RESUMEN

The aim of this study was to investigate the prognostic relevance of ß-catenin expression in oral squamous cell carcinoma (OSCC) and to explore relationships with the tumor immune microenvironment. Expression of ß-catenin and PD-L1, as well as lymphocyte and macrophage densities, were evaluated by immunohistochemistry in 125 OSCC patient specimens. Membranous ß-catenin expression was detected in 102 (81.6%) and nuclear ß-catenin in 2 (1.6%) tumors. There was an association between ß-catenin expression, tumoral, and stromal CD8+ T-cell infiltration (TIL) and also the type of tumor immune microenvironment (TIME). Tumors harboring nuclear ß-catenin were associated with a type II TIME (i.e., immune ignorance defined by a negative PD-L1 expression and low CD8+ TIL density), whereas tumors with membranous ß-catenin expression were predominantly type IV (i.e., immune tolerance defined by negative PD-L1 and high CD8+ TIL density). Combined, but not individual, high stromal CD8+ TILs and membranous ß-catenin expression was independently associated with better disease-specific survival (HR = 0.48, p = 0.019). Taken together, a combination of high stromal CD8+ T-cell infiltration and membranous ß-catenin in the tumor emerges as an independent predictor of better survival in OSCC patients.

RESUMEN

Purpose: The aim of this study was to investigate the prognostic significance of preoperative inflammatory markers in peripheral blood of patients with oral squamous cell carcinoma (OSCC), and to establish correlations with the infiltrate of macrophages and lymphocytes in the local immune tumor microenvironment (TME). Materials and Methods: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were retrospectively evaluated in a cohort of 348 OSCC patients, and correlated with overall (OS) and disease-specific survival (DSS). Immunohistochemical analysis of tumoral and stromal infiltration of CD8+, CD4+, FOXP3+ and CD20+ lymphocytes and CD68+ and CD163+ macrophages was performed in a subset of 119 OSCC patient samples, and correlations further assessed. Results: NLR, SII, and LMR were significantly associated with a poorer OS in univariate analysis; however, only NLR remained a significant independent predictor in the multivariate analysis (HR = 1.626, p = 0.04). NLR and SII were inversely and significantly correlated with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes. Moreover, a significant correlation between LMR was also found to significantly associate with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes, stromal CD68+ and CD163+ macrophages, and also tumoral infiltration of CD4+ and CD20+ lymphocytes. Conclusions: Preoperative NLR, SII, and LMR may serve as valuable systemic markers to predict OSCC patient survival, with NLR emerging as an independent predictor of poor OS. Moreover, strong significant correlations were exclusively observed between systemic inflammatory markers and the local stromal infiltration of lymphocytes in the TME.

Asunto(s)

RESUMEN

Tumor-associated macrophages (TAMs) can be polarized into antitumoral M1 and protumoral and immunosuppressive M2 macrophages. This study investigated the clinical relevance of TAM infiltration in oral squamous cell carcinoma (OSCC), evaluating CD68 (M1 and M2 macrophage marker) and CD163 expression (M2 macrophage marker) in the tumor nests and surrounding stroma. Immunohistochemical analysis of both stromal/tumoral CD68+ and CD163+ TAMs was performed in paraffin-embedded tissue specimens from 125 OSCC patients, and correlated with clinical data. Potential relationships with the expression of cancer stem cell (CSC) markers and PD-L1 in the tumors were also assessed. Stromal CD163+ infiltration was significantly associated with the tumor location in the tongue, and stromal and tumoral CD68+ and CD163+-infiltrating TAMs were more abundant in nonsmokers and non-alcohol-drinkers. Strikingly, this study uncovers an inverse relationship between CD68+ and CD163+ TAMs and CSC marker expression (NANOG and SOX2) in OSCC. High infiltration of CD163+ TAMs in both tumor and stroma was strongly and significantly correlated with the absence of NANOG expression. Moreover, infiltration of both CD68+ and CD163+ TAMs was also significantly associated with high tumor expression of PD-L1. Our results suggest that there is a link between TAM infiltration and immune escape in OSCC.

RESUMEN

Resumen: Introducción: La lesión renal aguda se define como una elevación de la creatinina superior a 0.3 mg/dL o una disminución en los flujos urinarios en las últimas seis horas en cualquier paciente. Métodos: Sostuvimos la hipótesis de que los pacientes admitidos en la Unidad de Terapia Intensiva (UTI) durante 2013 presentaban mayor incidencia de lesión renal aguda, puesto que eran reanimados con mayor cantidad de solución salina al 0.9% que los pacientes ingresados en la actualidad. Comparamos dos grupos de pacientes en dos periodos distintos (años 2013 y 2015). Se recabaron diariamente datos sobre el balance de líquidos (BL), criterios de lesión renal (LR) y tipo y cantidades de soluciones administradas. Resultados: Durante el periodo entre julio y agosto de 2013 se incluyó un total de 30 pacientes y durante el periodo comprendido entre julio y agosto de 2015 se incluyeron 36, obteniendo un tamaño de muestra de 66 pacientes (n = 66). No se encontró asociación estadísticamente significativa en cuanto al tipo y cantidad de solución cristaloide administrada con respecto a la presencia de lesión renal aguda (p = 0.8) y días de estancia en la UTI (p = 0.45). Se observó asociación estadísticamente significativa entre lesión renal y el uso de coloides como solución intravenosa (p = 0.01). Conclusiones: Actualmente se tiene una tendencia a utilizar más soluciones intravenosas balanceadas, la lesión renal aguda debe prevenirse en la UTI.

Abstract: Introduction: Acute Kidney Injury (AKI) is defined as an elevation of serum creatinine of 0.3 mg/dL and more, or as the presence of low urine output for less tan 0.3 mL/kg/hour for at least six hours. Methods: We had the hypothesis that the patients atmitted to the Intensive Care Unit (ICU) during 2013 used to have high incidence of AKI because they were resucitated with more saline 0.9% solution than patients today. We compare two groups of patients in different periods of time (years 2013 and 2015). We recorded every day different data like fluid balance (FB), cirteria of acute kidney injury (AKI) and type and quantity of intravenous fluids. Results: During the period of July-August 2013 we included 30 patients, and during the lapse of time of July-August 2015 we included 36 patients, for a total number of 66 patients (n = 66). There was no statistic association between the type or the quantity of cristalloid intravenous fluid administered with the incidence of AKI (p = 0.8) and the lenght of ICU stay (p = 0.45). We found only statistic significance between AKI and the use of colloids as an intravenous fluid (p = 0.01). Conclusions: Nowadays we have the trend of use more balance intravenous fluids, the acute kidney injury has to be forewarned and avoided in the ICU.

Resumo: A lesão renal aguda é definida como uma elevação da creatinina de 0.3 mg/dL ou uma diminuição do fluxo urinário nas últimas 6 horas em qualquer paciente. Métodos: Nossa hipótese foi que os pacientes admitidos na Unidade de Terapia Intensiva durante 2013 apresentaram uma maior incidência de lesão renal aguda, devido a que foram reanimados com maior quantidade de solução salina 0.9% que os pacientes admitidos atualmente. Comparou-se dois grupos de pacientes em dois períodos de tempo diferentes (2013 e 2015). Recoletamos diariamente os dados sobre o balance de líquidos (BL), critérios de lesão renal (LR), tipo e quantidades de soluções administradas. Resultados: Durante o período de Julho-Agosto de 2013, foram incluídos um total de 30 pacientes e durante o período compreendido entre Julho-Agosto de 2015 foram incluídos 36 pacientes, dando um tamanho de amostra de 66 pacientes (n = 66). Não encontramos uma associação estatisticamente significativo em quanto ao tipo e quantidade de solução cristalóide administrada, no que diz respeito a apresentação da lesão renal aguda (p = 0.8) e dias de permanência na UTI (p = 0.45). Encontramos uma associação estatisticamente significativa entre a lesão renal e o uso de colóides como solução intravenosa (p = 0.01). Conclusões: Atualmente existe uma tendência para utilizar soluções intravenosas mais equilibradas, devemos prevenir a lesão renal aguda na UTI.

RESUMEN

Cannabinoids have emerged as brain protective agents under neurodegenerative conditions. Many neuroprotective actions of cannabinoids depend on the activation of specific receptors, cannabinoid receptor type 1 (CB1R) and type 2 (CB2R). The aim of the present study was to determine whether the CB2R and CB1R agonist WIN 55,212-2 (WIN) protects neonatal brain against focal cerebral ischemia-reperfusion and whether anti-inflammatory mechanisms play a role in protection. Seven-day-old rats were subjected to 90-min middle cerebral artery occlusion (MCAO), and injured rats were identified by diffusion-weighted MRI during the occlusion. After reperfusion, rats were subcutaneously administered 1 mg/kg of WIN or vehicle twice daily until sacrifice. MCAO led to increased mRNA expression of CB2R (but not CB1R), chemokine receptors (CCR2 and CX3CR1), and cytokines (IL-1ß and TNFα), as well as increased protein expression of chemokines MCP-1 and MIP-1α and microglial activation 24 h after MCAO. WIN administration significantly reduced microglial activation at this point and attenuated infarct volume and microglial accumulation and proliferation in the injured cortex 72 h after MCAO. Cumulatively, our results show that the cannabinoid agonist WIN protects against neonatal focal stroke in part due to inhibitory effects on microglia.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Foram analisados retrospectivamente os prontuários de 87 pacientes portadores de hérnia inguinais recidivadas, operados no Hospital das Clínicas da Faculdade de Medicina da Universidade de Säo Paulo, em período recente de seis anos. Confirmando a experiência de outros autores, estas recidivas säo mais freqüentes e em proporçöes quese idênticas sob forma direta (43,5%) ou indireta (50%), ocorrendo mais raramente sob forma mista (3,9%) ou crural (2,6%). Discutem os fatores etiopatogênicos locais e sistêmicos, dentre estes aparecendo os esforços físicos acentuados no período pós-operatório precoce como os mais freqüentes assinalados (43,1%. Mais da metade destas recidivas (48/85) ocorreram até o primeiro ano de evoluçäo, podendo também se manifestar após períodos mais longos (30,6%) acima de três anos). As técnicas de reparaçäo mais empregadas foram as de Bassini modificada (sutura do arco do transverso ao ligamento inguinal) e a de Lotheissen-MacCay, respectivamente em 46,1 e 42,5 por cento dos casos. Em 9/85 casos foi suficiente o angustiamento do ânulo inguinal profundo. A análise de incucesso cirúrgico com aparecimento de novas recidivas é prejudicado pelo seguimento difícil e precário dests pacientes. O índice de recidivas aumenta progressivamente com o número de reoperaçöes. Das oito recidivas referidas pelos autores, seis ocorreram nos primeiros seis meses

Asunto(s)

Asunto(s)

Asunto(s)