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1.
Respir Res ; 24(1): 19, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36653833

RESUMEN

BACKGROUND: The objective of the present study is to describe the characteristics of interstitial pneumonia with autoimmune features (IPAF) patients, to assess the incidence rate of functional respiratory impairment over time and to evaluate the influence of therapeutic alternatives on the prognosis of these patients. METHODS: A longitudinal observational multicenter study was performed (NEREA registry). It was carried out by a multidisciplinary team in seven Hospitals of Madrid. Patients were included from IPAF diagnosis. MAIN OUTCOME: poor prognosis as functional respiratory impairment (relative decline in FVC % defined as ≥ 5% every 6 months). Covariates: therapy, sociodemographic, clinical, radiological patterns, laboratory and functional tests. STATISTICS: Survival techniques were used to estimate IR per 100 patients-semester with their 95% confidence interval [CI]. The influence of covariates in prognosis were analyzed through cox multivariate regression models (hazard ratio (HR) and [CI]). RESULTS: 79 IPAF were included, with a mean and a maximum follow-up of 3.17 and 12 years respectively. Along the study, 77.2% received treatment (52 glucocorticoids, 25 mycophenolate, 21 azathioprine, 15 rituximab and 11 antifibrotics). IR was 23.9 [19.9-28.8], and 50% of IPAF developed functional respiratory impairment after 16 months from its diagnosis. Multivariate analysis: usual interstitial pneumonia (UIP) had poorer prognosis compared to non-specific interstitial pneumonia (NSIP) (p = 0.001). In NSIP, positive ANA, increased the risk of poor prognosis. In UIP, glucocorticoids (HR: 0.53 [0.34-0.83]), age (HR: 1.04 [1.01-1.07]), and Ro-antibodies (HR: 0.36 [0.19-0.65]) influenced the prognosis. CONCLUSIONS: IPAF have functional impairment during the first years of disease. Factors predicting deterioration differ between radiographic patterns. Our real-life study suggests the potential benefit of particular therapies in IPAF.


Asunto(s)
Enfermedades Autoinmunes , Neumonías Intersticiales Idiopáticas , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Insuficiencia Respiratoria , Humanos , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/epidemiología , Neumonías Intersticiales Idiopáticas/diagnóstico
2.
Neurourol Urodyn ; 42(2): 539-546, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36524789

RESUMEN

INTRODUCTION: The use of public bathrooms is a challenge for everyone, but especially for those who are affected by a bathroom-dependent condition. Being dependent on bathrooms is linked with different negative emotions. One of them is a clinically relevant emotion: shame associated with the chronic condition. MATERIALS AND METHODS: In a cross-sectional survey study (n = 193) of people who suffer a bathroom-dependent condition we asked about health conditions, well-being, and shame related to chronic condition outcomes. RESULTS: We show a link between negative public bathroom experiences, and diminished well-being and feelings of shame related to chronic illness. We found that this relationship between negative experiences with public bathrooms and shame is not specific to the different conditions. CONCLUSION: We conclude that the negative experiences which people with different gastrointestinal illnesses face is an environmental stressor associated with more embarrassment as a result of the condition suffered.


Asunto(s)
Vergüenza , Cuartos de Baño , Humanos , Estudios Transversales , Emociones , Enfermedad Crónica
3.
PLoS Pathog ; 16(6): e1008555, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32579593

RESUMEN

Exhaustion is a dysfunctional state of cytotoxic CD8+ T cells (CTL) observed in chronic infection and cancer. Current in vivo models of CTL exhaustion using chronic viral infections or cancer yield very few exhausted CTL, limiting the analysis that can be done on these cells. Establishing an in vitro system that rapidly induces CTL exhaustion would therefore greatly facilitate the study of this phenotype, identify the truly exhaustion-associated changes and allow the testing of novel approaches to reverse or prevent exhaustion. Here we show that repeat stimulation of purified TCR transgenic OT-I CTL with their specific peptide induces all the functional (reduced cytokine production and polyfunctionality, decreased in vivo expansion capacity) and phenotypic (increased inhibitory receptors expression and transcription factor changes) characteristics of exhaustion. Importantly, in vitro exhausted cells shared the transcriptomic characteristics of the gold standard of exhaustion, CTL from LCMV cl13 infections. Gene expression of both in vitro and in vivo exhausted CTL was distinct from T cell anergy. Using this system, we show that Tcf7 promoter DNA methylation contributes to TCF1 downregulation in exhausted CTL. Thus this novel in vitro system can be used to identify genes and signaling pathways involved in exhaustion and will facilitate the screening of reagents that prevent/reverse CTL exhaustion.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Metilación de ADN/inmunología , Factor Nuclear 1-alfa del Hepatocito/inmunología , Coriomeningitis Linfocítica/inmunología , Virus de la Coriomeningitis Linfocítica/inmunología , Regiones Promotoras Genéticas/inmunología , Animales , Linfocitos T CD8-positivos/patología , Factor Nuclear 1-alfa del Hepatocito/genética , Coriomeningitis Linfocítica/genética , Coriomeningitis Linfocítica/patología , Virus de la Coriomeningitis Linfocítica/genética , Ratones , Ratones Transgénicos , Transducción de Señal/genética , Transducción de Señal/inmunología
4.
Haematologica ; 107(1): 143-153, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33596640

RESUMEN

T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease. Multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups, and no clear T-cell receptor a or ß CDR3 skewing was observed between different T-PLL cases. We revealed that the expression of microRNA (miRNA) is aberrant and often heterogeneous in T-PLL. We identified 35 miRNA that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR- 200c/141 and miR-181a/181b expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 correlated with downregulation of their targets ZEB2 and TGFßR3 and aberrant TGFß1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFß pathway is affected in T-PLL. Our results thus highlight the potential role for aberrantly expressed oncogenic miRNA in T-PLL and pave the way for new therapeutic targets in this disease.


Asunto(s)
Leucemia Prolinfocítica de Células T , MicroARNs , Perfilación de la Expresión Génica , Humanos , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/terapia , Linfocitos , MicroARNs/genética , Factor de Crecimiento Transformador beta , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética
5.
Rheumatol Int ; 42(10): 1819-1829, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34783890

RESUMEN

Patients with rheumatoid arthritis (RA) have a significantly increased risk of sexual dysfunction. However, it is not properly included in commonly used questionnaires to assess health-related quality of life in RA. Qualisex is a questionnaire developed in France to assess the impact of RA on patients´ sexual function. Our aim was to adapt and validate this questionnaire for use with Spanish RA patients. Two independent translations and a backward translation were obtained. The final version was tested in a pilot study with 10 RA patients to detect any aspects that could hinder interpretation. The validity and reliability of the linguistically validated questionnaire were studied in a multicenter cross-sectional study, with a longitudinal component for reliability estimation. 125 RA patients were included. The response process, discrimination, internal consistency, internal structure, convergent validity (correlation with MGH-SFQ questionnaire, DAS-28, physician global assessment, patient global health assessment, RAID, HAQ, HADS and SF-12©) and reliability were analyzed. The inclusion of two extra items was proposed in the pilot study. The validity analysis detected responses for item 10 that were not coherent with responses for the rest of items. The Cronbach alpha coefficient was 0.971. The highest correlation (0.665) was obtained with MGH-SFQ (questionnaire measuring sexual functioning), followed by RAID (0.516). The intra-class correlation was 0.880 (95% CI 0.815; 0.923), higher than 0.85, which indicates excellent reliability. All parameters used to assess this questionnaire show highly acceptable values. Qualisex allows for a global score of RA patients' sexual functioning and can be self-administered.


Asunto(s)
Artritis Reumatoide , Calidad de Vida , Artritis Reumatoide/diagnóstico , Estudios Transversales , Humanos , Proyectos Piloto , Psicometría , Reproducibilidad de los Resultados , Sexualidad , España , Encuestas y Cuestionarios
6.
Mod Rheumatol ; 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36516217

RESUMEN

OBJECTIVES: To evaluate risk factors for severe Coronavirus Disease 2019 (COVID-19) in patients with immune-mediated rheumatic diseases, stratified by systemic autoimmune conditions and chronic inflammatory arthritis. METHODS: An observational, cross-sectional multicenter study was performed. Patients from 10 Rheumatology departments in Madrid who presented with SARS-CoV-2 infection between Feb 2020 and May 2021 were included. The main outcome was COVID-19 severity (hospital admission or mortality). Risk factors for severity were estimated, adjusting for covariates (sociodemographic, clinical and treatments), using logistic regression analyses. RESULTS: 523 patients with COVID-19 were included, among whom 192 (35.6%) patients required hospital admission and 38 (7.3%) died. Male gender, older age and comorbidities such as diabetes mellitus, hypertension and obesity were associated with severe COVID-19. Corticosteroid doses over 10 mg/day, rituximab, sulfasalazine and mycophenolate use, were independently associated with worse outcomes. COVID-19 severity decreased over the different pandemic waves. Mortality was higher in the systemic autoimmune conditions (univariate analysis, p<0.001), although there were no differences in overall severity in the multivariate analysis. CONCLUSIONS: This study confirms and provides new insights regarding the harmful effects of corticosteroids, rituximab and other therapies (mycophenolate and sulfasalazine) in COVID-19. Methotrexate and anti-TNF therapy were not associated with worse outcomes.

7.
PLoS Pathog ; 15(10): e1008072, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31603951

RESUMEN

Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways. This is critical for protection, as neonatal mice intranasally pre-treated with IFNß before influenza virus infection are also protected. Using transgenic mice, we demonstrate that the protective effect of LGG is mediated through a MyD88-dependent mechanism, specifically via TLR4. LGG can improve both early control of virus and transcriptional responsiveness and could serve as a simple and safe intervention to protect neonates.


Asunto(s)
Virus de la Influenza A/fisiología , Lacticaseibacillus rhamnosus/crecimiento & desarrollo , Pulmón/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Administración Intranasal , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Pulmón/virología , Ratones , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología
8.
Psychooncology ; 30(11): 1894-1901, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34197018

RESUMEN

OBJECTIVE: Clinical guidelines recommend psychological screening in cancer patients. However, most scales cover many items and hamper detection. In addition, patients are generally referred from routine consultations. The specific objective of the present study was to develop and validate a tool, Anxiety, Depression, Coping (ADAF), to screen for anxiety and depression and assess coping in cancer patients. METHODS: Cross-sectional, multicenter study performed in the medical and radiotherapy-oncology services of five hospitals in Madrid and coordinated by the Medical Oncology Service of Hospital Clínico San Carlos (CEIC nº19/265-E). To determine psychometric properties, the ADAF screening questionnaire ADAF was administered. ADAF includes five items (1 related to anxiety symptoms, 2 related to depressive symptoms, 1 for helplessness coping, and 1 for avoidance coping). Hospital Anxiety and Depression Scale and Mini-Mental Adjustment to Cancer scale were used as the gold standards. Intraclass correlation coefficients were calculated and receiver operating characteristic (ROC) curves constructed. A p value of <0.05 was considered significant. RESULTS: A total of 186 patients completed the evaluation. The correlation coefficients were significant for all dimensions (anxiety, depression, helplessness coping, and avoidance coping) (p < 0.001). The statistical analysis of the ROC curves suggested that the cut-off point for screening was >2 points (3 in the case of depression), with a sensitivity and specificity between 62% and 90%, and an area under the curve above 0.8 for the first 4 items. CONCLUSIONS: ADAF screening has adequate reliability and good sensitivity and specificity. This instrument is useful and can be easily applied to identify emotional and coping problems in cancer patients.


Asunto(s)
Depresión , Neoplasias , Adaptación Psicológica , Ansiedad/diagnóstico , Ansiedad/psicología , Estudios Transversales , Depresión/diagnóstico , Depresión/psicología , Detección Precoz del Cáncer , Humanos , Neoplasias/psicología , Escalas de Valoración Psiquiátrica , Psicometría/métodos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
9.
BMC Pulm Med ; 21(1): 205, 2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34193085

RESUMEN

BACKGROUND: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. METHODS: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. RESULTS: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR. CONCLUSIONS: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.


Asunto(s)
Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , España/epidemiología , Análisis de Supervivencia , Tomografía Computarizada por Rayos X
10.
Int J Mol Sci ; 22(23)2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34884740

RESUMEN

Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) are a potential therapy for immunological and degenerative diseases. However, large-scale production of EV free from contamination by soluble proteins is a major challenge. The generation of particles from isolated membranes of MSC, membrane particles (MP), may be an alternative to EV. In the present study we generated MP from the membranes of lysed MSC after removal of the nuclei. The yield of MP per MSC was 1 × 105 times higher than EV derived from the same number of MSC. To compare the proteome of MP and EV, proteomic analysis of MP and EV was performed. MP contained over 20 times more proteins than EV. The proteins present in MP evidenced a multi-organelle origin of MP. The projected function of the proteins in EV and MP was very different. Whilst proteins in EV mainly play a role in extracellular matrix organization, proteins in MP were interconnected in diverse molecular pathways, including protein synthesis and degradation pathways and demonstrated enzymatic activity. Treatment of MSC with IFNγ led to a profound effect on the protein make up of EV and MP, demonstrating the possibility to modify the phenotype of EV and MP through modification of parent MSC. These results demonstrate that MP are an attractive alternative to EV for the development of potential therapies. Functional studies will have to demonstrate therapeutic efficacy of MP in preclinical disease models.


Asunto(s)
Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proteoma , Membrana Celular/metabolismo , Humanos , Interferón gamma , Proteómica
11.
Ann Rheum Dis ; 79(11): 1393-1399, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32769150

RESUMEN

OBJECTIVES: To describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19. METHODS: An observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission. RESULTS: The study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model. CONCLUSION: Our results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.


Asunto(s)
Enfermedades Autoinmunes/epidemiología , Infecciones por Coronavirus/terapia , Hospitalización/estadística & datos numéricos , Neumonía Viral/terapia , Enfermedades Reumáticas/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Enfermedades Autoinmunes/tratamiento farmacológico , Betacoronavirus , COVID-19 , Diabetes Mellitus/epidemiología , Femenino , Glucocorticoides/uso terapéutico , Cardiopatías/epidemiología , Humanos , Hipertensión/epidemiología , Tiempo de Internación/estadística & datos numéricos , Estudios Longitudinales , Enfermedades Pulmonares/epidemiología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Enfermedad Mixta del Tejido Conjuntivo/tratamiento farmacológico , Enfermedad Mixta del Tejido Conjuntivo/epidemiología , Análisis Multivariante , Pandemias , Polimialgia Reumática/tratamiento farmacológico , Polimialgia Reumática/epidemiología , Factores Protectores , Enfermedades Reumáticas/tratamiento farmacológico , Factores de Riesgo , SARS-CoV-2 , Factores Sexuales , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/epidemiología , España/epidemiología , Espondiloartropatías/tratamiento farmacológico , Espondiloartropatías/epidemiología , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico
12.
Rheumatology (Oxford) ; 59(8): 2099-2108, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31990338

RESUMEN

OBJECTIVES: To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS: A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS: A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION: RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Capacidad Vital
13.
Haematologica ; 105(1): 182-192, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31097630

RESUMEN

Chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical and biological characteristics. Differences in Ca2+ levels among cases, both basal and upon B-cell receptor (BCR) stimulation, may reflect heterogeneity in the pathogenesis due to cell-intrinsic factors. Our aim was to elucidate cell-intrinsic differences between BCR-responsive and -unresponsive cases. We therefore determined BCR responsiveness ex vivo based on Ca2+ influx upon α-IgM stimulation of purified CLL cell fractions from 52 patients. Phosphorylation levels of various BCR signaling molecules, and expression of activation markers were assessed by flow cytometry. Transcription profiling of responsive (n=6) and unresponsive cases (n=6) was performed by RNA sequencing. Real-time quantitative polymerase chain reaction analysis was used to validate transcript level differences in a larger cohort. In 24 cases an α-IgM response was visible by Ca2+ influx which was accompanied by higher phosphorylation of PLCγ2 and Akt after α-IgM stimulation in combination with higher surface expression of IgM, IgD, CD19, CD38 and CD43 compared to the unresponsive cases (n=28). Based on RNA sequencing analysis several components of the canonical nuclear factor (NF)-κB pathway, especially those related to NF-κB inhibition, were expressed more highly in unresponsive cases. Moreover, upon α-IgM stimulation, the expression of these NF-κB pathway genes (especially genes coding for NF-κB pathway inhibitors but also NF-κB subunit REL) was upregulated in BCR-responsive cases while the level did not change, compared to basal level, in the unresponsive cases. These findings suggest that cells from CLL cases with enhanced NF-κB signaling have a lesser capacity to respond to BCR stimulation.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , FN-kappa B , Humanos , Proteínas I-kappa B , Leucemia Linfocítica Crónica de Células B/genética , FN-kappa B/metabolismo , Receptores de Antígenos de Linfocitos B/genética , Transducción de Señal
14.
Clin Exp Rheumatol ; 38 Suppl 123(1): 40-46, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31928594

RESUMEN

OBJECTIVES: Fibromyalgia (FM) is a chronic syndrome characterised by widespread musculoskeletal pain associated with other symptoms, including psychological distress. While negative mood (anxiety, depression, and anger) has been widely explored in FM, few studies have investigated emotional dysregulation. Our purpose was to evaluate problems in the processes of emotional regulation and to explore their influence on the severity of pain and disability. METHODS: Emotional regulations, anxiety, depression, anger, pain and disability were evaluated in 47 FM patients and 47 healthy subjects. Regression analyses were performed to evaluate the role that emotional regulation processes have on pain severity and disability of FM patients. RESULTS: Results showed that although FM patients do not differ in terms of the attention paid to their emotional states, FM patients had greater difficulties in the emotional regulation process. In addition, emotional rejection and interference are two variables that influence the pain severity and disability. CONCLUSIONS: FM patients need to be trained in strategies for regulating their emotions, in order to achieve a reduction in negative mood states, as well as their impact in pain and disability.


Asunto(s)
Regulación Emocional , Fibromialgia/psicología , Dolor/psicología , Ira , Ansiedad , Depresión , Evaluación de la Discapacidad , Fibromialgia/fisiopatología , Humanos , Dolor/fisiopatología
15.
J Clin Rheumatol ; 25(2): 78-84, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29561466

RESUMEN

OBJECTIVE: The aim of this study was to assess the reliability and validity of the Spanish version of the Rosser classification system for disease states in patients with musculoskeletal disorders. METHODS: Our study was based on a questionnaire validation design. Patients were attended at an outpatient rheumatology clinic at Hospital Clínico San Carlos, Madrid, Spain. The Rosser classification system was completed by the physician from the research team (PMQ) and by the patient (HMQ). Criterion standards: The EuroQol-5D for the HMQ and the physician global estimate (DOCGL) for the PMQ. Internal consistency reliability was assessed using Cronbach α. Test-retest reliability and interobserver reliability were analyzed using the intraclass correlation coefficient. The criterion validity between HMQ and EuroQol-5D and between PMQ and DOCGL was assessed using the Spearman correlation coefficient. RESULTS: The full analysis was based on 4 samples of patients (104 to 266 patients), most of whom were middle-aged women. For HMQ, Cronbach α was 0.70. Test-retest reproducibility was 0.7. With respect to criterion validity, significant correlations in the expected direction were observed. For PMQ, Cronbach α was 0.70, indicating excellent intraobserver and interobserver reliability. With respect to criterion validity, strong correlations were observed between the PMQ and the DOCGL. CONCLUSIONS: The Rosser classification system showed satisfactory reliability and suitable criterion validity for patients with musculoskeletal disorders. The instrument seems to be suitable for clinical decision making and research.


Asunto(s)
Calidad de Vida , Enfermedades Reumáticas/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/fisiopatología , España , Traducciones
18.
Clin Exp Rheumatol ; 36(1): 29-35, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28598787

RESUMEN

OBJECTIVES: Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients. METHODS: A 14-year retrospective longitudinal study was performed. RA patients followed in an out-patient clinic starting bDMARDs after the age of 65 were included. PRIMARY OUTCOME: discontinuation due to a severe ADR related to bDMARDs (etanercept, infliximab, adalimumab, rituximab, golimumab, certolizumab, abatacept and tocilizumab). Covariables: sociodemographic, clinical and therapy. Incidence rates of discontinuation were estimated using survival techniques and comparison between bDMARDs discontinuation rates and other associated factors were run by Cox regression models. RESULTS: We analysed 286 courses of bDMARDs therapy in 146 elderly patients (604 patient-years). 78% were women, with a mean age at diagnosis of 66.5±7 years, and a median time to the start of the first bDMARDs of 6±4 years. The incidence of discontinuation due to severe ADR estimated was 10.2% patient-years, with a median survival of around 7 years. The most frequent cause was infections. Etanercept had the lowest risk of severe ADR compared to other bDMARDs. CONCLUSIONS: Our study reflects the 'real world' experience in elderly RA patients on bDMARDs, with non-selected patients for a 14-year follow-up.


Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Factores de Edad , Anciano , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Femenino , Humanos , Huésped Inmunocomprometido , Incidencia , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Análisis Multivariante , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inmunología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , España/epidemiología , Resultado del Tratamiento
19.
Clin Exp Rheumatol ; 36 Suppl 111(2): 121-128, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29303708

RESUMEN

OBJECTIVES: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated. METHODS: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014. MAIN OUTCOME: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models. RESULTS: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA. CONCLUSIONS: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.


Asunto(s)
Antirreumáticos/uso terapéutico , Arteritis de Células Gigantes/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Anciano de 80 o más Años , Sedimentación Sanguínea , Quimioterapia Combinada , Femenino , Arteritis de Células Gigantes/sangre , Glucocorticoides/administración & dosificación , Humanos , Incidencia , Masculino , Análisis Multivariante , Modelos de Riesgos Proporcionales , Recurrencia , Riesgo
20.
Rheumatol Int ; 38(12): 2167-2182, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29808295

RESUMEN

OBJECTIVE: To establish feasible and practical recommendations for the management of the psychological needs of patients with rheumatoid arthritis (RA) from the moment of diagnosis through the course of the disease. METHODS: A nominal group meeting was held with an RA expert team including rheumatologists and psychologists, at which a guided discussion addressed the most important psychological and emotional needs in RA. Based on the comments collected, and a literature review, a matrix document of recommendations for telematics discussion was prepared, as well as a Delphi survey to test agreement with these recommendations. Agreement was defined if at least 80% of participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grading of recommendations was established following the Oxford criteria, and the degree of agreement through the Delphi. RESULTS: Thirteen recommendations were established, addressing several key processes: (1) identification of psychological problems and needs in patients with RA, and a guideline for their management in daily practice; (2) communication with patients; (3) referral criteria to mental health professionals. CONCLUSIONS: These recommendations are intended to help health care professionals openly address the psychological aspects of patients in daily practice to follow and treat them properly.


Asunto(s)
Adaptación Psicológica , Artritis Reumatoide/terapia , Costo de Enfermedad , Emociones , Servicios de Salud Mental/normas , Psiquiatría/normas , Psicología/normas , Reumatología/normas , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/fisiopatología , Artritis Reumatoide/psicología , Consenso , Técnica Delphi , Humanos , Comunicación Interdisciplinaria , Salud Mental , Grupo de Atención al Paciente , Reumatólogos/normas
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