Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis.

PURPOSE: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAFV600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAFV600E ATC patients. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAFV600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs). RESULTS: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I2 = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I2 = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I2 = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I2 = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found. CONCLUSIONS: Our study demonstrated BRAFi/MEKi have a decent activity for BRAFV600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.

Differential gene expression profile of multinodular goiter.

INTRODUCTION: The goiter, a neglected heterogeneous molecular disease, remains a major indication for thyroidectomies in its endemic regions. OBJECTIVES: This study analyzed differential gene expression in surgical specimens diagnosed with multi nodular and compared the data to that of thyroid tissue without multinodular goiter from patients undergoing thyroidectomy in Manaus-AM, Brazil using RNA-seq technology. METHODOLOGY: The transcriptome information of the surgical specimen fragments with and without multinodular goiter was accessed by Illumina HiSeq 2000 New Generation Sequencing (NGS) using the RNA-seq NEBNext® Ultra™ RNA Library Prep Kit for Illumina®-#E7530L protocol and differential gene expression analysis. RESULTS: Differences were found between the gene expression profiles of the diseased tissues and those of the healthy control tissues; at least 70 genes were differentially expressed. The HOTS gene was expressed only in multinodular goiter tissues (p < 0.05). CONCLUSION: These results demonstrate that the gene expression profile of multinodular goiter is pro-tumoral and that HOTS can play a central role in multinodular goiter development.

Produção e validação do Programa Telediabetes: tecnologia educacional para profissionais da atenção primária / Production and validation of the Telediabetes Program: educational technology for primary care professionals

Objetivo: produzir e validar o roteiro de aulas do Programa Telediabetes como uma tecnologia educacional para profissionais de saúde da atenção primáriado interior do Amazonas. Métodos: pesquisa metodológica, realizada em três etapas: produção do roteiro, com conteúdo para qualificar a assistência prestada na atenção primáriaàs pessoas que convivem com diabetes, baseada em uma revisão da literatura e nas dificuldades dos profissionais de saúde compartilhadas no Telessaúde; validação dos conteúdos por juízes-especialistas; reestruturação do roteiro para elaboração da versãofinal. Resultados: na etapa de produção, emergiu a versão inicial com seis aulas. Na etapa de validação, participaram 18 juízes da área da saúde das cinco regiões do país. Na validação de conteúdo, obteve-se índice de validade de conteúdo de 0,89. A validação ocorreu por meio digital em uma única rodada. Na etapa de reestruturação, foram acatadas as sugestões para a versão final.Conclusão: o roteiro de aulas do Programa Telediabetes foi considerado válido e adequado para a educação permanente de profissionais da atenção primária.

Objective: To produce and validate the Telediabetes Program's classroom script as an educational technology for primary care health professionals in the interior of Amazonas. Methods: Methodological research, carried out in three stages: production of a script with content to qualify the care provided in primary care to people living with diabetes, based on a literature review and on the difficulties of health professionals shared in Telehealth; content validation by expert judges; restructuring of the script to prepare the final version. Results: In the production phase, the initial version with six classes emerged. In the validation phase, 18 health judges from five regions of the country participated. In content validation, a content validity index of 0.89 was obtained. Validation took place digitally in a single round. During the restructuring phase, the suggestions for the final version were accepted. Conclusion: The Telediabetes Program class script was considered valid and adequate for the continuing education of primary care professionals.

Hiperaldosteronismo primário, como descrito por Conn. Relato decaso / Hyperaldosteronism, as described by Conn. Case report

O hiperaldosteronismo primário é causa de hipertensão arterialsecundária, com possibilidade de cura após cirurgia em 30a 75% dos casos. O objetivo deste estudo foi relatar um casode hipertensão arterial secundária a adenoma adrenal produtorde aldosterona. Paciente feminino, 35 anos, natural de Beruri(AM), procedente de Manaus, foi admitida com pressão arterialde 220x125mmHg associada a fraqueza muscular de membrosinferiores e câimbras. Na história patológica pregressa, havia orelato de hipertensão arterial diagnosticada há 2 anos, em tratamentocom três classes de anti-hipertensivos. Durante internaçãoem hospital geral, o quadro relatado associado à hipocalemiae alcalose metabólica sugeriram diagnóstico de hipertensão arterialsecundária a hiperaldosteronismo primário. Níveis elevadosde aldosterona plasmática, com renina suprimida e relação aldosterona-renina elevada, confirmaram o diagnóstico de hiperaldosteronismoprimário. A tomografia computadorizada deabdome evidenciou lesão tumoral com 2,3x2,0cm em glândulasuprarrenal esquerda sugestiva de adenoma adrenal. Pacientefoi submetida a adrenalectomia à esquerda com histopatologiacompatível com adenoma adrenal. Seis meses após a cirurgia,paciente evoluiu com normalização da calemia, porém mantevehipertensão arterial com necessidade de terapia anti-hipertensiva,sem novos picos hipertensivos. Se hiperaldosteronismo primáriodiagnosticado precocemente, há possibilidade de cura dahipertensão arterial secundária após adrenalectomia, reduzindo o efeito deletério da mesma sobre os sistemas cardiovascular, cerebrovasculare renal.(AU)

The primary hyperaldosteronism is a cause of secondaryhypertension, with the possibility of healing after surgery in 30to 75% of cases. The objective of this study was to report a caseof secondary hypertension to aldosterone-producing adrenaladenoma. A female patient, 35 years, from Beruri (AM), Brazil,who came to Manaus, was admitted into the emergency room withblood pressure of 220x125mmHg, associated with lower limbmuscle weakness and cramps. In the past medical history, there wasa report of hypertension diagnosed 2 years before, and she was undertreatment with three classes of antihypertensive drugs. Duringhospitalization in a general hospital, the case reported associatedto hypokalemia and metabolic alkalosis suggested a diagnosis ofhypertension secondary to primary hyperaldosteronism. Elevatedlevels of plasmatic aldosterone, suppressed renin and highaldosterone-renin relation suggested primary hyperaldosteronism.The abdominal computerized tomography scan revealed a tumor of2.3x2.0cm in the left adrenal gland, suggesting adrenal adenoma.Patient underwent left adrenalectomy and histopathology wascompatible to adrenal adenoma. After 6 months of surgery, thepatient experienced normalization of kalemia but kept arterialhypertension, requiring anti-hypertensive therapy, but had no othershypertensive peaks. Early diagnosis of primary hyperaldosteronismallowed the cure of hypertension after adrenalectomy, reducingdeleterious effects of high blood pressure levels on the cardiovascular,cerebrovascular and renal systems.(AU)

Cândida esofágica em paciente diabético tipo 2 ? relato de caso / Esophageal candidiasis in type 2 diabetic patients ? case report

A cândida sp. são fungos comensais dos seres humanos e consideradasflora normal do trato gastrointestinal e genitourinário.Entretanto alterações na imunidade do hospedeiro podem culminarem infecção por estes fungos, definida como candidíase.Uma causa importante do desequilíbrio imunológico são asdoençasendócrinas, principalmente o Diabetes tipo 2. Pacientesdiabéticos estão mais propensos a desenvolver formas infecciosasde candidíase, destacando o comprometimento esofágicoque muitas vezes, não é diagnosticado. O objetivo deste estudofoi relatar um caso de paciente diabético tipo 2 com processoinfeccioso importante à esclarecer decorrente de extensa cândidíaseesofágica. Paciente masculino, 55 anos, procedente deItacoatiara-AM, tabagista de longa data. Após história prévia deinternação hospitalar para tratamento de Diabetes tipo 2 descompensadae piomiosite de coxa esquerda, evoluiu com asteniainsidiosa, anorexia, mal-estar e febre diária (38,5 ºC), intermitente,vespertina, sendo diagnosticado e tratado para infecçãodo trato urinário, sem melhora. Após piora do quadro, acrescidode disfagia para sólidos e perda ponderal, foi re-internado paraelucidaçãodiagnóstica. Durante a investigação apurou-se sangueoculto nas fezes positivo, seguida de endoscopia digestivaalta mostrando várias placas elevadas esbranquiçadas linearese confluentes ocupando todo o trajeto do esôfago, compatívelcom candidíase esofágica grau III de KODSI. As sorologias paraHIV e Hepatites B e C, foram negativas. A biopsia revelou esofagiteaguda erosiva. Devemos estar atentos à possibilidade de infecção por cândida, em especial, o comprometimento esofágico,nos pacientes diabéticos descompensados que apresentemfatores de risco associados a sinais e sintomas da doença e/ouinfecciosos, sem foco definido.(AU)

Candida sp. are commensal fungi of humans and are considerednormal flora of the gastrointestinal and genitourinary tracts.However, changes in the host immunity may lead to infection bythese fungi, defined as candidiasis. A major cause of the imbalanceare immune endocrine diseases, especially type 2 diabetesmellitus. Diabetic patients are more likely to develop infectiousforms of candidiasis, in particular the esophageal involvementthat often goes undiagnosed. The aim of this study was to reporta case of a type 2 diabetic patient with an infectious processwhich is important to clarify the result of extensive esophagealcandidiasis. Male patient, 55 years, coming from Itacoatiara-AM,a longtime smoker. After a history of hospitalization for treatmentof decompensated diabetes mellitus type 2 and pyomyositis of theleft thigh, it progressed with insidious asthenia, anorexia, malaiseand intermittent evening daily fever (38.5 °C), he was diagnosedand treated for urinary tract infection with no improvement.After the condition worsened, followed by dysphagia for solidsand weight loss, he was re-admitted for diagnosis. During theinvestigation it was found positive fecal occult blood, upperendoscopy showed multiple elevated confluent whitish linearplaques occupying the entire course of the esophagus, esophagealcandidiasis compatible with grade III KODSI. Serology forHIV and Hepatitis B and C were negative. The biopsy revealed acute erosive esophagitis. We must be alert to the possibility ofinfection by Candida, in particular, esophageal involvement inpatients presenting decompensated diabetic risk factors associatedwith signs and symptoms of disease and/or infections, without adefined focus.(AU)

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil.

BACKGROUND: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). METHODS: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. RESULTS: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). CONCLUSIONS: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.

Poor glycaemic control in Brazilian patients with type 2 diabetes attending the public healthcare system: a cross-sectional study.

OBJECTIVES: To describe the clinical profile of Brazilian patients with type 2 diabetes attending the public healthcare system and identify factors associated with poor glycaemic control. DESIGN: Cross-sectional study. SETTING: 14 centres in five regions of Brazil, including primary care units and outpatient clinics of University Hospitals. PARTICIPANTS: Patients with type 2 diabetes attending outpatient clinics of public healthcare system. MAIN OUTCOME MEASURED: Glycated haemoglobin (HbA1c), centrally measured by high-performance liquid chromatography (National Glycohemoglobin Standardization Program certified). RESULTS: A total of 5750 patients aged 61±10 years, with 11±8 years of diabetes duration (66% women, 56% non-white, body mass index: 28.0±5.3 kg/m(2)) were analysed. Mean HbA1c was 8.6±2.2%, and median HbA1c was 8.1% (6.9% to 9.9%). HbA1c <7% was observed in only 26% of patients. Mean HbA1c was higher (p < 0.01) in the North (9.0±2.6%) and Northeast (8.9±2.4%) than in the Midwest (8.1±2%), Southeast (8.4±2.1%) and South regions (8.3±1.9%). Using the cut-off value of HbA1c above the median, age (0.986 (0.983 to 0.989)), white ethnicity (0.931 (0.883 to 0.981)) and being from Midwest region (0.858 (0.745 to 0.989)) were protective factors, while diabetes duration (1.015 (1.012 to 1.018)), use of insulin (1.710 (1.624 to 1.802)) and living in the Northeast region (1.197 (1.085 to 1.321)) were associated with HbA1c >8%. CONCLUSIONS: The majority of Brazilian patients with type 2 diabetes attending the public healthcare system had HbA1c levels above recommended targets. The recognition of Northeast residents and non-white patients as vulnerable populations should guide future policies and actions to prevent and control diabetes.