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1.
Chest ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610577

RESUMO

BACKGROUND: Whilst estimates of sub-optimal adherence to oral corticosteroids in asthma range from 30 to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. RESEARCH QUESTIONS: 1. What is the prevalence of suboptimal adherence detected using self-reporting and direct measures? 2. Is suboptimal adherence associated with disease activity? STUDY DESIGN AND METHODS: Data were included from individuals with severe asthma taking part in the U-BIOPRED study prescribed daily oral corticosteroids. Participants completed the MARS, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid-chromatography mass spectrometry. RESULTS: Data from 166 participants were included in this study, mean (SD) age 54.2 (11.9) years, FEV1 65.1 (20.5) % predicted, 58% female. 37% completing the MARS reported sub-optimal adherence, and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 35% participants who had both performed; adherence detection did not match between methods in 53%. Self-reported high-adherers had better asthma control and quality of life, whereas directly-measured high-adherers had lower blood eosinophils. INTERPRETATION: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

2.
Clin Exp Rheumatol ; 38 Suppl 126(4): 85-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095152

RESUMO

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative. RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group. CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.


Assuntos
Síndrome de Sjogren , Estudos de Coortes , Feminino , Humanos , Fenótipo , Sistema de Registros , Síndrome de Sjogren/diagnóstico
3.
Eur Respir J ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122336

RESUMO

AIM: Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck®, a 6-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. METHODS: A case-control European training set (102 lung cancer cases/265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case-control European and Chinese validation sets (cases/controls: 179/137 and 30/15). RESULTS: The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The respective sensitivity/specificity with LCO were 87.2%/64.2% and 76.7%/93.3% and with HCO were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I NSCLC sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. SCLC was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942. CONCLUSIONS: Lung EpiCheck demonstrated strong performance in lung cancer prediction in case-control European and Chinese samples, detecting high proportions of early stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.

4.
Nanomaterials (Basel) ; 10(9)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878344

RESUMO

(1) Background. The main goal of this work was to develop a fluorescent dye-labelling technique for our previously described nanosized platform, citrate-coated Prussian blue (PB) nanoparticles (PBNPs). In addition, characteristics and stability of the PB nanoparticles labelled with fluorescent dyes were determined. (2) Methods. We adsorbed the fluorescent dyes Eosin Y and Rhodamine B and methylene blue (MB) to PB-nanoparticle systems. The physicochemical properties of these fluorescent dye-labeled PBNPs (iron(II);iron(III);octadecacyanide) were determined using atomic force microscopy, dynamic light scattering, zeta potential measurements, scanning- and transmission electron microscopy, X-ray diffraction, and Fourier-transformation infrared spectroscopy. A methylene-blue (MB) labelled, polyethylene-glycol stabilized PBNP platform was selected for further assessment of in vivo distribution and fluorescent imaging after intravenous administration in mice. (3) Results. The MB-labelled particles emitted a strong fluorescent signal at 662 nm. We found that the fluorescent light emission and steric stabilization made this PBNP-MB particle platform applicable for in vivo optical imaging. (4) Conclusion. We successfully produced a fluorescent and stable, Prussian blue-based nanosystem. The particles can be used as a platform for imaging contrast enhancement. In vivo stability and biodistribution studies revealed new aspects of the use of PBNPs.

5.
Nat Commun ; 11(1): 4686, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943633

RESUMO

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges for operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to gold standard histology. Adjustment of the recording depth with micro-drives or early termination of unsuccessful experiments saves many working hours, and fast 3-dimensional feedback helps surgeons avoid systematic errors. Increased aiming precision enables more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical or hippocampal layers.


Assuntos
Encéfalo/diagnóstico por imagem , Eletrodos Implantados , Processamento de Imagem Assistida por Computador/métodos , Fibras Ópticas , Microtomografia por Raio-X/métodos , Animais , Comportamento Animal , Encéfalo/patologia , Mapeamento Encefálico , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/cirurgia , Técnicas Histológicas/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Silício , Técnicas Estereotáxicas
6.
Artigo em Inglês | MEDLINE | ID: mdl-32667261

RESUMO

RATIONALE: New approaches are needed to guide personalized treatment of asthma. OBJECTIVE: To test if urinary eicosanoid metabolites can direct asthma phenotyping. METHODS: Urinary metabolites of prostaglandins (PGs), cysteinyl-leukotrienes (LTs) and isoprostanes were quantified in the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy controls (HC). Validation was performed internally in 302 SA subjects followed-up after 12-18 months, and externally in 95 adolescents with asthma. MEASUREMENT AND MAIN RESULTS: Metabolite levels in HC were unrelated to age, BMI and sex, except for the PGE2-pathway. Eicosanoid levels were generally greater in MMA relative to HC, with further elevations in SA. However, PGE2-metabolite levels were either the same or lower in male non-smoking asthmatics as in HC. Metabolite levels were unchanged in asthmatics adherent to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas SA treated with omalizumab had lower levels of LTE4 and the PGD2 metabolite 2,3-dinor-11ß-PGF2α. High levels of LTE4 and PGD2-metabolites were associated with lower lung-function, and increased levels of exhaled nitric oxide and eosinophil markers in blood, sputum and urine in U-BIOPRED and in adolescents with asthma. These type-2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study, and found to be as sensitive to detect T2 inflammation as the established biomarkers. CONCLUSIONS: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new non-invasive approach for molecular phenotyping of adult and adolescent asthma. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

7.
Pharmaceutics ; 12(5)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32443790

RESUMO

Liposomes containing copper and the copper ionophore neocuproine were prepared and characterized for in vitro and in vivo anticancer activity. Thermosensitive PEGylated liposomes were prepared with different molar ratios of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and hydrogenated soybean phosphatidylcholine (HSPC) in the presence of copper(II) ions. Optimal, temperature dependent drug release was obtained at 70:30 DPPC to HSPC weight ratio. Neocuproine (applied at 0.2 mol to 1 mol phospholipid) was encapsulated through a pH gradient while using unbuffered solution at pH 4.5 inside the liposomes, and 100 mM HEPES buffer pH 7.8 outside the liposomes. Copper ions were present in excess, yielding 0.5 mM copper-(neocuproine)2 complex and 0.5 mM free copper. Pre-heating to 45 °C increased the toxicity of the heat-sensitive liposomes in short-term in vitro experiments, whereas at 72 h all investigated liposomes exhibited similar in vitro toxicity to the copper(II)-neocuproine complex (1:1 ratio). Thermosensitive liposomes were found to be more effective in reducing tumor growth in BALB/c mice engrafted with C26 cancer cells, regardless of the mild hyperthermic treatment. Copper uptake of the tumor was verified by PET/CT imaging following treatment with [64Cu]Cu-neocuproine liposomes. Taken together, our results demonstrate the feasibility of targeting a copper nanotoxin that was encapsulated in thermosensitive liposomes containing an excess of copper.

8.
Eur Respir J ; 55(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31601713

RESUMO

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m-2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day-1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day-1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.

9.
Rejuvenation Res ; 23(3): 256-261, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31094281

RESUMO

The klotho protein is secreted primarily by the kidneys. It is responsible for phosphate homeostasis and has an anti-aging, anti-inflammatory, and anti-oxidative stress role. Obstructive sleep apnea (OSA) is associated with an enhanced systemic inflammation and oxidative stress, but mechanisms that regulate these processes are poorly understood. The aim of the study was to investigate the plasma levels of klotho in OSA. Twenty-one previously untreated patients with OSA (56 ± 13 years, 12 males) and 41 non-OSA control volunteers (48 ± 16 years, 8 males) participated in the study. Medical history has been taken; participants filled out the Epworth Sleepiness Scale. C-reactive protein and renal function, glucose and lipid profile measurements were performed in sera; klotho was determined in citrate-treated plasma samples. Levels of plasma klotho were decreased in OSA (519.1 ± 164.9 pg/mL) versus controls (700.8 ± 431.4 pg/mL, p = 0.02). Reduced klotho concentrations were associated with markers of overnight hypoxemia determined with O2 desaturation index (r = -0.31, p = 0.01), percentage of sleep time spent with saturation <90% (r = -0.41, p < 0.01), and minimal saturation during sleep (r = 0.33, p = 0.01). Interestingly, there was no relationship with apnea-hypopnea index, total sleep time, or arousal index (all p > 0.05). Significant association was also found between low plasma klotho levels and the presence of hypertension (p < 0.05). Our results suggest that chronic intermittent hypoxia reduces the levels of klotho in OSA, which may contribute to the development of hypertension. Decreased klotho levels may play a role in enhanced systemic inflammation in OSA and may be a future target for drug development.

10.
Pathol Oncol Res ; 26(1): 233-238, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29948618

RESUMO

The anti-aging factor, klotho has been identified as a tumor suppressor in various human cancers, including lung cancer. In vitro studies provided evidence that klotho expression influences the characteristics of lung cancer cells, however, in vivo results are lacking. The aim of our study was to evaluate whether circulating klotho protein might serve as a potential biomarker of lung cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31 NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured using ELISA. No difference in plasma klotho values was detected between patients and control subjects (366.3 (257.9-486.8) vs. 383.5 (304.6-489.7) pg/ml respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with distant metastasis did not differ from less advanced stage disease (354.2 (306.9-433.3 vs. 328.5 (242.5-419.7) pg/ml, p > 0.05). In contrast, analyzed with one-way ANOVA, significant difference (p = 0.04) was found between the examined histological types of lung cancer: adenocarcinoma (353 (329.4-438.5) pg/ml), squamous cell carcinoma (308 (209.6-348.1) pg/ml) and small cell lung cancer (388.8 (289.9-495.4) pg/ml). However, Tukey's post hoc test did not reveal significant difference between any pairs of histological groups. There was no difference between any histological subtype and health either. Our results suggest that circulating klotho protein cannot be considered as a biomarker for lung cancer. Further studies are warranted in order to examine the relationship between klotho expression in lung tissue and circulating levels of the protein, and to explore its mechanism of action in lung cancer.

11.
Rheumatology (Oxford) ; 59(9): 2350-2359, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31873754

RESUMO

OBJECTIVE: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents. RESULTS: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

12.
Chron Respir Dis ; 16: 1479973119881777, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645111

RESUMO

Randomized controlled trials (RCTs) are essential for the approval of new therapies; however, because of their design, they provide little insight concerning disease epidemiology/etiology and current clinical practice. Particularly, in lung disease, rigid inclusion/exclusion criteria can limit the generalizability of pivotal trial data. Noninterventional studies (NIS), conducted through the well-established mechanism of patient registries, are undervalued as a means to close data gaps left by RCTs by providing essential data that can guide patient care at different levels from clinical decision-making to health-care policy. While NIS contribute valuable data in all disease areas, their importance in rare diseases cannot be underestimated. In respiratory disease, registries have been essential in understanding the natural history and different phenotypes of rare conditions, such as alpha 1 antitrypsin deficiency, cystic fibrosis, and idiopathic pulmonary fibrosis. Importantly, additional therapeutic outcome data were generated. While measures for enhancing data quality in RCTs have evolved significantly, the approach and effectiveness of registries is variable. Within this article, we review the contribution of registries to pulmonary disease and make recommendations for their effective management. Additionally, we assess limitations of registry data as well as challenges to registry operation, including the impact of the European Union General Data Protection Regulation.


Assuntos
Pneumopatias/epidemiologia , Pneumopatias/etiologia , Melhoria de Qualidade , Sistema de Registros/normas , Tomada de Decisão Clínica , Confiabilidade dos Dados , Política de Saúde , Humanos , Pneumopatias/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Raras/tratamento farmacológico
13.
Clin Exp Rheumatol ; 37 Suppl 118(3): 97-106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464664

RESUMO

OBJECTIVES: To analyse the frequency and characterise the systemic presentation of primary Sjögren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded. RESULTS: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons). CONCLUSIONS: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.


Assuntos
Síndrome de Sjogren , Estudos de Coortes , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/fisiopatologia
14.
Eur Respir J ; 54(3)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31467120

RESUMO

Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.


Assuntos
Asma/terapia , Progressão da Doença , Pneumologia/normas , Adulto , Ansiedade , Asma/economia , Asma/psicologia , Europa (Continente) , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Adesão à Medicação , Modelos Teóricos , Pneumologia/organização & administração , Fatores de Risco , Sociedades Médicas
15.
EJNMMI Res ; 9(1): 67, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346827

RESUMO

BACKGROUND: Our aim was to present a new data analysis technique for the early detection of tumorous lesions using single-photon emission computed tomography (SPECT) imaging. Beyond standardized uptake value (SUV) and standardized uptake concentration (SUC), the skewness and kurtosis parameters of whole liver activity distribution histograms were examined in SPECT images to reveal the presence of tumorous cells. METHODS: Four groups of mice were used in our experiment: a healthy control group, a group of obese mice with high body mass index, and two tumorous groups (primary liver cancer group with chemically induced hepatocellular carcinoma (HCC); metastatic liver tumor group-xenograft of human melanoma (HM)). For the SPECT measurements, 99mTc-labeled aggregated albumin nanoparticles were administered intravenously 2 h before the liver SPECT scans (NanoSPECT/CT, Silver Upgrade, Mediso Ltd., Hungary) to image liver macrophages. Finally, SUV, SUC, skewness, and kurtosis of activity distributions were calculated from segmented whole liver volumes. RESULTS: HCC animals showed moderate 99mTc-albumin particle uptake with some visually identified cold spots indicating the presence of tumors. The visual detection of cold spots however was not a reliable marker of tumorous tissue in the metastatic group. The calculated SUV, SUC, and kurtosis parameters were not able to differentiate between the healthy and the tumorous groups. However, healthy and tumorous groups could be distinguished by comparing the skewness of the activity distribution. CONCLUSION: Based on our results, 99mTc-albumin nanoparticle injection followed by liver SPECT activity distribution skewness calculation is a suitable image analysis tool. This makes possible to effectively and quantitatively investigate liver macrophage inhomogeneity and identify invisible but present liver cold spot lesions. Skewness as a direct image-derived parameter is able to show altered tissue function even before the visual manifestation of liver tumor foci. The skewness of activity distribution might be related to an inhomogeneous distribution of macrophage cells as a consequence of microscopic tumor burden in the liver.

16.
Orv Hetil ; 160(30): 1193-1199, 2019 Jul.
Artigo em Húngaro | MEDLINE | ID: mdl-31327246

RESUMO

Introduction: The mistrust of vaccinations is already experienced among physicians. It is important for physicians to be well informed, able to convince their patients of the usefulness of vaccinations and set good example for them in this field. Aim: The aim of the study was to assess the vaccine knowledge and attitudes of the general medical students of Semmelweis University and their attitudes towards vaccinations before and after the education of 'Public Health and Preventive Medicine'. Emphasis was placed on the students' opinion on the vaccines against influenza, measles and hepatitis B virus and their effectiveness. Method: Data collection was done with volunteer participants, using anonymous self-administered questionnaires. The relationship between education and vaccination coverage was proved by calculating Pearson's correlation and one-way analysis of variance. Results: The knowledge of medical students is incomplete, with negative attitudes towards vaccination against influenza. Generally, respondents found the vaccines useful, but only two-thirds of them considered the influenza vaccine to be important. Students had 6.5% flu vaccination coverage before education, and 24% after education. Two-thirds (67.8%) of the students were aware that the flu vaccine could be given during an epidemic. Surprisingly, the importance of hand washing has been given a greater role in the primary prevention of influenza than flu vaccine. Conclusions: Education plays an important role in shaping the attitudes and responsible behaviour of future physicians. They need to acquire reliable knowledge to persuade their patients as practitioners to use the most effective means of primary prevention of infectious diseases. A change of attitude is needed to stop the route of infection through vaccination, to protect not only their own health but also that of their environment and thus of their patients. Orv Hetil. 2019; 160(30): 1193-1199.


Assuntos
Infecção Hospitalar/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Estudantes de Medicina , Cobertura Vacinal , Vacinologia , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários , Vacinação
17.
Respir Med ; 154: 133-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31252206

RESUMO

INTRODUCTION: Drug emission from DPIs is dependent on the inspiratory flow parameters through them, which are not directly measured by standard spirometry. Their estimation based on native spirometric data could help in choosing the appropriate device and optimizing the drug deposition. OBJECTIVES: The aim of this study was to survey patient preferences and to find correlations between breathing parameters of COPD patients through DPI devices and their baseline spirometric data, age, gender, disease severity and anthropometric characteristics. Another objective was to establish relationships between peak inspiratory flows (PIFdev) through Breezhaler®, Genuair® and Turbuhaler® inhalers and their determinants. METHODS: Breathing parameters of 49 patients with previously diagnosed COPD and currently using one of the above inhalers were recorded by normal spirometry and while inhaling through the selected DPIs. Statistical analysis of the measured data was completed. All specific data are provided as (mean ±â€¯standard deviation). RESULTS: More than 60% of the patients stated that their current device is the easiest to use. The means of the measured PIFdev values were 91.4 L/min, 77.1 L/min and 77.5 L/min for Breezhaler®, Genuair®, and Turbuhaler®, respectively. PIFdev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant (at p = 0.05). Peak inspiratory flows through the inhalers (PIFdev) correlated best with their native spirometric counterparts (PIF) and linear PIFdev-PIF relationships could be determined (Breezhaler®: r = 0.60, p = 0.002, Genuair®: r = 0.55, p = 0.001, Turbuhaler®: r = 0.57, p = 0.002). Physical background of the deduced equations was also provided. CONCLUSIONS: Present correlations may be used to assess the success of inhalation of COPD patients through the studied devices and to choose the appropriate device for each patient. As a consequence, the amount of the drug emitted by the device can be optimized, the deposition efficiency within the lungs increased and the related therapeutic effect improved.


Assuntos
Inaladores de Pó Seco/instrumentação , Preferência do Paciente/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Espirometria/estatística & dados numéricos , Administração por Inalação , Idoso , Algoritmos , Antropometria/métodos , Desenho de Equipamento/estatística & dados numéricos , Desenho de Equipamento/tendências , Feminino , Humanos , Hungria/epidemiologia , Capacidade Inspiratória/efeitos dos fármacos , Capacidade Inspiratória/fisiologia , Masculino , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários
18.
Orv Hetil ; 160(23): 908-913, 2019 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-31155879

RESUMO

Introduction: The increased metabolism of nutrients and the low energy intake may lead to malnutrition among chronic obstructive pulmonary disease (COPD) patients. Aim: The goal of our study was to examine the nutritional status of our population aged over 40, and its relationship with the severity of the disease. Method: We conducted a retrospective study at the National Korányi Institute of Pulmonology in 2017. Pulmonary function and anthropometric data were obtained from the electronic health record system. Inclusion criteria were age over 40 and the diagnosis of COPD. Severity of disease was assessed by forced expiration volume and categorized according to GOLD stages. We used SPSS Statistics V22.0 for data analysis. Results: The mean age of participants was 66; 49.3% were men, 50.7% were women. Average BMI was 27.14 kg/m², with values comprising cachexia and severe obesity. According to the FEV1%pred results of the 3236 patients, 30% fell in the GOLD I, 40% in the GOLD II, 23% in the GOLD III, and 7% in the GOLD IV categories. Pearson coefficient found positive correlation between FEV1 and nutritional status (H = 0.2297, r = 0.1401), specifically between severity of cachexia and severity of disease. The analysis of variance showed significant correlation between severity of disease and nutritional status; patients with higher BMI had better pulmonary function. Conclusion: Malnutrition had an adverse effect on pulmonary functions and performance of respiratory muscles, whereas higher BMI had a positive effect on FEV1. Our results suggest that BMI could be used as a lung function prognostic indicator for COPD patients. Orv Hetil. 2019; 160(23): 908-913.


Assuntos
Desnutrição/epidemiologia , Estado Nutricional , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Desnutrição/diagnóstico , Avaliação Nutricional , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
J Allergy Clin Immunol ; 144(5): 1198-1213, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30998987

RESUMO

BACKGROUND: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. OBJECTIVE: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. METHODS: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17-high and IL-13-high asthma phenotypes. RESULTS: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17-high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and ß-defensin. CONCLUSION: The IL-17-high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.


Assuntos
Asma/imunologia , Brônquios/patologia , Células Epiteliais/metabolismo , Interleucina-17/metabolismo , Neutrófilos/imunologia , Psoríase/imunologia , Adulto , Biomarcadores/metabolismo , Estudos de Coortes , Células Epiteliais/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Interleucina-13/metabolismo , Masculino , Fenótipo , Transdução de Sinais , Transcriptoma , Regulação para Cima
20.
J Allergy Clin Immunol ; 144(1): 70-82, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30928653

RESUMO

BACKGROUND: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. OBJECTIVE: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. METHODS: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. RESULTS: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. CONCLUSION: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.


Assuntos
Asma/metabolismo , Proteoma , Escarro/metabolismo , Adulto , Idoso , Asma/imunologia , Asma/fisiopatologia , Biomarcadores/metabolismo , Eosinofilia/imunologia , Eosinofilia/metabolismo , Eosinofilia/fisiopatologia , Eosinófilos/imunologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Fenótipo , Proteômica , Adulto Jovem
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