STARTVerso1: A Randomized Trial of Faldaprevir Plus Pegylated Interferon/Ribavirin for Chronic HCV Genotype-1 Infection

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

Mixomas Cardíacos, 13 Anos de Experiência no seu Diagnóstico Ecocardiográfico

INTRODUCTION: Transthoracic echocardiography is the method of choice for the diagnosis of cardiac myxomas, but the transesophageal approach provides a better definition of the location and characteristics of the tumor. The authors review their thirteen years' experience on the echocardiographic diagnosis of this pathology. METHODS: From 1994 to 2007, 41 cardiac tumors were diagnosed in our echocardiographic laboratory, of which 27 (65.85%) were cardiac myxomas. The exams and the patients' clinical files were retrospectively reviewed. RESULTS: Of the 27 patients, 22 (81.5%) were female, with a mean age of 62.1 +/- 13.6 years (25-84 years). The predominant clinical features were due to the obstruction caused by the tumor in more than two thirds of the patients, followed by constitutional symptoms in one third and embolic events in 30%. In the lab results, anemia was found in three patients and elevated sedimentation rate and CRP in two. In two patients the myxoma was found by chance. All the cases were of the sporadic type, although we found a prevalence of thyroid disease of 14% (4 patients). All patients underwent urgent surgical resection except one, in whom surgery was refused due to advanced age and comorbidities. The myxomas followed a typical distribution with 24 (88.8%) located in the left atrium, 18 of them attached to the atrial septum (AS) and two to the mitral valve. In one patient, the tumor involved both atria. The other two cases originated in the right atrium at the AS. Embolic phenomena were more frequent in small tumors (p = 0.027) and in those with a villous appearance (p = 0.032). Obstructive manifestations were associated with larger tumors (p = 0.046) and larger left atria (p = 0.048). In our series, there were no deaths during hospitalization or in the follow-up period of 5.2 +/- 3.7 years in 19 patients. There were two recurrences, both patients being successfully reoperated. CONCLUSION: Myxoma is the most common cardiac tumor. Transesophageal echocardiography provides excellent morphologic definition, aiding in diagnosis and follow-up. Most clinical manifestations are obstructive and are associated with larger tumors. Small tumors with a friable appearance have a higher chance of embolization. Surgical resection is usually curative and the long-term prognosis is excellent.

Diabetes Gestacional - Rastreio Pós-Parto

Introdução: Um terço das mulheres com diabetes gestacional terá o diagnóstico de diabetes ou alteração do metabolismo da glicose no rastreio pós-parto. Objectivo: Avaliar a percentagem de mulheres submetidas a rastreio pós-parto e associar o resultado com a história materna. Métodos: Estudo retrospectivo de 1013 gravidezes com diabetes gestacional (2005-2009). Dividiu-se a população em dois grupos de acordo com o resultado: normal (grupo 1) e com diabetes ou alteração do metabolismo da glicose (grupo 2). Para ambos os grupos foram avaliados: idade materna, índice de massa corporal, ganho de peso na gravidez, idade gestacional do diagnóstico, necessidade de administração de insulina, factores de risco para diabetes gestacional e peso do recém-nascido. Resultados: O rastreio pós-parto foi realizado em 76,8% das mulheres (n=778). O teste foi considerado normal (grupo 1) em 628 mulheres(80,7%) e alterado (grupo 2) em 150 mulheres (19,3%). O Grupo 2 teve mulheres mais velhas (idade média de 34 vs 33 anos;p-value 0,013), com maior índice de massa corporal (28,5 vs 25,8kg / cm2; p-value 0,000), maior número de mulheres com história familiar em primeiro grau de diabetes mellitus (50,3% vs 39,9%; p-value 0,026) e história pessoal de macrossomia prévia (12,1% vs 5,4%; p-value 0,003). O diagnóstico mais precoce da diabetes gestacional foi também feito nesse grupo (27 vs 31 semanas; p-value 0,000) e uma maior percentagem efectuou insulina (41% vs 15%; p-value 0,000), tendo iniciado mais cedo a sua administração (28 vs 30 semanas; p-value 0,010). Verificou-se uma maior percentagem de grávidas multíparas no grupo 2 (64% vs 49,4%; p-value = 0,001) e um maior número de casos de recém-nascidos grandes para a idade gestacional (17,1% vs 8,3%; p-value = 0,001). A história pessoal de diabetes gestacional e ganho de peso durante a gestação foi semelhante nos dois grupos. Conclusões: As mulheres com alteração nos resultados do rastreio pós-parto são geralmente mais velhas, mais pesadas, multíparas, com história familiar em primeiro grau de diabetes Mellitus e história pessoal de macrossomia prévia. O diagnóstico de diabetes gestacional foi mais precoce neste grupo, mais frequentemente necessitaram de terapêutica com insulina com início mais cedo e verificou-se um maior número de recém-nascidos grandes para a idade gestacional.

Recurrence After Operative Management of Intrahepatic Cholangiocarcinoma

INTRODUCTION: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC. METHODS: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. RESULTS: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. CONCLUSION: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.

Alergia a Medicamentos Reportada em Crianças que Frequentam Infantários

Introdução: A prevalência de alergia a fármacos na população geral não se encontra devidamente caraterizada, existindo poucos estudos publicados que tenham abordado esta situação em crianças com idades inferior a seis anos de idade. Este estudo tem como objetivo principal estimar a prevalência de alergia a medicamentos reportada pelos pais de crianças de infantários de Lisboa e do Porto. Material e Métodos: No âmbito da Fase II do projeto “ENVIRH – Ambiente e Saúde em Creches e Infantários” foi aplicado um questionário sobre alergia a medicamentos aos pais das crianças, recrutadas por amostragem aleatória estratificada dos infantários. Resultados: Foram analisados 1 169 questionários, 52,5% de rapazes. A idade média foi de 3,5 ± 1,5 anos. A prevalência de alergia a medicamentos reportada foi de 4,1% (IC 95%: 3,0 - 5,2%). Os fármacos mais referidos foram os antibióticos (em 27 reações) e os AINEs (em seis reações). Na análise multivariável, a alergia a medicamentos reportada associou-se diretamente com a idade da criança (OR 1,19; IC 95% 1,01 - 1,41) e com a referência a alergia alimentar (OR 3,19; IC95% 1,41 - 7,19) e inversamente com o nível de escolaridade dos pais (OR 0,25; IC95% 0,10 - 0,59). Discussão: Apesar das limitações do estudo, os resultados encontram-se de acordo com o reportado por outros autores e sugerem que a prevalência reportada de alergia a medicamentos seja elevada no grupo etário estudado. Conclusão: Torna-se necessário que situações de alergia a medicamentos reportadas pelos pais sejam devidamente estudadas, no sentido de evitar evicções desnecessárias que possam condicionar opções terapêuticas em futuras situações de doença.

Clinical Outcome and Morphologic Determinants of Mural Thrombus in Abdominal Aortic Endografts

OBJECTIVE:Endograft mural thrombus has been associated with stent graft or limb thrombosis after endovascular aneurysm repair (EVAR). This study aimed to identify clinical and morphologic determinants of endograft mural thrombus accumulation and its influence on thromboembolic events after EVAR. METHODS: A prospectively maintained database of patients treated by EVAR at a tertiary institution from 2000 to 2012 was analyzed. Patients treated for degenerative infrarenal abdominal aortic aneurysms and with available imaging for thrombus analysis were considered. All measurements were performed on three-dimensional center-lumen line computed tomography angiography (CTA) reconstructions. Patients with thrombus accumulation within the endograft's main body with a thickness >2 mm and an extension >25% of the main body's circumference were included in the study group and compared with a control group that included all remaining patients. Clinical and morphologic variables were assessed for association with significant thrombus accumulation within the endograft's main body by multivariate regression analysis. Estimates for freedom from thromboembolic events were obtained by Kaplan-Meier plots. RESULTS: Sixty-eight patients (16.4%) presented with endograft mural thrombus. Median follow-up time was 3.54 years (interquartile range, 1.99-5.47 years). In-graft mural thrombus was identified on 30-day CTA in 22 patients (32.4% of the study group), on 6-month CTA in 8 patients (11.8%), and on 1-year CTA in 17 patients (25%). Intraprosthetic thrombus progressively accumulated during the study period in 40 patients of the study group (55.8%). Overall, 17 patients (4.1%) presented with endograft or limb occlusions, 3 (4.4%) in the thrombus group and 14 (4.1%) in the control group (P = .89). Thirty-one patients (7.5%) received an aortouni-iliac (AUI) endograft. Two endograft occlusions were identified among AUI devices (6.5%; overall, 0.5%). None of these patients showed thrombotic deposits in the main body, nor were any outflow abnormalities identified on the immediately preceding CTA. Estimated freedom from thromboembolic events at 5 years was 95% in both groups (P = .97). Endograft thrombus accumulation was associated with >25% proximal aneurysm neck thrombus coverage at baseline (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3), neck length ≤ 15 mm (OR, 2.4; 95% CI, 1.3-4.2), proximal neck diameter ≥ 30 mm (OR, 2.4; 95% CI, 1.3-4.6), AUI (OR, 2.2; 95% CI, 1.8-5.5), or polyester-covered stent grafts (OR, 4.0; 95% CI, 2.2-7.3) and with main component "barrel-like" configuration (OR, 6.9; 95% CI, 1.7-28.3). CONCLUSIONS: Mural thrombus formation within the main body of the endograft is related to different endograft configurations, main body geometry, and device fabric but appears to have no association with the occurrence of thromboembolic events over time.