Eletrodo intramuscular para estimulação elétrica do diafragma

Hospital de Clínicas de Porto AlegreHospital de Clínicas de Porto AlegreDepositad

Lung transplantation in cystic fibrosis

A progressão do acometimento pulmonar e a evolução para insuficiência respiratória são responsáveis por importante morbimortalidade em pacientes com fibrose cística. O transplante pulmonar está consolidado como tratamento de escolha para diversas pneumopatias em estágios terminais e vem sendo realizado em pacientes com fibrose cística avançada desde a década de 1980. A seleção de pacientes candidatos ao transplante envolve a análise cuidadosa de parâmetros clínicos, fisiológicos e laboratoriais, com atenção a fatores conhecidos de mau prognóstico como: piora acentuada e acelerada da função pulmonar, aumento da frequência e gravidade das exacerbações, desnutrição, diabetes melito, hemoptise volumosa, pneumotórax, hipoxemia e hipercapnia em ar ambiente, hipertensão pulmonar e distância reduzida no teste de caminhada de seis minutos. Embora o tema ainda gere controvérsias, a maioria dos centros transplantadores contraindica o transplante para portadores de Burkholdelia cepacia. A presença de outros germes colonizantes no escarro, ainda que com perfil adverso de sensibilidade aos antibióticos, não costuma impedir a realização do transplante em pacientes com fibrose cística. A avaliação pré-transplante nesta população segue os mesmos padrões das demais indicações, com atenção especial ao suporte nutricional, ao perfil microbiológico e à evolução recente do contexto clínico global e da função pulmonar. Os resultados do transplante pulmonar bilateral na fibrose cística são em regra superiores aos das demais indicações.Progressive involvement of the lungs and the development of respiratory failure are major causes of morbidity and mortality in patients with cystic fibrosis. Lung transplantation is a well-established treatment for several end-stage respiratory diseases and it has been successfully performed in cystic fibrosis patients since the 1980’s. Patient selection involves careful analysis of clinical, physiologic and laboratorial parameters, with special consideration of well-known adverse prognostic factors such as: accelerated loss of lung function, increase in frequency and severity of exacerbations, poor nutritional status, diabetes mellitus, massive hemoptysis, pneumothorax, hypoxemia and hypercapnia while breathing room air, pulmonary hypertension, and reduced distance in the 6-minute walk test. Despite some controversy, most transplant centers refuse patients with Burkholderia cepacia for transplantation. Other colonizing pathogens, even with extensive antibiotic resistant patterns, do not, in general, preclude the procedure in patients with cystic fibrosis. Pre-transplant evaluation of this population is similar for other indications, with special attention to nutritional support, microbiological profile analysis and recent changes of the clinical context and lung function. The results of bilateral lung transplantation for cystic fibrosis are generally better than for other indications

Evaluation of systemic inflammation in patients being weaned from mechanical ventilation

OBJECTIVES: The aim of this study was to evaluate systemic inflammatory factors and their relation to success or failure in a spontaneous ventilation test. METHODS: This cross-sectional study included a sample of 54 adult patients. Demographic data and clinical parameters were collected, and blood samples were collected in the first minute of the spontaneous ventilation test to evaluate interleukin (IL)-1b, IL-6, IL-8, and IL-10, tumour necrosis factor alpha (TNFa) and C-reactive protein. RESULTS: Patients who experienced extubation failure presented a lower rapid shallow breathing index than those who passed, and these patients also showed a significant increase in C-reactive protein 48 hours after extubation. We observed, moreover, that each unit increase in inflammatory factors led to a higher risk of spontaneous ventilation test failure, with a risk of 2.27 (1.001 – 4.60, p=0.049) for TNFa, 2.23 (1.06 – 6.54, p=0.037) for IL-6, 2.66 (1.06 – 6.70, p=0.037) for IL-8 and 2.08 (1.01 – 4.31, p=0.04) for IL-10, and the rapid shallow breathing index was correlated with IL-1 (r=-0.51, p=0.04). CONCLUSIONS: C-reactive protein is increased in patients who fail the spontaneous ventilation test, and increased ILs are associated with a greater prevalence of failure in this process; the rapid shallow breathing index may not be effective in patients who present systemic inflammation

Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells

Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICD-associated DAMPs in an index that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment. Conclusions: Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapy may be a promising therapeutic strategy in NSCLC