Resumo Fundamento: A segurança e a eficácia da varfarina dependem da qualidade do controle da anticoagulação. Estudos observacionais associam controle deficiente com aumento de morbidade, mortalidade e custos com saúde. Objetivos: Desenvolver um perfil de pacientes com fibrilação atrial não valvar (FANV) tratados com varfarina em ambiente ambulatorial e hospitalar privado brasileiro, avaliar a qualidade do controle da anticoagulação e sua associação com resultados clínicos e econômicos. Métodos: Este estudo retrospectivo, por meio de um conjunto de dados de seguros privados de saúde no Brasil, identificou pacientes com FANV tratados com varfarina entre 01 de maio de 2014 a 30 de abril de 2016, descreveu seu manejo da anticoagulação e quantificou os custos relacionados à doença. Foram recuperados dados demográficos, histórico clínico, medicação concomitante e tempo na faixa terapêutica (TTR) dos valores da razão normalizada internacional (RNI). Os pacientes foram agrupados em quartis de TTR, com um bom controle sendo definido como TTR ≥65% (método de Rosendaal). Sangramentos maiores e custos médicos diretos por todas as causas foram calculados e comparados entre subgrupos de controle bons e ruins. Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: A análise incluiu 1220 pacientes (mediana de seguimento: 1,5 anos; IIQ: 0,5-2,0). Em média, cada paciente recebeu 0,95 medidas mensais de RNI (RNI média: 2,60 ± 0,88, com 26,1% dos valores < 2 e 24,8% > 3), (mediana de TTR: 58%; IIQ: 47-68%), (TTR médio: 56,6% ± 18,9%). Apenas 31% dos pacientes estavam bem controlados (TTR médio: 78% ± 10%), com 1,6% apresentando grandes sangramentos na mediana do seguimento e custos médicos diretos por membro por ano (PMPY) de R$25.352 (± R$37.762). Pacientes com controle abaixo do ideal (69%) foram associados a 3,3 vezes mais sangramentos graves (5,3% vs. 1,6%; p <0,01) e custos 40% maiores (R$35.384 vs. R$25.352; p < 0,01). Conclusões: Mais de 60% dos pacientes estavam abaixo da meta desejada e os custos associados foram significativamente maiores nesta população.

Abstract Background: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. Objectives: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. Methods: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. Results: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). Conclusions: More than 60% of the patients were below the desired target and the associated costs were higher.

Little is known about the use of dermoscopy in skin grafting. We describe the case of a patient with skin grafting and surrounding pigmentation on acral region. The dermoscopic findings were similar to those of benign acral lesions (lattice-like pattern) and reactive pigmentations (fine striae). Histopathology revealed pigment leakage and increased number of melanocytes. It is believed that this phenomenon occured as the result of an inflammatory stimulus.

A esclerose múltipla é a doença inflamatória auto-imune mais comum do sistema nervoso central. Sua etiologia já foi creditada apresentar tanto causas genéticas quanto ambientais. Vários vírus já foram implicados como desencadeadores desta doença e existem inúmeros trabalhos fazendo correlação entre a família Herpesviridae e a patogênese da esclerose múltipla. As características mais importantes dos Herpesviridae são as de apresentarem períodos de latência e exacerbação e terem como seu principal santuário biológico o sistema nervoso central. O vírus Epstein-Barr, o citomegalovírus, o herpesvirus tipo 6 e herpesvirus tipo 7 são os membros mais estudados como desencadeadores da esclerose múltipla. Conforme as evidencias que a literatura apresenta a família Herpesviridae está fortemente envolvida na patogênese da esclerose múltipla, porém é pouco provável que sejam os únicos responsáveis pelo seu início. É provável que esta doença apresente inúmeros desencadeadores e mais estudos são necessários para determinar estas interações.

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

OBJECTIVE: The ideal ratio between liver graft mass and recipient body weight for liver transplantation in small infants is unknown; however, if this ratio is over 4%, a condition called large-for-size may occur. Experimental models of large-for-size liver transplants have not been described in the literature. In addition, orthotopic liver transplantation is marked by high morbidity and mortality rates in animals due to the clamping of the venous splanchnic system. Therefore, the objective of this study was to create a porcine model of large-for-size liver transplantation with clamping of the supraceliac aorta during the anhepatic phase as an alternative to venovenous bypass. METHOD: Fourteen pigs underwent liver transplantation with whole-liver grafts without venovenous bypass and were divided into two experimental groups: the control group, in which the weights of the donors were similar to the weights of the recipients; and the large-for-size group, in which the weights of the donors were nearly 2 times the weights of the recipients. Hemodynamic data, the results of serum biochemical analyses and histological examination of the transplanted livers were collected. RESULTS: The mortality rate in both groups was 16.5% (1/7). The animals in the large-for-size group had increased serum levels of potassium, sodium, aspartate aminotransferase and alanine aminotransferase after graft reperfusion. The histological analyses revealed that there were no significant differences between the groups. CONCLUSION: This transplant method is a feasible experimental model of large-for-size liver transplantation.

BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions.

OBJECTIVE: Non-pituitary tumors have been reported in a subset of patients harboring germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. However, no detailed investigations of non-pituitary tumors of AIP-mutated patients have been reported so far. PATIENTS: We examined a MEN1- and p53-negative mother-daughter pair with acromegaly due to somatotropinoma. Subsequently, the mother developed a large virilizing adrenocortical carcinoma and a grade II B-cell non-Hodgkin's lymphoma. DESIGN: Mutational analysis was performed by automated sequencing. Loss-of-heterozygosity (LOH) analysis was carried out by sequencing and microsatellite analysis. AIP expression was assessed through quantitative PCR (qPCR) and immunohistochemistry. RESULTS: The functional inactivating mutation c.241C>T (R81X), which blocks the AIP protein from interacting with phosphodiesterase 4A (PDE4A), was identified in the heterozygous state in the leukocyte DNA of both patients. Analyzing the tumoral DNA revealed that the AIP wild-type allele was lost in the daughter's somatotropinoma and the mother's adrenocortical carcinoma. Both tumors displayed low AIP protein expression levels. Low AIP gene expression was confirmed by qPCR in the adrenocortical carcinoma. No evidence of LOH was observed in the DNA sample from the mother's B-cell lymphoma, and this tumor displayed normal AIP immunostaining. CONCLUSIONS: Our study presents the first molecular analysis of non-pituitary tumors in AIP-mutated patients. The finding of AIP inactivation in the adrenocortical tumor suggests that further investigation of the potential role of this recently identified tumor suppressor gene in non-pituitary tumors, mainly in those tumors in which the cAMP and the 11q13 locus are implicated, is likely to be worthwhile.