During the month of 2009 December, the blazar 3C 454.3 became the brightest gamma-ray source in the sky, reaching a peak flux F {approx} 2000 x 10{sup -8} photons cm{sup -2} s{sup -1} for E > 100 ...MeV. Starting in 2009 November intensive multifrequency campaigns monitored the 3C 454 gamma-ray outburst. Here, we report on the results of a two-month campaign involving AGILE, INTEGRAL, Swift/XRT, Swift/BAT, and Rossi XTE for the high-energy observations and Swift/UVOT, KANATA, Goddard Robotic Telescope, and REM for the near-IR/optical/UV data. GASP/WEBT provided radio and additional optical data. We detected a long-term active emission phase lasting {approx}1 month at all wavelengths: in the gamma-ray band, peak emission was reached on 2009 December 2-3. Remarkably, this gamma-ray super-flare was not accompanied by correspondingly intense emission in the optical/UV band that reached a level substantially lower than the previous observations in 2007-2008. The lack of strong simultaneous optical brightening during the super-flare and the determination of the broadband spectral evolution severely constrain the theoretical modeling. We find that the pre- and post-flare broadband behavior can be explained by a one-zone model involving synchrotron self-Compton plus external Compton emission from an accretion disk and a broad-line region. However, the spectra of the 2009 December 2-3 super-flare and of the secondary peak emission on 2009 December 9 cannot be satisfactorily modeled by a simple one-zone model. An additional particle component is most likely active during these states.
Aim To evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the differentiation of hepatic abscesses from non-infected fluid collections. Materials and methods In this ...retrospective study, 22 hepatic abscesses and 27 non-infected hepatic fluid collections were examined in 27 patients who underwent abdominal MRI including DW-MRI. Two independent observers reviewed T2-weighted + DW-MRI and T2-weighted + contrast-enhanced T1-weighted (CET1W) images in two sessions. Detection rates and confidence levels were calculated and compared using McNemar's and Wilcoxon's signed rank tests, respectively. Apparent diffusion coefficient (ADC) values of abscesses and non-infected fluid collections were compared using the t -test. Receiver operating characteristic (ROC) curves were constructed. Results There was no statistically significant difference in the accuracy of detecting abscesses using T2-weighted + DW-MRI (both observers: 21/22, 95.5%) versus T2-weighted + CET1W images (observer 1: 21/22, 95.5%; observer 2: 22/22, 100%; p < 0.01). Mean ADC values were significantly lower with abscesses versus non-infected fluid collections (0.83 ± 0.24 versus 2.25 ± 0.61 × 10−3 mm2 /s; p < 0.001). With ROC analysis there was good discrimination of abscess from non-infected fluid collections at a threshold ADC value of 1.36 × 10−3 mm2 /s. Conclusion DW-MRI allows qualitative and quantitative differentiation of abscesses from non-infected fluid collections in the liver.
Summary
Background Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates.
Aim To assess the safety and efficacy of ...pegylated‐interferon (PEG‐IFN) alfa‐2b + ribavirin (RBV) in patients with post‐LT recurrent genotype‐1 HCV and to establish stopping rules according to response.
Methods Fifty‐three patients with post‐LT HCV recurrence were enrolled. Patients received PEG‐IFN alfa‐2b 1.0 μ/kg/week plus RBV 8–10 mg/kg/day for 24 weeks. Those with ‘early virological response at week 24’ (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C).
Results Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV‐RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02–106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end‐of‐treatment response. One patient in group B had SVR.
Conclusions Pegylated‐interferon alfa‐2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with ≥2 log10 drop in HCV‐RNA at week 24.
Summary
Long‐term functional outcomes of sofosbuvir‐based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for ...post‐transplant hepatitis C virus (HCV) recurrence. Seventy‐three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24‐week sofosbuvir with ribavirin±pegylated interferon or interferon‐free sofosbuvir‐based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82‐112) weeks. Twelve of 73 (16.4%) died (10 non‐FCH, 2 FCH) and two underwent re‐LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non‐FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow‐up, MELD and Child‐Turcotte‐Pugh scores improved both in non‐FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short‐treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long‐term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child‐Turcotte‐Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals‐based treatments for severe post‐transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long‐term survival. The setting of severe HCV recurrence may require the identification of “too‐sick‐to‐treat patients” to avoid futile treatments.
Abstract Background Cytomegalovirus (CMV) is a major cause of graft failure and posttransplantation mortality in intestinal/multivisceral transplantation. CMV infection exhibits a wide range of ...clinical manifestations from asymptomatic infection to severe CMV disease. Study's Purpose The purposes of this study were to assess the utility of measuring CMV-specific cellular immunity in bowel/multivisceral transplant recipients and to provide additional information on the risk of infection and development of CMV disease. Methods We studied 10 bowel/multivisceral transplant recipients to investigate the kinetics of CMV infection using real-time polymerase chain reaction (on blood and biopsy tissue samples) and CMV-specific T-cell reconstitution by Enzyme-linked ImmunoSPOT Assay (ELISPOT) that enumerates Interferon-γ–secreting CMV-specific T cells upon in vitro stimulation with viral antigens (pp65 and IE-1). Results All patients were seropositive for CMV. According to the pattern of T-cell reconstitution occurring either within the first month after transplantation or later, patients were classified as early (n = 7) or late responders (n = 3). Clinically, early responder patients (3/7; 43%) experienced asymptomatic or mild CMV infections, whereas all late responders (3/3; 100%) developed moderate or severe CMV disease. A reduction in mean and peak CMV viral load was observed in early responders, whereas the onset time of infection did not differ significantly between early and late CMV responders. Conclusions A good and early reconstitution of CMV-specific T-cell immune responses after transplantation is a critical determinant in controlling CMV infections. Simultaneous monitoring of CMV infection and CMV-specific T-cell immunity predicts T-cell–mediated control of CMV infection.
This study was designed to compare the effects of a 6-month treatment with budesonide 100 μg bid (low dose) and 400 μg bid (standard reference dose) in controlling symptoms and lung function in a ...group of asthmatics with moderate asthma (baseline FEV1 ≥ 50% and ≤ 90% of predicted values) previously treated with inhaled beclomethasone dipropionate (500 to 1,000 μg/d). Moreover, we investigated whether or not asthma exacerbations could be treated by a short-term increase in the daily dose of budesonide.
After a 2-week run-in period and 1-month treatment with a high dose of budesonide (800μ g bid), 213 patients with moderate asthma were assigned to randomized treatments. Daily treatment included budesonide (bid) plus an additional treatment in case of exacerbation (qid for 7 days). Treatments were as follows: budesonide 400 μg plus placebo (group 1); budesonide 100 μg plus budesonide 200 μg (group 2); and budesonide 100 μg plus placebo (group 3). Symptoms and a peak expiratory flow (PEF) diary were recorded and lung function was measured each month. An exacerbation was defined as a decrease in PEF > 30% below baseline values on 2 consecutive days.
We found that that 1-month treatment with a high budesonide dose remarkably reduced all asthma symptoms. Moreover, symptoms were under control in all treatment groups throughout the study period. Similarly, lung function improved and remained stable, and no relevant differences between groups were observed. In each treatment group, the majority of patients had no exacerbations. In patients treated with the standard budesonide dose (group 1), the number of exacerbations and days with exacerbations were significantly lower than in group 3 (intention-to-treat analysis). Additionally, patients treated with low budesonide dose plus budesonide (group 2) experienced a significantly lower number of exacerbations and days with exacerbations compared to group 3 (per-protocol analysis).
This study demonstrates that when patients with moderate asthma had reached a stable clinical condition with a high dose of budesonide, a low dose of budesonide (200 μg/d) is as effective as the standard dose (800 μg/d) in the control of symptoms and lung function over a period of several months. Furthermore, results showed that the addition of inhaled budesonide (800 μg/d) at onset of an asthmatic exacerbation has a beneficial clinical effect.
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