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.

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.

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.

Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice.

Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug, and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also increases the rate of developing hepatic damages with inflammatory activity, termed chemotherapy-associated steatohepatitis (CASH). In the present study, we aimed to compare the effects of a series of antioxidant compounds on simultaneous development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting in mechanical allodynia and hepatic steatosis. We administered the following antioxidant compounds--rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg), quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)--daily by gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control. Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when compared to the OXA group, and this effect was associated with decreased c-Fos immunopositivity in the lumbar spinal cord. Regarding the effects on steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver weight increase induced by OXA. In accordance with these previous data, histological evaluation indicated attenuation of all features of hepatic steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to reduce the immunopositivity for the apoptosis marker caspase-3. On the other hand, only QT and NQT treatments were able to reduce neutrophil migration measured by myeloperoxidase (MPO) activity. These results suggest that the compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical treatment of neuro- and hepatoxicity induced by oxaliplatin.

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.