Doença de Behçet - Infliximab no Tratamento das Manifestações Mucocutâneas

A Doença de Behçet (DB) é uma doença inflamatória multisistémica, crónica e recidivante, cujo diagnóstico é essencialmente clínico. Em estudos recentes, os antagonistas do factor de necrose tumoral a têm mostrado bons resultados no tratamento das manifestações mucocutâneas da DB. Os autores descrevem três casos de DB com envolvimento mucocutâneo grave tratados com infliximab. Caso Clínico 1: Doente do sexo feminino de 16 anos de idade, com aftose bipolar grave com 8 anos de evolução. Verificou-se uma rápida resposta clínica à terapêutica biológica, com remissão parcial e total das úlceras à 2ª e 6ª semana de tratamento, respectivamente Caso Clínico 2: Doente do sexo feminino de 56 anos de idade com paniculite nodular crónica dos membros inferiores, artralgias e ulcerações orogenitais recorrentes. Após 6 semanas de terapêutica com infliximab, verificou-se uma remissão clínica completa. Caso Clínico 3: Doente do sexo feminino de 50 anos de idade, com ulcerações orofaríngeas recorrentes com 15 anos de evolução. Observou-se uma boa resposta clínica à terapêutica biológica, que foi interrompida à 22ª semana por abcessos dentários recorrentes. Na nossa experiência, o infliximab é uma alternativa terapêutica eficaz a considerar na presença de manifestações mucocutâneas resistentes aos tratamentos convencionais.

Utilidade do Doppler Tecidular na Predição de Eventos Arrítmicos em Adultos com Tetralogia de Fallot Corrigida

INTRODUCTION: Adults with repaired tetralogy of Fallot (TOF) may be at risk for progressive right ventricular (RV) dilatation and dysfunction, which is commonly associated with arrhythmic events. In frequently volume-overloaded patients with congenital heart disease, tissue Doppler imaging (TDI) is particularly useful for assessing RV function. However, it is not known whether RV TDI can predict outcome in this population. OBJECTIVE: To evaluate whether RV TDI parameters are associated with supraventricular arrhythmic events in adults with repaired TOF. METHODS: We studied 40 consecutive patients with repaired TOF (mean age 35 +/- 11 years, 62% male) referred for routine echocardiographic exam between 2007 and 2008. The following echocardiographic measurements were obtained: left ventricular (LV) ejection fraction, LV end-systolic volume, LV end-diastolic volume, RV fractional area change, RV end-systolic area, RV end-diastolic area, left and right atrial volumes, mitral E and A velocities, RV myocardial performance index (Tei index), tricuspid annular plane systolic excursion (TAPSE), myocardial isovolumic acceleration (IVA), pulmonary regurgitation color flow area, TDI basal lateral, septal and RV lateral peak diastolic and systolic annular velocities (E' 1, A' 1, S' 1, E' s, A' s, S' s, E' rv, A' rv, S' rv), strain, strain rate and tissue tracking of the same segments. QRS duration on resting ECG, total duration of Bruce treadmill exercise stress test and presence of exercise-induced arrhythmias were also analyzed. The patients were subsequently divided into two groups: Group 1--12 patients with previous documented supraventricular arrhythmias (atrial tachycardia, fibrillation or flutter) and Group 2 (control group)--28 patients with no previous arrhythmic events. Univariate and multivariate analysis was used to assess the statistical association between the studied parameters and arrhythmic events. RESULTS: Patients with previous events were older (41 +/- 14 vs. 31 +/- 6 years, p = 0.005), had wider QRS (173 +/- 20 vs. 140 +/- 32 ms, p = 0.01) and lower maximum heart rate on treadmill stress testing (69 +/- 35 vs. 92 +/- 9%, p = 0.03). All patients were in NYHA class I or II. Clinical characteristics including age at corrective surgery, previous palliative surgery and residual defects did not differ significantly between the two groups. Left and right cardiac chamber dimensions and ventricular and valvular function as evaluated by conventional Doppler parameters were also not significantly different. Right ventricular strain and strain rate were similar between the groups. However, right ventricular myocardial TDI systolic (Sa: 5.4+2 vs. 8.5 +/- 3, p = 0.004) and diastolic indices and velocities (Ea, Aa, septal E/Ea, and RV free wall tissue tracking) were significantly reduced in patients with arrhythmias compared to the control group. Multivariate linear regression analysis identified RV early diastolic velocity as the sole variable independently associated with arrhythmic history (RV Ea: 4.5 +/- 1 vs. 6.7 +/- 2 cm/s, p = 0.01). A cut-off for RV Ea of < 6.1 cm/s identified patients in the arrhythmic group with 86% sensitivity and 59% specificity (AUC = 0.8). CONCLUSIONS: Our results suggest that TDI may detect RV dysfunction in patients with apparently normal function as assessed by conventional echocardiographic parameters. Reduction in RV early diastolic velocity appears to be an early abnormality and is associated with occurrence of arrhythmic events. TDI may be useful in risk stratification of patients with repaired tetralogy of Fallot.

Variantes Genéticas Pró-Trombóticas como (Improváveis?) Factores de Risco para as Grandes Crises Vaso-Oclusivas na Drepanocitose

CONTEXTO: A drepanocitose é uma anemia hemolítica hereditária com características pró-adesivas, pró-inflamatórias e pró-coagulantes, incluindo alterações na hemostase e activação da cascata da coagulação. PLANO DO ESTUDO: Neste estudo analisaram-se, em 140 drepanocíticos africanos e 126 indivíduos sem hemoglobina S também de origem africana, variantes genéticas polimórficas em quatro loci envolvidos na coagulação (F2 20210G>A e F5 R506Q), na fibrinólise (PAI-1 5G>4G), ou no metabolismo da homocisteína (MTHFR 677C>T). Estratificaram-se os pacientes em dois grupos de acordo com a ocorrência ou não de, pelo menos, uma complicação vaso-oclusiva (CVO) grave até à data da sua participação no estudo. RESULTADOS: Não se observou uma associação estatisticamente significativa entre a ocorrência de uma CVO grave e a herança do alelo predisponente à trombose, 4G no locus PAI-1 ou 677T no locus MTHFR. Nenhum drepanocítico apresentava os alelos F2 20210A ou F5 506Q (factor V Leiden). Visando excluir a possibilidade de que genuínas diferenças inter-grupos fossem mascaradas pela presença de indivíduos mais jovens no grupo sem-CVO, dividiu-se este num sub-grupo de pacientes mais novos e num sub-grupo de pacientes cuja idade não diferia significativamente do grupo com-CVO grave. Mesmo assim, não foi encontrada associação significativa. No entanto, pode observar-se, no grupo de doentes com o alelo PAI-1 4G (cuja expressão resulta numa diminuição da actividade fibrinolítica), uma tendência (OR=1,6) para um risco acrescido de CVO. Esta tendência era ligeiramente maior (OR=2,1) se se considerasse apenas a CVO síndrome torácica aguda. CONCLUSÕES: O alelo 4G no promotor do PAI-1 poderá ser um factor de risco para CVO na drepanocitose, uma hipótese a testar numa série maior de doentes, idealmente oriunda de uma população homogénea e com alta prevalência de drepanocitose.

Achieving K/DOQI Targets with Cinacalcet in Dialysis Patients with Secondary Hyperparathyroidism. A Portuguese Observational Study

Secondary hyperparathyroidism is a common complication of chronic kidney disease. The elevated serum intact parathyroid hormone, phosphorus, calcium and calcium x phosphorus product have been independently associated with an increased relative risk of mortality. The standard therapy for secondary hyperparathyroidism, including active vitamin D analogues and phosphate binders, is often insufficient to allow patients to achieve the recommended Kidney Disease Outcomes Quality Initiative targets for bone and mineral metabolism. Randomised controlled phase III clinical studies in chronic kidney disease patients with secondary hyperparathyroidism have shown that cinacalcet treatment increases the proportion of patients achieving the recommended Kidney Disease Outcomes Quality Initiative targets for intact parathyroid hormone, phosphorus, calcium and calcium x phosphorus product. Aims: This observational multicentre study aims to evaluate cinacalcet’s ability to achieve and maintain Kidney Disease Outcomes Quality Initiative targets in a population with secondary hyperparathyroidism on chronic haemodialysis in Portugal. Patients and Methods: Patients on chronic dialysis that received cinacalcet during a free sampling programme were enrolled. Retrospective and prospective monthly data were collected from 3 months before until 6 months after the beginning of cinacalcet treatment. Additional assessment included a 12 month evaluation of all parameters. Results: 140 dialysis patients with secondary hyperparathyroidism were enrolled, 60% male, mean age 57.4±14.1 years. The mean intact parathyroid hormone, calcium, phosphorus, and calcium x phosphorus product values at baseline were 751.7±498.8 pg/ml, 9.7±3.8 mg/dl, 5.5±1.5 mg/dl, and 52.7±25.3 mg2/dl2, respectively. After 6 months’ cinacalcet treatment, 26.2%, 53.6%, 59.3%, and 81.0% of the patients achieved the Kidney Disease Outcomes Quality Initiative recommended levels for intact parathyroid hormone, calcium, phosphorus, and calcium x phosphorus product, respectively. The mean dose of cinacalcet at 6 months was 57.1±29.7 mg/day. Conclusions: The use of cinacalcet in clinical practice is an effective option for the treatment of secondary hyperparathyroidism in chronic dialysis patients, allowing more patients to reach and maintain the Kidney Disease Outcomes Quality Initiative targets.

Genomic Signatures and Antiviral Drug Susceptibility Profile of A(H1N1)pdm09

Background: Genetic changes in influenza surface and internal genes can alter viral fitness and virulence. Mutation trend analysis and antiviral drug susceptibility profiling of A(H1N1)pdm09 viruses is essential for risk assessment of emergent strains and disease management. Objective: To profile genomic signatures and antiviral drug resistance of A(H1N1)pdm09 viruses and to discuss the potential role of mutated residues in human host adaptation and virulence. Study design: A(H1N1)pdm09 viruses circulating in Portugal during pandemic and post-pandemic periods and 2009/2010 season. Viruses were isolated in MDCK-SIAT1 cell culture and subjected to mutation analysis of surface and internal proteins, and to antiviral drug susceptibility profiling. Results: The A(H1N1)pdm09 strains circulating during the epidemic period in Portugal were resistant to amantadine. The majority of the strains were found to be susceptible to oseltamivir and zanamivir, with five outliers to neuraminidase inhibitors (NAIs) identified. Specific mutation patterns were detected within the functional domains of internal proteins PB2, PB1, PA, NP, NS1, M1 and NS2/NEP, which were common to all isolates and also some cluster-specific. Discussion: Modification of viral genome transcription, replication and apoptosis kinetics, changes in antigenicity and antiviral drug susceptibility are known determinants of virulence. We report several point mutations with putative roles in viral fitness and virulence, and discuss their potential to result in more virulent phenotypes. Monitoring of specific mutations and genetic patterns in influenza viral genes is essential for risk assessing emergent strains, disease epidemiology and public health implications.

Stress-Related Mucosal Disease: Incidence of Bleeding and the Role of Omeprazole in its Prophylaxis

BACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole.

Budesonide Reverses Lung Hyperinflation in Childhood Asthma: a Controlled Study

Budesonide (800 mg bid, for 2 months) was administered to 12 asthmatic children (mean age, 11.293.3 years) with lung hyperinflation (TGV]130% predicted and:or RV]140% predicted) in a randomised, placebo controlled, double blind, crossover study. Body plethysmography (panting frequency controlled at 1·s 1) was performed at the beginning, 2 months afterwards (before crossover) and at the end of the study. Budesonide significantly reduced TGV (2.3590.90 l BTPS or 126924% predicted) compared with placebo (2.5491.08 l BTPS, P 0.014 or 140921% predicted, PB0.05). In addition, budesonide significantly increased mean specific conductance (0.0690.02 cm H2O 1 l s 1 to 0.0790.01 cm H2O 1 l s 1, PB0.05). It was concluded that budesonide reduced lung hyperinflation most likely by decreasing airway inflammation.

Gastroenterite Aguda em Crianças Internadas na Área de Lisboa

Introdução: A Gastroenterite Aguda (GEA) é uma patologia com importante morbilidade sendo a segunda causa de internamento na idade pediátrica. Objetivo: Caracterizar a GEA, em crianças internadas em dois hospitais da área de Lisboa com diferentes características demográficas. Métodos: Estudo prospetivo de maio 2011 a junho 2012. Pesquisados potenciais agentes etiológicos por técnicas convencionais e de biologia molecular em amostras de fezes e analisados dados epidemiológicos e clínicos. Resultados: Total de 140 amostras de crianças com GEA com identificação do agente em 83,6%: 64,3% vírus, 27,9% parasitas e 21,4% bactérias. Os agentes mais frequentes foram rotavírus (26,4%), norovírus II (13,6%), enterovírus (12,1%), Microsporidia (11,4%), Escherichia coli (9,3%), Campylobacter jejuni (7,9%), Giardia sp. (5,7%), Cryptosporidium sp. (5%) e Salmonella sp. (4,3%). Coinfecções (2 ou mais agentes) em 40 doentes (28,6%). Mediana de idade de 1,4 anos (min-5 dias; max-17 anos) sendo a etiologia viral mais frequente abaixo dos 5 anos (p<0.01), com o rotavírus identificado em crianças mais jovens (média=1,7 anos). Dois picos sazonais: o rotavírus entre Janeiro e Março e norovírus entre Agosto e Outubro. Apenas 10 (7,1%) doentes estavam vacinados para rotavírus, mas nenhum com o esquema completo. A presença de sangue nas fezes (p=0,02) e a febre (p=0,039) foram mais frequentes na infeção bacteriana, os vómitos (p<0.01) e os sintomas respiratórios (p=0,046) na infeção por rotavírus. Registaram-se complicações clínicas em 50 doentes (35,7%): desidratação (47), invaginação íleo-cecal (1), adenite mesentérica (1) e apendicite fleimonosa (1). Conclusão: Os vírus são os agentes mais frequentes de GEA sobretudo na criança pequena (idade <5 anos), sendo o rotavírus e norovírus os principais agentes. O número de coinfecções foi significativo mas não se associou a maior morbilidade. A ausência de identificação de agente em alguns casos pode refletir a necessidade de outros meios diagnósticos ou a existência de agentes ainda desconhecidos.