Search

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumor-initiating cells in stage I and II breast cancer. [ABSTRACT FROM AUTHOR]

Objective: Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario., Methods: This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period., Results: We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52)., Conclusion: Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario., Competing Interests: Conflicts to interest: none to declare.

Objectives: The COVID-19 pandemic has had a significant global impact since its declaration in March 2020. The COVID-19 pandemic has disproportionately impacted cancer patients, particularly those with breast cancer. This study aims to analyze the effects of the pandemic on women diagnosed with breast cancer recurrence., Methods: A cohort study was conducted at a tertiary public hospital in São Paulo State, Brazil. Data were collected from electronic records. Patients diagnosed with breast cancer and experiencing recurrence between January 2011 and March 2022 were included. Survival analysis was performed using the Kaplan-Meier estimator and Cox regression., Results: The study included 187 patients, 45 in the pandemic group (recurrence after March 23, 2020) and 142 in the pre-pandemic group. Distant recurrences were more frequent in both groups (pre-pandemic: 62.7 %, pandemic: 75.5 %). Compared to the pre-pandemic group (1.8 years), the pandemic group experienced a longer mean time to recurrence detection (2.9 years) and significantly decreased median survival (9 months vs. 22 months). The Cox regression analysis confirmed an increased risk of death for women diagnosed with breast cancer recurrence during the pandemic period (HR = 1.92, 95 % CI 1.19‒3.12)., Conclusion: The present study is among the first to investigate the pandemic's specific effects on breast cancer recurrence, revealing concerning delays in detection and a decrease in survival rates. Prompt diagnosis, timely treatment initiation, and comprehensive support are crucial during public health crises. These findings urge healthcare systems to prioritize tailored care for breast cancer patients during pandemics., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUC inf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUC inf , maximum plasma concentration (C max ), and time to C max . Postmenopausal patients showed a significant increase in C max (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUC inf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher C max values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The identification of filamentous fungi through culture characterization may be hampered by phenotypic variability. Information obtained from the identification of microorganisms are important for investigation of sources of contamination of a product or process. The aim of this study was to identify filamentous fungal strains (n = 50) isolated from a pharmaceutical facility by using Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), as well as D2 domain of the large-subunit (LSU) ribosomal RNA gene and internal transcribed spacer regions (ITS) sequencing. MALDI-TOF MS system only identified five strains at the species level, while 45 were not identified. The analysis through GenBank allowed the identification of up to 19 strains at the species level, while MycoBank allowed the identification of up to nine strains at the species level. The databases identified up to 11 genera: Penicillium, Aspergillus, Cladosporium, Chaetomium, Coniochaeta, Curvularia, Diaporthe, Fusarium, Trichoderma, Rhizopus and Microdochium. MALDI-TOF MS showed an insufficient database to identify the species of fungi. DNA sequencing was the best methodology to identify to the genus level but was unable to differentiate between closely related species. Therefore further methods for the identification of filamentous fungi from pharmaceutical areas at species level need to be developed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Health literacy (HL) refers to knowledge, motivation and skills to understand, evaluate and apply health information, enabling appropriate decision making in daily life on health care and health promotion. Studies show that HL is associated with several social determinants, health outcomes, and health promotion. In Brazil, studies on the thematic are still scarce. Thus, the present study aimed to adapt, seek evidence of validity, reliability and estimate the parameters of the items of the European Health Literacy Survey Questionnaire Short Form (HLS-Q12) for the Brazilian context. 770 individuals participated, recruited through advertisements in the media and social networks, 82.1% female, aged between 18 and 83 (M = 35.5, SD = 13.52), from 21 Federative Units of Brazil and the Federal District. The subjects answered the HLS-Q12 and a sociodemographic questionnaire. Exploratory factor analysis indicated a unifactorial structure with good psychometric characteristics (GFI = 0.98; CFI = 0.98; RMSEA = 0.08; RMSR = 0.07). Cronbach's alpha, Guttman's lambda 2 and McDonald's omega reliability indicators were equal to 0.87. We conclude that the HLS-Q12 is an adequate instrument to assess the level of HL in the Brazilian population., (© 2023. Graduate Program in Psychology (Federal University of Rio Grande do Sul, Porto Alegre).)

The pharmaceutical industry must comply with the requirements for good manufacturing practices to reduce inherent contamination risks in the production process. Bacillus and related genera are among the main bacterial isolated from clean areas, raw material, and products in the pharmaceutical industries, but the correct identification of these species is still a challenge. The aim of this study was to characterize by phenotyping, protein profiling, and 16S rRNA gene sequencing Sutcliffiellahorikoshii strains (n = 6) isolated from an immunobiological pharmaceutical facility, and to propose the reclassification of Bacillus tianshenii to the genus Sutcliffiella, and Sutcliffiella tianshenii sp. nov. The strains were characterized by VITEK®2, matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) using VITEK®MS, and 16S rRNA gene sequencing analysis. MALDI-TOF/MS did not identify any strains that were identified by 16S rRNA as S. horikoshii. VITEK®2 showed false-positive results, with misidentification as B. sporothermodurans (reclassified as Heyndrickxia sporothermodurans) and Geobacillus thermoleovorans. After MALDI-TOF/MS database expansion, with the creation of SuperSpectrum, the strains were correctly identified as S. horikoshii. This study is the first report of isolation of S. horikoshii strains from a pharmaceutical industry. More studies are necessary to better understand the ability of S. horikoshii to contaminate the environment and products., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Mammographic screening has been used to reduce breast cancer mortality worldwide and remains the main modality for the early detection of this disease. Women from low- and middle-income countries still lack access to periodic mammograms and efficient health care. This cross-sectional study aimed to explore opportunistic mammographic coverage in Brazil, while considering the privately insured population and its association with early breast cancer (EBC) detection., Methods: Data on population, gross domestic product (GDP), number of mammograms performed under the Sistema Único de Saúde (SUS) public health system or private system, and women diagnosed with early-stage breast cancer from 2010 to 2019 were retrieved from publicly available databases., Results: A total of 39 555 636 mammograms with an average of 3 955 564 ± 395 704 mammograms were obtained per year from 2010 to 2019 in Brazil. Most examinations (58.6%) were performed in the target population (50-69 years old), while 32% were performed in women aged 40-49, and 9.4% were performed in women <40 years or >70 years of age. The 10-year mammogram coverage was 30.6% in the target population and 24.8% in the population aged 40-49 years, with significant variation across states and municipalities. The overall EBC detection rates in Brazil were 30.6% in populations aged 50-70 and 24.8% in those aged 40-50 years. We observed a positive correlation between coverage and EBC detection rate (r = 0.68; P = 0.0001 (50-70 years) and r = 0.75; P < 0.0001 (40-50 years)). According to the GDP, the municipalities with higher GDP per capita had higher mammogram coverage (P < 0.0001)., Conclusions: The coverage of mammographic screening for women under the SUS is far below the international guidelines. Additionally, a significant number of mammograms have been performed in non-target populations. This scenario reflects the problematic screening programs in developing countries and reflects low rates of EBC diagnosis. As Brazil is a continental country with heterogeneous socioeconomic indicators, we observed significant variations in the number of mammograms performed by age groups when separated by states and municipalities. Even when considering supplemental health system coverage, municipalities with higher GDP per capita were associated with higher mammogram coverage., Competing Interests: Disclosure of interest: The authors have completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: Axillary lymph node involvement is one important prognostic factor in breast cancer, but the way to access this information has been modified over the years. This study evaluated if axillary ultrasound (US) coupled with fine-needle aspiration cytology (FNAC) can accurately predict clinically relevant node metastasis in patients with breast cancer, and thus assist clinical decisions METHODS: This is a cross-sectional study with retrospective data collection of 241 individuals (239 women and 2 men) with unilateral operable breast cancer who were submitted to preoperative axillary assessment by physical exam, US and FNAC if suspicious nodes by imaging. We calculated sensitivity, specificity, and accuracy of the methods. We compared the patient's characteristics using chi-square test, parametrics and non-parametrics statistics according to the variable., Results: The most sensible method was US (0.59; 95% CI, 0.50-0.69), and the most specific was US coupled with FNAC (0.97; 95% CI, 0.92-0.99). Only 2.7% of the patients with normal axillary US had more than 2 metastatic nodes in the axillary lymph node dissection, against 50% of the patients with suspicious lymph nodes in the US and positive FNAC., Conclusions: Axillary US coupled with FNAC can sort patients who have a few metastatic nodes at most from those with heavy axillary burden and could be one more tool to initially evaluate patients and define treatment strategies., (© 2021. The Author(s).)

Background: The Kessler Distress Scale (K10) is a self-report scale for the assessment of non-specific psychological distress in the general and clinical population. Because of its ease of application and good psychometric properties, the K10 has been adapted to several cultures. The present study seeks to adapt the K10 to Brazilian Portuguese and estimate its validity evidence and reliability., Methods: A total of 1914 individuals from the general population participated in the study (age = 34.88, SD = 13.61, 77.7% female). The adjustment indices were compared among three different measurement models proposed for the K10 through confirmatory factor analysis (CFA). The items' properties were analyzed by Andrich's Rating Scale Model (RSM). Furthermore, evidence based on relations to other variables (depression, stress, anxiety, positive and negative affects, and satisfaction with life) was estimated., Results: CFA indicated the adequacy of the bifactor model (CFI= 0.985; TLI= 0.973; SMR= 0.019; RMSEA= 0.050), composed of two specific factors (depression and anxiety) and one general factor (psychological distress), corresponding to the theoretical hypothesis. Additionally, it was observed multiple-group invariance by gender and age range. The RSM provided an understanding of the organization of the continuum represented by the psychological distress construct (items difficulty), which varied from -0.89 to 1.00; good adjustment indexes; infit between 0.67 and 1.32; outfit between 0.68 and 1.34; and desirable reliability, α= 0.87. Lastly, theoretically coherent associations with the external variables were observed., Conclusions: It is concluded that the Brazilian version of the K10 is a suitable measure of psychological distress for the Brazilian population., (© 2021. The Author(s).)

The experience of the pandemic caused by the Coronavirus and the consequent disease triggered by it (COVID-19) brought to light fragilities that have been long overlooked by the scientific community and by various political and social institutions. The pandemic also brought to the fore certain social practices resulting from individual behaviors, such as wearing a mask and practicing social isolation. It demonstrated the need for social commitment and pro-social behaviors if societies are to respond successfully. The purpose of this article is to evaluate psychological and sociodemographic characteristics associated with compliance or noncompliance of individuals with these practices in two different phases of the pandemic experience in Brazil: in the first month and after three months. Participants for the first phase of the study were recruited through advertisements in the media and social networks. 1,914 individuals aged between 14 and 81 years agreed to participate, 78.2% of these were women, from 25 Federative Units in Brazil. In the second phase, 761 individuals who participated in the first phase, were reassessed. The authors used the following instruments for data collection: a standardized questionnaire collecting information of sociodemographic characteristics and dynamics of social isolation; the Kessler Psychological Distress Scale; the Life Satisfaction Scale; the Positive and Negative Affections Scale; and the Reduced Personality Markers and Stress Mindset Scale. All instruments used presented evidence of validity and adequate reliability indexes. The comparison of categorical exploratory variables with motives for following social isolation protocols was performed using Pearson's Chi-square, and the comparison of continuous exploratory variables was performed using the Mann-Whitney test. Covariance Analysis was performed using as covariates those that showed significance/effect on isolation in previous analyses. The results showed that respondents practicing social isolation to comply with governmental recommendations had lower scores on the scales of neuroticism and conscientiousness. They reported also less stress, anxiety, and depression, and less general distress. Overall, these respondents also displayed more positive affect, and tended to reframe stress in a more positive way than others. These preliminary results describe the psychological characteristics of individuals and their associations with social behaviors in a period of collective stress and high social risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zanini, Peixoto, Andrade and Tramonte.)

Purpose: Breast cancer screening is not recommended for young women (< 40 years old); therefore, those diagnosed are more likely to have advanced and metastatic disease, reducing treatment outcomes. This study aimed to investigate breast cancer epidemiology among young women in Brazil., Methods: Data from three publicly available databases and a cohort from a university hospital in Brazil were analyzed in a retrospective study. Descriptive statistics was performed on disease prevalence and stage distribution across age groups. Incidence was estimated using age-standardized incidence ratio. The impact of age in disease-specific survival was also analyzed., Results: Invasive breast cancer prevalence data by age group revealed that 4.4% and 20.6% of patients were < 35 and < 45 years old, respectively. In the United States, this prevalence was 1.85% and 11.5%, respectively (odds ratio [OR], 2.2; P < .0001). The percentage of regional and metastatic diseases were higher in São Paulo State (Fundação Oncocentro de São Paulo [FOSP]) compared with the United States (45% and 9.8% v 29% and 5.7%, respectively; P < .0001). In FOSP, regional and metastatic disease prevalence were higher among young patients (53.5% and 11.3%, respectively). The median tumor size in patients < 40 years old was higher (25.0 mm × 20.9 mm; P < .0001), and young patients have higher risk to be diagnosed with positive lymph nodes (OR, 1.5; P = .004) and higher proportion of luminal-B and triple-negative (TNBC) tumors. Young patients have a poor disease-specific survival because of late-stage diagnosis and more aggressive breast cancer subtypes (human epidermal growth factor receptor 2-enriched and TNBC) ( P < .0001)., Conclusion: In Brazil, breast cancer prevalence among young patients and late-stage incidence during this age span is higher. Advanced disease and more aggressive subtypes lead to a significant impact on breast cancer-specific survival in young patients.

Background and Objectives: The management of ovarian cancer requires complex surgical and medical interventions. Specialized care is associated with superior outcomes in early and advanced stages. This study aimed to estimate the effect of hospital characteristics on the overall survival of women with epithelial ovarian cancer., Methods: We established a cohort with data recorded by the Fundação Oncocentro de São Paulo cancer registry. We included 6111 women treated for ovarian cancer in the state of Sao Paulo from January 2000 to December 2018. From 76 hospitals analyzed, 7 were high volume (20 or more cases a year) and 69 low volume. Twenty-nine were teaching and 47 community hospitals. A 10-year survival was analyzed using the Kaplan-Meyer estimator and the Cox model., Results: Fifty-two percent of the epithelial ovarian cancer patients were treated in high-volume hospitals. High-volume - (HR, 0.86; 95% CI, 0.8-0.92; P < .001) and teaching - (HR, 0.91; 95% CI, 0.85-0.99; P = .019) were hospital characteristics associated with low risk of death in 10 years., Conclusions: High-volume and teaching hospitals are associated with better overall survival in ovarian cancer. Our data suggest that both hospital characteristics are important indicators of good quality of care in ovarian cancer treatment., (© 2020 Wiley Periodicals LLC.)

Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study., Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests., Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016)., Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

Doxorubicin (DOX) is a cytotoxic drug which has remained as an essential component of chemotherapy regiment for breast cancer. The cardiotoxicity of DOX is related to the accumulation of its main metabolite doxorubicinol (DOXOL) in the cardiac tissue. Although the pharmacokinetics of DOX shows high interindividual variability, there are no significant covariates to improve dose adjustment. The present study reports the pharmacokinetics of both DOX and DOXOL in a homogeneous population of young female patients with breast cancer (n = 12) making use of a standardized drug association, evaluated in the very first chemotherapy cycle, using plasma and urine data that allowed the calculation of the renal clearance of DOX, the formation clearance of DOXOL and the hepatic clearance of DOX. The extensive data availability also made it possible to estimate the hepatic extraction ratio of DOX for the investigated population, as well as to determine DOXOL unbound fraction in plasma for the first time in humans. DOX and DOXOL simultaneous analysis in plasma, plasma ultrafiltrate, and urine were performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The pharmacokinetics profile of both DOX and DOXOL showed high variability (geometric coefficient of variation of area under the plasma concentration versus time curve extrapolated to infinity was approximately 215 %). The geometrics means were 0.26 for DOXOL/DOX AUC ratio, 15 % and 17 % for unbound fractions of DOX and DOXOL, respectively, 30.70 L⋅h -1 for total clearance, 0.66 L⋅h -1 for renal clearance, 29.97 L⋅h -1 for hepatic clearance and 0.39 L⋅h -1 for the formation clearance of the metabolite DOXOL. The 95 % confidence interval of the estimated hepatic extraction ratio of DOX ranged from 0.14 to 0.79, which characterizes DOX as a drug of low, intermediate or high hepatic extraction ratio., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Tamoxifen is considered a prodrug of its active metabolite endoxifen, which is dependent on the CYP2D6 and CYP3A enzymes. Tamoxifen pharmacokinetic variability influences endoxifen exposure and, consequently, its clinical outcome. This study investigated the impact of hormonal status on the pharmacokinetics of tamoxifen and its metabolites in TAM-treated breast cancer patients., Methods: TAM-treated breast cancer patients (n = 40) previously believed to have CYP3A activity within the normal range based on oral midazolam and phenotyped as CYP2D6 normal metabolizers using oral metoprolol were divided into two groups according to premenopausal (n = 20; aged 35-50 years) or postmenopausal (n = 20; aged 60-79 years) status. All patients were treated with 20 mg/day tamoxifen for at least three months. Serial plasma samples were collected within the 24 h dose interval for analysis of unchanged tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen quantified by LC-MS/MS. CYP activities were assessed using midazolam apparent clearance (CYP3A) and the metoprolol/alfa-hydroxymetoprolol plasma metabolic ratio (CYP2D6). CYP3A4, CYP3A5 and CYP2D6 SNPs and copy number variation were investigated using TaqMan assays., Results: Postmenopausal status increased steady-state plasma concentrations (Css) of tamoxifen (116.95 vs 201.23 ng/mL), endoxifen (8.01 vs 18.87 ng/mL), N-desmethyltamoxifen (485.16 vs 843.88 ng/mL) and 4-hydroxytamoxifen (2.67 vs 4.11 ng/mL). The final regression models included hormonal status as the only predictor for Css of tamoxifen [β-coef ± SE, p-value (75.03 ± 17.71, p = 0.0001)] and 4-hydroxytamoxifen (1.7822 ± 0.4385, p = 0.0002), while endoxifen Css included hormonal status (8.578 ± 3.402, p = 0.02) and race (11.945 ± 2.836, p = 0.007). For N-desmethyltamoxifen Css, the final model was correlated with hormonal status (286.259 ± 76.766, p = 0.0007) and weight (- 8.585 ± 3.060, p = 0.008)., Conclusion: The premenopausal status was associated with decreased endoxifen plasma concentrations by 135% compared to postmenopausal status. Thus, the endoxifen plasma concentrations should be monitored mainly in the premenopausal period to maintain plasma levels above the efficacy threshold value., Trial Registration: RBR-7tqc7k.

Objective:  The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs)., Methods:  We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B ( n  = 39), HER2 enriched ( n  = 25), and triple-negative (TNBC) ( n  = 23), based on the IHC expression., Results:  We have observed that luminal A and B tumors lack the VIM + /CDH1 -/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors ( p  = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM + /CDH1 -/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) ( p  = 0.02). The median Ki67 index in the VIM + /CDH1 -/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors ( p  = 0.0007). The presence of lymph node metastasis was less frequent in patients with VIM + /CDH1 -/low tumors (23% versus 61%; X2 test; p  = 0.01)., Conclusion:  Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index., Competing Interests: The authors have no conflicts of interest to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition., (© 2018 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Objective: Recently it has been demonstrated that constitutively activated signal transducer and activator of transcription 1 (STAT1) gene expression may act as a biomarker of ovarian cancer chemotherapy response. In this study, our objective was to validate the use of STAT1 immunohistochemistry as a prognostic biomarker for disease outcome using a cohort derived from Latin America., Methods: We evaluated a cohort of Brazilian high-grade serous ovarian cancer, comprising 65 patients with outcome data covering more than 5 years to determine the prognostic and predictive value of STAT1 expression levels. High-grade serous ovarian cancer tumors were used to construct a tissue microarray. Exploratory analyses were conducted on clinical, histopathological, and STAT1 expression data that included descriptive statistics and Pearson correlative analyses. Survival curves for disease-free survival and overall survival were obtained by the Kaplan-Meier method, and the significance of homogeneity between the classes was assessed by log-rank statistics (Mantel-Cox)., Results: High expression of STAT1 in tumors was significantly associated with improved disease-free survival (P = 0.0256) and overall survival (P = 0.0193). Proportional hazards regression analysis showed STAT1 expression had an independent effect on both disease-free survival (P = 0.0358) and overall survival (P = 0.0469)., Conclusions: These findings from a Brazilian cohort of patients with ovarian cancer reinforce the association of high STAT1 expression with better response to chemotherapy, providing additional validation of this protein as both a prognostic and predictive biomarker. Collectively, these results together with other recently published studies increase the feasibility of using the STAT1 pathway for the development of novel immunomodulator drugs that could enhance response to treatment.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival., Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong)., Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively)., Conclusion: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Subcutaneous (SC) trastuzumab has long been approved as a cancer treatment for early and advanced HER2-positive (HER2+) breast cancer by both the European Medicines Agency (EMA) and Agência Nacional de Vigilância Sanitária (ANVISA), the Brazilian National Health Surveillance Agency. A pivotal non-inferiority phase III trial, which aimed to provide a more convenient and cost-effective treatment in the HER2+ breast cancer neoadjuvant setting, showed that the SC group met prespecified efficacy endpoints and the SC formulation was considered as safe as the intravenous (IV) formulation. Considering the recent approval of several biosimilars, new SC formulations are also an interesting manufacturer strategy as these drugs can obtain patent protection. Despite being considered non-inferior to the IV formulation of trastuzumab, in clinical development, the SC formulation elicited higher immunogenicity, mainly related to overall anti-drug antibodies (ADAs); however, this finding was classified as clinically non-significant. In this article, we explore different aspects of the benefits and risks of the SC trastuzumab formulation according to published data., Competing Interests: Franklin Fernandes Pimentel has participated in a consulting or advisory role for Libbs Farmacêutica and has received speaker honorarium from AstraZeneca and Libbs Farmacêutica. Gilberto Morgan, Daniel Guimarães Tiezzi, and Jurandyr Moreira de Andrade declare that they have no conflicts of interest that might to be relevant to the contents of this manuscript.

Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors., Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer., Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years., Exposures: Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines., Main Outcomes and Measures: Overall survival time., Results: The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form., Conclusions and Relevance: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

Type 2 diabetes mellitus currently ranks high among indicators used in Global Burden of Disease Studies. The current study estimated the burden of disease attributable to type 2 diabetes mellitus and its chronic complications in Brazil, 2008. We calculated disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) stratified by gender, age bracket, and major geographic region. Type 2 diabetes mellitus accounted for 5% of the burden of disease in Brazil, ranking 3rd in women and 6th in men in the composition of DALYs. The largest share of DALYs was concentrated in the 30-59-year age bracket and consisted mainly of YLDs. The highest YLL and YLD rates were in the Northeast and South of Brazil, respectively. Chronic complications represented 80% of YLDs from type 2 diabetes mellitus. Type 2 diabetes mellitus ranked as a leading health problem in Brazil in 2008, accounting for relevant shares of mortality and morbidity.

Background: The diagnosis and treatment of breast cancer may negatively affect the quality of life (QOL) of women., Objectives: The aim of this study is to assess QOL in women with breast cancer who were treated with or without chemotherapy and to identify factors associated with improved or worsening QOL in these women., Methods: This cross-sectional study enrolled 112 women who were treated with chemotherapy (CTX group, with 85 [75.9%] women) or without chemotherapy (non-CTX group, with 27 [24.1%] women) for breast cancer. The Short-Form Health Survey (SF-36) assessed QOL and the Hospital Anxiety and Depression scale assessed anxiety and depression., Results: The overall mean SF-36 score was below 50 in all domains. Relative to CTX women, non-CTX women were significantly older (P = .001) and more likely to engage in physical exercise (P = .002). The non-CTX group had higher scores in the Physical Functioning (P = .001) and Role-Physical (P = .0009) domains of the SF-36 relative to the CTX group, and the fluoruracil + epirubicin + cyclophosphamide group had significantly lower scores in the SF-36 domains Physical Functioning (P = .009) and Role-Physical (P = .02)., Conclusion: Chemotherapy treatment for breast cancer worsens QOL in the Physical Functioning and the Role-Physical domains of the SF-36 relative to women treated without chemotherapy., Implications for Practice: Nurses should assess Physical Functioning and the Role-Physical before treatment, as a woman who was not physically active before breast cancer is not likely to become physically active after treatment. Establishing support groups and providing educational sessions about the disease and its management, supportive care can improve the QOL of this population.

This study analyzes the number of medical appointments and referrals performed in primary health care in Brazil focusing on the Mais Médicos Program (More Doctors Program). It is a cross-sectional study on the work of physicians included, or not, to the Mais Médicos Program in 2014. Based on validation protocols, a unified database was created from two health information system databases - SIAB and ESUS. Absolute indicators were defined: the total of medical appointments per month; medical referrals and community health education activities. In addition, other indicators were considered, such as weekly rates and productivity of appointments, in line with the profile of Brazilian municipalities. The mean of all appointments was 285 per month corresponding to an average of 14.4 appointments/day. In the poorest municipalities, the figures for the Mais Médicos Program physicians were higher than national rates. The educational activities provided by primary care teams that included a Mais Médicos Program professional were higher in Brazilian capital cities. The Mais Médicos Program achieved one of its main goals, which was to increase health access for vulnerable populations and to contribute towards the consolidation of primary health care in Brazil.

Objective: to describe the proportion of duplicate records held on the Brazilian Notifiable Diseases Information System, 2008-2009., Methods: identification of duplicate records of dengue, leprosy, visceral leishmaniasis and cutaneous leishmaniasis, meningitis and tuberculosis was conducted using Reclink III(r); the proportion of duplicate records was calculated by geographical region, state and municipal population size categories., Results: visceral leishmaniasis (VL) and meningitis had higher proportions of duplicate notification (5.3% and 3.6%, respectively) whilst leprosy had the lowest (0.7%); the states with highest repetitions were Rio Grande do Norte (VL 6.8% and leprosy 5.1%), Rio de Janeiro (tuberculosis 2.5% and meningitis 4.9%) and Goiás (dengue 2.0% and meningitis 7.2%)., Conclusion: the Northeast region had the highest proportion of duplicate records for four of the six diseases analyzed; with the exception of dengue, percentage repetition was lower in municipalities with larger population size.

Background and Objectives: The incidence of difficult airway reaches 10% of emergency intubations. Although few studies address the use of handmade introducer guides in emergency and intensive care environment, there are descriptions of handmade guides available on the Internet. We describe a case series on the use of a handmade introducer guide (bougie) for emergency intubation in patients with difficult airway., Case Report: The handmade introducer guide was used in five consecutive patients with difficult airways, and clinical instability and in the absence of another immediate method to obtain an airway. This technique provided successful intubation and there were no complications., Conclusions: The use of the handmade introducer guide can be a useful option for the management of difficult airways., (Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Mammaglobin A (MGA), mainly expressed in the breast epithelium, is overexpressed in breast cancer, and has been established as a tumor and promissory marker for the early detection of metastasis., Aim: The main aim of this study was to evaluate the association between the presence of the MGA transcript in the peripheral blood of Brazilian breast cancer patients and healthy women and the development of breast cancer and tumor progression., Material and Methods: The expression of the MGA transcript in peripheral blood of 102 breast cancer patients and 102 healthy women was assessed by RT-PCR., Results: MGA mRNA was expressed in the peripheral blood of 39 breast cancer patients and in none of the women from the control group. The presence of MGA was significantly associated with presence of metastasis and age at onset after 60 years. The presence of MGA mRNA in peripheral blood displayed a sensitivity of 38.2%, specificity of 100.0%, positive predictive value (PPV) of 100.0%, and negative predictive value (NPV) of 61.8% as a breast cancer marker., Conclusion: This study provides additional evidence of the presence of MGA in the peripheral blood of breast cancer patients, and its applicability as an efficient biomarker for breast cancer (High specificity and PPV). To our knowledge, this is the first study to assess the expression of MGA mRNA in peripheral blood obtained from the Brazilian population., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2(+) cells in breast carcinomas is a marker of resistance to chemotherapy, and based on in vitro assays and the genetic profile, we show, for the first time, that ABCG2 protein can be used as an independent marker for TIC identification in breast cancer.

One of the challenges facing solid organ transplantation programs globally is the identification of low immunological risk donors for sensitized recipients by HLA allele genotype. Because recognition of donor HLA alleles by host antibodies is at the core of organ rejection, the objective of this work was to develop a new version of the EpHLA software, named EpViX, which uses an HLAMatchmaker algorithm and performs automated epitope virtual crossmatching at the initiation of the organ donation process. EpViX is a free, web-based application developed for use over the internet on a tablet, smartphone or computer. This program was developed using the Ruby programming language and the Ruby-on-Rails framework. To improve the user experience, the EpViX software interface was developed based on the best human–computer interface practices. To simplify epitope analysis and virtual crossmatching, the program was integrated with important available web-based resources, such as OPTN, IMGT/HLA and the International HLA Epitope Registry. We successfully developed a program that allows people to work collaboratively and effectively during the donation process by accurately predicting negative crossmatches, saving time and other resources.

The objective of this study was to compare estimates of external causes based on the Global Burden of Disease in Brazil Study for the years 1998 and 2008. Methods included estimation of DALYs (disability-adjusted life years) and YLL (years of life lost), based on the methodology proposed in the Global Burden of Disease Study. Calculation of YLD (years lived with disability) required applying the same methodology in both years, with the 2008 methodology as the standard. Although external causes accounted for some 10% of total DALYs in both years, their internal distribution showed marked differences between regions of Brazil, with a decrease in the Southeast and increase in the North and Northeast. There was an increase in intentional causes, and YLLs accounted for the largest share of DALYs. The results can support new policies and/or improve existing ones to address external causes.

The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors., (©2015 American Association for Cancer Research.)

The current study estimated DALY (disability-adjusted life years), an indicator of burden of disease, for Brazil in 2008. The North and Northeast regions showed higher burden of disease. Chronic noncommunicable diseases predominated in all regions of the country, especially cardiovascular diseases, mental disorders (particularly depression), diabetes, and chronic obstructive pulmonary disease. The study also showed a high burden of homicides and traffic accidents. Brazil's epidemiological profile appears even more complex when one considers the non-negligible burden of communicable diseases, maternal and perinatal conditions, and nutritional deficiencies. The analyses allowed a more detailed understanding of the Brazilian's population's health status, underscoring the need for crosscutting actions beyond specific health sector policies and greater attention to the quality of information on morbidity and mortality.

Background: The use of trastuzumab is associated with an increased survival rate in HER2 positive breast cancer patients. However, it is related to different levels of cardiotoxicity leading to treatment discontinuation, which can deprive patients of the benefits of this therapy., Objective: This study aimed to identify the incidence of trastuzumab induced cardiotoxicity (TIC) and the rate of discontinuation of trastuzumab in clinical practice. Possible factors associated with TIC were also investigated., Setting: This study was conducted in the General Hospital of the School of Medicine of Ribeirão Preto, University of São Paulo., Methods: We retrospectively reviewed the medical records of patients without distant metastasis that started trastuzumab between 2007 and 2011 in the tertiary hospital. TIC was defined as symptomatic heart failure or a decrease in left ventricular ejection fraction (LVEF) by ≥10 % compared to the first echocardiography measurement or to <50 % at any time. Logistic regression models were used to estimate odds ratios and their respective 95 % confidence intervals for TIC associated with variables such as age, body mass index, smoking history, cardiac risks, type of surgery, presence of positive lymph nodes, chemotherapy regimen and epirubicin cumulative dose., Main Outcome Measure: The incidence and factors associated with TIC and the rate of discontinuation of trastuzumab in clinical practice., Results: We analyzed the records of 79 patients. TIC developed in 26 (32.9 %) patients, being the LVEF decline by ≥10 % observed in 21 (26.6 %), a decreased to <50 % in four (5.1 %) and one (1.2 %) was symptomatic without LVEF decline. Thirteen (16.4 %) patients discontinued permanently the treatment, three (3.8 %) discontinued temporarily and 10 (12.6 %) finished it without interruption. None of the covariates influenced on the incidence of TIC in this population., Conclusion: Although most patients finished their treatment, TIC led to trastuzumab discontinuation in a significant proportion of patients suggesting the need of a closer cardiac monitoring. None of the covariates influenced on the incidence of TIC, which can be due to the relatively small sample. Thus, larger scale studies should be conducted in order to establish which specific factors are associated with the development of TIC in order to avoid it.

Alcohol use/dependence are an important risk factor for cirrhosis of the liver. The article aims to describe and conduct a comparative analysis of Disability Adjusted Life Years (DALY), Years of Life Lost (YLL) and Years Lived with Disability (YLD) of alcohol use disorders and non-viral cirrhosis in Brazil in 2008. DALY was calculated as the sum of YLL and YLD. For YLL estimates, the mean number of deaths from 2007- 2009 in the country was considered. After revision of epidemiological data, prevalence of each disease was modelled with the DisMod tool, which generated incidence data for YLD estimates. Alcohol and non-viral cirrhosis were responsible for 3% and 1% of total DALYs, respectively. In both diseases, men contributed to a greater proportion of DALYs. Among the first ten causes of DALYs, alcohol use disorders occupied the second, third and sixth positions at the ages of 15-29, 30-44 and 45- 59, respectively. Non-viral cirrhosis was the eighth cause of DALY in the 30-44 age group in men; the fifth, in the 45-59 group and the eighth, in the 60-69 group. Age distribution suggests that interventions directed against alcohol use/dependence would have effects on the burden of alcoholic cirrhosis in the country.

OBJECTIVE To estimate the burden of type 2 diabetes mellitus and its percentage attributable to overweight and obesity in Brazil. METHODS The burden of diabetes mellitus was described in terms of disability-adjusted life years, which is the sum of two components: years of life lost and years lived with disability. To calculate the fraction of diabetes mellitus attributable to overweight, obesity, and excess weight, we used the prevalence of these risk factors according to sex and age groups (> 20 years) obtained from the 2008 Pesquisa Dimensões Sociais das Desigualdades (Social Dimensions of Inequality Survey) and the relative risks derived from the international literature. RESULTS Diabetes mellitus accounted for 5.4% of Brazilian disability-adjusted life years in 2008, with the largest fraction attributed to the morbidity component (years lived with disability). Women exhibited higher values for disability-adjusted life years. In Brazil, 49.2%, 58.3%, and 70.6% of diabetes mellitus in women was attributable to overweight, obesity, and excess weight, respectively. Among men, these percentages were 40.5%, 45.4%, and 60.3%, respectively. Differences were observed with respect to Brazilian regions and age groups. CONCLUSIONS A large fraction of diabetes mellitus was attributable to preventable individual risk factors and, in about six years, the contribution of these factors significant increased, particularly among men. Policies aimed at promoting healthy lifestyle habits, such as a balanced diet and physical activity, can have a significant impact on reducing the burden of diabetes mellitus in Brazil.

The aim of this study was to estimate the global burden of disease from external causes in 2008 in Brazil, based on DALYs (disability-adjusted life years). YLLs (years of life lost) were estimated according to the method proposed by Murray & Lopez (1996). Meanwhile, the method for estimating YLDs (years lived with disability) included methodological adjustments taking the Brazilian reality into account. The study showed a total of 195 DALYs per 100 thousand inhabitants, of which 19 DALYs were related to external causes. Among YLLs, 48% were from unintentional causes and 52% from intentional causes. Among YLDs, unintentional causes predominated, with 95%. The share of YLLs in DALYs was 90%. The cause with the highest proportion of YLLs was "homicide and violence" (43%), followed by "road traffic accidents" (31%). Falls accounted for the highest share of YLDs (36%). The sex ratio (male-to-female) was 4.8 for DALYs, and the predominant age bracket was 15-29 years. Since external causes are avoidable, the study provides potentially useful information for policymakers in public security and health.

Background: Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants., Aim: To determine the incidence, risk factors and etiology of LOS., Methods: LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days., Results: Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation., Conclusion: LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU., (© The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The World Health Organization (WHO) defines essential medicines as those that meet the population's priority healthcare needs. Their selection aims to reflect collective needs, thus recommending the use of studies on global burden of disease. An exploratory study was performed to link the medicines from the RENAME lists to Global Burden of Disease in Brazil (1998 and 2008) and the scientific evidence. The study thus sought to verify whether the RENAME (2002 to 2012) met WHO guidelines for drug selection. Although RENAME 2010 and 2012 both adhere to Global Burden of Disease in Brazil 2008, the 2012 version includes a longer list of medicines and appears to be pressured by the growing market for new technologies. Thus, RENAME is no longer a list of essential medicines, but has become a list of financing for pharmaceutical care.

Objective: In clinical intensive care practice, weaning from mechanical ventilation is accompanied by concurrent early patient mobilization. The aim of this study was to compare the success of extubation performed with patients seated in an armchair compared to extubation with patients in a supine position., Methods: A retrospective study, observational and non-randomized was conducted in a mixed-gender, 23-bed intensive care unit. The primary study outcome was success of extubation, which was defined as the patient tolerating the removal of the endotracheal tube for at least 48 hours. The differences between the study groups were assessed using Student's t-test and chi-squared analysis., Results: Ninety-one patients were included from December 2010 and June 2011. The study population had a mean age of 71 years ± 12 months, a mean APACHE II score of 21±7.6, and a mean length of mechanical ventilation of 2.6±2 days. Extubation was performed in 33 patients who were seated in an armchair (36%) and in 58 patients in a supine position (64%). There were no significant differences in age, mean APACHE II score or length of mechanical ventilation between the two groups, and a similar extubation success rate was observed (82%, seated group versus 85%, supine group, p>0.05). Furthermore, no significant differences were found between the two groups in terms of post-extubation distress, need for tracheostomy, duration of mechanical ventilation weaning, or intensive care unit stay., Conclusion: Our results suggest that the clinical outcomes of patients extubated in a seated position are similar to those of patients extubated in a supine position. This new practice of seated extubation was not associated with adverse events and allowed extubation to occur simultaneously with early mobilization.