Background
Many concerns about liver transplantation in alcoholic patients are related to the risk of alcohol recidivism. Starting from 2002, an Alcohol Addiction Unit (AAU) was formed within the ...liver transplant center for the management of alcoholic patients affected by end‐stage liver disease and included in the waiting list for transplantation. We evaluated retrospectively the impact of the AAU on alcohol recidivism after transplantation. The relationship between alcohol recidivism and the duration of alcohol abstinence before transplant was evaluated as well.
Methods
Between 1995 and 2010, 92 cirrhotic alcoholic patients underwent liver transplantation. Clinical evaluation and management of alcohol use in these patients was provided by psychiatrists with expertise in addiction medicine not affiliated to the liver transplant center before 2002 (n = 37; group A), or by the clinical staff of the AAU within the liver transplant center starting from 2002 (n = 55; group B).
Results
Group B, as compared with group A, showed a significantly lower prevalence of alcohol recidivism (16.4 vs. 35.1%; p = 0.038) and a significantly lower mortality (14.5 vs. 37.8%; p = 0.01). Furthermore, an analysis of group B patients with either ≥6 or <6 months of alcohol abstinence before transplantation showed no difference in the rate of alcohol recidivism (21.1 vs. 15.4%; p = ns).
Conclusions
The presence of an AAU within a liver transplant center reduces the risk of alcohol recidivism after transplantation. A pretransplant abstinence period <6 months might be considered, at least in selected patients managed by an AAU.
Objective
To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme.
Patients and Methods
Patients with metastatic renal cell ...cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0.
Results
A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non‐clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any‐grade treatment‐related AEs were fatigue (13%) and rash (9%). Twenty‐two patients (5.7%) discontinued treatment because of AEs. There were no treatment‐related deaths. The objective response rate was 23.1%. At a median follow‐up of 12 months, the median progression‐free survival was 4.5 months (95% confidence interval 3.7–6.2) and the 12‐month overall survival rate was 63%. Similar survival rates were reported among patients with non‐clear‐cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first‐line sunitinib or pazopanib, or prior everolimus.
Conclusion
The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non‐clear‐cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients.
Objectives
Evidence about the cross‐talk between iron, glucose metabolism, and cardiac disease is increasing. We aimed to explore the link of pancreatic iron by Magnetic Resonance Imaging (MRI) with ...glucose metabolism and cardiac complications (CC) in sickle cell disease (SCD) patients.
Methods
We considered 70 SCD patients consecutively enrolled in the Extension‐Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified by R2* technique and biventricular function by cine images. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement technique. Glucose metabolism was assessed by the oral glucose tolerance test.
Results
Patients with an altered glucose metabolism showed a significantly higher pancreas R2* than patients with normal glucose metabolism. Pancreatic siderosis emerged as a risk factor for the development of metabolic alterations (OddsRatio 8.25, 95%confidence intervals 1.51–45.1; p = .015). Global pancreas R2* values were directly correlated with mean serum ferritin levels and liver iron concentration. Global pancreas R2* was not significantly associated with global heart R2* and macroscopic myocardial fibrosis. Patients with history of CC showed a significantly higher global pancreas R2* than patients with no CC.
Conclusions
Our findings support the evaluation of pancreatic R2* by MRI in SCD patients to prevent the development of metabolic and cardiac disorders.
Even if cancer specific biomarkers are present in peripheral blood of cancer patients, it is very difficult to detect them with conventional technology because of their low concentration. A potential ...cancer biomarker is the HMGA1b protein, whose overexpression is a feature of several human malignant neoplasias. By taking advantage of the surface plasmon resonance (SPR) phenomenon, we realized a specific nano/technology-based assay for cancer detection. More in details, anti-HMGA1b monoclonal antibodies, whose affinity was previously defined by ELISA, were immobilized onto metallic surfaces to develop a direct SPR-based assay. After having analyzed blood samples from colorectal cancer patients and healthy people for the presence of HMGA1b, we observed a 2-fold increase of the HMGA1b levels in the blood of cancer patients with respect to the healthy control people. We conclude that the set-up technology might allow to detect a tumoral mass through the evaluation of HMGA1b protein blood levels.
We generated a specific nano/technology-based assay for detecting diagnostic biomarkers in the blood of cancer patients. Nano-structured gold surfaces were employed to immobilize anti-HMGA1b monoclonal antibodies to develop a direct surface plasmon resonance (SPR)-based assay. Plasma samples from colorectal cancer patients and healthy control people were analyzed for the presence of HMGA1b. A two-fold mean value increase of the HMGA1b was detected in the plasma from cancer patient, in comparison with healthy control people. Display omitted
Objectives
The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y12‐inhibitors (Is) in terms of angiographic endpoints and in relation to the time of the ...loading dose (LD) administration.
Background
The goal of ST‐elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y12‐Is prasugrel and ticagrelor have improved the angiographic outcome of primary percutaneous coronary intervention (pPCI) and patients' prognosis. However, their onset of action is impaired in STEMI and delayed by their oral administration.
Methods
The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of “P2Y12‐I LD administration‐to‐balloon time”: Group 2 included patients that received P2Y12‐I LD at least 60 min prior to pPCI, Group 1 within 60 min prior to pPCI, and Group 0 at the moment of pPCI. Angiographic, clinical, and biochemical parameters were evaluated. Pre‐ and post‐pPCI TIMI flow grade (TFG) and ST resolution (STR) were used as outcome measures to determine efficacy and optimal timing of pretreatment.
Results
Pre‐pPCI TFG improved with increasing P2Y12‐I LD administration‐to‐balloon time; pre‐PCI TFG 0/1 was 74.5% in Group 0, 65.5% in Group 1 and 54.9% in Group 2 (P < 0.002). Post‐pPCI TFG 3 results also differed significantly between the three groups: 85.2% in Group 0, 88.1% in Group 1, 97.6% in Group 2 (P < 0.013). ST resolution rates were also positively associated with longer pretreatment intervals.
Conclusions
This observational study suggests that the angiographic benefit of P2Y12‐I administration is time‐dependent: longer pretreatment improves coronary reperfusion in terms of pre‐ and post‐pPCI TFG and STR.
Vineyards containing vines affected with grapevine leaf stripe disease (GLSD), one of the diseases of the esca complex, suffer losses in grape yield and quality every growing season. To examine the ...relation between GLSD foliar symptoms and levels of phytoalexins in grapevine, phytoalexin levels were monitored in the leaves of symptomatic, asymptomatic/diseased, and healthy grapevine leaves, at various growth stages, in two vineyards in Italy, over four growing seasons. At the same time, the leaf symptoms of the vines at some of those growth stages were recorded in each vineyard and in each growing season. The compounds extracted and identified were: trans-resveratrol, trans-pterostilbene, trans-ε-viniferin and trans-δ-viniferin. The most common phytoalexin found was resveratrol. Amounts of all the phytoalexins were generally greater in symptomatic leaves than in asymptomatic/diseased or healthy leaves. In symptomatic leaves, resveratrol levels were greatest at pre-bunch closure, and peaks in pterostilbene occurred at the same time. Leaves of each category (symptomatic, asymptomatic/ diseased, healthy) had lower amounts of these compounds at veraison and generally higher amounts at the stages of harvesting and/or the softening of berries. It seems therefore that the formation and pattern over time of the phytoalexins was linked to the growth stage of the vines. Leaf symptoms never occurred before pre-bunch closure, but became much more common from veraison to harvest. This study provides evidence of a relationship between the levels of phytoalexins, grapevine growth stage, and the seasonal pattern of development of GLSD symptoms.
We report the Transiting Exoplanet Survey Satellite detection of a multi-planet system orbiting the V = 10.9 K0 dwarf TOI-125. We find evidence for up to five planets, with varying confidence. Three ...transit signals with high signal-to-noise ratio correspond to sub-Neptune-sized planets (2.76, 2.79, and 2.94 R⊕), and we statistically validate the planetary nature of the two inner planets (Pb = 4.65 days, Pc = 9.15 days). With only two transits observed, we report the outer object (P.03 = 19.98 days) as a planet candidate with high signal-to-noise ratio. We also detect a candidate transiting super-Earth (1.4 R⊕) with an orbital period of only 12.7 hr and a candidate Neptune-sized planet (4.2 R⊕) with a period of 13.28 days, both at low signal-to-noise ratio. This system is amenable to mass determination via radial velocities and transit-timing variations, and provides an opportunity to study planets of similar size while controlling for age and environment. The ratio of orbital periods between TOI-125 b and c (Pc/Pb = 1.97) is slightly lower than an exact 2:1 commensurability and is atypical of multiple planet systems from Kepler, which show a preference for period ratios just wide of first-order period ratios. A dynamical analysis refines the allowed parameter space through stability arguments and suggests that despite the nearly commensurate periods, the system is unlikely to be in resonance.
BRAF(V600E)-mediated MAPK pathway activation is associated in melanoma cells with IFNAR1 downregulation. IFNAR1 regulates melanoma cell sensitivity to IFNα, a cytokine used for the adjuvant treatment ...of melanoma. These findings and the limited therapeutic efficacy of BRAF-I prompted us to examine whether the efficacy of IFNα therapy of BRAF(V600E) melanoma can be increased by its combination with BRAF-I.
BRAF/NRAS genotype, ERK activation, IFNAR1, and HLA class I expression were tested in 60 primary melanoma tumors from treatment-naive patients. The effect of BRAF-I on IFNAR1 expression was assessed in three melanoma cell lines and in four biopsies of BRAF(V600E) metastases. The antiproliferative, pro-apoptotic and immunomodulatory activity of BRAF-I and IFNα combination was tested in vitro and in vivo utilizing three melanoma cell lines, HLA class I-MA peptide complex-specific T-cells and immunodeficient mice (5 per group for survival and 10 per group for tumor growth inhibition). All statistical tests were two-sided. Differences were considered statistically significant when the P value was less than .05.
The IFNAR1 level was statistically significantly (P < .001) lower in BRAF(V600E) primary melanoma tumors than in BRAF wild-type tumors. IFNAR1 downregulation was reversed by BRAF-I treatment in the three melanoma cell lines (P ≤ .02) and in three out of four metastases. The IFNAR1 level in the melanoma tumors analyzed was increased as early as 10 to 14 days following the beginning of the treatment. These changes were associated with: 1) an increased susceptibility in vitro of melanoma cells to the antiproliferative (P ≤ .04), pro-apoptotic (P ≤ .009) and immunomodulatory activity, including upregulation of HLA class I antigen APM component (P ≤ .04) and MA expression as well as recognition by cognate T-cells (P < .001), of BRAF-I and IFNα combination and 2) an increased survival (P < .001) and inhibition of tumor growth of melanoma cells (P < .001) in vivo by BRAF-I and IFNα combination.
The described results provide a strong rationale for the clinical trials implemented in BRAF(V600E) melanoma patients with BRAF-I and IFNα combination.
Results from exoplanet surveys indicate that small planets (super-Earth size and below) are abundant in our Galaxy. However, little is known about their interiors and atmospheres. There is therefore ...a need to find small planets transiting bright stars, which would enable a detailed characterization of this population of objects. We present the results of a search for the transit of the Earth-mass exoplanet alpha Centauri B b with the Hubble Space Telescope (HST). We observed alpha Centauri B twice in 2013 and 2014 for a total of 40 h. We achieve a precision of 115 ppm per 6-s exposure time in a highly saturated regime, which is found to be consistent across HST orbits. We rule out the transiting nature of alpha Centauri B b with the orbital parameters published in the literature at 96.6 per cent confidence. We find in our data a single transit-like event that could be associated with another Earth-sized planet in the system, on a longer period orbit. Our programme demonstrates the ability of HST to obtain consistent, high-precision photometry of saturated stars over 26 h of continuous observations.
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