Factors related to deep vein thrombosis in patients with cellulitis/erysipelas at two high-complexity facilities. A case-control study

Lower extremity venous thromboembolism in the presence of soft tissue infection (cellulitis/erysipelas) is difficult to diagnose using clinical findings alone. This leads to an overuse of Doppler ultrasound, which is unnecessary in many cases. In Colombia, there are no studies to date reporting the simultaneous prevalence of these two conditions. Objective: to determine which factors are related to deep vein thrombosis in patients with lower extremity cellulitis/erysipelas. Materials and methods: a case-control study. Patients seen at Hospital Pablo Tobón Uribe and the university hospital between January 2018 and December 2019 who were diagnosed with cellulitis/erysipelas and underwent lower extremity venous Doppler. Demographic, clinical, laboratory and imaging variables were considered. Results: altogether, 637 patients with a diagnosis of lower extremity cellulitis and erysipelas were found during the study period in both institutions. Of these, 18.5% (118 patients) had a lower extremity Doppler ultrasound ordered to rule out deep vein thrombosis, finding a total of 25 positive studies (21.19%). Out of the total sample, 56 (47.4%) were male, with a mean age of 65 years. Most of the cases (55.08%) had an intermediate risk according to the Wells scale. The most common patient factors related to thrombosis were: immobility 33%, lymphedema 29.66%, and chronic kidney disease 23.73%. Neoplasms were the factor which showed statistical significance for the presence of thrombosis OR 5 (1.64-15.16) (P=0.0056). Conclusions: cellulitis is not a unique finding to justify carrying out a Doppler test, and the routine use of this imaging technique in the diagnostic approach is not justified if there are no other risk factors for thrombosis. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2109).

El diagnóstico de enfermedad tromboembólica venosa de miembros inferiores en presencia de infección de tejidos blandos (celulitis/erisipela): es difícil de determinar con sólo los hallazgos clínicos, lo que lleva a un sobreuso de la ecografía Doppler que resulta innecesaria en muchos casos. En Colombia a la fecha no hay estudios que reporten la prevalencia simultánea de éstas dos condiciones. Objetivo: determinar cuáles son los factores que se relacionan con trombosis venosa profunda (TVP) en pacientes con celulitis/erisipela en miembros inferiores. Materiales y métodos: estudio de casos y controles. Pacientes atendidos en el Hospital Pablo Tobón Uribe y la IPS universitaria entre enero de 2018 y diciembre de 2019 con diagnóstico de celulitis/erisipela y a quienes se les realizó Doppler venoso de miembros inferiores. Se consideraron variables demográficas, clínicas, paraclínicas e imagenológicas. Resultados: en total se identificaron 637 pacientes con diagnóstico de celulitis y erisipela de miembros inferiores en el periodo de estudio en ambas instituciones. De estos en 18.5% (118 pacientes) se solicitó ecografía Doppler de miembros inferiores para descartar trombosis venosa profunda, encontrando un total de 25 estudios positivos (21.19%). Del total de esta muestra fueron 56 hombres (47.4%) con una media de edad de 65 años. La mayoría de casos (55.08%), tuvieron riesgo intermedio según la escala de Wells. Los antecedentes más frecuentes relacionados con trombosis fueron: inmovilización 33%, linfedema 29.66%, enfermedad renal crónica 23.73%. La presencia de neoplasia fue el antecedente que demostró significancia estadística para la presencia de trombosis OR 5 (1.64-15.16) (P=0.0056). Conclusiones: la presencia de celulitis no es un hallazgo único que justifique la realización de Doppler, y el uso de imagen de rutina dentro del abordaje diagnóstico no está justificado si no existen otros factores de riesgo de trombosis. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2109).

It is time to adapt the definition of chronic kidney disease according to age

Abstract Chronic kidney disease is a condition with high morbidity, mortality and healthcare costs which affects all population groups, having a significant impact on their quality of life. Its classification has been modified over time and there is still no universal consensus to differentiate a physiological change in kidney clearance from a pathological change. Below, we will discuss the importance of reconsidering the definition and classification in the general population according to age, including children and adults. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2080).

Manejo de la terapia anticoagulante durante el embarazo / Management of anticoagulant therapy during pregnancy

Resumen El embarazo se asocia con 5 a 10 veces mayor riesgo de enfermedad tromboembólica venosa, convirtiéndose en un escenario particular y complejo para la anticoagulación dada la necesidad de seguridad fetal y limitada representación en estudios de eficacia disponibles. Durante la gestación existen tres principales situaciones clínicas: la enfermedad tromboembólica venosa sin factor de riesgo precipitante, el síndrome antifosfolípido y las portadoras de válvulas mecánicas protésicas; todas con un alto riesgo de complicaciones materno-fetales, por lo que es vital conocer los anticoagulantes disponibles para cada patología, su evidencia científica, eventos adversos y características farmacológicas con el fin de realizar el mejor abordaje terapéutico y disminuir complicaciones asociadas. El objetivo es describir los avances de los anticoagulantes en escenarios clínicos de mayor impacto antes de la concepción, durante el embarazo y postparto y servir de herramienta con el fin de realizar el mejor abordaje terapéutico y disminuir complicaciones asociadas. MÉD.UIS.2020;33(2):65-73.

Abstract Pregnancy is associated with a 5 to 10-fold increased risk of venous thromboembolic disease, making it a complex setting for anticoagulation, given the need for fetal safety and limited representation in available efficacy studies. During pregnancy there are three main clinical situations: venous thromboembolic disease without a precipitating risk factor, antiphospholipid syndrome and prosthetic mechanical valve carriers; all with a high risk of maternal-fetal complications, so it is vital to know the anticoagulants available for each pathology, their scientific evidence, adverse events and pharmacological characteristics in order to perform the best therapeutic approach and reduce associated complications. The objective is to describe the advances of anticoagulants in clinical scenarios of greater impact before conception, during pregnancy and postpartum and to serve as a tool in order to carry out the best therapeutic approach and reduce associated complications. MÉD.UIS.2020;33(2):65-73.

Miocardiopatía periparto: patología potencialmente mortal / Cardiomyopathy peripartum: potentially deadly disease

Introducción: la cardiomiopatía periparto es una condición clínica subestimada, lo que conlleva a que sea una entidad olvidada, con un retraso en su diagnóstico y tratamiento y con ello a altas tasas de morbi-mortalidad. El diagnóstico se basa en síntomas y signos clínicos, además de la evidencia de falla cardíaca que se desarrolle durante el último mes de embarazo y los primeros cinco meses posparto con una disfunción ventricular izquierda evidenciada ecocardiográficamente. Objetivo: realizar una revisión actual de los diferentes componentes de la enfermedad, desde su epidemiología, etiología, fisiopatología, avances en diagnóstico clínico y tratamiento. Metodología de búsqueda: se realizó una búsqueda en múltiples bases de datos como PubMed, Cochrane, Science Direct y Google académico en donde se encontraron 96 artículos de los cuales fueron seleccionados 38 artículos descartándose varios que no cumplían criterios de inclusión. Resultados: se escogió la información más actualizada de las bases de datos encontradas, en donde se hallaron 55 artículos. Se revisó clasificación, etiología, fisiopatología, diagnóstico, Tratamiento y pronóstico de la enfermedad. Conclusiones: la cardiomiopatía Periparto continua siendo un gran reto médico diagnóstico y de tratamiento para todo un gran equipo multidisciplinario; debe existir una sospecha diagnostica para poder iniciar un adecuado abordaje y tratamiento oportuno en donde pueda lograrse una disminución en la morbimortalidad tanto para la madre como para el feto. Existen nuevos avances para el tratamiento de forma quirúrgica, que ayudan a mejorar la calidad de vida en aquellas mujeres que quedan con una falla cardiaca posterior. MÉD.UIS. 2016;29(2):103-11.

Introduction: peripartum cardiomyopathy is a clinical condition underestimated, leading to a forgotten it, with a delay in diagnosis and treatment and thus to high rates of morbidity and mortality entity. The diagnosis is based on clinical signs and symptoms, plus evidence of heart failure that develops during the last month of pregnancy and the first five months postpartum echocardiography evidenced a left ventricular dysfunction. Objective: a current review of the different components of the disease, from the epidemiology, etiology, pathophysiology, clinical advances in diagnosis and treatment. Searching methodology: a search was performed in multiple databases such as PubMed, Cochrane, Sciencedirect and academic Google; where 96 articles were found, 38 were selected ruling out several items that did not meet inclusion criteria. Results: the most current databases of information found was chosen, 55 articles were selected and classification, etiology, pathophysiology, diagnosis, treatment and prognosis were reviewed. Conclusions: peripartum cardiomyopathy remains a major medical diagnosis and treatment for all large multidisciplinary team challenge; there must be a suspicion diagnosis to initiate appropriate and timely treatment approach wherein a decrease in morbidity and mortality can be achieved for both mother and fetus. There are new developments for the treatment of surgically, that help improve the quality of life for women who are with subsequent heart failure. MÉD.UIS. 2016;29(2):103-11.

Síndrome de transfusión feto fetal: una mirada global a la enfermedad / Fetofetal transfusion syndrome: a comprehensive look at the disease / Síndrome de transfusão feto no feto: um olhar mais abrangente sobre a doença

Introducción: El síndrome de transfusión feto- feto es una enfermedad compleja producida aproximadamente en 15% de los embarazos monocoriales; a pesar de su baja incidencia, su importancia radica en las graves complicaciones perinatales. Su fisiopatología está basada en el proceso por el cual los gemelos comparten las dos circulaciones a través de vasos sanguíneos anómalos, con posterior alteración hemodinámica del gemelo receptor y donante. El diagnóstico es primordialmente ecográfico y su tratamiento definitivo actual, consiste en estrategias in útero realizadas con el fin de ubicar y sellar los vasos, proporcionando una circulación individual, buscando contrarrestar su mal pronóstico, que puede llegar a una mortalidad de hasta un 100% en aquellos sin tratamiento. Objetivo: Realizar una revisión de la literatura sobre el síndrome de transfusión feto - feto abarcando una actualización en los diferentes componentes que incluyen: epidemiología, fisiopatología, avances en Diagnóstico clínico y tratamiento. Metodología: Se hizo una búsqueda en bases de datos como PubMed, Cochrane, Sciencedirect y Google académico; se encontraron 78 artículos, de los cuales finalmente cumplieron con los criterios de actualización, pertinencia y calidad 32 artículos; se revisó fisiopatología, diagnóstico y tratamiento. Se descartaron artículos que no cumplían con criterios de inclusión. Resultados: Se seleccionó la información más actualizada y completa de las bases de datos encontradas, respecto a clasificación, etiología, fisiopatología, diagnóstico, tratamiento y pronóstico. Conclusiones: El síndrome de Transfusión Feto-Feto consiste en un desbalance hemodinámico de anastomosis placentarias, niveles aumentados de vasopresina y finalmente cambios en el eje renina angiotensina aldosterona, que requiere un diagnóstico temprano con tratamiento oportuno para mejorar el pronóstico y prevenir complicaciones fetales.

Introduction: Fetofetal transfusion syndrome is a complex disease produced in about 15% of monochorionic pregnancies, despite its low incidence, its importance lies in its serious perinatal complications. Its pathophysiology is based on the process in which twins share the two circulations through abnormal blood vessels, with a subsequent hemodynamic alteration of the receptor twin and donor twin. Its diagnosis is primarily with an ultrasound scan and its current definitive treatment consists in-utero strategies performed in order to locate and seal the vessel, providing a single movement, seeking to counteract its poor prognosis, which can lead to a mortality rate of up to 100% in those patients without treatment. Objective: To review the literature about fetofetal transfusion syndrome, covering an update about various components including epidemiology, pathophysiology, clinical advances in its clinical diagnosis and treatment. Methodology: A search was conducted in databases such as PubMed, Cochrane, Sciencedirect and Google scholar and 78 articles were found, but only 32 of them finally achieved the criteria for updating, relevance and quality; also the pathophysiology, diagnosis and treatment were revised in each one. The articles that did not fulfill the inclusion criteria were discarded. Outcomes: The most updated and comprehensive information found in databases was selected according to its classification, etiology, pathophysiology, diagnosis, treatment and prognosis. Conclusions: Fetofetal transfusion Syndrome is a hemodynamic imbalance of placental anastomosis, increased levels of vasopressin and finally, changes in the renin angiotensin aldosterone axis, which requires an early diagnosis and treatment to improve the prognosis and prevent fetal complications.

Introdução: A doença de transfusão feto-fetal é complexa e aproximadamente 15% das gestações monocoriônicas, padece deste síndrome, embora a incidência seja baixa, sua importância esta nas complicações perinataies. A sua patofisiologia baseia-se no processo pelo qual os gêmeos partilham duas circulações através de vasos sanguíneos anormais, com alteração na hemodinâmica subsequente do gêmeo receptor como do doador. Seu diagnóstico é ultrassonográfico e atualmente o seu tratamento consiste em realizar as estratégias uterinas para localizar e selar os vasos, a fim de cambiar o seu mau prognóstico, caso contrário pode ocasionar a norte até de 100% dos pacientes. Objetivo: Revisar a literatura, sobre el síndrome de transfusão feto – feto, incluindo uma atualização nos diferentes componentes como epidemiologia, fisiopatologia, avanços clínicos no diagnóstico e tratamento. Metodologia: se investigou a base de dados como PubMed, Cochrane, Sciencedirect e Google acadêmico, entre os 78 artigos pesquisados, 32 apresentaram os criterios de atualização, pertinência e qualidade científica, também foi revisto fisiopatologia, diagnóstico e tratamento. Se descartaram, os artigos que não continham os critérios requeridos. Resultados: se escolheu a informação mais atualizada e completa da base de datos pesquisada, com relação à classificação, etiologia, fisiopatologia, diagnóstico, tratamiento e pronóstico.

Unusual remodeling of the hyalinization band in vulval lichen sclerosus by type V collagen and ECM 1 protein

OBJECTIVES: The vulva is the primary site affected in lichen sclerosus, a chronic dermatosis in women that is histologically characterized by a zone of collagen remodeling in the superior dermis. The normal physiological properties of the vulva depend on the assembly of collagen types I (COLI), III (COLIII) and V (COLV), which form heterotypic fibers, and extracellular matrix protein interactions. COLV regulates the heterotypic fiber diameter, and the preservation of its properties is important for maintaining normal tissue architecture and function. In the current work, we analyzed the expression of COLV and its relationship with COLI, COLIII, elastic fibers and extracellular matrix protein 1 in vulvar biopsies from patients with lichen sclerosus. METHODS: Skin biopsies from 21 patients with lichen sclerosus, classified according to Hewitt histological criteria, were studied and compared to clinically normal vulvar tissue (N=21). Morphology, immunohistochemistry, immunofluorescence, 3D reconstruction and morphometric analysis of COLI, COLIII, COLV deposition, elastic fibers and extracellular matrix 1 expression in a zone of collagen remodeling in the superior dermis were performed. RESULTS: A significant decrease of elastic fibers and extracellular matrix 1 protein was present in the hyalinization zone of lichen sclerosus compared to healthy controls. The non-homogeneous distribution of collagen fibers visualized under immunofluorescence in the hyalinization zone of lichen sclerosus and control skin was confirmed by histomorphometry. Lichen sclerosus dermis shows a significant increase of COLI, COLIII and COLV expression compared to the healthy controls. Significant inverse associations were found between elastic fibers and COLV and between COLV and extracellular matrix 1 expression. A direct association was found between elastic fiber content and extracellular matrix 1 expression. Tridimensional reconstruction of the heterotypic fibers ...

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis

OBJECTIVE: To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. METHODS: We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. RESULTS: We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. CONCLUSION: We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis. .

Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis / Avaliacao imuno-histoquimica e morfometrica de COX-1 e COX-2 no remodelamento pulmonar na fibrose pulmonar idiopatica e na esclerose sistemica

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. .

OBJETIVO: Estudar a expressão de COX-1 e COX-2 em áreas pulmonares remodeladas em pacientes com esclerose sistêmica (ES) ou fibrose pulmonar idiopática (FPI) e correlacioná-la com a sobrevida desses pacientes. MÉTODOS: Examinamos espécimes de biópsia pulmonar a céu aberto de 24 pacientes com ES e de 30 pacientes com FPI, utilizando-se tecido pulmonar normal como controle. Os padrões histológicos incluíram pneumonia intersticial não específica (PINE) fibrótica em pacientes com ES e pneumonia intersticial usual (PIU) nos pacientes com FPI. Imuno-histoquímica e histomorfometria foram usadas para avaliar a expressão celular de COX-1 e COX-2 em septos alveolares, vasos e bronquíolos, sua correlação com provas de função pulmonar e seu impacto na sobrevida. RESULTADOS: A expressão de COX-1 e COX-2 em septos alveolares foi significativamente maior em FPI-PIU e ES-PINE do que no tecido controle. Não houve diferença entre FPI-PIU e ES-PINE quanto à expressão de COX-1 e COX-2. A análise multivariada baseada no modelo de regressão de Cox mostrou que os fatores associados a baixo risco de morte foram ter idade menor, valores elevados de DLCO/volume alveolar, FPI, e alta expressão de COX-1 em septos alveolares, ao passo que os fatores associados a alto risco de morte foram ter idade maior, valores baixos de DLCO/volume alveolar, ES (com PINE) e baixa expressão de COX-1 em septos alveolares. CONCLUSÕES: Nossos resultados sugerem que estratégias de prevenção de baixa síntese de COX-1 terão maior impacto sobre a ES, ao passo que as de prevenção de alta síntese de COX-2 terão maior impacto sobre a FPI. Porém, são necessários ensaios clínicos randomizados prospectivos para confirmar essa hipótese. .

Increased fibroblast telomerase expression precedes myofibroblast α-smooth muscle actin expression in idiopathic pulmonary fibrosis

OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of inter leu kin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.

Imunofenotipagem e remodelamento da matriz extracelular na sarcoidose pulmonar e extrapulmonar / Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis

OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.

OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Efeitos hemodinâmicos da sobrecarga ventricular direita aguda experimental / Hemodynamic effects of experimental acute right ventricular overload / Efectos hemodinámicos de la sobrecarga ventricular derecha aguda experimental

FUNDAMENTO: A sobrecarga ventricular direita aguda está associada a situações clínicas de elevada morbimortalidade, tais como: ressecções pulmonares extensas, tromboembolismo pulmonar, transplante pulmonar e edema pulmonar das altitudes. Alguns pontos de sua fisiopatologia permanecem obscuros. OBJETIVO: Avaliar os efeitos hemodinâmicos da sobrecarga ventricular direita aguda experimental em suínos. MÉTODOS: A sobrecarga ventricular direita foi induzida pela oclusão das artérias pulmonares através de ligaduras. Vinte porcos foram utilizados no estudo, sendo alocados em 04 grupos: um controle, não submetido à oclusão vascular pulmonar, e três de sobrecarga ventricular direita submetidos à oclusão das seguintes artérias pulmonares: SVD1 (artéria pulmonar esquerda); SVD2 (artéria pulmonar esquerda e do lobo inferior direito) e SVD3 (artéria pulmonar esquerda, do lobo inferior direito e do lobo mediastinal), obstruindo a vasculatura pulmonar em 42, 76 e 82,0 por cento respectivamente. Variáveis de hemodinâmica foram medidas a cada 15 minutos durante a uma hora do estudo. Na análise estatística, foram utilizados ajustes de modelos lineares mistos com estrutura de variâncias e covariâncias. RESULTADOS: Nas comparações intergrupais, houve aumento significativo da frequência cardíaca (p = 0,004), pressão arterial pulmonar média (p = 0,001) e pressão capilar pulmonar (p < 0,0001). Houve redução significativa da pressão arterial média (p = 0,01) e do índice sistólico (p = 0,002). Não houve diferença significativa no índice cardíaco (p = 0,94). CONCLUSÃO: Apesar da intensa sobrecarga ventricular direita promovida pela obstrução de 82,0 por cento da vasculatura pulmonar e pelo aumento significativo da pressão arterial pulmonar não houve disfunção cardiovascular severa e/ou choque circulatório no período estudado.

BACKGROUND: Acute right ventricular overload is associated with high morbidity and mortality clinical situations such as: extensive lung resection, pulmonary thromboembolism, lung transplantation and high altitude pulmonary edema. Some points of its pathophysiology remain unclear. OBJECTIVE: To assess the hemodynamic effects of experimental acute right ventricular overload in pigs. METHODS: Right ventricular overload was induced through the occlusion of the pulmonary arteries using ligationss. Twenty pigs were used in the study, divided into 04 groups: one control group not subject to pulmonary vascular occlusion, and three right ventricular overload groups subject to occlusion of the following pulmonary arteries: SVD1 (left pulmonary artery); SVD2 (left pulmonary artery and right lower lobe) and SVD3 (left pulmonary artery, right lower lobe and mediastinal lobe), obstructing the pulmonary vasculature in 42, 76 and 82.0 percent respectively. Hemodynamic variables were measured every 15 minutes during one hour of study. The statistical analysis employed mixed linear models with variance and covariance structures. RESULTS: Group comparisons revealed significant increases in heart rate (p = 0.004), mean pulmonary artery pressure (p = 0.001) and pulmonary capillary wedge pressure (p < 0.0001). There was no significant difference in cardiac index (p = 0.94). CONCLUSION: Despite the severe right ventricular overload promoted by 82.0 percent obstruction of the pulmonary vasculature and the significant increase in pulmonary arterial pressure, there was no severe cardiovascular dysfunction and/or circulatory shock during the study period.

FUNDAMENTO: La sobrecarga ventricular derecha aguda está asociada a situaciones clínicas de elevada morbimortalidad, tales como: resecciones pulmonares extensas, tromboembolismo pulmonar, transplante pulmonar y edema pulmonar de las alturas. Algunos puntos de su fisiopatología permanecen obscuros. OBJETIVO:Evaluar los efectos hemodinámicos de la sobrecarga ventricular derecha aguda experimental en porcinos. MÉTODOS:La sobrecarga ventricular derecha fue inducida por la oclusión de las arterias pulmonares a través de ligaduras. Veinte cerdos fueron utilizados en el estudio, siendo divididos en 4 grupos: uno control, no sometido a la oclusión vascular pulmonar, y tres de sobrecarga ventricular derecha sometidos a la oclusión de las siguientes arterias pulmonares: SVD1 (arteria pulmonar izquierda); SVD2 (arteria pulmonar izquierda y del lóbulo inferior derecho) y SVD3 (arteria pulmonar izquierda, del lóbulo inferior derecho y del lóbulo mediastinal), obstruyendo la vasculatura pulmonar en 42, 76 y 82,0 por ciento respectivamente. Variables de hemodinámica fueron medidas cada 15 minutos durante una hora del estudio. En el análisis estadístico, fueron utilizados ajustes de modelos lineares mixtos con estructura de variancias y covariancias. RESULTADOS:En las comparaciones intergrupales, hubo aumento significativo de la frecuencia cardíaca (p = 0,004), presión arterial pulmonar media (p = 0,001) y presión capilar pulmonar (p < 0,0001). Hubo reducción significativa de la presión arterial media (p = 0,01) y del índice sistólico (p = 0,002). No hubo diferencia significativa en el índice cardíaco (p = 0,94). CONCLUSIÓN:A pesar de la intensa sobrecarga ventricular derecha promovida por la obstrucción de 82,0 por ciento de la vasculatura pulmonar y por el aumento significativo de la presión arterial pulmonar no hubo disfunción cardiovascular severa y/o shock circulatorio en el período estudiado.

Aumento na expressão de telomerase por fibroblastos ocorre precocemente à expressão de alfa-actina de músculo liso por miofibroblastos no processo de remodelamento da pneumonia intersticial usual / Increased telomerase expression in fibroblasts occurs earlier than myofibroblast alfa-smooth muscle actin expression in the remodeling process of usual interstitial pneumonia

Objetivo: Identificar potenciais marcadores associados à expressão de telomerase em fibroblastos e de α-actina de músculo liso (α-AMS) em miofibroblastos de pulmões de pacientes com fibrose pulmonar idiopática/pneumonia intersticial usual (FPI/PIU). Métodos: Utilizamos cortes histológicos de 34 biópsias cirúrgicas de pulmão de pacientes com FPI, caracterizados, à histopatologia, pelo padrão de PIU. As expressões de telomerase por fibroblastos, de α-AMS por miofibroblastos e tecidual deinterleucina-4 (IL-4), de fator de crescimento transformador-β (TGF- β) e de fator de crescimento de fibroblastos básico (bFGF) foram avaliados por imunohistoquímica e quantificadas pela técnica de contagem de pontos nas áreas pulmonares de colapso (COL),de fibrose mural (FM) e de faveolamento (FV). Resultados: Aexpressão de telomerase foi significativamente maior nas áreasde COL que nas áreas de FM e FV. O mesmo foi observado para a expressão de bFGF. Interleucina-4 e α-AMS tiveram expressão significativamente maior nas áreas de FM. A expressão de TGF-β foi maior nas áreas de COL e FV. Observamos uma associação positiva entre expressão de telomerase e bFGF nas áreas COL, FM e FV. O mesmo ocorreu com a expressão de α-AMS e IL-4. Nas áreas de FM, houve uma correlação negativa entre IL-4e bFGF, e TGF-β apresentou tendência a associação positiva com α-AMS. Análise multivariada revelou que a expressão de IL-4 e α-AMS nas áreas de FM são indicadores independentes de menor sobrevida em modelo estatístico significante incluindo idade, tabagismoe FVC (capacidade vital forçada). Pacientes com expressão de IL-4 menor que 13,5% nas áreas de FMapresentaram melhor sobrevida. O mesmo foi observado para expressão de α-AMS menor que 8,5%. Conclusão: Fibroblastos, com capacidade multiplicativa caracterizada pela expressão de telomerase e de bFGF tecidual, tendem a predominar no estágio precoce de remodelamento da FPI/PIU...

Objective: To identify potential markers associated with fibroblast telomerase and interstitial myfibroblast alpha-smooth muscle actin (α-AMS) expression in patients with idiopathic pulmonary fibrosis/usual intersticial pneumonia (IPF/UIP). Methods:Pulmonary specimens included 34 surgical lung biopsies, histologicallyclassified as UIP, from patients clinically diagnosed with IPF. Fibroblast telomerase expression, interstitial myofibroblast α-AMSexpression and IL-4 (interleukin 4), TGF-β (transforming growth factor beta) and bFGF (basic fibroblast growth factor) tissue expressionwere evaluated by immunohistochemistry and quantifiedin collapsed (COL), mural fibrosis (MF) and honeycombing areas (HC). Results: Telomerase expression was significantly higher in COL areas than in MF and HC areas. The same was observed for b-FGF. Interleukin-4 and α-AMS expression were significantly higher in MF areas. TGF-β expression ws higher in COL and HC areas. We observed a positive correlation between telomerase and bFGF expression in COL, MF and HC areas. The same was noted for α-AMS and IL-4. In MF areas, a negative correlation between IL-4 and b-FGF was obtained and TGF-β tended to positively correlate with α-AMS. In multivariate analysis, IL-4 tissue andα-AMS myofibroblast expression in MF areas were independently predictive of mortality in a statistically significant model including age, tobacco use and FVC (full vital capacity). Patients with IL-4 expression lower than 13.5% in MF areas had better survival. The same was noted for α-AMS expression lower than 8.5%. Conclusion: Fibroblast multiplicative capacity, characterized by telomerase expression and associated with bFGF tissue expression, seems to predominate in the early remodeling process of IPF/UIP, whereas myofibroblast differentiation, characterized by alpha-smooth muscleactin expression and associated with IL-4 tissue expression, seems to lead to the later fibrotic response...

Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9 percent of the cases and cancer in 28.1 percent. The pulmonary histopathology showed diffuse alveolar damage in 40.7 percent (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/ AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.

Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine-origin influenza type A/H1N1 and acute respiratory failure

BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co-infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment. OBJECTIVE: To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1. METHODS: Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS. RESULTS: The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response. Ultrastructural analysis showed viral-like particles in all cases. CONCLUSIONS: Viral-like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT-PCR on nasopharyngeal aspirates. Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.

Association between decreases in type V collagen and apoptosis in mouse lung chemical carcinogenesis: a preliminary model to study cancer cell behavior

OBJECTIVE: The importance of type V collagen and its relationships with other types of collagen and with vascular and epithelial apoptosis were studied in a model of chemical carcinogenesis in the mouse lung. METHODS: Two groups of male Balb/c mice were studied: a) animals that received two intraperitoneal doses of 3 g/kg urethane carcinogen (urethane group = 24); and b) animals submitted to a sham procedure, comparable to the test group (control group = 7). Both groups were sacrificed after 120 days. In situ detection of apoptosis, immunohistochemistry, immunofluorescence and histomorphometry were used to evaluate the fraction occupied by the tumor, vascular and epithelial apoptosis, and type V, III and I collagen fibers in the lung parenchyma from both groups. RESULTS: The lung parenchyma from the urethane group showed low fractions of vascular and epithelial apoptosis as well as reduced type V collagen fibers when compared to the control group. A significant direct association was found between type V and III collagen fibers and epithelial apoptosis, type V collagen fibers and vascular apoptosis, and type V and type I collagen fibers. CONCLUSION: The results show that a direct link between low amounts of type V collagen and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis, suggesting that strategies aimed at preventing decreased type V collagen synthesis or local responses to reduced apoptosis may have a greater impact in lung cancer control.

Histomorphometric analysis of cutaneous remodeling in the early stage of the scleroderma model

INTRODUCTION/OBJECTIVES: Systemic sclerosis, or scleroderma, is a rheumatic disease characterized by autoimmunity, vasculopathy, and fibrosis of the skin and several internal organs. In the present study, our aim was to assess the skin alterations in animals with scleroderma during the first stages of disease induction. METHODS: To induce scleroderma, female New Zealand rabbits (n = 12) were subcutaneously immunized with 1 mg/ml of collagen V (Col V) in complete Freund's adjuvant, twice with a thirty-day interval. Fifteen days later, the animals received an intramuscular booster with type V collagen in incomplete Freund's adjuvant, twice with a fifteen-day interval. The control group was inoculated with 1 ml of 10 mM acetic acid solution diluted with an equal amount of Freund's adjuvant. Serial dorsal skin biopsies were performed at 7, 15, and 30 days and stained with H&E, Masson's trichrome and Picrosírius for morphological and morphometric analyses. RESULTS: Immunized rabbits presented a significant increase in collagen in skin collected seven days after the first immunization (p=0.05). CONCLUSION: The results from this experimental model may be very important to a better understanding of the pathogenic mechanisms involved in the beginning of human SSc. Therapeutic protocols to avoid early remodeling of the skin may lead to promising treatments for SSc in the future.

Systemic sclerosis and idiopathic interstitial pneumonia: histomorphometric differences in lung biopsies / Esclerose sistêmica e pneumonia intersticial idiopática: diferenças histomorfométricas em biópsias pulmonares

OBJECTIVE: The aim of this study was to examine the parenchymal and extracellular matrix remodeling process in two histologic patterns-nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP)-in cases of idiopathic and sclerosis/systemic sclerosis (SSc)-associated interstitial pneumonia. METHODS: We examined 15 cases of idiopathic NSIP, 10 cases of idiopathic UIP, 5 cases of SSc-UIP and 9 cases of SSc-NSIP. In the lung parenchyma, epithelial cells, endothelial cells and myofibroblasts were evaluated by immunohistochemical staining, whereas histochemical staining was used in order to evaluate collagen/elastic fibers in the extracellular matrix. RESULTS: The percentage of surfactant protein A-positive epithelial cells was significantly greater in idiopathic NSIP than in SSc-NSIP, as well as being greater in idiopathic UIP than in SSc-UIP. Idiopathic NSIP and idiopathic UIP presented significantly higher immunoexpression of alpha smooth muscle actin in myofibroblasts than did SSc-NSIP and SSc-UIP. The percentage of CD34 endothelial cells in the pulmonary microvasculature was significant lower in idiopathic UIP than in SSc-UIP. The density of collagen fibers was significantly greater in idiopathic NSIP and idiopathic UIP than in SSc-NSIP and UIP. In contrast, the elastic fiber density was significantly lower in idiopathic UIP than in SSc-UIP. CONCLUSIONS: Increased collagen synthesis, destruction of elastic fibers, high myofibroblast proliferation and poor microvascularization might represent a remodeling process found in idiopathic interstitial pneumonia, whereas the reverse might represent a repair process in SSc-associated interstitial pneumonia.

OBJETIVO: O objetivo deste trabalho foi examinar o processo de remodelamento no parênquima e na matriz extracelular em dois padrões histológicos-pneumonia intersticial não-específica (PINE) e pneumonia intersticial usual (PIU)-em casos associados à esclerose idiopática/esclerose sistêmica (ES). MÉTODOS: Investigamos 15 casos de PINE idiopática, 10 casos de PIU idiopática, 5 casos de PIU associada à ES (PIU-ES) e 9 de PINE associada à ES (PINE-ES). No parênquima pulmonar, as células epiteliais, células endoteliais e miofibroblastos foram avaliados através de coloração imuno-histoquímica, ao passo que a coloração histoquímica foi utilizada para avaliar as fibras elásticas e de colágeno na matriz extracelular. RESULTADOS: A porcentagem de células epiteliais positivas para proteína A do surfactante foi significativamente maior nos casos de PINE idiopática do que nos de PINE-ES, assim como nos casos de PIU idiopática do que nos de PIU-ES. A PINE e a PIU idiopáticas apresentaram valores significativamente maiores de imunoexpressão de alfa actina de músculo liso nos miofibroblastos do que a PINE-ES e a PIU-ES. A porcentagem de células endoteliais CD34 na microvasculatura pulmonar foi significativamente menor na PIU idiopática do que na PIU-ES. A densidade de fibras do colágeno foi significativamente maior em ambas as formas idiopáticas de PINE e PIU do que na PINE-ES e PIU-ES. Em contraste, a densidade de fibras elásticas foi significativamente menor na PIU idiopática do que na PIU-ES. CONCLUSÕES: A síntese aumentada de colágeno, a destruição de fibras elásticas, a alta proliferação miofibroblástica e a microvascularização diminuída podem representar um processo de remodelamento encontrado na pneumonia intersticial idiopática, enquanto o reverso pode representar mais um processo de reparo na pneumonia intersticial associada à ES.

Diagnóstico e prognóstico dos tumores pulmonares neuroendócrinos mediante microscopia eletrônica e análise multivariavel de agrupamento / Using electron microscopy and multivariate cluster analysis to determine diagnosis and prognosis in cases of neuroendocrine lung carcinoma

OBJECTIVE: To establish reproducible electron microscopic criteria for identifying the four major types of neuroendocrine tumors of the lung: carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; and small cell carcinoma. METHODS: Measurements were made on electron micrographs using a digital image analyzer. Sixteen morphometric variables related to tumor cell differentiation were assessed in 27 tumors. The examination under electron microscopy revealed that all of the tumors could be classified as belonging to one of the four categories listed above. Cluster analysis of the morphometry variables was used to group the tumors into three clusters, and Kaplan-Meier survival function curves were employed in order to draw correlations between each cluster and survival. RESULTS: All three clusters of neuroendocrine carcinomas were found to be associated with survival curves, demonstrating the prognostic significance of electron microscopic features. The tumors fell into three well-defined clusters, which represent the spectrum of neuroendocrine differentiation: typical carcinoid (cluster 1); atypical carcinoid and large cell neuroendocrine carcinoma (cluster 2); and small cell carcinoma (cluster 3). Cluster 2 represents an intermediate step in neuroendocrine carcinogenesis, between typical carcinoid tumors and small cell carcinomas. CONCLUSIONS: Our findings confirm that electron microscopy is useful in making the diagnosis and prognosis in cases of lung tumor.

OBJETIVO: Estabelecer, com ajuda do microscópio eletrônico, critérios que possibilitem uma diferenciação mais exata entre os quatro tipos maiores de tumores neuroendócrinos pulmonares: tumor carcinóide típico e atípico, carcinoma de grandes células neuroendócrino e carcinoma de pequenas células. MÉTODOS: Todos os tumores foram avaliados morfometricamente e 16 variáveis foram relacionadas com diferenciação das células tumorais; estas variáveis foram analisadas sob microscopia eletrônica com ajuda de um analisador de imagem digital em 27 tumores. A avaliação através da microscopia eletrônica revelou que todos os tumors investigados podiam ser classificados a um dos quarto tipos listados acima. A análise das variáveis morfométricas foi usada para agrupar os tumores em três grandes grupos, os quais foram relacionados à sobrevivência pelas curvas de Kaplan Meier. RESULTADOS: Os três grupos de carcinoma neuroendócrino associaram-se às curvas da sobrevivência, as quais mostraram características ultrastruturais na microscopia eletrônica de significância prognóstica distinta. Os tumores foram contidos em três grupos bem definidos, que representam o espectro da diferenciação neuroendócrina: tumor carcinóide (grupo 1); tumor carcinóide atípico e carcinoma de grandes células neuroendócrino (grupo 2); e carcinoma de pequenas células (grupo 3). O grupo 2 representa um espectro intermediário na carcinogênese neuroendócrina, entre o carcinóide típico e o carcinoma de pequenas células. CONCLUSÕES: Nossos achados confirmam que a microscopia eletrônica é uma ferramenta útil no diagnóstico e prognóstico dos casos de tumores pulmonares.

Detecção de micrometástases em câncer de pulmão não-pequenas células estádio pN0: um método alternativo combinando imunohistoquímica e análise em microsséries / Detection of micrometastases in pN0 non-small cell lung cancer: an alternative method combining tissue microarray and immunohistochemistry

OBJETIVO: Apresentar um método alternativo para detectar micrometástases em linfonodos previamente negativos para câncer de pulmão não-pequenas células (CPNPC) pela coloração de rotina com hematoxilina-eosina. MÉTODOS: Setenta e sete linfonodos hilares e mediastinais ressecados de 18 pacientes portadores de CPNPC foram investigados para a presença de micrometástases associando-se análise em microsséries e imunoistoquímica. RESULTADOS: Micrometástases foram detectadas após a identificação de células neoplásicas citoqueratina e cromogranina positivas em microsséries de linfonodos. Dos 18 pacientes inicialmente estadiados como pN0 pela coloração de rotina com hematoxilina-eosina, 9 (50 por cento) foram reestadiados como N1, e o prognóstico foi reavaliado em função de parâmetros histológicos e clínicos. A comparação das curvas de sobrevida mostrou que os pacientes sem micrometástases tiveram maior sobrevida do que os portadores de micrometástases. Além disso, após a análise multivariada controlada para idade, sexo, tipo histológico e reestadiamento, a presença de micrometástases mostrou-se como um fator independente na sobrevida. Entre os pacientes que haviam sido previamente estadiados como pN0, o risco de morte mostrou-se 7 vezes maior para os que foram posteriormente diagnosticados com micrometástases do que para aqueles nos quais não foram identificadas micrometástases. CONCLUSÃO: A combinação da análise em microsséries com a imunoistoquímica pode representar um método alternativo de baixo custo e menos demorado para identificar metástases ocultas e prever o prognóstico em pacientes portadores de CPNPC pN0 cujos tumores foram cirurgicamente ressecados. São necessários estudos prospectivos randomizados com casuísticas maiores para determinar a acurácia desse método alternativo.

OBJECTIVE: To present an alternative method of detecting micrometastases in lymph nodes previously testing negative for non-small cell lung cancer (NSCLC) by routine hematoxylin-eosin staining. METHODS: A total of 77 hilar and mediastinal lymph nodes resected from 18 patients with NSCLC were investigated for the presence of micrometastases using a combination of microarray analysis and immunohistochemistry. RESULTS: Micrometastases were detected by identifying cytokeratin- and chromogranin-positive cells in lymph node microarrays. Of the 18 patients initially staged as pN0 through routine hematoxylin-eosin staining, 9 (50 percent) were restaged as N1, and the prognoses were re-evaluated in terms of histological and clinical parameters. The comparison of the survival curves revealed that survival was higher in the patients without micrometastases than in those with micrometastases. In addition, in the multivariate analysis adjusted for age, gender, histological type, and restaging, the presence of micrometastases proved to be an independent predictor of survival. Among patients who had been previously staged as pN0, the risk of death was found to be 7-times greater for those later diagnosed with micrometastases than for those in whom no micrometastases were identified. CONCLUSION: The combination of microarray analysis and immunohistochemistry might represent a low-cost and less time-consuming alternative for identifying occult micrometastases and predicting prognoses in surgically resected patients with pN0 NSCLC. Larger randomized, prospective studies are needed in order to determine the accuracy of this method.

Pulmonary histopathological alterations in patients with acute respiratory failure: an autopsy study / Alterações histopatológicas pulmonares em pacientes com insuficiência respiratória aguda: um estudo em autopsias

OBJETIVOS: Apresentar alterações histopatológicas pulmonares encontradas em autopsias de pacientes falecidos por insuficiência respiratória aguda (IRA) e verificar se doenças de base e específicos fatores de risco associados aumentam a incidência dessas alterações. MÉTODOS: Foram revisados laudos finais de autopsias e selecionadas 3.030 autopsias de pacientes > 1 ano de idade, com infiltrado pulmonar radiológico, portadores de doença de base e fatores de risco associados, que morreram por alterações pulmonares decorrentes de IRA. RESULTADOS: As principais alterações histopatológicas pulmonares causadoras de morte imediata foram: dano alveolar difuso (DAD); edema pulmonar; pneumonia intersticial linfocítica (PIL) e hemorragia alveolar. As principais doenças de base encontradas foram: AIDS; broncopneumonia; sepse; cirrose hepática; tromboembolismo pulmonar; infarto agudo do miocárdio (IAM); acidente vascular cerebral; tuberculose; câncer; insuficiência renal crônica e leucemia. Os principais fatores de risco associados foram: idade > 50 anos; hipertensão arterial; insuficiência cardíaca congestiva; doença pulmonar obstrutiva crônica e diabetes mellitus. Pacientes com esses fatores de risco e AIDS apresentaram alta probabilidade de desenvolver PIL; pacientes com esses mesmos fatores, de desenvolver DAD, se portadores de sepse ou cirrose hepática; pacientes com tromboembolismo e os mesmos fatores de risco, de desenvolver hemorragia alveolar; pacientes com esses fatores de risco e IAM, de desenvolver edema pulmonar. CONCLUSÕES: Os achados pulmonares em pacientes com óbito por IRA apresentaram quatro padrões histopatológicos: DAD, edema pulmonar, PIL e hemorragia alveolar. Doenças de base e específicos fatores de risco associados correlacionaram-se positivamente com determinados padrões histopatológicos detectados à autópsia.

OBJECTIVE: To present the pulmonary histopathological alterations found in the autopsies of patients with acute respiratory failure (ARF) and determine whether underlying diseases and certain associated risk factors increase the incidence of these histopathological patterns. METHODS: Final autopsy reports were reviewed, and 3030 autopsies of patients > 1 year of age with an underlying disease and associated risk factors were selected. All had developed diffuse infiltrates and died of ARF-related pulmonary alterations. RESULTS: The principal pulmonary histopathological alterations resulting in immediate death were diffuse alveolar damage (DAD), pulmonary edema, lymphocytic interstitial pneumonia (LIP) and alveolar hemorrhage. The principal underlying diseases were AIDS, bronchopneumonia, sepsis, liver cirrhosis, pulmonary thromboembolism, acute myocardial infarction (AMI), cerebrovascular accident, tuberculosis, cancer, chronic kidney failure and leukemia. The principal associated risk factors were as follows: age > 50 years; arterial hypertension; congestive heart failure; chronic obstructive pulmonary disease; and diabetes mellitus. These risk factors and AIDS correlated with a high risk of developing LIP; these same risk factors, if concomitant with sepsis or liver cirrhosis, correlated with a risk of developing DAD; thromboembolism and these risk factors correlated with a risk of developing alveolar hemorrhage; these risk factors and AMI correlated with a risk of developing pulmonary edema. CONCLUSION: Pulmonary findings in patients who died of ARF presented four histopathological patterns: DAD, pulmonary edema, LIP and alveolar hemorrhage. Underlying diseases and certain associated risk factors correlated positively with specific histopathological findings on autopsy.