Highlights of three metabolites HDL and reduction in blood pressure values after dietary fiber supplementation in overweight and obese normotensive women: a metabolomic study.

INTRODUCTION: The prevalence of hypertension and obesity are a worldwide concern. OBJETIVES: Assess the metabolites profile after intervention with mixed dietary fiber in overweight and obese normotensive women. METHODS: This is a randomized double blind placebo-controlled study. Through a simple randomization process, two groups were allocated, with eleven women (group 1) receiving 12 g of mixed dietary fiber and thirteen women (group 2) receiving 12 g of placebo (corn starch) for eight weeks. Anthropometric and biochemical tests and lifestyle were analyzed. As for evaluation metabolomics, used a 1H NMR. The data matrix generated 96 samples and 225 variables, which was exported in the ASCII format for the "The Unscrumbler" statistics software (version 9.7, CAMO Process). RESULTS: After the intervention with mixed dietary fiber, significant differences were observed between the main types of metabolites, referring to the increase in the relative peak areas of in three HDL metabolites 4.94 ppm (0.0086*), HDL 1.28 ppm (0 .0337*), HDL 0.88 ppm (0.0224*) and an α-glucose metabolite 4.90 ppm (0.0106) and the reduction in systolic blood pressure (SBP) (0.0292*) of 7 mmHg in the reference range and in the placebo group there was a reduction in SBP (0.0118*) of 4 mmHg and of a choline metabolite 3.65 ppm (0.0266*), which does not call into question the validity of these results in the literature. CONCLUSION: The synergism of the functions of these statistically highlighted metabolites contributed to prevention the increase in SBP after fiber intervention in overweight and obese normotensive women.

Effects of preoperative sarcopenia-related parameters on the musculoskeletal and metabolic outcomes after bariatric surgery: a one-year longitudinal study in females.

Reduced muscle mass and/or strength are risk factors for metabolic and musculoskeletal impairment. The present study evaluated anthropometric, metabolic, and musculoskeletal outcomes in females with and without sarcopenic-obesity parameters who underwent bariatric surgery during a 1-year follow-up. A prospective, single-center cohort study was conducted in females with obesity undergoing preoperative evaluation for surgery. In the preoperative period, females were allocated into obesity with sarcopenic-obesity parameters (SOP group, n = 15) and without sarcopenic-obesity parameters (obesity group, n = 21). Sarcopenic obesity parameters were defined as lower appendicular skeletal mass adjusted for weight (ASM/wt) and/or low handgrip strength (HGS). Anthropometric, metabolic, and musculoskeletal parameters were assessed before surgery and at 3 months, 6 months, and a 1-year after bariatric surgery. Weight loss was similar between groups (p > 0.05). Weight, body mass index, fat mass, body fat percentage, skeletal muscle mass, fat-free mass, fat-free mass index, HGS were reduced in both groups during the 1-year follow-up (p < 0.05). However, when muscle mass and strength were analyzed relative to body size, an improvement after bariatric surgery was found in both groups (p < 0.05). Total cholesterol, LDL-c, triglycerides, fasting glucose, glycated hemoglobin, insulin, and insulin resistance were reduced in both groups during the 1-year follow-up (p < 0.05). In addition, HDL-c serum concentration increased in females with and without sarcopenic-obesity parameters over the 1-year follow-up (p < 0.05). Both groups had decreased bone mineral density (BMD) at all sites (lumbar spine, femoral neck, and total femur) over the 1-year follow-up (p < 0.05). The highest quartile of ASM/wt was positively associated with BMD variables in a longitudinal analysis, suggesting that preserved ASM/wt in pre-surgery may be beneficial for BMD after 1 year of bariatric surgery. The results showed that bariatric surgery promotes similar musculoskeletal and metabolic changes in females with preserved muscle mass and strength or in females with sarcopenia-related parameters.

Results of the daratumumab monotherapy early access treatment protocol in patients from Brazil with relapsed or refractory multiple myeloma

ABSTRACT Introduction: Daratumumab is a CD38-targeting monoclonal antibody with established efficacy and safety in patients with relapsed or refractory multiple myeloma (RRMM). We report results of an early access protocol (EAP) of daratumumab monotherapy for RRMM in a cohort of Brazilian patients. Methods: Patients with RRMM and ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and IMiD received daratumumab, 16 mg/kg, intravenously weekly for 8 weeks, biweekly for 16 weeks, and every 4 weeks thereafter until disease progression, unacceptable toxicity, loss of clinical benefit, or study conclusion or if daratumumab became available with reimbursement. Results: Forty-nine patients received ≥1 dose of daratumumab. The median (range) duration of treatment was 6.4 (0.3-11.8) months, with a median (range) of 8 (1-13) treatment cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 38.8% of patients, most frequently neutropenia and pneumonia (10.2% each). Seven (14.3%) patients discontinued treatment due to TEAEs; 3 patients discontinued due to daratumumab-related TEAEs. Serious TEAEs occurred in 38.8% of patients. Infusion-related reactions were reported in 25 (51.0%) patients, were primarily grade 1/2, and the majority (23 patients) occurred during the first infusion. Twenty (40.8%) patients achieved a partial response or better; median progression-free survival was 8.25 (95% confidence interval, 5.55-17.54) months. Conclusion: In this EAP, daratumumab monotherapy in Brazilian patients showed a safety and efficacy profile consistent with clinical studies of daratumumab monotherapy in patients with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.

Results of the daratumumab monotherapy early access treatment protocol in patients from Brazil with relapsed or refractory multiple myeloma.

INTRODUCTION: Daratumumab is a CD38-targeting monoclonal antibody with established efficacy and safety in patients with relapsed or refractory multiple myeloma (RRMM). We report results of an early access protocol (EAP) of daratumumab monotherapy for RRMM in a cohort of Brazilian patients. METHODS: Patients with RRMM and ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and IMiD received daratumumab, 16 mg/kg, intravenously weekly for 8 weeks, biweekly for 16 weeks, and every 4 weeks thereafter until disease progression, unacceptable toxicity, loss of clinical benefit, or study conclusion or if daratumumab became available with reimbursement. RESULTS: Forty-nine patients received ≥1 dose of daratumumab. The median (range) duration of treatment was 6.4 (0.3-11.8) months, with a median (range) of 8 (1-13) treatment cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 38.8% of patients, most frequently neutropenia and pneumonia (10.2% each). Seven (14.3%) patients discontinued treatment due to TEAEs; 3 patients discontinued due to daratumumab-related TEAEs. Serious TEAEs occurred in 38.8% of patients. Infusion-related reactions were reported in 25 (51.0%) patients, were primarily grade 1/2, and the majority (23 patients) occurred during the first infusion. Twenty (40.8%) patients achieved a partial response or better; median progression-free survival was 8.25 (95% confidence interval, 5.55-17.54) months. CONCLUSION: In this EAP, daratumumab monotherapy in Brazilian patients showed a safety and efficacy profile consistent with clinical studies of daratumumab monotherapy in patients with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.

Hodgkin's lymphoma unmet medical needs in Brazil: experts' perspective / Necessidades médicas não atendidas no tratamento de linfoma de Hodgkin no Brasil: perspectiva de médicos

Background: In 2016, Hodgkin's Lymphoma (HL) was responsible for 2,470 new cases in Brazil and, despite recent scientific advances, there are unmet medical needs that affects patients' outcome. Therefore, we aimed to explore the unmet medical needs in the management of HL patients in Brazil, based on experts' perspective. Methods: A questionnaire was developed to address the unmet medical needs including barriers for the diagnosis and treatment of HL in Brazil. The questionnaire results were presented in a panel discussion to validate participants' responses and to collect additional data. Main results: Eight experts participated in the panel. On both healthcare systems, public and private, a slight majority of patients was women and most of them were under 60 yearsold. In addition, the majority of patients were referred from another specialty on both systems. The time from onco-hematologist appointment to diagnosis was different between public and private sector (median of 30 and 12.5 days, respectively). Most patients in the public sector were on stage III (33%) and IV (33%); in the private sector, most patients were on stages II (36%) and III (24%). The most common barriers were the delayed diagnosis and the unavailability of diagnostic procedures and treatment options. Conclusion: According to participants, issues related to infrastructure and healthcare resource allocation affects the management of HL. Improvements in the infrastructure and educational measures for physicians and patients may contribute to minimize the barriers.

Introdução: Em 2016, o Linfoma de Hodgkin (LH) foi responsável por 2.470 novos casos no Brasil e, apesar dos recentes avanços científicos, há necessidades médicas não atendidas que afetam os pacientes. Portanto, o estudo teve como objetivo explorar as necessidades médicas não atendidas no manejo de pacientes com LH no Brasil, com base na perspectiva de especialistas. Métodos: Um questionário foi desenvolvido para abordar as necessidades médicas não atendidas, incluindo as barreiras para o diagnóstico e tratamento do LH no Brasil. Os resultados do questionário foram apresentados em um painel de discussão para validar as respostas dos participantes e coletar dados adicionais. Principais resultados: Oito especialistas participaram do painel. De acordo com os especialistas, em ambos os sistemas de saúde público e privado, uma pequena maioria dos pacientes era mulher e a maioria tinha menos de 60 anos. Além disso, a maioria dos pacientes foi encaminhada por outra especialidade em ambos os sistemas. O tempo entre a consulta com o onco-hematologista até o diagnóstico foi diferente entre o setor público e privado (mediana de 30 e 12,5 dias, respectivamente). A maioria dos pacientes do setor público apresenta estádios III (33%) e IV (33%); no setor privado, a maioria dos pacientes apresenta estádios II (36%) e III (24%). As barreiras mais comuns foram o atraso no diagnóstico e a indisponibilidade de procedimentos diagnósticos, e opções de tratamento. Conclusão: De acordo com os participantes, as questões relacionadas à infraestrutura e à alocação de recursos de saúde afetam o gerenciamento do LH. Melhorias na infraestrutura e medidas educacionais para médicos e pacientes podem contribuir para minimizar as barreiras.

α-Tocopherol influences glycaemic control and miR-9-3 DNA methylation in overweight and obese women under an energy-restricted diet: a randomized, double-blind, exploratory, controlled clinical trial.

BACKGROUND: Excess weight is a strong risk factor for the development of dysglycaemia. It has been suggested that changes in the metabolism microRNAs, small non-coding RNAs that regulate gene expression, could precede late glycaemic changes. Vitamin E in turn may exert important functions in methylation and gene expression processes. This study aimed to determine the effect of α-tocopherol on glycaemic variables and miR-9-1 and miR-9-3 promoter DNA methylation in overweight women. METHODS: A randomized, double-blind, exploratory, placebo-controlled study was conducted in overweight and obese adult women (n = 44) who ingested synthetic vitamin E (all-rac-α-tocopherol), natural source vitamin E (RRR-rac-α-tocopherol) or placebo capsules and were followed up for a period of 8 weeks. Supplemented groups also received dietary guidance for an energy-restricted diet. An additional group that received no supplementation and did not follow an energy-restricted diet was also followed up. The intervention effect was evaluated by DNA methylation levels (quantitative real-time PCR assay) and anthropometric and biochemical variables (fasting plasma glucose, haemoglobin A1C, insulin, and vitamin E). RESULTS: Increased methylation levels of the miR-9-3 promoter region (P < 0.001) and reduced haemoglobin A1C (P < 0.05) were observed in the natural source vitamin E group after intervention. Increased fasting plasma glucose was observed in the synthetic vitamin E group, despite the significant reduction of anthropometric variables compared to the other groups. CONCLUSIONS: α-Tocopherol from natural sources increased methylation levels of the miR-9-3 promoter region and reduced haemoglobin A1C in overweight women following an energy-restricted diet. These results provide novel information about the influence of vitamin E on DNA methylation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02922491. Registered 4 October, 2016.

Anxiolytic Effect of Citrus aurantium L. on Patients with Chronic Myeloid Leukemia.

The bone marrow aspiration procedure is used in hematological diseases and consists of a painful, invasive procedure causing anxiety-associated symptoms. The present study assessed the effect of Citrus aurantium L. essential oil on the treatment of anxiety, in the moment that precedes the collection of medullary material in patients with chronic myeloid leukemia (CML). Volunteers from both sexes were divided into groups receiving either the C. aurantium essential oil through inhalation, diazepam (10 mg), or the placebo. The evaluation was performed through psychometric scales [State-Trait Anxiety Inventory (STAI)] and physiological measurements (blood pressure and cardiac and respiratory frequency). Inhalation of C. aurantium was associated with a decrease in the STAI-S scores, suggesting an anxiolytic effect. In support of these results, a change in all the physiological measurements was observed in the group exposed to C. aurantium. In the diazepam group, only the diastolic pressure decreased, and no effect was observed in the placebo group. Therefore, the results showed that C. aurantium exhibits an anxiolytic effect and reduces the signs and symptoms associated with anxiety in patients with CML.

Ansiedade Patológica: Bases Neurais e Avanços na Abordagem Psicofarmacológica / Pathological Anxiety: Neural Bases and Advances in Psychopharmacological Approach

Apresentar uma visão atualizada e ampla da ansiedade emsua manifestação patológica, suas bases neurais e o avanço na suaabordagem terapêutica psicofarmacológica. Material e Métodos: Foirealizada uma revisão de literatura usando como fonte de pesquisaartigos indexados pela base de dados Pubmed, Medline e pesquisasem livros específicos que investigaram a ansiedade em seu aspectopatológico. Resultados: A literatura revelou que na gênese dostranstornos da ansiedade vários neurotransmissores são implicados,uma vez que eles participam, em maior ou menor grau, da modulaçãoe regulação dos comportamentos defensivos. As evidências obtidasaté então permitem constatar o progresso alcançado no tratamentodos transtornos da ansiedade com a utilização dos benzodiazepínicose, mais recentemente, com o uso de antidepressivos. Novasalternativas para o tratamento dos transtornos da ansiedade envolvempesquisas relacionadas à descoberta de novos antidepressivos, aouso de peptídeos neuroativos, como a colecistocinina (CCK), fatorde liberação de corticotropina (CRH), neuropetídeo Y, e antagonistasdo receptor glutamatérgico NMDA. Conclusão: Observa-se o progressoalcançado no tratamento farmacológico dos transtornos da ansiedadecom a utilização principalmente dos antidepressivos. Entretanto, umlongo caminho ainda haverá que ser trilhado em busca de novasopções terapêuticas para abordagem destes transtornos...

To present an updated and broad perspective of anxietyconcerning its pathological manifestation, neural bases and theprogress in its psychopharmacological therapeutic approach. Method:It was conduced a literature review whose source of research waspapers indexed by the database Pubmed, Medline and researchesfrom specific books that investigated the anxiety in its pathologicalaspect. Results: As regards the genesis of anxiety disorders, severalneurotransmitters are involved since they participate, in a greater orlesser degree, in the modulation and regulation of defensive behaviors.The evidence obtained so far allows noting the progress achieved inthe treatment of anxiety disorders with the use of benzodiazepinesand, more recently, antidepressants. New alternatives for the treatmentof the anxiety-related disorders involve researches related to thediscovery of new antidepressants, to the use of neuroactive peptidessuch as cholecystokinin (CCK), corticotropin releasing factor (CRH),neuropeptide Y, and antagonists of glutamatergic NMDA receptor.Conclusion: Advances can be observed in the pharmacologicaltreatment of anxiety disorders mainly by using antidepressants.However, there is still a long way to be followed in order to find newtherapeutic options for these disorders...

Traumatismos gástricos penetrantes / Penetrating gastric injuries

Sao analisados 24 casos de traumatismos gastricos penetrantes operados num periodo de 5 anos. Vinte e um pacientes (87,5%) eram do sexo masculino, e a media de idade foi de 24,6 anos. A arma branca foi o agente responsavel pela lesao gastrica em 50% dos casos. O indice de complicacoes foi de 29,2%, e a mortalidade operatoria atingiu a taxa de 16,6% (4 casos). A infeccao deiscencia da ferida cirurgica foi a complicacao mais frequente (12,5%) porem nao exerceu influencia decisiva na mortalidade, nesta casuistica. Em oito casos (33,3%), houve lesao diafragmatica assiciada, caracterizando o ferimento toraco-abdominal. Um destes pacientes desenvolveu empiema pleural no pos-operatorio e foi a obito em consequencia de infeccao pulmonar e insuficiencia respiratoria. Dois pacientes apresentaram fistulas digestivas de alto debito e evoluiram com disturbio metabolico grave, vindo a falecer. O quarto obito ocorreu por sepse abdominal, que culminou com falencia de multiplos orgaos. Todos os obitos desta serie foram de pacientes vitimas de ferimentos por arma de fogo e que apresentavam multiplas lesoes associadas. Estes resultados permitem afirmar que as lesoes gastricas isoladas raramentem representam risco de vida para os pacientes, e que os indices de complicacoes e mortalidade correlacionam-se diretamente com a natureza de lesao e com a multiplicidade de visceras lesadas nos traumatismos abdominais.