Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence

Background: Oral Squamous Cell Carcinoma (OSCC) is a major cause of cancer death worldwide, which is mainly due to recurrence leading to treatment failure and patient death. Histological status of surgical margins is a currently available assessment for recurrence risk in OSCC; however histological status does not predict recurrence, even in patients with histologically negative margins. Therefore, molecular analysis of histologically normal resection margins and the corresponding OSCC may aid in identifying a gene signature predictive of recurrence.Methods: We used a meta-analysis of 199 samples (OSCCs and normal oral tissues) from five public microarray datasets, in addition to our microarray analysis of 96 OSCCs and histologically normal margins from 24 patients, to train a gene signature for recurrence. Validation was performed by quantitative real-time PCR using 136 samples from an independent cohort of 30 patients.Results: We identified 138 significantly over-expressed genes (> 2-fold, false discovery rate of 0.01) in OSCC. By penalized likelihood Cox regression, we identified a 4-gene signature with prognostic value for recurrence in our training set. This signature comprised the invasion-related genes MMP1, COL4A1, P4HA2, and THBS2. Overexpression of this 4-gene signature in histologically normal margins was associated with recurrence in our training cohort (p = 0.0003, logrank test) and in our independent validation cohort (p = 0.04, HR = 6.8, logrank test).Conclusion: Gene expression alterations occur in histologically normal margins in OSCC. Over-expression of the 4-gene signature in histologically normal surgical margins was validated and highly predictive of recurrence in an independent patient cohort. Our findings may be applied to develop a molecular test, which would be clinically useful to help predict which patients are at a higher risk of local recurrence.

Red Blood Cell Transfusions are Independently Associated with Intra-Hospital Mortality in Very Low Birth Weight Preterm Infants

Objective To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality.Study design Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions.Results of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 +/- 3.4, with 2.1 +/- 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions.Conclusion Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion. (J Pediatr 2011; 159: 371-6).

Some predictors of cardiovascular mortality among the elderly population of Botucatu (SP)

OBJECTIVE: To detect factors associated with cardiovascular mortality in the elderly of Botucatu. METHODS: We evaluated 29 variables of interest in a cohort of patients aged ³60 using data from a survey conducted between 1983/84. The elderly cohort was analyzed in 1992 to detect the occurrence of cardiovascular deaths. Survival analysis was performed using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. Three models were adapted for each group of variables, and a final model was chosen from those variables selected from each group. RESULTS: We identified predictor for cardiovascular death according to age for elderly males not supporting the family, not possessing a vehicle, and previous cardiovascular disease. In elderly females, the predictor variables were previous cardiovascular disease and diabetes mellitus. CONCLUSION: Socioeconomic indicators (family heading and vehicle ownerrship) may be added to well stabilished medical factors (diabete mellitus and hypertension to select target groups for programs intended to reduce deaths due to cardiovascular diseases in elderly people.

Incidence of self-reported hearing loss and associated risk factors among the elderly in São Paulo, Brazil: the SABE survey

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Profile of cardiovascular risk factors and mortality in patients with symptomatic peripheral arterial disease

Introduction: The present study examines cardiovascular risk factor profiles and 24-month mortality in patients with symptomatic peripheral arterial disease. Design Study: Prospective observational study including 75 consecutive patients with PAD (67 ± 9.7 years of age; 52 men and 23 women) hospitalized for planned peripheral vascular reconstruction. Doppler echocardiograms were performed before surgery in 54 cases. Univariate analyses were performed using Student's t-test or Fisher's exact test. Survival analysis at 24-month follow-up was performed using the Cox regression model and Kaplan-Meier method including age and chronic use of aspirin as covariates. Survival curves were compared using the log-rank test. Results: Hypertension and smoking were the most frequent risk factors (52 cases and 51 cases, respectively), followed by diabetes (32 cases). Undertreated dyslipidemia was found in 26 cases. Fasting glycine levels (131 ± 69.1 mg/dl) were elevated in 29 cases. Myocardial hypertrophy was found in 18 out of 54 patients. Thirty-four patients had been treated with aspirin. Overall mortality over 24 months was 24% and was associated with age (HR: 0.064; CI95: 0.014-0.115; p=0.013) and lack of use of aspirin, as no deaths occurred among those using this drug (p<0.001). No association was found between cardiovascular death (11 cases) and the other risk factors. Conclusion: There is a high prevalence of uncontrolled (treated or untreated) cardiovascular risk factors in patients undergoing planned peripheral vascular reconstruction, and chronic use of aspirin is associated with reduced all-cause mortality in these patients.

Could albumin level explain the higher mortality in hemodialysis patients with pulmonary hypertension?

Background: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of thisstudy was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and toverify whether these factors might explain the highest mortality among them.Methods: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to theresults of echocardiography examination, patients were allocated in two groups: those with PH and those withoutPH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were comparedbetween the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed andhazard risk to death was evaluated by Cox regression analysis.Results: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellularwater, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular waterwas associated with PH (relative risk = 1.194; 95% CI of 1.006 1.416; p = 0.042); nevertheless, in a multiple model,only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 1.359;p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age;95% CI of 1.000 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis.However, when albumin was taken in account the only statistically significant association was between albuminlevel and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 0.984; p = 0.047) while the presence of PH lost itsstatistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had astatistically worse survival after the sixth year of follow up.Conclusions: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on itspathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain thisassociation.© 2012 Greenfield et al.; licensee BioMed Central Ltd.

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

Background: Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers. Methods: A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry. Results: IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years. Conclusions: The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients. Trial registration: No.:NCT00605540. © 2013 Ferrari et al; licensee BioMed Central Ltd.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.

Evolução dos marcadores diagnósticos e prognósticos de pacientes com DPOC no período de três anos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evolução da interleucina 6 e da proteína C-Reativa em pacientes com DPOC no período de três anos

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Impacto do acompanhamento com bioimpedância na predição de eventos cardiovasculares em pacientes em diálise crônica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Deficiência auditiva referida por idosos do município de São Paulo (Estudo SABE): prevalência, incidência e fatores associados. -

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparison between Itraconazole and Cotrimoxazole in the Treatment of Paracoccidiodomycosis

BackgroundThere are no published reports on studies comparing itraconazole (ITC), sulfamethoxazole-trimethoprim (cotrimoxazole, CMX), and ITC followed by CMX (ITC/CMX) in the treatment of paracoccidiodomycosis. This study aimed to compare the efficacy, effectiveness, safety and time to clinical and serologic cure in paracoccidioidomycosis patients treated with ITC or CMX, the antifungal agents most widely used.MethodologyA quasi-experimental study was performed in 177 patients with a confirmed or probable diagnosis of paracoccidioidomycosis. Treatment was divided into two stages: 1) initial, which was continued until clinical cure was achieved and the erythrocyte sedimentation rate decreased to normal values; 2) complementary, which was continued until serologic cure was achieved. Medians were compared via the Mann-Whitney test, and frequencies were compared via the chi-squared test. The assessment of variables as a function of time was performed using Kaplan-Meier curves and Cox regression. The significance level was established as p <= 0.05.Principal FindingsNo difference was found in the efficacy and effectiveness of the initial treatment of 47 individuals given ITC and 130 individuals given CMX; however, the time to clinical cure was shorter in the former compared with the latter group (105 vs. 159 days; p = 0.001), specifically in patients with the chronic form. Efficacy and effectiveness of the three regimens were similar in the complementary treatment; however, the time to serologic cure was shorter when ITC (161 days) or CMX (495 days) was used compared with ITC/CMX (881 days) [p = 0.02]. The independent predictors of a shorter time to serologic cure were treatment with ITC [risk ratio = 6.61 (2.01-21.75)] or with CMX [risk ratio = 5.11 (1.91-13.67)]). The prevalence of side effects was lower with ITC (6.4%) than with CMX (20.0%; p = 0.03).ConclusionsSince ITC induced earlier clinical cure and was better tolerated than CMX, such triazole should be considered the first-choice for PCM treatment.

Associação entre a concentração de selênio, o polimorfismo Pro198Leu da glutationa peroxidase 1 e a mortalidade em pacientes com choque séptico

Pós-graduação em Fisiopatologia em Clínica Médica - FMB