Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments.

Atherosclerosis represents one of the main risk factors for the development of cardiovascular diseases. Their etiologies have been studied in recent years in order to better define therapeutic targets for intervention and to identify diagnostic methods. Two different subtypes of macrophages, M1 and M2, have been described in physiological conditions. They can also be found in the atherosclerotic process, where they both have opposite roles in disease progression. Perivascular brown adipose tissue is also involved in inflammation and endothelial damage. In this work, we provide insights into the protective role of melatonin in the atherosclerotic process by morphological and 18F-FDG-PET/CT analyses. In particular, we examined the effects of melatonin on pathways that are linked to atherosclerosis development. We showed that melatonin, by suppressing M1 activity, reduced inflammation and directed macrophage polarization toward the M2 macrophage subtype. Moreover, melatonin preserved the activity of perivascular brown adipose tissue. In addition, 18F-FDG uptake is very high in mice treated with melatonin, confirming that other factors may alter 18F-FDG distribution. In conclusion, we showed that melatonin affects inflammatory pathways that have been linked to atherosclerosis, assessed the relationships of the 18F-FDG PET/CT parameters with macrophage markers and the production of their cytokines, which that have been defined by morphological evaluations

Melatonin atheroprotective effects in vivo

Chronic inflammatory fibro-proliferative changes leading to atherosclerotic plaques are considered hallmark of cardiovascular diseases [1]. Atherosclerosis pathogenesis is a complex entity, which has not been fully understood; however, many studies have demonstrated the role of oxidative stress and inflammation in its development. Melatonin effects on inflammation and oxidative stress process have been demonstrated in the last ten-year literature [2]. However, its role(s) and mechanism(s) of action as a therapeutic tool against atherosclerosis remain largely unexplored. Our aims were to assess the role of melatonin in the onset and developing of atherosclerotic plaques through radiologic and morphometrical tools in 20 apolipoprotein-E knockout (ApoE) mice fed with Western diet (42% calories from fat). 10/20 mice were treated with melatonin (10 mg/kg per os). 18F-FDG PET-CT is a widely used tool to assess inflammatory changes, even before macroscopic changes have taken place. Glucose metabolism is known to be higher in areas of inflammation due to an increased expression of GLUT transporters on the cell membranes both in animals and humans. Using this feature PET/CT is able to determinate metabolic cellular changes and therefore it can be used as biomarker of atherosclerosis. All mice were scanned both before starting melatonin treatment and at the end of the study. After the last scan mice were sacrificed and vascular remodeling, oxidative stress and inflammation at aortic arch level were evaluated. CT-corrected PET datasets were used for computation of SUVmax. Atherosclerotic vascular remodeling, oxidative stress and inflammation levels were significantly more conspicuous in the control cohort, compared to the treated mice (p≤0.05). 18F-FDG PET/CT did not show significant difference in SUVmax. In summary, also in vivo, melatonin may have a protective effect in the atherosclerotic pathogenesis. Flamma S.p.A.-Italy (www.flammagroup.com) provided with melatonin. Financial supports: Fondazione Cariplo e Regione Lombardia “New opportunities and ways towards ERC” (Project 2014-2256) and University of California - Radiology and Biomedical Imaging Nuclear Medicine Section

Isolated Bone Marrow Manifestation of HIV-Associated Hodgkin Lymphoma

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Molecular remission is an independent predictor of progression-free survival in patients with Waldenström macroglobulinemia treated with chemo-immunotherapy: Results from the FIL_BIOWM study

Waldenström macroglobulinemia (WM) is a mature B-cell neoplasm characterized by bone marrow (BM) infiltration by lymphoplasmacytic lymphoma and a monoclonal IgM protein in the serum.1 The past 2 decades have witnessed important treatment advances, with the introduction of chemo-immunotherapy (CIT) in the early 2000s and ibrutinib in more recent years. Despite these progresses, most patients eventually relapse after treatment. The depth of clinical response following rituximab-based therapy has revealed an important predictor of progression-free survival (PFS).International Waldenstrom's Macroglobulinemia Foundation

Is Weight Loss Associated with Less Progression of Changes in Knee Articular Cartilage among Obese and Overweight Patients as Assessed with MR Imaging over 48 Months? Data from the Osteoarthritis Initiative

Purpose To investigate the association of weight loss with progression of cartilage changes at magnetic resonance (MR) imaging over 48 months in overweight and obese participants compared with participants of stable weight. Materials and Methods The institutional review boards of the four participating centers approved this HIPAA-compliant study. Included were (a) 640 participants (mean age, 62.9 years ± 9.1 [standard deviation]; 398 women) who were overweight or obese (body mass index cutpoints of 25 and 30 kg/m2, respectively) from the Osteoarthritis Initiative, with risk factors for osteoarthritis or mild to moderate radiographic findings of osteoarthritis, categorized into groups with (a) weight loss of more than 10% (n = 82), (b) weight loss of 5%-10% (n = 238), or (c) stable weight (n = 320) over 48 months. Participants were frequency-matched for age, sex, baseline body mass index, and Kellgren-Lawrence score. Two radiologists assessed cartilage and meniscus defects on right knee 3-T MR images at baseline and 48 months by using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Progression of the subscores was compared between the weight loss groups by using multivariable logistic regression models. Results Over 48 months, adjusted mean increase of cartilage WORMS was significantly smaller in the 5%-10% weight loss group (1.6; 95% confidence interval [CI]: 1.3, 1.9; P = .002) and even smaller in the group with more than 10% weight loss (1.0; 95% CI: 0.6, 1.4; P = .001) when compared with the stable weight group (2.3; 95% CI: 2.0, 2.7). Moreover, percentage of weight change was significantly associated with increase in cartilage WORMS (β = 0.2; 95% CI: 0.02, 0.4; P = .007). Conclusion Participants who lost weight over 48 months showed significantly lower cartilage degeneration, as assessed with MR imaging; rates of progression were lower with greater weight loss. © RSNA, 2017

Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study

International audienceBACKGROUND & AIMS:All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting.METHODS:103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015.RESULTS:The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24weeks, 27.6% and 10.3% at 48weeks, 33.3% and 19.2% at 60weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p20:HR=0.042; p<0.0001), delta MELD (HR=1.349; p<0.0001) and delta albumin (HR=0.307; p=0.0069) both assessed after 12weeks of DAA therapy.CONCLUSIONS:This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained.LAY SUMMARY:The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, "direct acting antivirals" or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Primary lymphoma of the distal radius of a child: imaging features

Primary lymphoma of bone (PLB) is a rare entity, defined as a lymphoma confined to the bone without evidence of systemic involvement. The disease commonly affects middleaged to elderly population and it accounts for less than 1% of all malignant lymphomas. We present a case of a 10-year-old child affected by PLB of the forearm and the frontal bone. Characteristic imaging features of PLB and the main differential diagnosis were discussed