Impact of a multifaceted strategy in end-of-life care in a tertiary hospital: A quasi-experimental study.

OBJECTIVE: To evaluate the impact of a multifaceted strategy for quality end-of-life care in a tertiary public hospital in Brazil. METHODOLOGY: The study design was quasi-experimental. The multifaceted strategy was applied between January and June 2017, and involved training the healthcare team in end-of-life discussions, the creation and documentation of advance directives, and consultation with the team specialized in palliative care. The periods analyzed were the pre-test period (Time 1, July 2015 to June 2016) and the post-test period (Time 2, July 2017 to June 2018). RESULTS: Time 1 involved 302 deaths, with an average hospital stay of 21 days; Time 2 involved 410 deaths, with an average hospital stay of 16 days. Patients were prescribed morphine (44.04% vs. 36.3% [p = 0.367]), methadone (9.60% vs. 4.39% [p = 0.247]), midazolam (43.05% vs. 47.80% [p = 0.73]), blood transfusions (31.13% vs. 24.63% [p = 0.828]), enteral feeding (56.62% vs. 38.54% [p = 0.59]) and antibiotic therapy (50.73% vs. 50.73% [p = 0.435]). CONCLUSION: This study found no changes in the end-of-life care quality indicators after the strategy was implemented. Multimodal educational strategies that develop communication skills in palliative care may enhance the quality of end-of-life care.

Evaluation of Direct Medical Costs and Associated Factors Within the Last 30 days of Life of Hospitalized Cancer Patients.

Background: An estimated 9.6 million people died from cancer globally in 2018, which is a reflection of the quality of patients' end-of-life care and its costs. Aim: To estimate direct medical costs of the last 30 days of oncology patients admitted to an inpatient clinic and to evaluate factors associated with medical costs at the end of life. Design: Cost-of-illness study with data from a retrospective cohort. Setting/Participants: We included patients aged 18 and older who were diagnosed with incurable cancer and who were admitted to a tertiary hospital in Brazil between January 1, 2018 and December 31, 2019. Results: Our sample included 109 patients with an average age of 69 (61‒76). The median overall survival was 4.3 (.9‒12.9) months. The median cost per patient per day related to hospitalization was BRL 119 (73‒181)/United States dollars [USD] 21 (13‒33). The cost of medication was BRL 66 (40‒105)/USD 12 (7‒19), representing 55.46% of costs while that of materials and supplies was BRL 30 (18‒49)/USD 5 (3‒9). In the multivariate analysis, when the limitation of interventions was recorded in the medical record, the median cost is reduced by BRL 50 (USD 9) per patient per day. Conclusions: The median cost per patient per day was BRL 119 (73‒181). The recording of limitations of therapeutic interventions in the medical record was a predictor variable that influenced the final medical cost of patients, suggesting that medical practice and decision-making in end-of-life care impact costs.

Beyond technology: Can artificial intelligence support clinical decisions in the prediction of sepsis?

OBJECTIVE: To analyze the critical alarms predictors of clinical deterioration/sepsis for clinical decision making in patients admitted to a reference hospital complex. METHODS: An observational retrospective cohort study. The Machine Learning (ML) tool, Robot Laura®, scores changes in vital parameters and lab tests, classifying them by severity. Inpatients and patients over 18 years of age were included. RESULTS: A total of 122,703 alarms were extracted from the platform, classified as 2 to 9. The pre-selection of critical alarms (6 to 9) indicated 263 urgent alerts (0.2%), from which, after filtering exclusion criteria, 254 alerts were delimited for 61 inpatients. Patient mortality from sepsis was 75%, of which 52% was due to sepsis related to the new coronavirus. After the alarms were answered, 82% of the patients remained in the sectors. CONCLUSIONS: Far beyond technology, ML models can speed up assertive clinical decisions by nurses, optimizing time and specialized human resources.

In Vitro Evaluation of Antioxidant and Anticancer Activity of Lemongrass (Cymbopogon citratus (D.C.) Stapf).

Cancer is considered a multifactorial disease and its development could be associated with several factors, for example, rotenone exposition. Unfortunately, many cancers are resistant to chemotherapy, as cervical cancer. Regarding this, lemongrass is a remarkable natural product that presents antioxidant and anticancer activities, which could show therapeutic action against rotenone and cervical cancer. Thus, this study aimed to investigate the antioxidant and anticancer action of lemongrass. An in vitro study was conducted using VERO (kidney cells) and SiHa cell lines (cervical cancer cells). VERO cells were exposed to rotenone and lemongrass extract for 24 and 72 h. While SiHa cells were exposed to lemongrass isolated and associated to chemotherapy, 5-fluorouracil, during 24 and 48 h. After, levels of viability, proliferation, and oxidative metabolism were determined. The results showed that lemongrass presents antioxidant activity on VERO cells by increasing cell viability and proliferation and decreasing oxidative stress caused by rotenone. Moreover, lemongrass showed anticancer activity by decreasing cell viability and increasing oxidative stress parameters on SiHa. Besides, lemongrass had no alteration in the chemotherapy activity. Therefore, this study revealed that lemongrass presents antioxidant and anticancer activity since it can protect against the cytotoxicity of rotenone and reduce the cell viability of cervical cancer.

The Relevance of Ultrastructural Studies of Metastatic Cells from Women with Breast Cancer History.

The interaction between cancer cells and the surrounding microenvironment is determinant for metastasis success. In this study, the ultrastructural relevance of cells in the malignant pleural effusion (MPE) of women with breast cancer history was investigated. In MPE, it is possible to observe single cells and clusters. Women whose MPE presents carcinomas in aggregates have a better prognosis when compared to cases in which metastatic single cells are found. Samples were collected via fine-needle aspiration puncture (US-FNA). Subsequent to the material preparation and ultrathin cuts, they were observed using light and transmission electron microscopy (LM/TEM). LM and TEM images served as a basis for the creation of a digital sculpture using ZBrush® software. Clusters exhibited structural stability, en route vesicles allowing exocytosis of electron-dense fibrous elements, and cytoplasmic protrusions contributing to migratory and invasive skills. Single cells presented different necrotic phenotypes and many displayed leukocyte-like characteristics. Cluster cooperative relationships seem to be related to a long-term permanence in MPE. The absence of a collaborative network presumably triggers a more aggressive behavior of single cells. Its putative fusion with leukocytes can maximize the efficiency for transendothelial migration, increasing chances of metastatic success and, unfortunately, reducing survival of women with recidivism.

Hematological ratios as prognostic indicators in patients with triple-negative breast cancer in southern Brazil

Introduction: The heterogeneous nature and intrinsically aggressive tumor pathology of the triple negative breast cancer subtype results in an unfavorable prognosis and limited clinical success. The use of hematological components of the systemic inflammatory response for patients with triple-negative breast cancer can add important prognostic information to the criteria traditionally used for cancer patients, since inflammation can promote tumor progression support by affecting the stages of tumorigenesis. Objectives: The aim of this study was to evaluate the hematological parameters neutrophil/lymphocyte, monocyte/lymphocyte and platelet/lymphocyte ratios as prognostic indicators in patients with triple-negative breast cancer. Methods: This was a singlecenter retrospective observational study in an oncology referral hospital in the South region of Brazil. Electronic medical records of patients diagnosed with triple-negative breast cancer from 2012 to 2016 were reviewed and analyzed using SPSS. Results: The low blood cell ratio groups had significantly higher overall survival than the high blood cell ratio groups. Univariate analysis also confirmed the correlation of patients in the high blood cell ratio groups with unfavorable results. Conclusions: Hematological components of the systemic inflammatory response are promising prognostic indicators. More studies on the subject should be carried out to assist in future medical decision-making so these parameters of easy assessment and low cost can be introduced in clinical practice.

Beyond technology: Can artificial intelligence support clinical decisions in the prediction of sepsis? / Más allá de la tecnología: ¿La inteligencia artificial puede apoyar la toma de decisiones clínicas en la predicción de la sepsis? / Para além da tecnologia: a inteligência artificial pode apoiar decisões clínicas na predição da sepse?

ABSTRACT Objective: To analyze the critical alarms predictors of clinical deterioration/sepsis for clinical decision making in patients admitted to a reference hospital complex. Methods: An observational retrospective cohort study. The Machine Learning (ML) tool, Robot Laura®, scores changes in vital parameters and lab tests, classifying them by severity. Inpatients and patients over 18 years of age were included. Results: A total of 122,703 alarms were extracted from the platform, classified as 2 to 9. The pre-selection of critical alarms (6 to 9) indicated 263 urgent alerts (0.2%), from which, after filtering exclusion criteria, 254 alerts were delimited for 61 inpatients. Patient mortality from sepsis was 75%, of which 52% was due to sepsis related to the new coronavirus. After the alarms were answered, 82% of the patients remained in the sectors. Conclusions: Far beyond technology, ML models can speed up assertive clinical decisions by nurses, optimizing time and specialized human resources.

RESUMEN Objetivo: Analizar alarmas críticas predictoras de deterioración clínica/sepsis para toma de decisiones clínicas en pacientes internados en complejo hospitalario de referencia. Métodos: Estudio observacional de cohorte retrospectivo. La herramienta Machine Learning (ML), Robot Laura®, puntúa alteraciones en parámetros vitales y exámenes laboratoriales, clasificándolos por gravedad. Incluyeron pacientes internados y mayores de 18 años. Resultados: Extrajeron 122.703 alarmas de la plataforma, clasificadas de 2 hasta 9. La preselección de alarmas críticas (6 a 9) apuntó 263 alertas urgentes (0,2%), entre ellas, después del filtro de criterios de exclusión, delimitaron 254 alertas para 61 pacientes internados. La mortalidad de pacientes por sepsis fue de 75%, entre ellos 52% debido a sepsis relacionada al nuevo coronavirus. Después de las alarmas ser atendidas, 82% de los pacientes permanecieron en los sectores. Conclusiones: Más allá de la tecnología, modelos de ML pueden agilizar la decisión clínica asertiva de enfermeros, optimizando tiempos y recursos humanos especializados.

RESUMO Objetivo: Analisar os alarmes críticos preditores de deterioração clínica/sepse para tomada de decisão clínica nos pacientes internados em complexo hospitalar de referência. Métodos: Estudo observacional de coorte retrospectivo. A ferramenta de Machine Learning (ML), Robô Laura®, pontua alterações nos parâmetros vitais e exames laboratoriais, classificando-os por gravidade. Incluíram-se pacientes internados e maiores de 18 anos. Resultados: Extraíram-se 122.703 alarmes da plataforma, classificados de 2 até 9. A pré-seleção dos alarmes críticos (6 a 9) apontou 263 alertas urgentes (0,2%), dos quais, após o filtro de critérios de exclusão, delimitaram se 254 alertas para 61 pacientes internados. A mortalidade dos pacientes por sepse foi de 75%, dos quais 52% devido à sepse relacionada ao novo coronavírus. Após os alarmes serem atendidos, 82% dos pacientes permaneceram nos setores. Conclusões: Muito além da tecnologia, modelos de ML podem agilizar a decisão clínica assertiva dos enfermeiros, otimizando tempos e recursos humanos especializados.

Handling of antineoplastic drugs: a health concern among health care workers.

INTRODUCTION: Health care professionals are part of a group that is more exposed to a wide range of sources of risk that are very harmful to their own health. Antineoplastic drugs are widely used to treat many different types of cancer and are very aggressive to both patients and health care professionals. OBJECTIVES: To identify occupational risks and assess knowledge in health care professionals from Porto Alegre whose work involves handling antineoplastic drugs. METHODS: This was a prospective, descriptive, and cross-sectional study with qualitative and quantitative analyses. It was conducted in two stages. A questionnaire containing objective questions was administered in stage one. In stage two, observations were made during regular visits to the sites studied at different times, following a checklist based on the requirements of health regulation standards relating to handling of antineoplastic drugs. RESULTS: A total of 40 health care professionals took part in the study, 11 nurses, 14 pharmacists, and 15 nursing and/or pharmacy technicians. Twenty-seven of them had been involved in some type of accident during their professional practice. It was also observed that the institutions were making efforts to comply with legal requirements, since 32 reported that they took part in the Program for Medical Control of Occupational Health and 29 of the employees stated they had had some type of training in the antineoplastic area. CONCLUSIONS: Exposure to antineoplastic drugs through contact, aerosols, ingestion, and inhalation was detected. Additionally, ergonomic, physical, and biological risks were also present, since working with different pathological organisms and working processes impacts on these workers' health. Assessment of the health care professionals' knowledge identified a lack of knowledge and weaknesses with relation to handling this class of drugs.

Molecular markers associated with the outcome of tamoxifen treatment in estrogen receptor-positive breast cancer patients: scoping review and in silico analysis.

Tamoxifen (TMX) is used as adjuvant therapy for estrogen receptor-positive (ER+) breast cancer cases due to its affinity and inhibitory effects. However, about 30% of cases show drug resistance, resulting in recurrence and metastasis, the leading causes of death. A literature review can help to elucidate the main cellular processes involved in TMX resistance. A scoping review was performed to find clinical studies investigating the association of expression of molecular markers profiles with long-term outcomes in ER+ patients treated with TMX. In silico analysis was performed to assess the interrelationship among the selected markers, evaluating the joint involvement with the biological processes. Forty-five studies were selected according to the inclusion and exclusion criteria. After clustering and gene ontology analysis, 23 molecular markers were significantly associated, forming three clusters of strong correlation with cell cycle regulation, signal transduction of proliferative stimuli, and hormone response involved in morphogenesis and differentiation of mammary gland. Also, it was found that overexpression of markers in selected clusters is a significant indicator of poor overall survival. The proposed review offered a better understanding of independent data from the literature, revealing an integrative network of markers involved in cellular processes that could modulate the response of TMX. Analysis of these mechanisms and their molecular components could improve the effectiveness of TMX.

Superoxide imbalance triggered by Val16Ala-SOD2 polymorphism increases the risk of depression and self-reported psychological stress in free-living elderly people.

BACKGROUND: Oxidative stress and chronic inflammatory states triggered by a single-nucleotide polymorphism (SNP) in superoxide dismutase manganese-dependent gene (Val16Ala-SOD2) have been associated with the risk of developing several chronic, nontransmissible diseases. However, it is still not clear whether the VV-SOD2 genotype that causes higher basal superoxide anion levels has any impact on the risk for depression and self-reported psychological stress in elderly people. METHODS: In the present study, we tested this hypothesis using a case-control study where depression was detected using the Geriatric Depression Scale-15 (GDS-15). A total of 612 Brazilian free-living elderly subjects with a mean age of 67.1 ± 7.1 years old (number of controls, C = 497, and depressive individuals, D = 115) were included in this study. All participants had similar social, health, and lifestyle variables, with the exception of polypharmacy (≥5 medicines daily intake), which was higher in the D group, compared to C subjects. RESULTS: Our results showed that the VV-SOD2 genotype significantly increased the risk for depression and psychological stress in the elderly subjects, independently of sex/gender, age, and other prior diseases and health indicators (depression risk = 1.842, 1.109-3.061 95% CI, p = .018). VV-subjects also had a higher daily intake of antidepressants, anxiolytics, and anti-inflammatory drugs than A-allele subjects. CONCLUSION: Our findings support the hypothesis that genetically induced oxidative superoxide-hydrogen peroxide imbalance may be involved in an increased risk for developing depression and psychological stress in free-living elderly people without other chronic nontransmissible diseases.

Cell Cycle Markers in the Evaluation of Bladder Cancer.

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

Molecular detection of oncogenic subtypes of human papillomavirus (HPV) in a group of women in the Amazon region of Brazil

The natural history of cervical cancer is strongly related to the presence of human papillomavirus (HPV) infection, with its relationship with cervical cancer being a matter of concern. It is estimated that 70% of all cervical cancers worldwide are caused by HPV 16 and 18. Accordingly, the present study aimed to contribute to the identification of HPV subtypes circulating in a group of women of Manaus-Brazil. Cervical samples were collected from 49 women, following the eligibility criteria of the study, and DNA was then extracted from the samples, which were analyzed for the presence of the virus in the genetic material through the polymerase chain reaction (PCR) using generic primers (GP05/06). Finally, identification of the viral subtypes was performed using specific primers for the detection of the main subtypes already examined (16 and 18). Positive HPV DNA was detected in 100% of the samples included in the study. Human papillomavirus 16 was the most prevalent subtype in the majority of lesions, accounting for 29 (59.2%) of the positive cases, and HPV 18 was detected in four (8.2%) women. In these 4 cases there was co-infection, with the presence of both HPV 18 and HPV 16. Therefore, 40.8% (20 cases) in which HPV DNA was detected presented infection with other subtypes of HPV not included in the study. This data has clinical implications related to cervical cancer prevention, as the current prophylactic HPV vaccines are only effective against high-risk HPV 16 and 18 subtypes.

Follow-Up of Women with Cervical Cytological Abnormalities: Progression and Regression Events

Abnormalities in the cervix, when identified early by Pap smear, can be treated in the early stages or in the precursor stages of the neoplasia, which may increase the chances of regression of the lesion. The aim to verify the rate of cervical abnormalities and to evaluate the risk of progression or regression associated with age and cytological diagnosis. Methods: The study was conducted in a referral hospital in Southern Brazil, based on the results of pathology and cytopathology laboratory tests of uterine cervix. The historical cohort included patients with an abnormal cytology diagnosis in the period from January 2010 to December 2014, followed until July 2016. Results: A total of 42,389 cervical smears were analyzed, 4,427 of which were eligible for analysis of the evolution of cervical abnormalities. In progression and regression events analysis, we observed that patients with a cytological diagnosis of atypical glandular cells presented a higher risk of cervical abnormality progression (Hazard Ratio: 2.0 and 95% confidence intervals 1.36­3.48). We also observed that patients younger than 25 years old were more likely to regress the cervical lesions (Hazard Ratio:1.4 and 95% confidence intervals 1.20­1.74). Conclusions: The associations found between the events (progression and regression), age and cytological diagnosis, highlights the importance of cytological screening in populations at risk of precursor of cervical cancer lesions, especially in women older than 25 years.

Prognostic impact of MYD88 mutation, proliferative index and cell origin in diffuse large B cell lymphoma

Abstract Background Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. Objective The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. Method Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens. Results Median age was 64-years old and 58% were female patients. The median follow-up was 42 months. The progression free survival (PFS) at this time was 63% and overall survival (OS), 66%. In the patients with tumors expressing Myc proto-oncogene protein (MYC) and B-cell lymphoma 2 (BCL2), assessed by immunohistochemistry (IHC), known as dual protein expressers, median post-progression survival was 31 (15-45) months. An increased proliferative index were associated with a high rate of progression (hazard ratio 2.31 [95% confidence interval [1.05-5.12]; p = 0.04). The cell of origin (COO), identified by IHC, was not able to predict PFS (p = 0.76). The MYD88 L265P mutation was present in 10.8% (9/83) of patients and did not show a prognostic correlation. Conclusion In conclusion, the MYD88 mutation, although an important tool for diagnosis and a possible target drug, presented at a low frequency and was not a prognostic marker in this population.

Prognostic impact of MYD88 mutation, proliferative index and cell origin in diffuse large B cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. OBJECTIVE: The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. METHOD: Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens. RESULTS: Median age was 64-years old and 58% were female patients. The median follow-up was 42 months. The progression free survival (PFS) at this time was 63% and overall survival (OS), 66%. In the patients with tumors expressing Myc proto-oncogene protein (MYC) and B-cell lymphoma 2 (BCL2), assessed by immunohistochemistry (IHC), known as dual protein expressers, median post-progression survival was 31 (15-45) months. An increased proliferative index were associated with a high rate of progression (hazard ratio 2.31 [95% confidence interval [1.05-5.12]; p = 0.04). The cell of origin (COO), identified by IHC, was not able to predict PFS (p = 0.76). The MYD88 L265P mutation was present in 10.8% (9/83) of patients and did not show a prognostic correlation. CONCLUSION: In conclusion, the MYD88 mutation, although an important tool for diagnosis and a possible target drug, presented at a low frequency and was not a prognostic marker in this population.

Evaluation of Kindlin-1 and Ki-67 immunohistochemical expression in primary cutaneous malignant melanoma: a clinical series

Background: The capacity for prognostic prediction of cutaneous melanoma, one of the most aggressive cancers, is still difficult due to the tumor heterogeneity and lack of reliable tumor markers. The objective of this study is to correlate, through immunohistochemistry, a Ki-67 and Kindlin-1 staining in malignant melanomas with the prognosis of the disease. Methods: A historical cohort study. Immunohistochemistry, using mouse anti-human Kindlin-1 and Ki-67 monoclonal antibodies, was performed using tissue blocks from primary cutaneous melanoma patients treated between 2006 and 2014 at our institution. Information regarding pathological data and outcomes were retrieved from medical records. Statistical analyses were conducted in SPSS version 18.0. Results: Thirty patients were included. The median age was from 50.93 ± 15.31 years old. The expression of Ki-67 was detected in all patients with primary cutaneous melanoma, while Kindlin-1 was negative in two. Kindlin expression was not significantly correlated with Ki-67 expression by Spearman's rank correlation analysis (P = 0.46), as well as the expression of both markers and the clinical stage (P = 0.34 and 0.18, respectively). Breslow, Clark and mitotic rate were significantly correlated with AJCC stage (P = 0.001). Conclusion: Other studies investigating clinical evolution are needed to further test the potential of these markers as possible prognostic markers (AU)

Impact of Her-2 Overexpression on Survival of Patients with Metastatic Breast Cancer

Introduction: Breast cancer is a complex and heterogeneous disease which is increasingly important as a public health problem. In Brazil, 57,960 new cases have been estimated to be the burden in 2016 and 2017. Despite advances in early diagnosis and therapy, approximately 20-30% of patients, even with early stage lesions, will develop distant metastatic disease. Tumors with similar clinical and pathological presentations may have differing behavior, so it is important to understand specific biological characteristics. Objective: To investigate tumor markers of primary tumors featuring pleural metastasis to identify organ-specific characteristics of metastatic breast cancer. Methods: In a historical cohort study, immunohistochemistry was performed on cell blocks of neoplastic pleural effusions and results were compared with clinicopathological data. Results: The median survival time with Her-2 overexpression in malignant pleural effusions was 2.2 months, whereas cases without overexpression survived, on average, for seven months (p = 0.02). Conclusions: We emphasize that metastases may behave independently of primary tumors, but the present results indicate that therapeutic agents targeting Her-2 overexpression could increase survival in metastatic breast cancer cases.

Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality risk among Brazilian Amazon riparian elderly population.

OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established. METHODS: We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables. CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.

Immunohistochemistry Biomarkers in Nonmuscle Invasive Bladder Cancer.

Bladder cancer (BCa) is the most frequent urinary tract neoplasm. BCa results in significant mortality when the disease presents as muscle invasive. Around 75% to 80% of patients present with nonmuscle invasive bladder cancer (NMIBC), but recurrence and progression are significant issues, compelling current guidelines to recommend long-term surveillance. There is therefore an urgent and unmet need to identify and validate accurate biomarkers for the detection of disease recurrence to improve quality of life for the patients and reduce costs for health care providers, while maintaining or improving current outcomes. In this review, 38 publications on immunohistochemistry prognostic biomarkers, that were studied may be related in nonmuscle invasive bladder cancer, have been analyzed. The studies were organized according to the evaluated marker and their findings. It was demonstrated that the combination of independent complementary biomarkers could allow a more accurate prognosis than an isolated marker. Biomarkers, including p53, Ki-67, and CK20, with classic and prognostic factors with recurrence and novel markers such as EN2 may provide a more accurate prediction of outcome compared with any single marker, improving risk stratification and clinical management of patients with BCa.

Immunosuppression and the occurrence of HPV in kidney transplant patients verified by urinary cytology / Imunossupressão e ocorrência de HPV em pacientes transplantados renais a partir de exame citológico urinário

ABSTRACT Introduction: Human papillomavirus (HPV) is the main cause of cervical cancer, and immunosuppression is recognized as a risk factor for HPV infection and its persistence. After renal transplantation, immunosuppressive agents are used to prevent rejection, but predispose recipients to chronic infections and malignancies. Objective: This study aimed to verify, based on urinary cytology (UC), the prevalence of HPV in immunosuppressed kidney transplant patients. Material and method: In this cross-sectional study, the population was composed of kidney transplant patients that had undergone routine UC from August 2012 to August 2014. Results: There were 2,305 urine cytopathological tests. Thirteen patients with presence of koilocytes in such examination were observed. Therefore, the relative frequency of patients with HPV detected in urine was 0.56%. In the interval until the first post-transplant year, 10 (76.92%) patients presented koilocytes (p < 0.0001) in the UC. The dosages of immunosuppressive agents until the first post-transplant consultation, which showed correlation with the period between transplantation and the first UC test with the presence of koilocytes (p < 0.0001), were prednisone 10.5-20 mg/day, mycophenolate sodium 901-1,440 mg/day, and tacrolimus 4.5-12 mg/day. Conclusion: This study showed immunosuppression as an important risk factor for infection by HPV or its reactivation. Screening UC tests after transplantation may evidence HPV infection.

RESUMO Introdução: O papilomavírus humano (HPV) é a principal causa de câncer de colo do útero, e a imunossupressão é reconhecida como fator de risco para infecção pelo HPV e sua persistência. Após o transplante renal, agentes imunossupressores são usados para evitar rejeição, mas predispõem o receptor a infecções crônicas e doenças malignas. Objetivo: Este trabalho teve como objetivo verificar, a partir do exame citológico urinário, a prevalência do HPV em pacientes transplantados renais imunossuprimidos. Material e método: Neste estudo transversal, a população foi composta por pacientes transplantados renais que fizeram o exame de rotina citológico urinário no período de agosto de 2012 a agosto de 2014. Resultados: Realizaram-se 2.305 exames citopatológicos de urina. Foram observados 13 pacientes com presença de coilócitos no referido exame. A frequência relativa de pacientes com HPV detectado na urina foi de 0,56%. No intervalo até o primeiro ano pós-transplante, 10 (76,92%) pacientes apresentaram coilócitos (p < 0,0001) no exame citológico urinário (ECU). As dosagens de imunossupressores até a primeira consulta pós-transplante, que demonstraram correlação com o período entre o transplante e o primeiro ECU com presença de coilócito (p< 0,0001), foram prednisona 10,5-20 mg/dia, micofenolato de sódio 901-1.440 mg/dia e tacrolimo 4,5-12 mg/dia. Conclusão: Este estudo mostrou a imunossupressão como um fator de risco importante para infecção pelo HPV ou sua reativação. O acompanhamento por meio do ECU pós-transplante pode evidenciar a infecção por HPV.