Effects of the positive end-expiratory pressure increase on sublingual microcirculation in patients with acute respiratory distress syndrome / Efeitos do aumento de pressão positiva ao final da expiração sobre a microcirculação sublingual em pacientes com síndrome do desconforto respiratório agudo

Abstract Objective: The aim of this study was to evaluate the impact of increased positive end-expiratory pressure on the sublingual microcirculation. Methods: Adult patients who were sedated, under mechanical ventilation, and had a diagnosis of circulatory shock and acute respiratory distress syndrome were included. The positive end-expiratory pressure level was settled to obtain a plateau pressure of 30 cm H2O and then maintained at this level for 20 minutes. Microcirculatory (obtained by videomicroscopy) and hemodynamic variables were collected at baseline and compared with those at the end of 20 min. Results: Twelve patients were enrolled. Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, there was considerable interindividual variability. There was a negative, moderate correlation between the changes in the De Backer score (r = -0.58, p = 0.048), total vessel density (r = -0.60, p = 0.039) and baseline values. The changes in total vessel density (r = 0.54, p = 0.07) and perfused vessel density (r = 0.52, p = 0.08) trended toward correlating with the changes in the mean arterial pressure. Conclusion: Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, at individual level, such response was heterogeneous. The changes in the microcirculation parameters could be correlated with the baseline values and changes in the mean arterial pressure.

Resumo Objetivo: O objetivo deste estudo foi avaliar o impacto do aumento de pressão positiva no fim da expiração (PEEP) sobre a microcirculação sublingual. Métodos: Os pacientes adultos que foram sedados, sob ventilação mecânica, com diagnóstico de choque circulatório e síndrome do desconforto respiratório agudo foram incluídos. O nível da PEEP foi estabelecido para obter uma pressão de platô de 30 cmH2O e depois mantido nesse nível por 20 minutos. As variáveis de microcirculação (obtida por microscopia de vídeo) e hemodinâmica foram registradas na fase basal e comparadas com aquelas no fim de 20 min. Resultados: Doze pacientes foram incluídos. Em geral, os parâmetros da microcirculação não apresentaram alterações significativas após o aumento da PEEP. Porém, houve considerável variabilidade interindividual. Houve uma correlação negativa, moderada, entre as alterações no escore de De Backer (r = -0,58, p = 0,048), na densidade total do vaso (r = -0,60, p = 0,039) e nos valores basais. As alterações na densidade total do vaso (r = 0,54, p = 0,07) e na densidade do vaso perfundido (r = 0,52, p = 0,08) apresentaram tendência de correlação com as alterações na pressão arterial média. Conclusão: Em geral, os parâmetros da microcirculação não apresentaram alterações significativas após o aumento da PEEP. No entanto, individualmente, essa resposta foi heterogênea. As alterações nos parâmetros da microcirculação puderam ser correlacionadas com os valores basais e alterações na pressão arterial média.

Evaluation of sublingual microcirculation in children with dengue shock

OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target. .

Tumor-Infiltrating Macrophage and Microvessel Density in Oral Squamous Cell Carcinoma

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Macrófagos associados a tumores (MAT) representam o componente principal do estroma de muitos tumores, além de participar da angiogênese tumoral. Este estudo comparou a microdensidade vascular (MDV) e densidade de macrófagos infiltrando o tumor (DMIT) em carcinoma escamocelular da boca (CEC) com diferentes graus histológicos de malignidade. Análise histomorfométrica foi empregada após técnica imuno-histoquímica para os anticorpos fator von-Willebrand e CD68. Uma diferença significante entre MDV e carcinomas bem e moderadamente diferenciados foi observada (p<0,05). MAT estavam fortemente presentes em todos os tumores estudados e a DMIT não foi diferente entre os diferentes graus histológicos de malignidade do CEC (p=0,381). Correlação significante entre MDV e DMIT não foi observada (p=0,870). Em conclusão, os resultados desse estudo sugerem a influência de MAT e angiogênese nos diferentes graus histológicos de malignidade do CEC. Entretanto, a ausência de correlação entre MDV e DMIT sugere que a angiogênese não depende do número de macrófagos presentes neste tipo de câncer, mas do fenótipo predominante. Outros estudos devem ser realizados a fim de contribuir para melhor compreensão da participação de MAT na angiogênese tumoral.

Immunohistochemical evaluation of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth

The aim of this study was to evaluate the immunoexpression of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth and to correlate the results with demographic, survival, clinical (TNM staging) and histopathological variables (tumor grade, perineural invasion, embolization and bone invasion). Data from medical records and diagnoses of 41 patients were reviewed. Histological sections were subjected to immunostaining using primary antibodies for human MMP-2, MMP-9 and CD31 and streptavidin-biotin-immunoperoxidase system. Histomorphometric analyses quantified positivity for MMPs (20 fields per slide, 100 points grade, ×200) and for CD31 (microvessels <50 µm in the area of the highest vascularization, 5 fields per slide, 100 points grade, ×400). Statistical design was composed by non-parametric Mann-Whitney U test (investigating the association between numerical variables and immunostainings), chi-square frequency test (in contingency tables), Fisher's exact test (when at least one expected frequency was less than 5 in 2×2 tables), Kaplan-Meier method (estimated probabilities of overall survival) and Iogrank test (comparison of survival curves), all with a significance level of 5%. There was a statistically significant correlation between immunostaining for MMP-2 and lymph node metastasis. Factors associated negatively with survival were N stage, histopathological grade, perineural invasion and immunostaining for MMP-9. There was no significant association between immunoexpression of CD31 and the other variables. The intensity of immunostaining for MMP-2 can be indicative of metastasis in lymph nodes and for MMP-9 of a lower probability of survival.

O objetivo deste estudo foi avaliar a imunoexpressão de MMP-2, MMP-9 e CD31/densidade microvascular em carcinomas espinocelulares de soalho bucal e correlacionar os resultados com variáveis demográficas, de sobrevida, clínicas (estadiamento TNM) e histopatológicas (grau de diferenciação tumoral, invasão perineural, embolização e invasão óssea). Dados de prontuários e de diagnósticos de 41 pacientes foram revisados. Cortes histológicos foram submetidos à imunomarcação usando anticorpos primários para MMP-2, MMP-9 e CD31 humanos e sistema streptoavidina-biotina-imunoperoxidase. Análise histomorfométrica quantificou a positividade para MMPs (20 campos, grade de 100 pontos por lâmina, ×200) e para CD31 (microvasos <50 µm na área de maior vascularização, 5 campos, grade de 100 pontos por lâmina, ×400). O planejamento estatístico foi composto pelo teste não paramétrico U de Mann-Whitney (verificação da associação entre variáveis numéricas e imunomarcações), teste de frequências do qui-quadrado (em tabelas de contingência), teste exato de Fisher (quando pelo menos uma frequência esperada foi menor do que 5 em tabelas 2×2), método de Kaplan-Meier (estimativa de probabilidades de sobrevida global) e teste de Iogrank (comparação das curvas de sobrevida), todos com nível de significância de 5%. Houve correlação estatisticamente significante entre imunomarcação para MMP-2 e metástase em linfonodo. Os fatores relacionados negativamente com a sobrevida foram estadiamento N, gradação histopatológica, invasão perineural e imunomarcação de MMP-9. Não houve associação significativa entre imunoexpressão de CD31 e as demais variáveis. A intensidade de imunomarcação para MMP-2 pode ser indicativa de metástase em linfonodo e para MMP-9 de uma menor probabilidade de sobrevida.

Oral intra vascular papillary endothelial hyperplasia in the floor of the mouth.

Intravascular papillary endothelial hyperplasia (IPEH) is an unusual vascular lesion of proliferating endothelial cells. It is more frequently seen in the extremities, particularly in the fingers. Oral IPEH has been reported with the common sites being lip, tongue, and buccal mucosa. In this article, we present a case of oral IPEH of the floor of the mouth, an unusual location, presenting in a 9-month-old male. The histogenesis, histologic features, and ultrastructural features are also reviewed. A misdiagnosis of angiosarcoma can be made in a case of IPEH due to similar histopathologic features. It is imperative to rule out this error by an elaborate histopathologic evaluation ofthese lesions.