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1.
Dig Dis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569478

RESUMO

INTRODUCTION: CFTR modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with CF on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. METHODS: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. RESULTS: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only one patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 µg/g to 442.1 µg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). CONCLUSION: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

2.
Anal Chem ; 94(18): 6736-6744, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35471013

RESUMO

Alterations in oligosaccharides and types of sialic acid (SA) attachments have been associated with different pathological states. Matrix-assisted laser desorption mass spectrometry (MS) is commonly used for glycosylation studies. However, native sialylated glycans are suppressed or not detected during MS experiments. Consequently, different approaches have been employed to neutralize the negative charge of the carboxyl group. In this study, we present the advantage of phenylhydrazine (PHN) labeling for the detection and efficient discrimination of SA linkages when this derivatization follows alkyl esterification. As expected, PHN-labeled sialylated oligosaccharides with the 2,6-linkage type can be easily recognized according to the additional shift in mass corresponding to the presence of a methyl or ethyl group. Surprisingly, oligosaccharides with the 2,3-linked SA residue instead of a lactone were detected carrying the second PHN unit. This was beneficial as no further processing after esterification was needed to stabilize the lactone form. Moreover, during tandem mass experiments, all modified glycans produced favorable fragmentation patterns with a coherent recognition of SA linkages. Although both types of esterification, herein called the EST-PHN approach, provided comparable results, methylation exhibited marginally higher linkage specificity than ethyl esterification. The simplicity and effectiveness of the methodology are demonstrated on the model compound, sialyllactose, and its applicability for biological studies is presented on N-glycan profiling in the sera of lung cancer patients.


Assuntos
Neoplasias Pulmonares , Oligossacarídeos , Esterificação , Humanos , Lactonas , Neoplasias Pulmonares/diagnóstico , Ácido N-Acetilneuramínico/química , Oligossacarídeos/química , Fenil-Hidrazinas/química , Polissacarídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
3.
Mod Pathol ; 33(6): 1146-1156, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907375

RESUMO

Lung adenocarcinoma (LAC) is the most common form of lung cancer that increases in non-smokers at younger age. Altered protein glycosylation is one of the hallmarks of malignancy, its role in cancer progression is still poorly understood. In this study, we report mass spectrometric (MS) analysis of N-glycans released from fresh or defrosted tissue specimens from 24 patients with LAC. Comparison of cancerous versus adjacent healthy tissues revealed substantial differences in N-glycan profiles associated with disease. The significant increase in paucimannose and high-mannose glycans with 6-9 mannose residues and decline in the sialylated complex biantenary core fucosylated glycan with composition NeuAcGal2GlcNAc2Man3GlcNAc2Fuc were general features of tumors. In addition, 42 new N-glycan compositions were detected in cancerous tissues. The prominent changes in advanced disease stages were mostly observed in core fucosylated N-glycans with additional fucose (Fuc) residue/s and enhanced branching with non-galactosylated N-acetyl-glucosamine (GlcNAc) units. Both of these monosaccharide types were linked preferably on the 6-antenna. Importantly, as compared with noncancerous tissues, a number of these significant changes were clearly detectable early on in stage I. Application of N-glycan data obtained from tissues was next assessed and validated for evaluation of small sized biopsies obtained via bronchoscopy. In summary, observed alterations and data of newly detected N-glycans expand knowledge about the glycosylation in LAC and may contribute to research in more tailored therapies. Moreover, the results demonstrate effectiveness of the presented approach for utility in rapid discrimination of cancerous from healthy lung tissues.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Polissacarídeos/metabolismo , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Glicosilação , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
4.
Anal Chem ; 91(13): 7985-7990, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31141660

RESUMO

Fucosylation is a common modification, and its site in glycans refers to different normal and pathological processes. Despite intensive research, there is still a lack of methods to discriminate unambiguously the fucose position in one-step. In this work, we propose utility of phenylhydrazine (PHN) labeling for structural studies of fucosylated N-glycans by tandem MALDI mass spectrometry (MS) in the positive ion mode. PHN-tag influences the production of specific ion types, and the MS/MS fragmentation pattern provides useful structural information. All types of core fucosylated N-glycans have produced two abundant ions consistent with B- and C-glycosidic cleavages corresponding to the loss of the FucGlcNAcPHN residue with a mass 457 and 441 Da from the parent ions. These types of fragment ions in N-glycans without a core fucose were associated with the loss of the GlcNAcPHN unit (311 and 295 Da), and fucose cleavage followed the loss of the chitobiose residue. Since diagnostic useful cleavages produce peaks with significant intensities, this approach is also beneficial for rapid recognition of antenna from core fucosylation in glycans detected with low abundances. Moreover, in multifucosylated glycans, this type of labeling allows to distinguish how many fucose residues are on the specific antenna and provides additional information on the topology of N-glycans, such as type of antennarity or identification of bisecting moiety. The practical applicability of the approach is demonstrated on the analysis of multifucosylated N-glycans detected with lower abundances in lung cancer samples.


Assuntos
Fucose/análise , Polissacarídeos/química , Glicosilação , Humanos , Neoplasias Pulmonares/química , Fenil-Hidrazinas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
5.
J Clin Gastroenterol ; 53(5): 355-360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29863588

RESUMO

GOAL: To evaluate the analytical parameters of a lateral flow (LF) pepsin immunoassay (Peptest) and assess its suitability in the diagnostics of gastroesophageal reflux disease (GERD). BACKGROUND: Peptest is a noninvasive assay to analyze pepsin in saliva, intended for use in GERD diagnostics. Although commercialized, fundamental studies on its performance are missing. The assay therefore requires basic analytical parameter evaluation to assess its suitability in clinical practice. STUDY: Assay reaction's time dependence, reader device repeatability, and individual LF devices and longitudinal pepsin concentration reproducibility in individual subjects was evaluated. Salivary pepsin was analyzed in 32 GERD patients with extraesophageal reflux symptoms and 13 healthy individuals. RESULTS: The assay's signal increase is not completed at the recommend readout time and continues to increase for another 25 minutes. The relative standard deviation of measurement was good when using the same LF device, ranging from 2.3% to 12.9%, but the reproducibility of 10 different individual LF devices was poor. The random error when analyzing the same saliva sample on 10 LF devices was as high as 36 ng/mL and this value is thus suggested as the positivity cut-off. Pepsin concentration in individual subjects during a 10-day period varied significantly. The sensitivity of the Peptest was 36.8% in the group with acid reflux and 23.1% in the group with weakly acid reflux. The specificity was 61.5%. CONCLUSIONS: The Peptest assay's sensitivity and specificity is low, the results are highly variable and it should not be used as a near-patient diagnostic method in primary care.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Imunoensaio , Pepsina A/metabolismo , Saliva/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
6.
BMC Cancer ; 18(1): 1144, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458807

RESUMO

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.


Assuntos
Coleta de Dados/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Oncologia/estatística & dados numéricos , Coleta de Dados/métodos , Bases de Dados Factuais/estatística & dados numéricos , Europa (Continente) , Humanos , Oncologia/métodos
7.
Cas Lek Cesk ; 157(5): 226-236, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30441934

RESUMO

Lung cancer is one of the most common cancers worldwide. Approximately 85 % of lung cancers are non-small cell lung cancers while 15 % are small cell lung cancers. Histologically, following subtypes of non-small cell cancer are distinguished: adenocarcinoma (38.5 % of all lung cancers), squamous cell carcinoma (20 %) and large cell carcinoma (3 %). Over recent years, the incidence of adenocarcinoma has been increasing. Squamous cell carcinoma is more commonly associated with smoking while adenocarcinoma is the most common histological type in non-smokers. The treatment of non-small cell lung cancer is decided according to clinical stage, morphological diagnosis, and the performance status of the patient. Early-stage patients are typically indicated for surgery. In some cases, adjuvant therapy is indicated. In locally advanced and metastatic stages, chemotherapy, biological treatment, and, recently, immunotherapy is indicated. Radiotherapy should also be considered for locally advanced disease. In small-cell lung cancer, the combination of etoposide and cisplatin or etoposide and carboplatin is still considered standard chemotherapy. Radiotherapy is an integral part of treatment of either type of lung cancer. Keywords: lung cancer, non-small cell lung cancer, small cell lung cancer, chemotherapy, biological therapy, radiotherapy, immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias
8.
Vnitr Lek ; 63(11): 786-795, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29303280

RESUMO

In the broadest sense, the term immunocompromised individual means a person with any impairment of infection resistance, whether it is deficiency or impairment of innate resistance (by another name impairment of non-specific resistance), or impairment of acquired resistance (impairment of specific immunity). Pneumonia in immunocompromised patients is characterized by a different microbiological spectrum. Apart from common pathogens there are also opportunistic agents involved in this group of patients. Management of pneumonia in immunocompromised patients is often decisive for their future fate. Very rare are innate immune deficiencies. Acquired immune deficiencies are far more common. They are often combined with disorders of non-specific resistance. The most frequent cause of acquired immune deficiency is another illness or a medical treatment. The diagnosing and treatment of pneumonias in immunocompromised patients are usually highly specialized and they unquestionably require a collaboration with microbiologists who are concerned with these problems.Key words: diagnostics - etiology - pneumonia in immunocompromised patients - prophylaxis - treatment.


Assuntos
Hospedeiro Imunocomprometido , Pneumonia/imunologia , Humanos , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico
9.
Vnitr Lek ; 63(11): 861-874, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29303290

RESUMO

Non-small cell lung cancer (NSCLC) represents 80 % of diseases considering all patients with lung cancer. NSCLC comprises all histological types except for the small cell cancer. The treatment is chosen based on a clinical stage, morphological diagnosis and performance status of patients. In the low clinical stages a surgical solution is indicated. An alternative is radiotherapy. In some cases adjuvant treatment is indicated. In the locally advanced and metastatic stages chemotherapy and biological therapies are available and in recent time also immunotherapy is used. With regard to locally advanced diseases radiotherapy should also be considered.Key words: biological treatment - chemotherapy - immunotherapy - therapy - non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Humanos , Imunoterapia/métodos , Radioterapia/métodos
10.
Vnitr Lek ; 63(12): 987-997, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29334750

RESUMO

After elimination of infectious causes, neoplastic causes and the systemic autoimmune disease of connective tissue, a patient with high fevers over 39 °C was diagnosed with Stills disease. High doses of prednisone led to resolution of symptoms, however after reducing the doses of prednisone to 15 mg, high fevers over 39 °C returned, as well as joint pains. The high doses of prednisone led to decompensation of diabetes mellitus even with 4 daily insulin dosages. Therefore it was proceeded to regular subcutaneous administration of anakinra once a day. Anakinra enabled the reduction of prednisone to as much as the currently administered 2.5 mg a day, but it has not so far allowed for removing glucocorticoids from the treatment completely. Activity of the disease is shown by the findings within the FDG-PET/CT examination. At the time of maximum activity of the disease there was distinct lymphadenopathy with pathological accumulation of FDG visible as well as increased accumulation of FDG in the hematopoietic bone marrow. As the disease activity decreased, the size of nodules regressed and FDG accumulation in both the lymphatic nodes and bone marrow declined. FDG-PET/CT is a suitable method for monitoring the activity of Stills disease.Key words: anakinra - Adult-onset Stills disease.


Assuntos
Antirreumáticos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Doença de Still de Início Tardio/tratamento farmacológico , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Indução de Remissão/métodos , Doença de Still de Início Tardio/diagnóstico por imagem
11.
Tumour Biol ; 39(2): 1010428317691186, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28218046

RESUMO

Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ligação a DNA/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Transcrição , Adulto Jovem
12.
Anal Bioanal Chem ; 409(14): 3507-3514, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28357484

RESUMO

A new approach for sweat analysis used in cystic fibrosis (CF) diagnosis is proposed. It consists of a noninvasive skin-wipe sampling followed by analysis of target ions using capillary electrophoresis with contactless conductometric detection (C4D). The skin-wipe sampling consists of wiping a defined skin area with precleaned cotton swab moistened with 100 µL deionized water. The skin-wipe sample is then extracted for 3 min into 400 µL deionized water, and the extract is analyzed directly. The developed sampling method is cheap, simple, fast, and painless, and can replace the conventional pilocarpine-induced sweat chloride test commonly applied in CF diagnosis. The aqueous extract of the skin-wipe sample content is analyzed simultaneously by capillary electrophoresis with contactless conductometric detection using a double opposite end injection. A 20 mmol/L L-histidine/2-(N-morpholino)ethanesulfonic acid and 2 mmol/L 18-crown-6 at pH 6 electrolyte can separate all the major ions in less than 7 min. Skin-wipe sample extracts from 30 study participants-ten adult patients with CF (25-50 years old), ten pediatric patients with CF (1-15 years old), and ten healthy control individuals (1-18 years old)-were obtained and analyzed. From the analyzed ions in all samples, a significant difference between chloride and potassium concentrations was found in the CF patients and healthy controls. We propose the use of the Cl-/K+ ratio rather than the absolute Cl- concentration and a cutoff value of 4 in skin-wipe sample extracts as an alternative to the conventional sweat chloride analysis. The proposed Cl-/K+ ion ratio proved to be a more reliable indicator, is independent of the patient's age, and allows better differentiation between non-CF individuals and CF patients having intermediate values on the Cl- sweat test. Figure New approach for cystic fibrosis diagnosis based on skin-wipe sampling of forearm and analysis of ionic content (Cl-/K+ ratio) in skin-wipe extracts by capillary electrophoresis with contactless conductometric detection.


Assuntos
Cloretos/análise , Fibrose Cística/diagnóstico , Eletroforese Capilar/métodos , Potássio/análise , Suor/química , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Análise de Componente Principal , Sensibilidade e Especificidade , Manejo de Espécimes/métodos
13.
Vnitr Lek ; 63(7-8): 518-526, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-28933178

RESUMO

Nosocomial pneumonia (hospital-acquired pneumonia - HAP) is the form of pneumonia the symptoms of which present after more than 2 days (> 48 hours) of admission to hospital or as late as 14 days of discharge from hospital. The HAP pneumonias represent 13-18 % of all nosocomial infections. Incidence of HAP is the most frequent in mechanically ventilated patients. The type and representation of HAP agents primarily depends on the length of a patients stay in hospital and on their condition and character of treatment. Diagnosing of pneumonia is based on anamnesis, physical and X-ray findings, results of examination of microbiological samples from the respiratory tract, hemoculture, the pleural effusion test, serological, hematological and biochemical tests. Antibiotic treatment is key to the comprehensive treatment of HAP. The HAP treatment always requires the dosing of antibiotics near the upper limit of the possible range. A precondition for successful avoidance of HAP pneumonias is the creation of a preventive programme with active engagement of medical staff.Key words: diagnostics - HAP pneumonia - treatment - ventilator-associated pneumonia.


Assuntos
Infecção Hospitalar/diagnóstico , Pneumonia Bacteriana/diagnóstico , Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Hospitalização , Humanos , Incidência , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/epidemiologia , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/epidemiologia
14.
J Proteome Res ; 15(8): 2777-86, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27312819

RESUMO

Although the importance of glycosylation has been thoroughly recognized in association with a number of biological processes, efficient assessments of glycans have been hampered by both the limited size of specimens and lengthy sample preparations, particularly in clinical settings. Here we report a simple preparative method for N-glycan analyses. It involves only short one-step chloroform-methanol extraction in presence or absence of water prior to PNGase F deglycosylation. The procedure was successfully applied to the investigation of N-glycans obtained from small numbers of in vitro cultured cancer cells (≤1 × 10(5)) and to tumor tissues, including patient biopsies of small size. MALDI-MS analysis confirmed the efficient release of all N-glycan types including complex forms with poly-N-acetyllactosamine chains. In addition, nonaqueous extraction of specimens from several established cancer cell lines, as well as patient tumor tissues, yielded high-mannose glycans with one GlcNAc moiety (Man3-9GlcNAc), strongly suggesting preservation of enzymatic activity analogous to Endo H enzyme. In summary, the method is both a step toward the practical use of glycan profiling and a way to detect Endo H-like activity in cancer specimens.


Assuntos
Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidase/metabolismo , Neoplasias/patologia , Polissacarídeos/análise , Glicosilação , Humanos , Manose , Neoplasias/química , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/metabolismo , Tamanho da Amostra , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Células Tumorais Cultivadas
15.
Cas Lek Cesk ; 155(4): 22-8, 2016.
Artigo em Tcheco | MEDLINE | ID: mdl-27481198

RESUMO

UNLABELLED: Idiopathic pulmonary fibrosis (IPF) is a rare, progressive and usually fatal form of idiopathic interstitial pneumonia. IPF is characterized by failure of alveolar re-epithelization, persistence of fibroblasts, deposition of extracellular matrix, and distortion of lung architecture, which ultimately results in respiratory failure.We analysed 202 consecutive patients with IPF diagnosed at the Departments of Pulmonary Diseases and Tuberculosis in the Czech Republic, who they were included in the nationwide Czech IPF registry. Our aim was to determine prognostic factors of IPF and outcome of the disease.There were 129 males and 73 females who were the median age 67 years. IPF was biopsy-proven in 66 (33 %) of patients. Median time from the first symptom to diagnosis was 12 months. Diagnosis was made in 57 patients (28.3 %) within 6 months from the onset of respiratory symptoms. 8 (4 %) patients had an acute exacerbation during the course of the disease.In uniparametric (univariate) analysis as prognostic factors associated with poorer survival were found: higher age, higher degree dyspnea scores, clubbing fingers, comorbidities (arterial hypertension, osteoporosis), patients without histology biopsy, and bronchoalveolar increased neutrophil count. We found these positive prognostic factors: higher levels of VC (vital capacity), TLC (total lung capacity) and DLCO (diffusing capacity for carbon monooxide).In multiparametric (multivariate) analysis as prognostic factors associated with mortality were found: higher age, higher degree of dyspnoe score. Increased lymphocytes in bronchoalveolar fluid, higher level of VC a DLCO were associated with better survival. There was no difference in survival of patients by sex, by smoking status. No significant difference in survival rates was found between IPF with and without emphysema, between the extent of fibrosis on HRCT (high resolution computed tomography) of thorax and mortality. Median survival was 51.6 months. 58 (28.7 %) patients died. The most frequent reason of dead was IPF progression with respiratory failure. KEY WORDS: Idiopathic pulmonary fibrosis; prognosis; treatment.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/fisiopatologia , Fatores Etários , Idoso , República Tcheca , Feminino , Humanos , Masculino , Prognóstico , Sistema de Registros , Testes de Função Respiratória/estatística & dados numéricos , Índice de Gravidade de Doença , Taxa de Sobrevida
16.
J Am Coll Nutr ; 34(5): 425-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25941742

RESUMO

BACKGROUND: Malnutrition in cancer patients may be associated with poor tolerance of chemotherapy and lower response rate after oncological treatment. METHODS: Nutritional Risk Screening 2002 (NRS) adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 patients with lung cancer. The risk was evaluated on a 6-point scale according to common signs of nutritional status (weight loss, body mass index, and dietary intake), tumor, and its treatment risk factors. A score of 3 or more (called "nutritional risk") means significant risk of malnutrition and poor outcome. RESULTS: Acceptable NRS score was found in 50.6%, and in 45.3% a score of 3-5 suggested the risk of malnutrition (nutritional risk). Unexpectedly, the toxicity of anticancer treatment was not significantly different between the subgroups (acceptable score vs nutritional risk). The rate of treatment response evaluated by imaging techniques was significantly higher in patients with an acceptable score compared to nutritional risk. Overall survival rate was significantly higher in cytostatically treated patients with lung cancer with an acceptable score. CONCLUSION: Nutritional risk screening is a significant predictor of tumor response in patients with lung cancer. Early detection of malnutrition is important to determine the prognosis of cancer patients as well as to plan effective supportive care.


Assuntos
Neoplasias Pulmonares/complicações , Desnutrição/diagnóstico , Avaliação Nutricional , Índice de Massa Corporal , Feminino , Humanos , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Fatores de Risco
17.
Vnitr Lek ; 61(2): 119-24, 2015 Feb.
Artigo em Tcheco | MEDLINE | ID: mdl-25813254

RESUMO

Common variable immunodeficiency disorder belongs to the most common primary human immunodeficiencies and it is characterized by primary defective immunoglobulin production. Hypogammaglobulinemia manifests in every age, usually in adult people. There is no gender predisposition. The prevalence is 1 : 25 000-1 : 50 000. The ethiopathogenesis of the majority of CVIDs is unknown. The main clinical respiratory symptoms include recurrent respiratory infects, especially bacterial etiology, sinusitis, bronchitis, pneumonia, leading to bronchiectasis and lung fibrosis. Interstitial lung fibrosis and granulomatosis often manifest at diagnosis of CVID and they are negative prognostic factors of the disease.


Assuntos
Agamaglobulinemia/etiologia , Bronquiectasia/etiologia , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Pneumonia/etiologia , Adulto , Imunodeficiência de Variável Comum/epidemiologia , Feminino , Humanos , Masculino , Prevalência
18.
ScientificWorldJournal ; 2014: 125706, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24574864

RESUMO

Patients with lung cancer experience elevated risk of venous thromboembolism. Cancer patients with thrombosis have a shorter life expectancy and the occurrence of VTE worsens the quality of life and may delay, interrupt, or completely halt the cancer therapy. In a large cohort of lung cancer patients we monitored the incidence of venous thromboembolism and we identified groups of patients with the highest risk of venous thromboembolism suitable for antithrombotic prophylaxis, which could favourably affect their morbidity and mortality.


Assuntos
Neoplasias Pulmonares/mortalidade , Tromboembolia Venosa/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos , Humanos , Incidência , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/prevenção & controle
19.
J Cancer Res Clin Oncol ; 149(19): 17123-17131, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37768380

RESUMO

PURPOSE: The aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines. METHODS: We analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011-2019. "Succesful treatment " was defined as PFS ≥ 6 months, a "good responder " was a patient with ˃50% of "successful treatment " lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used. RESULTS: The first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort. CONCLUSION: We concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pemetrexede/uso terapêutico , Bevacizumab/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB
20.
Cancer Diagn Progn ; 2(2): 167-172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399169

RESUMO

Background/Aim: This study aimed at contributing to a better diagnosis of lung cancer by analyzing the patient's symptoms and their linkage to other characteristics. Patients and Methods: We analyzed the data of 3,322 patients from LUCAS (LUngCAncerfocuS) National Registry of the Czech Republic. Overall survival was assessed using the Kaplan-Meier method. Results: The most common symptoms were cough (47.5%), dyspnea (45.6%), pain (27.3%), and weight loss (25.7%). Among all patients, 16% were asymptomatic. We demonstrated the negative prognostic significance of increasing number of lung cancer symptoms, that was significant after adjustment for age, TNM stages, and performance status, and morphological types of the cancer. Conclusion: Monitoring the severity and type of symptoms in patients with lung cancer can help in the diagnostics of the disease and the estimation of prognosis.

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