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1.
Adv Med Sci ; 65(1): 156-162, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31958704

RESUMO

PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71). CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

2.
J Invest Dermatol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31945345

RESUMO

Neutrophils are broadly classified into conventional neutrophils (PMNs) and low-density granulocytes (LDGs). LDGs are better than PMNs at generating neutrophil extracellular traps (NETs), which may contribute to the pathology of autoimmune diseases. We hypothesized that LDGs and PMNs differ in their levels of unrestrained NE that supports NET generation. Here, we show that individuals with psoriasis contain elevated levels of LDGs and that in contrast to PMNs, the LDGs display higher staining for NE and lower staining for its inhibitor SLPI. The heterogeneity between blood-derived LDGs and PMNs was somewhat reminiscent of the differences in the NE and SLPI staining patterns observed in psoriasis skin-infiltrating neutrophils. Distinctive staining for NE and SLPI in LDGs and PMNs did not result from differences in their protein levels nor manifested in higher total proteolytic activity of NE in LDGs; rather, it likely depended on different cytosolic sequestration of these proteins. The disparate profile of NE and SLPI in LDGs and PMNs coincided with altered migratory responses of these cells to cutaneous chemoattractants. Collectively, differential NE and SLPI staining identifies common attributes of both circulating and skin-infiltrating neutrophils, which may guide neutrophil migration to distinct skin regions and determine the localization of LDGs-mediated cutaneous pathology.

3.
J Thromb Haemost ; 18(1): 169-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31519058

RESUMO

BACKGROUND: The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of lupus anticoagulant (LAC), anti-cardiolipin (aCL) and/or anti-ß2glycoprotein I (aß2GPI) antibodies of the immunoglobulin G/immunoglobulin M (IgG/IgM) isotype. However, the role of aCL and aß2GPI IgM as a serologic marker in APS is debated. OBJECTIVES: We aimed to assess the diagnostic and clinical value of IgM antiphospholipid antibodies (aPL) in APS within the classification criteria. PATIENTS/METHODS: Our multicenter study comprised 1008 patients, including APS patients and controls. Anti-CL and aß2GPI IgG and IgM antibodies were detected with four commercially available solid phase assays. RESULTS: Positivity for aCL and/or aß2GPI antibodies was significantly correlated with thrombosis and pregnancy morbidity, independent of the isotype and solid phase assay. Higher odds ratios were obtained for IgG compared to IgM positivity. Isolated IgM was rare in thrombotic APS, but more frequent in obstetric APS, ranging from 3.5% to 5.4% and 5.7% to 12.3%, respectively, dependent on the solid phase assay. In a multivariate logistic regression analysis of aPL, IgM positivity was found to be associated with pregnancy morbidity. However, detection of IgM was not independently associated with thrombosis. Combined positivity for LAC, IgG, and IgM was highly associated with thrombosis and pregnancy morbidity. CONCLUSIONS: Our data support testing for aCL and aß2GPI IgM in women suspected of obstetric APS. However, no added value was found for testing IgM in patients suspected of thrombotic APS. Still, IgM aPL might be useful as a second-line test to improve thrombotic risk stratification.

4.
Clin Exp Allergy ; 50(1): 15-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31532863

RESUMO

BACKGROUND: Airway structural changes are important in asthma pathology and require further investigations. OBJECTIVE: We sought to evaluate which computed tomography (CT) indices, bronchial histological traits, or blood and bronchoalveolar lavage (BAL) biomarkers correlate best with lung function abnormalities in asthma. METHODS: In 105 white adult asthmatics (53 with a component of fixed airflow obstruction), we determined airway cross-sectional geometry of two proximal (the right upper lobe apical segmental and the left apicoposterior) and two distal (the right and the left basal posterior) bronchi, quantified the low-attenuation lung area (LAA%), and analysed clusters based on airway CT-metrics. We also performed bronchofiberoscopy with BAL and endobronchial biopsy, assessed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, interferon (INF)γ and periostin, together with circulating a disintegrin and metalloproteinase domain-containing protein (ADAM)33, and investigated interplays between analysed variables. RESULTS: Patients with fixed airflow limitation were characterized by lower lumen area and increased wall area and wall thickness ratios in distal airways, accompanied by raised LAA%. They had also higher blood neutrophilia, blood and BAL eosinophilia, increased circulating fibrinogen, periostin, and ADAM33. Blood neutrophilia, serum high density lipoproteins, thyroid-stimulating hormone, and shortened activated partial thromboplastin time were determinants of thicker reticular basement membrane (RBM). BAL eosinophilia was the only positive predictor of collagen I accumulation. Surprisingly, we observed a negative correlation between RBM thickening and collagen I deposit. Cluster analysis based on CT-metrics of the right lower lobe basal posterior bronchus revealed three well-separated clusters similar in age, asthma duration, and BMI, but different in RBM thickness, collagen I accumulation, and inflammatory markers. CONCLUSIONS AND CLINICAL RELEVANCE: Airway remodelling traits are mainly related to the Th2 profile, higher circulating ADAM33, and blood neutrophilia. Lung function abnormalities and RBM thickening correlate better with CT-metrics of distal than proximal airways.

5.
J Thromb Haemost ; 18(2): 463-478, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31749277

RESUMO

BACKGROUND: Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-ß2glycoprotein I (ß2GPI) proved to be pathogenic, but are not included in the current classification criteria. OBJECTIVES: Investigate the clinical value of detecting anti-DI IgG in APS. PATIENTS/METHODS: From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-ß2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash® ß2GPI domain I assay. RESULTS: Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-ß2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-ß2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. CONCLUSIONS: Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-ß2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash® did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.

7.
Pol Arch Intern Med ; 129(9): 651-652, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566591
8.
Pol J Pathol ; 70(2): 148-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556568

RESUMO

Fibrosarcomas are placed among the most infrequent malignant tumors of the uterus. We present a case of a 38 years-old woman, whose benign looking uterine mass was primary diagnosed as a sclerosing leiomyoma. However, the tumor relapsed in two years with multisite metastases in the abdomen. The complex differential diagnosis excluded the most common mesenchymal tumors of the gynecological tract. Finally, we diagnosed the tumor as an epithelioid sclerosing fibrosarcoma arising from the uterine.


Assuntos
Fibrossarcoma/diagnóstico , Leiomioma/diagnóstico , Útero/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos
9.
Hamostaseologie ; 39(4): 368-376, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364092

RESUMO

Bleeding phenotype in patients with congenital factor VII (FVII) deficiency is highly variable. No direct correlation between FVII activity and bleeding tendency is noted. The aim of this study was to analyse clinical and laboratory phenotype of patients with FVII deficiency treated in one haemophilia treatment centre in Little Poland. Clinical and laboratory data of 106 patients were collected retrospectively. Bleeding symptoms were evaluated according to the Bleeding Assessment Tool. The mean FVII activity was 19.5% (range: 1.0-49.2) and the mean prothrombin time (PT) was 29.7 seconds (range: 13.2-64.8), comparable in both sexes. Activity was lower than 1% in 6.6% of individuals. The average age at diagnosis (31.2 years; range: 1-76) did not correlate with FVII activity. Half of the patients were diagnosed incidentally, mostly due to routine PT measurement. The most frequently reported symptoms were gum, nose and tooth extraction bleeds. A total of 22.6% of patients remained asymptomatic and 60.4% never required replacement therapy. Thrombotic episodes were diagnosed in five women (4.7%). In conclusion, the clinical picture of the analysed group is similar to the previously described. It should be stressed that a significant risk of bleeds, including joint haemorrhages, can be expected in patients with mildest FVII deficiency (>26%) as well. The rate of thrombosis (4.7%) was similar to other reports, with all affected patients having strong prothrombotic risk factors or being intensively treated with FVII concentrate.

10.
Res Pract Thromb Haemost ; 3(3): 515-527, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294336

RESUMO

Background: Anticardiolipin (aCL) and anti-ß2 glycoprotein I (aß2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach. Methods: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and aß2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods. Results: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated. Conclusions: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.

11.
Int J Mol Sci ; 20(14)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295965

RESUMO

Noninvasive Raman imaging of non-fixed and unstained human colon tissues based on vibrational properties of noncancerous and cancerous samples can effectively enable the differentiation between noncancerous and tumor tissues. This work aimed to evaluate the biochemical characteristics of colon cancer and the clinical merits of multivariate Raman image and spectroscopy analysis. Tissue samples were collected during routine surgery. The non-fixed, fresh samples were used to prepare micrometer sections from the tumor mass and the tissue from the safety margins outside of the tumor mass. Adjacent sections were used for typical histological analysis. We have found that the chemical composition identified by Raman spectroscopy of the cancerous and the noncancerous colon samples is sufficiently different to distinguish pathologically changed tissue from noncancerous tissue. We present a detailed analysis of Raman spectra for the human noncancerous and cancerous colon tissue. The multivariate analysis of the intensities of lipids/proteins/carotenoids Raman peaks shows that these classes of compounds can statistically divide analyzed samples into noncancerous and pathological groups, reaffirming that Raman imaging is a powerful technique for the histochemical analysis of human tissues. Raman biomarkers based on ratios for lipids/proteins/carotenoids content were found to be the most useful biomarkers in spectroscopic diagnostics.


Assuntos
Colo/diagnóstico por imagem , Colo/metabolismo , Neoplasias do Colo/etiologia , Neoplasias do Colo/metabolismo , Processamento de Imagem Assistida por Computador , Análise Espectral Raman , Biomarcadores , Neoplasias do Colo/diagnóstico , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estadiamento de Neoplasias , Análise Espectral Raman/métodos
12.
Braz J Cardiovasc Surg ; 34(3): 327-334, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310472

RESUMO

OBJECTIVE: The main goal of our study was to assess the impact of vascular procedures on the activity of hemostatic and fibrinolytic pathways. METHODS: We enrolled 38 patients with ≥ 45 years old undergoing surgery for abdominal aortic aneurysm or peripheral artery disease under general or regional anesthesia and who were hospitalized at least one night after the procedure. Patients undergoing carotid artery surgery and those who had acute bypass graft thrombosis, cancer, renal failure defined as estimated glomerular filtration rate < 30 ml/min/1.73m2, venous thromboembolism three months prior to surgery, or acute infection were excluded from the study. We measured levels of markers of hemostasis (factor VIII, von Willebrand factor:ristocetin cofactor [vWF:CoR], antithrombin), fibrinolysis (D-dimer, tissue plasminogen activator [tPA], plasmin-antiplasmin complexes), and soluble cluster of differentiation 40 ligand (sCD40L) before and 6-12h after vascular procedure. RESULTS: Significant differences between preoperative and postoperative levels of factor VIII (158.0 vs. 103.3, P<0.001), antithrombin (92.1 vs. 74.8, P<0.001), D-dimer (938.0 vs. 2406.0, P=0.005), tPA (10.1 vs. 12.8, P=0.002), and sCD40L (9092.9 vs. 1249.6, P<0.001) were observed. There were no significant differences between pre- and postoperative levels of vWF:CoR (140.6 vs. 162.8, P=0.17) and plasmin-antiplasmin complexes (749.6 vs. 863.7, P=0.21). CONCLUSION: Vascular surgery leads to significant alterations in hemostatic and fibrinolytic systems. However, the direction of these changes in both pathways remains unclear and seems to be different depending on the type of surgery. A study utilizing dynamic methods of coagulation and fibrinolysis assessment performed on a larger population is warranted.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Coagulação Sanguínea/fisiologia , Fibrinólise/fisiologia , Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-Operatório , Período Pré-Operatório , Valores de Referência , Fatores de Risco , Estatísticas não Paramétricas , Resultado do Tratamento
13.
J Thromb Haemost ; 17(10): 1746-1755, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31220407

RESUMO

BACKGROUND: Antiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are recognized as a marker for antiphospholipid syndrome (APS). Dense and poorly lysable fibrin clots occur in thrombotic APS. Compact clots predict thromboembolism, but determinants of the unfavorable clot phenotype remain unknown in APS. We hypothesized that elevated aPS/PT antibodies determine unfavorable clot features. METHODS: In a cohort study involving 124 consecutive patients with thrombotic APS, we measured at baseline plasma fibrin clot permeability (Ks ), efficiency of fibrinolysis (clot lysis time, CLT), and turbidity (off anticoagulation) along with immunoglobulin (Ig)G/IgM aPS/PT. During follow-up, symptomatic thromboembolic events were recorded. RESULTS: Elevated IgG and IgM aPS/PT antibodies >30 international enzyme units (UI) were detected in 54.8% and 42.7% of APS patients, including 76.2% and 54% of lupus anticoagulant- (LA, n = 63) positive patients, respectively. Elevated IgG and IgM aPS/PT antibodies predicted low Ks (lower quartile, <6 × 10-9  cm2 ; odds ratio [OR] = 5.93, 95% confidence interval [CI] 2.09-16.82 and OR = 11.79, 95% CI 4.10-33.92) and prolonged CLT (top quartile, ≥116 min; OR = 4.85, 95% CI 2.42-25.07 and OR = 6.04, 95% CI 2.42-15.07). No such associations were observed for anticardiolipin or ß2-glycoprotein I antibodies or LA presence. During follow-up (median 72.5, range 66-83 months), thromboembolic events observed in 32 (26.7%, 4.6%/year) patients were independently predicted by IgG aPS/PT antibodies >30 UI (hazard ratio [HR] = 3.04, 95% CI 1.20-8.88) and low Ks (HR = 3.00, 95% CI 1.41-6.50). CONCLUSIONS: We identified aPS/PT antibodies as a determinant of denser and poorly lysable plasma fibrin clot formation in APS patients. The association of elevated aPS/PT antibodies with thromboembolism in APS could be at least in part mediated by prothrombotic clot properties.

14.
Clin Rheumatol ; 38(9): 2553-2563, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31016580

RESUMO

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Avaliação de Sintomas
15.
Thromb Haemost ; 119(5): 797-806, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822809

RESUMO

BACKGROUND: The anti-phospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with persistent presence of anti-phospholipid antibodies (aPL). Laboratory criteria include aPL detection by coagulation tests for lupus anticoagulant (LAC) or solid phase assays measuring anti-ß2 glycoprotein I (aß2GPI) or anti-cardiolipin (aCL) immunoglobulin (Ig) G/IgM antibodies. External quality control programs illustrate that commercially available aPL assays produce variable results. OBJECTIVE: We aimed to investigate the agreement and diagnostic accuracy of solid phase assays. MATERIALS AND METHODS: In this multi-centre study, 1,168 patient samples were tested on one site for aCL and aß2GPI IgG/IgM antibodies by four solid phase test systems. Samples included APS patients, controls and monoclonal antibodies (MoAB) against different epitopes of ß2GPI. LAC was determined by the local centre. RESULTS: aCL IgM assays resulted in the most discrepancies (60%), while aCL IgG and aß2GPI IgM assays resulted in lower discrepancies (36%), suggesting better agreement. Discrepant samples displayed lower median aPL titers. Dependent on the solid phase test system, odds ratios (ORs) for thrombosis and pregnancy morbidity ranged from 1.98 to 2.56 and 3.42 to 4.78, respectively. Three platforms showed lower sensitivity for MoAB directed against the glycine (Gly) 40-arginine (Arg) 43 epitope of domain I of ß2GPI. CONCLUSION: Poor agreement was observed between different commercially available aCL and aß2GPI IgG/IgM assays, hampering uniformity in the identification of aPL-positive patients. Clinical association was globally concordant between solid phase test systems considering results of the four aPL together. An assay sensitive in detecting the MoAB against Gly40-Arg43 of domain I of ß2GPI reached the highest OR for thrombosis.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos/sangue , Cardiolipinas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Trombose/diagnóstico , beta 2-Glicoproteína I/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
J Asthma ; : 1-10, 2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30905217

RESUMO

INTRODUCTION: Immunoglobulin E is an important modulator of the inflammatory reaction in allergic asthma. It also contributes to airway remodeling in the course of the disease. The authors evaluated airway structural changes in severe allergic asthma during the omalizumab therapy. PATIENTS AND METHODS: The study included 13 patients with severe allergic asthma treated with omalizumab for at least one year. In each patient clinical, laboratory, and spirometry parameters were evaluated before and after the treatment. In addition, bronchoscopy with bronchial mucosa biopsy and bronchoalveolar lavage was performed. The basal lamina thickness, inflammatory cell infiltration, fibronectin, as well as type I and III collagen accumulation were assessed in bronchial mucosa specimens, together with the assessment of bronchoalveolar lavage cellularity. RESULTS: The omalizumab therapy led to a decrease in the basal lamina thickness (p = 0.002), and to a reduction in fibronectin (p = 0.02), but not collagen deposits in the bronchial mucosa. The decrease in fibronectin accumulation was associated with an improvement in asthma control and quality of life (p = 0.01, both), and a diminished dose of systemic corticosteroids (p = 0.001). It was also associated with a tendency towards reduction of the eosinophil count in the peripheral blood, bronchoalveolar lavage fluid, and bronchial mucosa specimens. CONCLUSION: Our study has shown that omalizumab, effective in the treatment of severe allergic asthma, may also decrease unfavorable structural airway changes in allergic asthmatics, at least with respect to the fibronectin deposit and an increased thickness of the basal lamina. However, more extensive observational studies are needed to verify the above hypothesis.

17.
Clin Rheumatol ; 38(2): 417-424, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30132147

RESUMO

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p < 0.001) and 41.9% of thrombomodulin (p < 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (p < 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (ß = - 0.3 [95% confidence interval (CI) - 0.5 to - 0.1]), serum level of IL-6 (ß = - 0.36 [95% CI - 0.62 to - 0.1]), and thrombomodulin (ß = - 0.34 [95% CI - 0.6 to - 0.08]). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.


Assuntos
Aterosclerose/etiologia , Biomarcadores/sangue , Endotélio Vascular/fisiopatologia , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/fisiopatologia , Adulto , Artéria Braquial/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Progressão da Doença , Endotélio Vascular/diagnóstico por imagem , Feminino , Humanos , Interleucina-6/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombomodulina/sangue , Molécula 1 de Adesão de Célula Vascular/sangue
18.
Hamostaseologie ; 39(1): 95-99, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30112740

RESUMO

Acquired haemophilia A (AHA) is a rare autoimmune disease caused by antibodies directed against clotting factor VIII. About half of cases are idiopathic, but AHA may also be secondary to autoimmune, dermatologic, or oncologic diseases. In approximately 10% of non-idiopathic cases, the disease occurs after or with the diagnosis of cancer as an extremely rare paraneoplastic syndrome. We describe the case of a 73-year-old male patient diagnosed with AHA and successfully treated with recombinant human activated factor VIIa and immunosuppression. Two and a half years later, however, the disease relapsed and a routine ultrasound revealed a liver tumour that was then diagnosed as hepatocellular carcinoma. We present this case to increase awareness that this life-threatening condition may develop years prior to the diagnosis of cancer.


Assuntos
Carcinoma Hepatocelular/complicações , Hemofilia A/complicações , Neoplasias Hepáticas/complicações , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Fator VIIa/uso terapêutico , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Hemofilia A/patologia , Humanos , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Proteínas Recombinantes/uso terapêutico , Recidiva
19.
J Allergy Clin Immunol ; 143(5): 1811-1820.e7, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30529449

RESUMO

BACKGROUND: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using "omics" technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes. OBJECTIVES: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to within-patient clinical and inflammatory changes. METHODS: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability. RESULTS: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNose-driven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045). CONCLUSIONS: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.

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