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.

High-intensity interval exercise promotes post-exercise hypotension of greater magnitude compared to moderate-intensity continuous exercise.

PURPOSE: Physical exercise is associated with reduced blood pressure (BP). Moderate-intensity continuous exercise (MCE) promotes post-exercise hypotension (PEH), which is highly recommended to hypertensive patients. However, recent studies with high-intensity interval exercise (HIIE) have shown significant results in cardiovascular disease. Thus, this study aimed to analyze PEH in hypertensive subjects submitted to HIIE and compare it to post MCE hypotension. METHODS: 20 hypertensive adults (51 ± 8 years), treated with antihypertensive medications, were submitted to two different exercise protocols and a control session. The MCE was performed at 60-70% of VO2 reserve, while HIIE was composed of five bouts of 3 min at 85-95% VO2 reserve with 2 min at 50% of VO2 reserve. The following variables were evaluated during exercise, pre- and post-session: clinical BP, heart rate (HR), double product, perception of effort, body mass, height and body mass index. RESULTS: Systolic BP decreased after exercise in both sessions, showing greater decrease after HIIE (- 7 ± 10 and - 11 ± 12 mmHg, after MCE and HIIE, respectively, p ≤ 0.01). Diastolic BP also decreased after both sessions, but there were no significant differences between the two sessions (- 4 ± 8 and - 7 ± 8 mmHg, after MCE and HIIE, respectively). CONCLUSION: Both exercise sessions produced PEH, but HIIE generated a greater magnitude of hypotension. The HIIE protocol performed in this study caused a greater cardiovascular stress during exercise; however, it was safe for the studied population and efficient for reducing BP after exercise.

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.

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.

NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution.

PURPOSE: The risk of developing childhood leukemia has been associated with gene polymorphisms that decrease the activity of detoxifying metabolic enzymes and enzymes involved in systemic oxidative stress. We investigated the NQO1 and PON1 polymorphisms for associations with susceptibility to childhood leukemia. METHODS: Samples from 1,027 Brazilian children (519 acute lymphoblastic leukemia, ALL; 107 acute myeloid leukemia, AML; 401 controls) were analyzed. TaqMAN real-time assays were used to determine the NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) frequencies. Logistic regression was used to evaluate the association of polymorphisms with cases and controls, with age and somatic fusion genes (MLL-r and ETV6-RUNX1) as covariables. RESULTS: Children with at least one NQO1 variant allele were at lower risk for developing infant AML (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10-0.68); no association was detected for ALL. PON1 rs854560 (L55M) was associated with an increased risk of developing childhood leukemia (LM + MM, OR 1.93, 95 % CI 1.32-2.81). The PON1 rs662 R192R genotype had a statistically significant decreased frequency in ALL (OR 0.64, 95 % CI 0.43-0.93). Infant ALL cases were more likely to harbor homozygous PON1 rs854560 alleles than controls (OR 1.72, 95 % CI 1.03-2.89); at least one M allele was associated with an increased risk of ALL in children older than 1 year (OR 1.99, 95 % CI 1.17-3.3). CONCLUSIONS: The NQO1 rs1800566 (C609T), PON1 rs854560 (L55M), and PON1 rs662 (Q192R) polymorphisms modified risk depending on leukemia subtype (decreased in AML, increased and decreased in ALL, respectively), age strata, and variant genotype combinations.

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.

Relationship Between Skeletal Muscle Mass Indexes and Muscular Function, Metabolic Profile and Bone Mineral Density in Women with Recommendation for Bariatric Surgery.

BACKGROUND AND AIM: We evaluated low skeletal muscle mass (LMM) in women prior to bariatric surgery (BS) through different skeletal muscle mass indexes (MMIs) regarding body fat percentage (BFP), handgrip strength (HS), six-minute walk test (6MWT), metabolic profile and bone mineral density (BMD). METHODS: Women (n=62) were allocated into two groups according to LMM: obesity with low muscle mass (OLMM) or obesity with normal muscle mass (ONMM). LMM was defined by the appendicular skeletal muscle mass (ASM) adjusted for weight (ASM/wt × 100) and ASM adjusted for body mass index (ASM/BMI), considering the lowest quintile of the indexes studied. RESULTS: OLMM was found in 30.5% by ASM/wt × 100 and 20.3% by ASM/BMI. Using the ASM/wt × 100, OLMM group had a high BFP, low HS and BMD in L1-L4, femoral neck (FN) and total femur (TF) when compared with ONMM (p < 0.05). Using ASM/BMI, OLMM group had increased BFP, reduced HS and 6MWT in comparison to ONMM (p < 0.05). Metabolic profile was similar between OLMM and ONMM groups by the two MMIs. MMIs were negatively correlated with BFP (p < 0.05) and positively correlated with HS (p < 0.05), and none of them with 6MWT (p > 0.05). ASM/wt × 100 was positively correlated with all BMD sites assessed (p < 0.05). There was positive correlation between ASM/wt × 100 and ASM/BMI. CONCLUSION: OLMM identified by the ASM/wt × 100 and ASM/BMI had higher adiposity and lower HS. Using ASM/BMI, we found that OLMN had a poor physical performance, while the ASM/wt × 100 identified a lower BMD at all sites.

Impact of arterial hypertension and type 2 diabetes on cardiac autonomic modulation in obese individuals with recommendation for bariatric surgery.

BACKGROUND AND AIM: Obese individuals with recommendation for bariatric surgery (BS) exhibit increased cardiovascular risk. The association of obesity with comorbidities, such as arterial hypertension (HTN) and type 2 diabetes mellitus (T2DM) can worsen cardiovascular dysfunction. This study aimed to investigate the effect of HTN on cardiac autonomic function and whether diabetes exacerbates HTN-related impairment of autonomic function in obese subjects. METHODS: Samples (n=63) were allocated to three groups: Obese without HTN and T2DM (n=29), Obese with HTN (OHTN, n=17) and OHTN with T2DM (OHTN+T2DM, n=17), in which anthropometric measures, body composition, blood biochemical parameters, blood pressure (BP) and heart rate variability (HRV) were evaluated. RESULTS: The age was higher in OHTN+T2DM and OHTN than in obese groups (p<0.05). OHTN+T2DM individuals had increased neck circumference and compromised glycemic profile when compared to obese and OHTN groups (p<0.05). Mean values for standard deviation of RR (SDRR), square root of the mean squared differences of successive RR interval (RMSSD) and number of pairs of successive normal-to-normal beat intervals that differed by 50 ms (pRR50) were significantly lower in OHTN+T2DM and OHTN groups when compared to patients with obesity alone (p<0.05). The low frequency (LF), low frequency/high frequency (LF/HF) ratio were higher in the OHTN+T2DM and OHTN than subjects with obesity alone (p<0.05). Nonlinear parameters SD2 and SD1 were also lower in the OHTN+T2DM when compared to the obese group (p<0.05). However, the SD2/SD1 ratio was higher in the OHTN+T2DM and OHTN groups than the obese group. CONCLUSION: T2DM and/or HTN impair the cardiac autonomic function in obese patients. However, the presence of T2DM did not exacerbate the hypertension-related impairment of autonomic function.

Processing parameters matching effects upon Rhizobium tropici biopolymers' rheological properties.

The combined effects of the processing parameters upon rheological properties of biopolymers produced by Rhizobium tropici were studied as a function of the Ca(+2) ions' concentration variation, yeast extract concentration added to the medium, aeration, and agitation, maintaining the mannitol concentration in 10 g/L. The experiments were carried out using a fermenter with 20-L capacity as a reactor. All processing parameters were monitored online. The temperature [(30 +/- 1) degrees C] and pH values (7.0) were kept constant throughout the experimental time. As a statistical tool, a complete 2(3) factorial design with central point and response surface was used to investigate the interactions between relevant variables of the fermentation process: calcium carbonate concentration, yeast extract concentration, aeration, and agitation. The processing parameter setup for reaching the maximum response for rheological propriety production was obtained when applying mannitol concentration of 10.0 g/L, calcium carbonate concentration 1.0 g/L, yeast extract concentration 1.0 g/L, aeration 1.30 vvm, and agitation 800 rpm. The viscosimetric investigation of polysaccharide solutions exposed their shear-thinning behavior and polyelectrolytic feature.

Prevalence ratio of HTLV-1 in nursing mothers from the state of Paraiba, Northeastern Brazil.

The human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus known as a direct causal agent of a malignant disease. The vertical route of HTLV transmission is the most frequent pathway of the virus contamination. This study was performed to determine the prevalence ratio of HTLV-1 infection among nursing women. From January 2004 to January 2005, blood samples from 1033 nursing mothers from Paraíba, Brazil were evaluated for HTLV antibodies by ELISA and HTLV-1 viral particles confirmed by polymerase chain reaction (PCR). HTLV antibodies were detected in 7 women. The overall seroprevalence ratio was 0.68% and HTLV-1 viral sequences were confirmed by PCR in 2 women. These preliminary data suggest that HTLV screening should be introduced as a mandatory test before breastfeeding and breast milk donation in Paraíba, Brazil. Additionally, counseling programs would help reduce the prevalence ratio of HTLV-1 infected individuals in this Brazilian region.

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.

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.

Anxiolytic-like activity and GC-MS analysis of (R)-(+)-limonene fragrance, a natural compound found in foods and plants.

The traditional use of essential oils in aromatherapy has offered numerous health benefits. However, few scientific studies have been conducted with these oils to confirm their therapeutic efficacy. (+)-Limonene is a chemical constituent of various bioactive essential oils. The present study reports on the anxiolytic-like effects of (+)-limonene in an elevated maze model of anxiety in mice. At concentrations of 0.5% and 1.0%, (+)-limonene, administered to mice by inhalation, significantly modified all the parameters evaluated in the elevated plus maze test. The pharmacological effect of inhaled (+)-limonene (1%) was not blocked by flumazenil. Analysis of (+)-limonene using gas chromatography-mass spectrometry (GC-MS) showed its volatility to be high. These data suggest possible connections between the volatility of (+)-limonene and its anxiolytic-like effect on the parameters evaluated in the elevated plus maze test. The data indicate that (+)-limonene could be used in aromatherapy as an antianxiety agent.

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.

Treatment patterns of Hodgkin's lymphoma in Brazil: experts' perspective / Padrões de tratamento do linfoma de Hodgkin no Brasil: a perspectiva dos especialistas

Background: Hodgkin's Lymphoma (HL) is a curable type of cancer, with a wide variety of therapies, especially for refractory/relapsing cases. Therefore, the study aims to explore the treatment patterns used in the management of HL patients in Brazil. Methods: A survey was developed to explore the treatment patterns in Brazil, addressing topics such as clinical characteristics, lines of therapy, transplant information and cure rates. Then, results were presented in a panel discussion to validate participants' responses and gain additional insights. Main results: The eight experts reported that most patients are women and under 60 years old. In both private and public healthcare systems, ABVD was the most commonly used first-line therapy for patients of all stages. The median cure rates for patients in stages I and II were 80% and 87.5%, and for stages III and IV 60% and 67.5%, respectively, in public and private sectors. For the subsequent lines of therapy, different regimens such as DHAP, GVD, GEV, ICE and allogeneic transplant are used, among others. Brentuximab vedotin was present mainly in the private sector. In the public sector, 70% of the patients are eligible for autologous stem cell transplant; of them, 75% actually receive the transplant. In the private sector, 80% of the patients are eligible, and 100% of them receive the transplant. Conclusion: Similarities were found between the public and private sectors in first-line therapy and cure rates. However, barriers for subsequent lines of therapy are more evident in the public system.

Introdução: O linfoma de Hodgkin (LH) é um tipo de câncer curável, com ampla variedade de terapias, especialmente para casos refratários/recidivantes. Portanto, o estudo visa explorar os padrões de tratamento utilizados no manejo de pacientes com LH no Brasil. Métodos: Uma pesquisa foi desenvolvida para explorar os padrões de tratamento no Brasil, abordando tópicos como: características clínicas, linhas de terapia, informações sobre transplantes e taxas de cura. Em seguida, os resultados foram apresentados em um painel de discussão para validar as respostas dos participantes e coletar os insights adicionais. Principais resultados: Os oito especialistas relataram que maioria dos pacientes é composta por mulheres com idade menor de 60 anos. Em ambos os sistemas de saúde, privado e público, ABVD foi a terapia de primeira linha mais comumente usada para pacientes de todos os estágios. As medianas das taxas de cura para pacientes nos estágios I e II foram de 80% e 87,5%, e para os estádios III e IV, de 60% e 67,5%, nos setores público e privado, respectivamente. Para as linhas subsequentes de terapia, diferentes regimes como DHAP, GVD, GEV, ICE e transplante alogênico são utilizados, entre outros. Brentuximabe vedotina estava presente principalmente no setor privado. No setor público, 70% dos pacientes são elegíveis para transplante autólogo de células-tronco; deles, 75% recebem o transplante. No setor privado, 80% dos pacientes são elegíveis e 100% recebem o transplante. Conclusão: Foram encontradas semelhanças entre o setor público e privado na terapia de primeira linha, bem como nas taxas de cura. No entanto, as barreiras para as linhas subsequentes de terapia são mais evidentes no sistema público.

Detection of mutations in GATA1 gene using automated denaturing high-performance liquid chromatography and direct sequencing in children with Down syndrome.

Denaturing high-performance liquid chromatography (dHPLC) was developed to screen DNA variations by separating heteroduplex and homoduplex DNA fragments by ion-pair reverse-phase liquid chromatography. In this study, we have evaluated the dHPLC screening method and direct sequencing for the detection of GATA1 mutations in peripheral blood and bone marrow aspirates samples from children with Down syndrome (DS). Cases were ascertained consecutively as part of an epidemiological study of DS and hematological disorders in Brazil. A total of 130 samples corresponding to 115 children with DS were analysed using dHPLC and direct sequencing methods to detect mutations in GATA1 exons 2, 3 and 4 gene sequences. The overall detection rate of sequencing and dHPLC screening methods was similar. Twenty mutations were detected in exon 2 and one mutation in exon 3 (c.231_232 dupGT) sequences of acute megakaryoblastic leukemia and transient leukemia samples. Four GATA1 mutations were newly described [c.155C > G; c.156_178 del23 bp; c.29_30 del GG; c.182C > A and c.151A > T,c.153_162 del 10 bp). Out of four, three had single nucleotide change. In conclusion, our results indicate that dHPLC is an efficient and valuable tool for GATA1 mutational analysis.

Zumbido e ansiedade: uma revisão da literatura / Tinnitus and anxiety: a literature review

O zumbido, som percebido pelo indivíduo sem que haja estímulo externo, resulta da interação dinâmica de centros do sistema nervoso central, incluindo vias auditivas e não auditivas. O resultado desta interação, especialmente sistema límbico e sistema nervoso autônomo, seria responsável pelo desencadeamento de associações emocionais negativas e reações de incômodo em pacientes com zumbido. A ansiedade, condição fisiológica inerente ao ser humano, quando exacerbada gera um transtorno de humor, comprometendo o pensamento, o comportamento e a atividade psicológica. Se um estímulo interno ou externo for interpretado como perigoso ou ameaçador, desencadeará uma reação emocional caracterizada como estado de ansiedade. Este artigo tem como objetivo realizar uma revisão da literatura sobre a relação do zumbido e da ansiedade. Em se tratando do zumbido, a forma como o som é percebido pode ser alterado pela ansiedade, aguçando assim a sensibilidade para detectar sons que parecem uma ameaça em potencial, pois para muitos o zumbido é sinônimo de enfermidade grave. A etiologia do desenvolvimento da depressão e ansiedade pode estar relacionada ao zumbido. Muitos adquirem esse sintoma por problemas físicos e, consequentemente, desenvolvem a depressão e a ansiedade. Outros com graus diferentes de angústias adquirem o zumbido devido ao comprometimento emocional. Dessa forma, existe um vínculo entre o zumbido e problemas emocionais, mas nem sempre é fácil identificar o precursor. Estudos demonstram que pacientes acometidos pelo zumbido apresentam maior tendência ao suicídio, depressão e ansiedade. Além disso, referem o efeito aditivo da ansiedade e da depressão na qualidade de vida e no zumbido dos indivíduos.

Tinnitus is a sound perceived without external stimulus, and results from the dynamic interaction of the centers in the central nervous system, including non-auditory and auditory ways. The result of this interaction, especially with the limbic system and autonomic nervous system, would be responsible for triggering negative emotional associations and distress in patients with tinnitus. Anxiety, a physiological condition inherent to human beings, when exacerbated, generates a mood disorder, affecting thinking, behavior and physiological activity. If an inner or outer stimulus is interpreted as dangerous or threatening, it may trigger an emotional reaction characterized as a state of anxiety. This work aims to review the relationship between tinnitus and anxiety. The tinnitus sound is perceived can be altered by anxiety, thereby, sharpening the sensitivity in detecting sounds that seem a potential threat, because for many people, tinnitus is synonymous with a serious illness. The etiology for the development of depression and anxiety may be related to tinnitus. Many people acquire this symptom by physical problems and hence develop depression and anxiety. Others with different degrees of distress due to tinnitus acquire emotional problems. Thus, there is a probable link between tinnitus and emotional problems, but it is not always easy to identify which one occurs first. Studies show that patients affected by tinnitus have a greater trend for suicide, depression and anxiety. They also refer to the additive cumulative effects of anxiety and depression on the quality of life of tinnitus sufferers.

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...

Macroglobulinemia de Waldenström: remissão completa após tratamento com rituximabe / Successful outcome in Waldenström's macroglobulinemia treated with rituximab

A macroglobulinemia de Waldenstrõm (MW) é uma patologia rara dos linfócitos B caracterizada pela produção monoclonal de IgM, e que pode manifestar-se clinicamente com fadiga, astenia, perda de peso, sangramento de mucosas e do trato gastrintestinal, lifonodonomegalias, hepatoesplenomegalia e alterações neurológicas. A doença é mais comum em pacientes idosos, e seus sintomas são decorrentes da hiperviscosidade sangüínea. Na MW observa-se hipergamaglobulinemia com pico monoclonal na eletroforese de proteínas séricas, níveis elevados de IgM e demais imunoglobulinas normais ou diminuídas, imunofenotipagem com linfócitos B CD19+, CD20+ e CD24+, aspirado de medula óssea hipercelular, e biópsia de medula óssea hipercelular com infiltração difusa de linfócitos, linfócitos plasmocitóides e plasmócitos. Atualmente, anticorpos monoclonais estão sendo usados na terapêutica da MW com grande sucesso. O rituximabe, anticorpo monoclonal anti -CD20, tem mostrado excelentes resultados no tratamento da MW, inclusive naqueles indivíduos que não obtiveram resposta adequada ao tratamento convencional. Nós reportamos o caso de uma mulher de 78 anos de idade com história de fadiga, astenia, anorexia, sonolência, inquietação, urticária, dificuldade para deambular e perda excessiva de peso, aproximadamente 22 kg em um período de cinco meses, cujo tratamento foi realizado com rituximabe. O objetivo deste relato é apresentar uma paciente com diagnóstico de MW e revisar aspectos clínicos e terapêutico atual da doença.

Waldenstrõm's macroglobulinemia is a rare pathology of B lymphocytes characterized by the production of monoclonal IgM, causing clinical manifestations which may include fatigue, asthenia, weight loss, bleeding of the mucosa and intestinal tract, lymphadenomegaly, hepatosplenomegaly and neurological alterations. The disease is more frequent among elderly patients and its symptoms are a result of the hyperviscosity of blood. Waldenstrõm's macroglobulinemia presents hypergammaglobulinemia with a monoclonal peak of serum proteins seen by electrophoresis, high IgM levels and other normal or diminished immunoglobulin levels, immunophenotyping with CD19+, CD20+ and CD24+ B lymphocytes aspirated from hypercellular bone marrow and hypercellular bone marrow biopsy with diffuse infiltration of lymphocytes, plasmocytoid lymphocytes and plasmocytes. Currently, monoclonal antibodies are successfully being used in the treatment of Waldenstrõm's macroglobulinemia. Rituximab, an anti-CD20 monoclonal antibody, has shown excellent results in the treatment of Waldenstrõm's macroglobulinemia even for individuals who did not obtain satisfactory responses to conventional treatment. This work reports the case of a 78-year-old woman with a history of fatigue, asthenia, anorexia, somnolence, restlessness, urticaria, difficulties in walking, and excessive weight loss (approximately 22 Kg within a period of 5 months) who was successfully treated using rituximab. The objective of this report is to present the case of this patient and to review current clinical and therapeutic aspects of the disease.

Doenca de Castleman localizada abdominal / Abdominal Castleman's disease

A doenca de Castleman é um distúrbio linfoproliferativo raro. Há três tipos histológicos: hialino-vascular (mais comum), variante de células plasmáticas e forma mista. A forma hialino-vascular é caracterizada tipicamente por apresentar uma evolucão clínica benigna, sem sintomas constitucionais (doenca localizada). É geralmente tratada com cirurgia e/ou radioterapia. A doenca multicêntrica apresenta sintomas sistêmicos. Ainda não há um consenso sobre qual a melhor abordagem terapêutica. Nós reportamos o caso de um homem de 47 anos de idade com uma massa abdominal e sintomas compressivos. Após resseccão cirúrgica parcial, os exames histopatológico e imuno-histoquímico revelaram doenca de Castleman variante hialino vascular. Como as células foliculares eram CD20+, administramos rituximab (anticorpo monoclonal anti-CD20). A maioria dos casos revisados não consideram este tipo de abordagem, exceto no caso de doenca de Castleman multicêntrica associada a infeccão pelo HHV-8 e sarcoma de Kaposi. Geralmente considera-se o paciente curado após retirada cirúrgica da massa na doenca localizada, mas realmente há um risco do paciente desenvolver um linfoma não-Hodgkin no seguimento a longo prazo. O objetivo deste relato é apresentar um caso raro que deve ser incluído no diagnóstico diferencial de desordens linfóides e discutir o tratamento desta doenca.