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1.
Theranostics ; 14(1): 176-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164161

RESUMO

The discovery of extracellular vesicles (EVs) as efficient exogenous biotransporters of therapeutic agents into cells across biological membranes is an exciting emerging field. Especially the potential of EVs as targeted delivery systems for diseases with selective treatments, such as fibrosis, whose treatment causes side effects in other organs not involved in the disease. Methods: In this study, we collected embryonic fibroblast-derived EVs from two different centrifugation fractions, 10 K g and 100 K g fractions from a NIH-3T3 cell line loaded with an experimental drug. Mice with fibrotic hearts and lungs were obtained by administration of angiotensin II. We generated fluorescent EVs and bioluminescent drug to observe their accumulation by colocalization of their signals in fibrotic heart and lung. The biodistribution of the drug in various organs was obtained by detecting the Au present in the drug nanostructure. Results: The drug-loaded EVs successfully reduced fibrosis in pathological fibroblasts in vitro, and modified the biodistribution of the experimental drug, enabling it to reach the target organs in vivo. We described the pre-analytical characteristics of EVs related to physical variables, culture and harvesting conditions, crucial for their in vivo application as nanotransporters using a previously validated protein-based antifibrotic drug. The results showed the colocalization of EVs and the experimental drug in vivo and ex vivo and the efficient reduction of fibrosis in vitro. This work demonstrates that 10K-EVs and 100K-EVs derived from fibroblasts can act as effective biotransporters for targeted drug delivery to profibrotic fibroblasts, lungs, or heart. Conclusion: We observed that fibroblast-derived 10K-EVs and 100K-EVs are useful biotransporters encapsulating a new generation drug leading to a reduction of fibrosis in profibrotic fibroblasts in vitro. In addition, drug containing EVs were shown to reach fibrotic heart and lungs in vivo, enhancing free drug biodistribution.


Assuntos
Vesículas Extracelulares , Nanopartículas , Animais , Camundongos , Distribuição Tecidual , Pulmão/metabolismo , Fibroblastos , Vesículas Extracelulares/metabolismo , Fibrose
2.
J Clin Med ; 12(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38137815

RESUMO

BACKGROUND: Retrospective studies support that mean perfusion pressure (MPP) deficit in cardiac surgery patients is associated with a higher incidence of acute kidney injury (CS-AKI). The aim of our study was to apply an algorithm based on MPP in the postoperative period to determine whether management with an individualized target reduces the incidence of CS-AKI. METHODS: Randomized controlled trial of patients undergoing cardiac surgery with extracorporeal circulation. Adult patients submitted to valve replacement and/or bypass surgery with a high risk of CS-AKI evaluated by a Leicester score >30 were randomized to follow a target MPP of >75% of the calculated baseline or a standard hemodynamic management during the first postoperative 24 h. RESULTS: Ninety-eight patients with an eGFR of 54 mL/min were included. There were no differences in MAP and MPP in the first 24 h between the randomized groups, although a higher use of noradrenaline was found in the intervention arm (38.78 vs. 63.27, p = 0.026). The percentage of time with MPP < 75% of measured baseline was similar in both groups (10 vs. 12.7%, p = 0.811). MAP during surgery was higher in the intervention group (73 vs. 77 mmHg, p = 0.008). The global incidence of CS-AKI was 36.7%, being 38.6% in the intervention group and 34.6% in the control group (p = 0.40). There were no differences in extrarenal complications between groups as well. CONCLUSION: An individualized hemodynamic management based on MPP compared to standard treatment in cardiac surgery patients was safe but did not reduce the incidence of CS-AKI in our study.

3.
Respir Med Res ; 84: 101064, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38029650

RESUMO

BACKGROUND: Tocilizumab is presumed to be an effective and safe treatment for severe SARS-Cov-2, but its usefulness has not been investigated yet for long-term outcomes. This study aimed to evaluate the influence of tocilizumab on mortality in patients with SARS-CoV-2 throughout the year following discharge. METHODS: A retrospective observational analysis was performed on electronic medical records of patients with SARS-CoV2 who were discharged from our hospital after surviving the first wave in March-April 2020. Logistic regression was used to analyse the effect of tocilizumab on mortality, as the main outcome, and propensity-score analysis to further validate their effect. Secondary outcomes were readmissions, persistent symptoms and lung function evolution. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. RESULTS: A total of 405 patients were included in the mortality study (33.6 % were treated with tocilizumab) and 390 were included in the assessment of persistent symptoms. After propensity-score analysis, no association between tocilizumab use and 1-year overall mortality was found (HR= 2.05, 95 % CI: 0.21-19.98). No differences regarding persistent symptoms (OR= 1.01 95 %CI 0.57-1.79), nor lung function parameters (forced vital capacity: coefficient -0.16 95 %CI -0.45 to 0.14) were found throughout the year follow-up between control and tocilizumab group. CONCLUSIONS: The administration of tocilizumab in patients with SARS-CoV-2 did not show any effect on long-term mortality. Identically, no association were found regarding readmissions, persistent symptoms or lung function evolution and tocilizumab administration in our cohort of patients after 1 year follow-up.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Estudos de Coortes , Tratamento Farmacológico da COVID-19 , Hospitais , Pulmão , Alta do Paciente , Readmissão do Paciente , Estudos Retrospectivos , RNA Viral , Resultado do Tratamento
4.
Pharmacoeconomics ; 41(8): 999-1010, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37249823

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease associated with dyspnoea, cough and impaired quality of life affecting around 7500 patients in Spain. OBJECTIVE: Our aim was to estimate the economic impact of IPF according to forced vital capacity (FVC) % predicted level in adult patients. METHODS: We conducted a prospective, observational, multicentric study of patients with confirmed IPF in Spain. Total annual IPF-related costs were estimated per patient, and categorised according to the FVC% predicted value (FVC < 50%, FVC 50-80%, FVC > 80%) and total sample. Incurred direct health- and non-health-related costs and indirect costs were calculated considering the IPF-related healthcare resource use and the corresponding unitarian costs. Results were updated to 2023 euros. RESULTS: Two hundred and four consecutive patients with IPF were included: 77% male, average age (standard deviation) 70.8 (7.6) years. At baseline, FVC% was < 50%, 50-80% and > 80% of predicted value in 10.8%, 74.5% and 14.7% of patients, respectively. The final cost-evaluable population included 180 subjects. The mean (standard deviation) total annual IPF-related cost was €26,997 (17,555), with statistically significant differences (p = 0.0002) between groups: €44,412 (33,389) for the FVC < 50%, €25,803 (14,688) for the FVC 50-80% and €23,242 (13,642) for the FVC > 80%. Annual direct health costs had the greatest weight and included pharmacological treatments [€22,324 (13,773)] and hospitalisation days [€1659 (7362)]. 14 patients had ≥ 1 acute exacerbation of IPF during the study; mean total cost of an acute exacerbation of IPF was €10,372. According to the multivariate analysis, an impaired lung function (FVC < 50%) and use of antifibrotic treatment were determinants of cost (p < 0.0001 both). CONCLUSIONS: We observed a significantly higher annual IPF-related cost at a lower level of predicted FVC%, the direct cost having the greatest weight to the total costs. Maintaining patients at early disease stages by slowing IPF progression is relevant to reduce the economic impact of IPF. CLINICAL TRIAL REGISTRATION: EU PAS register number EUPAS19387 (1 June, 2017).


Assuntos
Estresse Financeiro , Fibrose Pulmonar Idiopática , Idoso , Feminino , Humanos , Masculino , Fibrose Pulmonar Idiopática/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Espanha
5.
Nutr Hosp ; 40(3): 567-573, 2023 Jun 21.
Artigo em Espanhol | MEDLINE | ID: mdl-37073743

RESUMO

Introduction: Introduction: malnutrition, both due to deficiency and excess of nutrients, correlates to the morbidity of the surgical patient. Objectives: to analyze the nutritional status, body composition and bone health of patients undergoing elective knee and hip arthroplasty. Methods: an observational cross-sectional study was carried out evaluating patients undergoing hip and knee replacement surgery from February to September 2019. The Malnutrition Universal Screening Tool (MUST), anthropometry, hand-grip dynamometry, bone densitometry, lumbar spine X-ray and bioimpedance analysis were performed. Results: eighty-six patients (61.6 % women) were evaluated, with a mean age of 69.5 ± 9.5 years. The mean body mass index (BMI) was 31.3 ± 4.5. According to MUST, 21.3 % were at risk of malnutrition; 16.9 % had decreased triceps skinfold with respect to p50 and 20 % had a pathological hand-grip dynamometry. In 91.4 %, vitamin D was < 30 pg/ml. In the bioimpedanciometry, the women presented significantly decreased muscle mass values. Age was correlated with a lower presence of fat-free mass, total and appendicular muscle mass. In those over 65 years of age, 52.6 % of men vs 14.3 % of women had a decreased muscle mass index; 58.5 % had low bone mineral density. We observed vertebral bone collapses in 13.9 %. Conclusion: there is a high prevalence of obesity in patients who are candidates for arthroplasty and this does not exclude the existence of a risk of malnutrition. They may also have decreased muscle mass and strength. Nutritional education and physical exercise recommendations are essential in order to optimize nutritional status for surgery.


Introducción: Introducción: la malnutrición tanto por defecto como por exceso de nutrientes se relaciona con la morbilidad del paciente quirúrgico. Objetivos: analizar el estado nutricional, la composición corporal y la salud ósea de pacientes sometidos a artroplastia electiva de rodilla y cadera Método: se realiza un estudio transversal observacional evaluando pacientes que ingresan para cirugía de prótesis de cadera y rodilla de febrero a septiembre de 2019. Al ingreso, se realizan Malnutrition Universal Screening Tool (MUST), antropometría, dinamometría manual, densitometría ósea, radiografía de columna lumbar y bioimpedanciometría. Resultados: se evaluó a 86 pacientes (61,6 % mujeres), con edad media de 69,5 ± 9,5 años. El índice de masa corporal (IMC) medio fue de 31,3 ± 4,5. Según MUST, el 21,3 % estaba en riesgo de desnutrición. El 16,9 % tenía disminuido el pliegue tricipital respecto al p50 y el 20 % tenía una dinamometría manual patológica. En el 91,4 % la vitamina D fue < 30 pg/ml. En la bioimpedanciometría, las mujeres presentaban valores de masa muscular significativamente disminuidos. La edad se correlacionó con menor presencia de masa libre de grasa, masa muscular total y apendicular. En mayores de 65 años, el 52,6 % de varones vs. 14,3 % de mujeres presentaban un índice de masa muscular disminuido. El 58,5 % tenía densidad mineral ósea baja. Objetivamos aplastamientos vertebrales en el 13,9 %. Conclusiones: existe una alta prevalencia de obesidad en pacientes candidatos a artroplastia y esto no excluye la existencia de riesgo de desnutrición. Además, pueden presentar disminución de masa y fuerza muscular. Es fundamental la educación nutricional y recomendaciones de ejercicio físico de cara a optimizar el estado nutricional para cirugía.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Desnutrição , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Composição Corporal/fisiologia , Índice de Massa Corporal , Estado Nutricional , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Densidade Óssea/fisiologia
6.
Rev. cuba. med. trop ; 74(3)dic. 2022.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1449978

RESUMO

Introducción: La enfermedad del Zika es causada por el virus de igual nombre, un arbovirus transmitido principalmente por la picadura del mosquito Aedes. Existe riesgo de reintroducción y circulación autóctona del virus Zika en Cuba, por tanto, constituye una problemática vigente. Objetivo: Caracterizar el comportamiento clínico de la infección por virus Zika en pacientes ingresados en el Instituto de Medicina Tropical Pedro Kourí (IPK). Método: Se realizó un estudio descriptivo de corte trasversal con componente analítico, en pacientes con diagnóstico de Zika ingresados en el IPK en el periodo de noviembre de 2016 a mayo de 2017. Se analizaron variables sociodemográficas, clínicas, biomédicas y microbiológicas. Resultados: En los pacientes confirmados con virus Zika, las manifestaciones clínicas significativas (p ≤ 0,05) fueron prurito y adenomegalias; con una duración de la erupción cutánea significativamente superior. En cuanto a los estudios de confirmación mediante reacción en cadena de la polimerasa en tiempo real, la muestra de orina tuvo valores de positividad significativamente superiores a las de suero desde el comienzo del cuadro clínico. Conclusiones: Los casos autóctonos de Zika estudiados presentaron un cuadro clínico donde predominaron el prurito y las adenomegalias. Esto permitió realizar un diagnóstico presuntivo y diferencial ante otros pacientes con síndrome febril. El diagnóstico microbiológico para confirmación de esta arbovirosis fue realizado mediante técnicas moleculares. En la mayoría de los casos las muestras de orina demostraron ser de gran utilidad desde los primeros días luego de la fecha de inicio de los síntomas.


Introduction: Zika is caused by the virus of the same name, an arbovirus transmitted mainly by the bite of the Aedes mosquito. The risk of reintroduction and autochthonous circulation of Zika virus in Cuba remains; therefore, it is considered a current problem. Objective: To characterize the clinical behavior of Zika virus infection in patients admitted to the Institute of Tropical Medicine Pedro Kourí (IPK). Methods: It was conducted a cross-sectional, descriptive study with an analytic component in patients with a diagnosis of Zika admitted to IPK from November 2016 to May 2017. Sociodemographic, clinical, biomedical and microbiological variables were analyzed. Results: In patients confirmed with Zika virus, the main clinical manifestations (p≤ 0.05) were pruritus and adenomegaly; with significantly longer duration of rash. Regarding confirmation studies by real-time polymerase chain reaction, the urine sample had significantly higher positivity values than the serum samples from the onset of the clinical picture. Conclusions: Pruritus and adenomegaly prevailed in the autochthonous cases of Zika under study. This allowed conducting a presumptive and differentiated diagnosis to other patients with a febrile syndrome. The microbiological diagnosis to confirm this arbovirus was performed by molecular methods. In the majority of cases, the urine samples were very useful from the first days after the onset of the symptoms.


Assuntos
Humanos
10.
Respir Res ; 23(1): 235, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071483

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with decline in lung function and poor prognosis entailing significant impairment in quality of life and high socioeconomic burden. The aim of this study was to characterize clinical management and resources utilization of patients with IPF in Spain, according to predicted forced vital capacity (FVC) % at baseline. METHODS: Prospective, non-interventional, multicentric real-world data study in patients with IPF in Spain with 12-months follow-up. Clinical management and resources utilization during study period were recorded and compared between groups. FVC decline and acute exacerbations occurrence and associated healthcare resource use were also analysed. FVC decline after 12 months was estimated as relative change. RESULTS: 204 consecutive patients with IPF were included and divided according to baseline FVC % predicted value. At baseline, patients with FVC < 50% received significantly more pharmacological and non-pharmacological treatments, and more help from caregiver. During the 12-months follow-up, patients with FVC < 50% required more specialized care visits, emergency visits, hospitalizations, pulmonary functions tests, non-health resource use (special transportation), and pharmacological treatments (p < 0.05 for all comparisons). Moreover, patients with FVC < 50% at baseline experienced more AE-IPF (p < 0.05), requiring more health-related resources use (primary care visits, p < 0.05). FVC decline was observed in all groups over the 12 months. FVC decreased on average by 2.50% (95% CI: - 5.98 to 0.98) along the year. More patients experienced an FVC decline > 10% in the more preserved lung function groups than in the FVC < 50% group, because of their already deteriorated condition. CONCLUSIONS: We observed a significantly higher annual IPF-related resource use in patients with more impaired lung function at baseline. Since FVC decreases irrespective of FVC% predicted at baseline, slowing IPF progression to maintain patients at early disease stages is relevant to improve IPF management and to optimize resource use. TRIAL REGISTRATION: EU PAS register number EUPAS19387 [June 01, 2017].


Assuntos
Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/terapia , Estudos Prospectivos , Qualidade de Vida , Espanha/epidemiologia
12.
J Allergy Clin Immunol Pract ; 10(9): 2414-2423, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35788062

RESUMO

BACKGROUND: YKL-40 (chitinase 3-like-1) and Krebs von den Lungen-6 (KL-6) are 2 promising biomarkers that may have an important role in the management of interstitial lung diseases (ILD). OBJECTIVE: The aim of this study was to investigate the values of KL-6 and YKL-40 as biomarkers in the diagnosis and prognosis of patients with hypersensitivity pneumonitis (HP). METHODS: A cross-sectional study conducted in 49 patients diagnosed with HP due to exposure to birds (n = 32) or fungi (n = 17), 48 patients with other ILD, and 67 healthy volunteers. Patients with HP were divided into fibrotic and nonfibrotic. Serum and sputum YKL-40 and KL-6 levels were determined using commercial enzyme-linked immunosorbent assay kits. Receiver operating characteristic (ROC) curves were used to determine the sensitivity and specificity of both biomarkers for the diagnosis of HP. Pulmonary function tests were performed in patients during follow-up. RESULTS: KL-6 and YKL-40 levels were significantly higher in serum of patients with HP exposed to birds with a fibrotic pattern than in controls (P < .0001 and .0055, respectively). Serum KL-6 levels were also significantly higher in patients with fibrotic HP exposed to fungi compared with the control group (P = .0001). In patients with HP exposed to fungi, sputum KL-6 and YKL-40 levels were higher in those with a fibrotic pattern (P = .0289 and .016, respectively). ROC analysis showed that the range between 55-121 ng/mL for serum YKL-40 levels and 346-1441 U/mL for serum KL-6 levels had the best sensitivity and specificity for discriminating between patients with HP, healthy controls, and patients with idiopathic pulmonary fibrosis (IPF). In patients with HP, serum KL-6 levels correlated negatively with total lung capacity (r = -0.485; P = .0103) and diffusing capacity of the lungs for carbon monoxide (r = -0.534; P = .0002) at 12 months. CONCLUSIONS: Both KL-6 and YKL-40 proteins seem to be capable of distinguishing patients with HP from healthy individuals and from patients with IPF. Their sensitivity and specificity confirm their potential role as biomarkers. KL-6 may also be a predictor of disease progression.


Assuntos
Alveolite Alérgica Extrínseca , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Alveolite Alérgica Extrínseca/diagnóstico , Biomarcadores , Proteína 1 Semelhante à Quitinase-3 , Estudos Transversais , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Escarro
13.
Arch. bronconeumol. (Ed. impr.) ; 58(7): 554-560, jul. 2022. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-207036

RESUMO

Background: Feather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier's lung (BFL). Methods: Specific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n=31), BFL (n=15) controls exposed (n=15) and unexposed to feathers (n=15). Results: The sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5 (AUC: 0.89). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms. Conclusions: The new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet. (AU)


Assuntos
Humanos , Pulmão dos Criadores de Aves , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/diagnóstico , 28599 , Testes Sorológicos
14.
J Immunol ; 209(1): 38-48, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35715007

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-ß, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform α (Hsp90α). Available evidence supports overexpression and secretion of Hsp90α as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90α in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90α mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90α-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90α levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90α levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90α isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Escleroderma Sistêmico , Dermatopatias , Animais , Bleomicina , Modelos Animais de Doenças , Doxorrubicina/metabolismo , Fibroblastos , Fibrose , Proteínas de Choque Térmico/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Escleroderma Sistêmico/metabolismo , Pele , Dermatopatias/patologia
15.
Occup Environ Med ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504722

RESUMO

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

16.
Arch Bronconeumol ; 58(7): 554-560, 2022 Jul.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35312541

RESUMO

BACKGROUND: Feather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier's lung (BFL). METHODS: Specific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n=31), BFL (n=15) controls exposed (n=15) and unexposed to feathers (n=15). RESULTS: The sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5 (AUC: 0.89). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms. CONCLUSIONS: The new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet.


Assuntos
Pulmão dos Criadores de Aves , Plumas , Alérgenos , Animais , Roupas de Cama, Mesa e Banho/efeitos adversos , Pulmão dos Criadores de Aves/diagnóstico , Pulmão dos Criadores de Aves/etiologia , Humanos , Pulmão , Metilcelulose , Projetos Piloto , Testes Sorológicos/efeitos adversos
17.
Arch Bronconeumol ; 58(2): 135-141, 2022 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33895005

RESUMO

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. METHODS: Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. RESULTS: 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. CONCLUSIONS: Patients with preserved FVC but presenting UIP radiological pattern and moderate-severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

18.
Rev. cuba. med. trop ; 73(3)dic. 2021.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1408881

RESUMO

RESUMEN Introducción: La leucoencefalopatía multifocal progresiva es una enfermedad desmielinizante del sistema nervioso central, de etiología viral. Se presenta en pacientes con enfermedades inmunosupresoras y la localización en fosa posterior es rara. Debido a sus formas clínicas inespecíficas se hace infrecuente su diagnóstico lo que conlleva a daño irreversible y/o a la muerte del paciente. Objetivo: Orientar sobre la posibilidad de leucoencefalopatía multifocal progresiva cerebelosa en pacientes inmunodeprimidos con manifestaciones neurológicas de daño en fosa posterior. Caso clínico: Paciente masculino, de 25 años de edad, sin antecedentes de enfermedades aparentes, que comienza con lenguaje escandido, temblor mixto dismetría y ataxia. Se diagnostica leucoencefalopatía multifocal progresiva cerebelosa por cuadro clínico, neuroimagen y presencia de virus JC en líquido cefalorraquídeo, además de una inmunosupresión severa causada por virus de inmunodeficiencia humana diagnosticado por pruebas serológicas. Conclusiones: Considerar leucoencefalopatía multifocal progresiva cerebelosa en todo paciente con manifestaciones neurológicas de afectación en fosa posterior y estudiar causas de inmunosupresión subyacente.


ABSTRACT Introduction: Progressive multifocal leukoencephalopathy is a demyelinating disease of viral etiology that affects the central nervous system. It presents in patients with immunosuppressive conditions and location in the posterior fossa is rare. Due to its unspecific clinical forms, its diagnosis is infrequent, leading to irreversible damage and/or the patient's death. Objective: Instruct about the possibility of cerebellar progressive multifocal leukoencephalopathy in immunocompromised patients with neurological manifestations of posterior fossa damage. Clinical case: A case is presented of a male 25-year-old patient without apparent pathological antecedents who started out with slurred speech, mixed tremor, dysmetria and ataxia. Cerebellar progressive multifocal leukoencephalopathy was diagnosed by clinical picture, neuroimaging and the presence of JC virus in the cerebrospinal fluid, alongside severe immunosuppression caused by human immunodeficiency virus diagnosed by serological testing.

20.
J Mol Cell Cardiol ; 159: 38-47, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34119506

RESUMO

Cardiac fibrosis is a pathological process that presents a continuous overproduction of extracellular matrix (ECM) components in the myocardium, which negatively influences the progression of many cardiac diseases. Transforming growth factor ß (TGFß) is the main ligand that triggers the production of pro-fibrotic ECM proteins. In the cardiac fibrotic process, TGFß and its canonical signaling mediators are tightly regulated at different levels as well as epigenetically. Cardiac fibroblasts are one of the most important TGFß target cells activated after cardiac injury. TGFß-driven fibroblast activation is subject to epigenetic modulation and contributes to the progression of cardiac fibrosis, mainly through the expression of pro-fibrotic molecules implicated in the disease. In this review, we describe epigenetic regulation related to canonical TGFß signaling in cardiac fibroblasts.


Assuntos
Epigênese Genética/genética , Fibrose/genética , Coração/fisiopatologia , Miocárdio/metabolismo , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/genética , Animais , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Miocárdio/patologia
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