Contribuição da biópsia pulmonar a céu aberto na avaliação de pneumopatias difusas e agudas em unidade de terapia intensiva pediátrica

Introdução: Os dados clínico-laboratoriais convencionais raramente fornecem o diagnóstico em pneumopatias difusas. O objetivo deste estudo foi avaliar o papel da biópsia pulmonar a céu aberto no que se refere ao seu potencial diagnóstico, ao impacto dos resultados sobre a conduta clínica e à incidência de complicações do procedimento. Material e métodos: No período de janeiro/1987 a janeiro/1997, 29 biópsias pulmonares foram realizadas em crianças com pneumopatias difusas, em insuficiência respiratória aguda, sem etiologia e sem resposta à terapêutica empírica prévia. Foram excluídos os recém-nascidos, crianças com pneumopatias crônicas prévias e crianças com coagulopatia ou choque intratáveis. Todas as biópsias foram realizadas através de microtoracotomia no pulmão mais acometido ao exame radiológico. O fragmento de tecido pulmonar foi analisado por meio de culturas e de exames de microscopia ótica, eletrônica e imunofluorescência. Resultados: O processamento do material da biópsia forneceu pelo menos um diagnóstico histopatológico em todas as crianças estudadas (100%) e em 20 (68,9%) obteve-se um diagnóstico etiológico. Os principais diagnósticos histopatológicos foram: pneumonite intersticial não específica com fibrose variável em 18 casos; bronquiolite em oito casos e hipertensão pulmonar em três casos. Nos diagnósticos etiológicos, os principais agentes foram: citomegalovírus em seis crianças; Pneumocystis carinii em três; adenovírus em três e infecção pelo vírus respiratório sincicial em três casos. Os resultados geraram mudanças no tratamento em 20 casos (68,9%). As principais alterações de conduta foram a introdução de corticoterapia em 14 pacientes e a revisão da antibioticoterapia em seis. Sete casos (24,1%) apresentaram complicações, que foram resolvidas, e nenhum óbito foi relacionado ao procedimento. Conclusão: Conclui-se que a biópsia pulmonar a céu aberto é um procedimento que, mesmo invasivo, deve ser considerado na avaliação de crianças com pneumopatias difusas graves, sem etiologia definida, sem resposta à terapêutica previamente instituída e em insuficiência respiratória.<br>Introduction: The diagnosis of diffuse lung disease is still a challenge for the pediatric intensive care physician. Routine clinical examinations and laboratory tests are frequently negative. The objective of this study was to evaluate the diagnostic potential, the impact on therapy and the rate of complications of open lung biopsy in children with undiagnosed diffuse lung disease, respiratory failure and inappropriate response to initial therapy. Methods: From January 1987 to January 1997, 29 children with diffuse pulmonary disease of unknown etiology, respiratory failure (PaO2/FiO2 < 300) and no response to previous treatments were considered for open lung biopsy. Newborns, children with known chronic pulmonary disease and children with untreatable shock or coagulopathy were excluded. All biopsies were performed by a thoracic surgeon by a microthoracotomy in the lung shown to be the most affected by X-ray examination. Tissue samples were analyzed in terms of cultures, light microscopy, electron microscopy and immunofluorescence microscopy, according to the pathologist's decision. Results: All biopsies (100%) resulted in at least one histological diagnosis and in 20 patients (68.9%) it was obtained a specific diagnosis. The most frequent histological patterns found were: non-specific interstitial pneumonitis with variable degrees of fibrosis in 18 cases; bronchiolitis in eight cases and pulmonary hypertension in three cases. Regarding the most frequent specific diagnosis, six children were found with cytomegalovirus infection, three with Pneumocystis carinii, three with adenovirus and three with respiratory syncytial virus infection. These data induced a change in therapy in 20 children (68.9%). The most frequent changes in therapy were the use of corticosteroids in 14 children and a review of the antibiotic regimen in six patients. Seven patients (24.1%) presented with complications that were easily resolved. There were 13 deaths, probably due to the critical conditions of these patients, all unrelated to the procedure. Conclusions: Open lung biopsy, though an invasive procedure, should be considered in the evaluation of selected children with undiagnosed diffuse lung disease, respiratory failure and with no satisfactory response to previous therapies

2013 WSES guidelines for management of intra-abdominal infections

Peer reviewe

The clinical positioning of telavancin in Europe

Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today's antimicrobials, with particular focus on the implications of its licensing requirements. Telavancin has potent in vitro activity against isolates of Gram-positive pathogens, including MRSA and glycopeptide-intermediate S. aureus strains. In addition, at clinically attainable doses telavancin inhibits Gram-positive isolates of antibiotic-resistant strains from biofilm models. The in vitro potency of telavancin has been corroborated in the clinical setting. Comparative clinical studies of telavancin demonstrate non-inferiority compared with vancomycin in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin-treated patients with monomicrobial S. aureus infection, including isolates with reduced vancomycin susceptibility. These studies also demonstrate an overall similar safety profile for telavancin and vancomycin, although importantly, patients with moderate-to-severe renal impairment at baseline are at greater risk for mortality with telavancin and this feature must be taken into account when selecting patients for its usage. In Europe, telavancin is a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. For example, it should be considered in such patients when vancomycin and linezolid are not suitable and where renal function permits

Carbon Nanotube- and Asbestos-Induced DNA and RNA Methylation Changes in Bronchial Epithelial Cells

Carbon nanotubes (CNTs) are nanoscale tube-shaped carbon materials used in many industrial areas. Their fiber shape has caused concerns about their toxicity given their structural similarity with asbestos. The aim here was to elucidate the effect of CNTs and asbestos exposure on global DNA and RNA methylation and the methylation of genes associated with cell cycle, inflammation, and DNA damage processes in human lung cells. Human bronchial epithelial cells (16HBE14o-) were exposed for 24 h to 25 and 100 μg/mL CNTs (single-walled CNTs [SWCNTs] and multiwalled CNTs [MWCNTs]) and 2.5 μg/mL asbestos (chrysotile, amosite, and crocidolite). Global DNA and RNA (hydroxy)methylation to cytosines was measured by a validated liquid chromatography tandem-mass spectrometry method. Global RNA methylation to adenines was measured by a colorimetric ELISA-like assay. Gene-specific DNA methylation status at certain cytosine-phosphate-guanine (CpG) sites of cyclin-dependent kinase inhibitor 1A ( CDKN1A), serine/threonine kinase ( ATM), and TNF receptor-associated factor 2 ( TRAF2) were analyzed by using bisulfite pyrosequencing technology. Only MWCNT-exposed cells showed significant global DNA hypomethylation of cytosine and global RNA hypomethylation of adenosine. SWCNT, MWCNT, and amosite exposure decreased DNA methylation of CDKN1A. ATM methylation was affected by chrysotile, SWCNT, and MWCNT. However, SWCNT exposure led to DNA hypermethylation of TRAF2. These findings contribute to further understanding of the effect of CNTs on different carcinogenic pathways.status: publishe