A meta-analysis of published clinical trials has shown that interferon-a therapy has a limited ef®cacy in patients with chronic hepatitis induced by hepatitis C virus (HCV) infection. 1 A sustained response, de®ned on the basis of normal alanine aminotransferase levels or no detectable HCV RNA at the end of treatment and throughout the follow-up period after stopping treatment, is observed in approximately 20% of these patients. 1, 2 Two other patterns of response to interferon-a have been de®ned: biochemical response (alanine aminotransferase normalization) at the end of treatment and subsequent relapse (at least 50% of the cases); and nonresponse, where alanine aminotransferase is persistently abnormal or serum HCV RNA is positive during treatment (50% of the cases). 3 Re-treatment with interferon-a after failure of the initial course of therapy is unsatisfactory and has caused researchers to look beyond the monotherapy of interferon-a. 4 SUMMARYBackground: Up to 80% of hepatitis C patients are refractory to treatment with interferon-a. These patients are not likely to bene®t from higher dosages or longer duration of interferon alone. The addition of ribavirin has been shown to improve the response rate in patients resistant to a previous course of interferon-a alone. Aim: To evaluate whether a sustained hepatitis C virus (HCV) RNA 1 response could be obtained with combination therapy of interferon-a and ribavirin in patients who did not respond to or relapsed after a standard interferon-a treatment. Methods: A total of 73 patients, 59 non-responders and 14 relapsers after interferon-a alone, were treated with a combination of ribavirin (1000±1200 mg/day) and interferon-a (3 MU three times a week) for 24 weeks.

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Objective: To determine whether an early lifestyle change program (consisting of customized nutritional advices and a constant moderate physical activity) can reduce the incidence of unfavorable maternal and neonatal outcomes among overweight/obese women. Research design and methods: This is a case-control study: women included in a lifestyle change program were labeled as cases; controls were randomly selected from the next three women delivering after one case and not undergoing any specific lifestyle change program, but only referred by the obstetrics of the National Health System. Cases attended a multidisciplinary counselling (by both the dietitian and the gynecologist) from enrollment (9 th-12 th week) until delivery (with four follow-up visits), consisting of a hypocaloric, low-glycemic index diet and a moderate physical activity program. Results: Three-hundred seventy-five women were included: 95 cases and 275 controls. Overall gestational weight gain and the rate of women remaining within the Institute of Medicine recommendations was similar between groups. The occurrence of gestational diabetes mellitus was lower in cases (21.5%) than in controls (32.7%; p = 0.041), and remained statistically significant after correcting for confounding factors (BMI ≥30 kg/m 2 , a family history of diabetes, age ≥35 y and ethnicity; p = 0.005). Pre-term births were significantly lower in cases (1.1%) than in controls (10.2%; p = 0.004). A higher number of controls developed hypertensive disorders (p = 0.024), in particular pregnancy-induced hypertension (1.1% in cases vs. 11.6% in controls, p = 0.0007). The frequency of macrosomic or large-for-gestational-age babies was significantly lower among cases (vedi prima) (p = 0.015 and p = 0.003 respectively). Conclusion: An early behavioral intervention among overweight/obese pregnant women (an individualized counseling by a dietician, a physical activity program and a close follow-up) reduces the preterm birth, the hypertensive disorders and the gestational diabetes mellitus, thus the occurrence of macrosomic and large-forgestational-age babies, while it doesn't affect the occurrence of small-for-gestational-age.

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Objectives: To evaluate the feasibility of Doppler-ultrasound (DUS) gated four-dimensional (4D) flow magnetic resonance imaging (MRI) in the human fetus at 3 Tesla. Methods: 4D flow MRI measurements of the thoracic aorta were acquired in six healthy fetuses (gestational week 30-35) at 3T (Philips, Ingenia). Fetal cardiac gating was performed using an MR-compatible Doppler-ultrasound sensor. 4D flow MRI was performed in parasagittal orientation using compressed sensing (sense factor = 4) and free maternal breathing. For each 4D dataset, fetal aortic blood flow was visualised and quantified using dedicated software (GTFlow 3.2, GyroTools LLC, Zurich, Switzerland). Results: 4D flow MRI was successfully performed in 5/6 (83%) fetuses. One dataset could not be analysed due to fetal movements and inadequate image quality. Blood flow of the thoracic aorta was successfully visualised in the remaining five fetuses including foramen ovale and ductus arteriosus. The transverse diameter of the descending aorta was 7.8 mm (± 1.2 mm). Time-velocity curves based on 4D flow measurements demonstrated typical arterial blood flow patterns with early systolic peaks and low positive diastolic flow. Mean blood flow velocity in the descending aorta was 24 ml/s (± 4 ml/s). Conclusions: Direct cardiac Doppler-ultrasound gating allowed successful 4D flow MRI acquisition of the thoracic aorta in the human fetuses at 3 Tesla. DUS-gated 4D flow MRI of the fetal thoracic aorta visualised patterns of hemodynamics and allowed blood flow quantifications. The feasibility of DUS-gated 4D flow MRI could be demonstrated, yet the diagnostic performance of this technique, e.g. regarding congenital cardiovascular disease, is still unclear and requires further investigation. DUS-gated 4D flow MRI of the fetal heart and great thoracic vessels might potentially provide a valuable adjunct to echocardiography in the diagnosis of congenital cardiovascular disease.