, P = 0.01; βitem6 = 0.13, P < 0.001), but these small differences were without practical measurement implications. Analyses demonstrated high internal consistency with no language-based convergent validity differences. Conclusion: Analyses demonstrated evidence of acceptable reliability and validity of ULS-6 scores in English- and French-speaking adults with SSc. DIF analysis supported use of the ULS-6 to examine comparative experiences of loneliness without adjusting for language
Pain levels and associated factors in the Scleroderma Patient-centered Intervention Network (SPIN) cohort: a multicentre cross-sectional study
Background: Pain is an important and detrimental feature of systemic sclerosis but is often overlooked or deprioritised in research and clinical care. Raynaud's phenomenon, arthritis, and cutaneous ulcers are among the commonly reported disease manifestations of systemic sclerosis that could be associated with pain. We aimed to assess levels of pain intensity and interference and to evaluate disease factors associated with pain intensity and interference. Methods: In this multicentre cross-sectional study, participants from the Scleroderma Patient-centered Intervention Network cohort who completed pain intensity and interference measures (Patient Reported Outcomes Information System-29 profile, version 2·0) as part of baseline assessments were included. Patients were recruited from 46 centres in Australia, Canada, France, Mexico, Spain, the UK, and the USA between April 15, 2014, and Jan 7, 2020. Eligible patients included those aged 18 years or older who met the criteria for systemic sclerosis devised by the American College of Rheumatology and the European League Against Rheumatism. Associations of pain intensity and pain interference with systemic sclerosis-related variables and overlap syndromes, controlling for sociodemographic variables, were assessed with multiple linear regression. Continuous independent variables were standardised. Findings: Among 2157 participants with systemic sclerosis (268 [12%] males and 1889 [88%] females), 1870 (87%) reported mild, moderate, or severe pain (defined as ≥1 on a 0 to 10 scale), and 815 (38%) reported moderate or severe pain (defined as ≥5). Moreover, 757 (35%) participants reported moderate or severe pain interference. Greater pain intensity was independently associated with female sex (0·58 points [95% CI 0·26–0·90]), non-White race or ethnicity (0·50 points [0·21–0·79]), fewer years in formal education (0·30 points per SD [0·19–0·41]), country (reference: USA; Canada: 0·29 points [0·01–0·57] and UK: 0·58 points [0·21–0·95]), greater body-mass index (0·35 points per SD [0·24–0·45]); joint contractures (0·67 points [0·39–0·94]), digital ulcers (0·33 points [0·10–0·55]), gastrointestinal involvement (0·66 points [0·33–0·98]), skin involvement (measured using modified Rodnan skin score; 0·22 points per SD [0·10–0·35]), rheumatoid arthritis (0·96 points [0·50–1·43]), and Sjögren's syndrome (0·42 points [0·01–0·83]). Pain interference results were similar. Interpretation: Pain is common among people with systemic sclerosis. Controlling for sociodemographic variables, greater pain was associated with multiple systemic sclerosis-related manifestations, including joint contractures, digital ulcers, gastrointestinal involvement, skin involvement, and the presence of overlap syndromes. Health-care providers should work with patients to address pain, including identifying and addressing systemic sclerosis manifestations associated with their pain, and supporting behavioural approaches to minimise impact on function and quality of life. Funding: Canadian Institutes of Health Research, Arthritis Society, The Lady Davis Institute for Medical Research of the Jewish General Hospital, Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland
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