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Overall survival (OS) varies widely in patients with stage IV non-small cell lung cancer (NSCLC). Strong prognostic factors are still needed to improve decision-making regarding standard treatment options, to stratify patients for inclusion in innovative therapeutic trials and to identify patients who would be best treated with palliative care rather than with systemic chemotherapy. Mid-arm muscle circumference (MAMC) is a bedside anthropometric measurement that estimates somatic protein reserve, an early indicator of nutritional depletion. This measurement is simple, non-invasive, objective and inexpensive to perform. We evaluated MAMC as a potential prognostic factor in patients with stage IV NSCLC. A total of 56 non-selected consecutive patients with stage IV NSCLC were evaluated. The MAMC measurement results for these patients were expressed as a percentage of the expected reference values, adjusted for gender and age. Patients were categorized as normal (MAMC ≥90%) or depleted (MAMC <90%). The mean age of patients was 63 years (range 47-80), and the mean MAMC was 89 (range 66-122), with 55% of patients classified as depleted. The median OS was 6.2 months (95% CI, 5.1-7.3). In the subgroup with normal MAMC, the median OS was 10.2 months (95% CI, 9.2-11.1). In patients classified as depleted, the median OS was 5.0 months (95% CI, 4.2-5.8). The difference in OS between these two subgroups was highly significant (p<0.001 by the log-rank test; HR=0.21; 95% CI, 0.09-0.5 for patients with normal MAMC). In a multivariate analysis with Karnofsky status, age and gender as covariates, the difference in OS between the MAMC groups remained statistically significant (p<0.001, according to the Cox proportional hazards model). MAMC is a strong independent prognostic factor in stage IV NSCLC patients. Patients with MAMC <90% of the expected value had poor OS.
RESUMO
PURPOSE: Cofilin is a cytoskeletal protein whose overexpression has been associated with aggressiveness in several types of malignancies. Here, we established and optimized a simple semi-quantitative immunohistochemistry (SQ-IHC) method for cofilin quantification in tumor biopsies, and applied it in a retrospective cohort of NSCLC patients aiming at validating the use of cofilin-1 as a prognostic biomarker. METHODS: The SQ-IHC method for cofilin-1 quantification was established and applied in a NSCLC cohort. An archival collection of biopsies from 50 patients with clinicopathological information and 5 years follow-up was accessed. Association between cofilin-1 immunocontent and clinical outcome was assessed using standard Kaplan-Meier mortality curves and the log-rank test. To evaluate the robustness of our findings, three different partitional clustering strategies were used to stratify patients into two groups according to the biomarker expression level (hierarchical clustering, Kmeans and median cutoff). RESULTS: In all the three different partitional clustering we used, survival analysis showed that patient with high cofilin-1 immunocontent had a lower overall survival rate (P < 0.05), and could be used to discriminate between good and bad prognosis. No other correlation was found when the variables age, sex or histological type were tested in association with patients outcome or with cofilin immunocontent. CONCLUSIONS: Our method showed good sensitivity/specificity to indicate the outcome of patients according to their cofilin immunocontent in biological samples. Its application in a retrospective cohort and the results presented here are an important step toward the validation process of cofilin-1 as a prognostic biomarker.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Cofilina 1/fisiologia , Neoplasias Pulmonares/diagnóstico , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cofilina 1/análise , Cofilina 1/metabolismo , Estudos de Coortes , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
BACKGROUND: One of the reasons why jejunoileal bypass (JIB) was abandoned were reports of liver failure. The aim of this study was to describe histological findings in the intraoperative and follow-up liver biopsies of a cohort of super-obese patients who had undergone JIB. METHODS: 50 consecutive patients underwent JIB. Samples of liver biopsies performed intraoperatively (41 patients) and in the follow-up (31 patients) were evaluated. Brunt's scale was used. RESULTS: Mean age at operation was 37.9 +/- 7.6 years, and 15 patients (30.6%) had diabetes type 2, 20 (40.8%) had dyslipidemia, 29 (59.2%) had high blood pressure, and one (0.5%) had hepatitis C. Mean BMI preoperatively was 52.8 +/- 7.5 kg/m(2). Mean follow-up time was 67.0 +/- 42.8 months. At the time of the latest liver biopsy, the mean BMI was 35.7 +/- 7.5 kg/m(2). The % excess weight loss (%EWL) was 62.4 +/- 20.0%. 8 deaths (16%) have occurred, none from liver-related complications. At liver biopsy during the JIB operation, NAFLD was confirmed in 36 patients (86.7%) and NASH in 13 (31.7%). In 25 patients with mean follow-up of 4.8 +/- 4.0 years, there was no statistically significant change in the liver histology regarding the extent of steatosis (P=0.20), steatohepatitis (P=0.74) and fibrosis (P=0.71). CONCLUSIONS: There was a significant metabolic improvement, maintenance of the %EWL, and no worsening of liver histology. There has possibly been a publication bias concerning liver outcomes, where the type of JIB and the concomitance of hepatitis C were not taken into account.
Assuntos
Derivação Jejunoileal , Fígado/patologia , Obesidade Mórbida/cirurgia , Adulto , Índice de Massa Corporal , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
Os autores relatam o caso de recém-nascido do sexo feminino com crises convulsivas e lesöes vesiculosas no nariz e lábio inferior, desde o quinto dia de vida. O exame do LCR mostrou alteraçöes compatíveis a encefalite. Houve deterioraçäo do quadro neurológico e respiratório, com morte da paciente. A autópsia paracial do crânio revelou cérebro edemaciado com área necro-hemorrágica envolvendo ambos os lobos temporais. O exame histopatológico revelou encefalite necro-hemorrágica, sem a presença de inclusöes intranucleares. O exame imuno-histoquímico, realizado pela técnica da avidina-biotina-peroxidase utilizando anticorpos policlonais contra vírus Herpes simplex tipo 1 e tipo 2, mostrou-se positivo em numerosas células neuronais, astrocíticas e, principalmente, oligodendrogliais para o anticorpo contra o vírus Herpes simples tipo 2