Statin use and survival in resectable pancreatic cancer: confounders and mechanisms.

A first point regards the possible activity of drugs other than statins, such as aspirin or metformin, against pancreatic cancer. As many patients use a combination of these drugs, one might speculate that the association between simvastatin and overall survival in resected pancreatic cancer patients might also be explained by the concomitant use of aspirin or metformin, or that these drugs might result synergistic, as hypothesized for colorectal cancer (3). We wonder whether the authors had access to data on aspirin or metformin use for their population. A second point regards the very high 45% rate of simvastatin or lovastatin users reported by the authors. This figure is different from that of many European countries, thus possibly limiting the attributable fraction of cases for whom the observed findings can be replicated

Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic 'mucosal healing' and implication for management

OBJECTIVE: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up. PATIENTS AND METHODS: We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/ histological repor ts performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up. RESULTS: Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score. CONCLUSIONS: Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mildmoderate disease

Development of an Ex Vivo Organ Culture Technique to Evaluate Probiotic Utilization in IBD

The consistent technical and conceptual progress in the study of the microbiota has led novel impulse to the research for therapeutical application of probiotic bacteria in human pathologies, such as inflammatory bowel disease (IBD). Considering the heterogenous results of probiotics in clinical studies, the model of translational medicine may lead to a more specific and efficacious utilization of probiotic bacteria in IBD. In this regard, the selection and utilization of appropriate experimental models may drive the transition from pure in vitro systems to practical clinical application. We developed a simple and reproducible ex vivo organ culture method with potential utilization for the evaluation of probiotic bacteria efficacy in IBD patients

Bounded Decentralised Coordination over Multiple Objectives

We propose the bounded multi-objective max-sum algorithm (B-MOMS), the first decentralised coordination algorithm for multi-objective optimisation problems. B-MOMS extends the max-sum message-passing algorithm for decentralised coordination to compute bounded approximate solutions to multi-objective decentralised constraint optimisation problems (MO-DCOPs). Specifically, we prove the optimality of B-MOMS in acyclic constraint graphs, and derive problem dependent bounds on its approximation ratio when these graphs contain cycles. Furthermore, we empirically evaluate its performance on a multi-objective extension of the canonical graph colouring problem. In so doing, we demonstrate that, for the settings we consider, the approximation ratio never exceeds 2, and is typically less than 1.5 for less-constrained graphs. Moreover, the runtime required by B-MOMS on the problem instances we considered never exceeds 30 minutes, even for maximally constrained graphs with $100$ agents. Thus, B-MOMS brings the problem of multi-objective optimisation well within the boundaries of the limited capabilities of embedded agents

Optimal Experience and Meaning: Which Relationship?

A large number of studies conducted in the last twenty years show that optimal experience is a positive and complex condition in which cognitive, motivational and emotional components coexist in a coherent and articulated reciprocal integration. By virtue of its positive psychological features, optimal experience has been sometimes misunderstood as a state which automatically brings about well-being and development. Several studies have disconfirmed this assumption, showing that the outcomes of optimal experience are not automatically positive. Rather, they vary according to the features of the associated activities and to the value system of the cultural environment. Researchers in this domain have been primarily devoted their attention to the structure of the activities that promote optimal experience, and to the goal pursuit they facilitate. Goals are given a prominent role in development in that they provide individuals with practical orientation and purpose in life. But something is missing in this framework: meaning. What do we know about the relationship between optimal experience and meaning making? Based on findings coming from different contexts and cultures, this paper tries to give optimal experience a role within the long-term process of meaning-making

Detecting and Evaluating Therapy Induced Changes in Radiomics Features Measured from Non-Small Cell Lung Cancer to Predict Patient Outcomes

The purpose of this study was to investigate whether radiomics features measured from weekly 4-dimensional computed tomography (4DCT) images of non-small cell lung cancers (NSCLC) change during treatment and if those changes are prognostic for patient outcomes or dependent on treatment modality. Radiomics features are quantitative metrics designed to evaluate tumor heterogeneity from routine medical imaging. Features that are prognostic for patient outcome could be used to monitor tumor response and identify high-risk patients for adaptive treatment. This would be especially valuable for NSCLC due to the high prevalence and mortality of this disease. A novel process was designed to select feature-specific image preprocessing and remove features that were not robust to differences in CT model or tumor volumes. These features were then measured from weekly 4DCT images. These features were evaluated to determine at which point in treatment they first begin changing if those changes were different for patients treated with protons versus photons. A subset of features demonstrated significant changes by the second or third week of treatment, however changes were never significantly different between patient groups. Delta-radiomics features were defined as relative net changes, linear regression slopes, and end of treatment feature values. Features were then evaluated in univariate and multivariate models for overall survival, distant metastases, and local-regional recurrence. In general, the delta-radiomics features were not more prognostic than models built using clinical factors or features at pre-treatment. However one shape descriptor measured at pre-treatment significantly improved model fit and performance for overall survival and distant metastases. Additionally for local-regional recurrence, the only significant covariate was texture strength measured at the end of treatment. A separate study characterized radiomics feature variability in cone-beam CT images to increased scatter, increased motion, and different scanners. Features were affected by all three parameters and specifically by motion amplitudes greater than 1 cm. This study resulted in strong evidence that a set of robust radiomics features change significantly during treatment. While these changes were not prognostic or dependent on treatment modality, future studies may benefit from the methodologies described here to explore delta-radiomics in alternative tumor sites or imaging modalities

Elevated C-reactive protein in asymptomatic Crohn's disease patients. listen to the sound of silence

Bhattacharya et al1 confirmed and extended their previous finding2 indicating that “silent” Crohn’s disease (CD) patients (i.e., asymptomatic patients with elevated C-reactive protein [CRP] level) are a subgroup of patients at the higher risk of hospitalization and of more disabling disease

The use of complementary and alternative medicine is frequent in patients with pancreatic disorder

BACKGROUND: Herbal remedies and other complementary and alternative medicine (CAM) are used by 30% of the patients with liver and inflammatory bowel diseases. However, there are no data regarding CAM use in patients with pancreatic disorders, including potential pancreatotoxicity. AIM OF THE STUDY: The aim of the study was to assess the prevalence of CAM use in patients with pancreatic disorders and screen for pancreatotoxicity. MATERIALS AND METHODS: This was a cross-sectional survey of consecutive outpatients seen at a Pancreas Center. Data were collected in a specific questionnaire. Descriptive statistics were used to analyze the prevalence and the patterns of CAM use. Characteristics associated with CAM use were analyzed by appropriate statistics. RESULTS: Of 108 patients (52% male; mean age, 65±13 years), 47 (43.5%) used CAM. The use of CAM was more frequent among patients with previous acute pancreatitis (47%). Reported reasons for the use of CAM were to help standard therapies and for an overall better feeling. About 61% of the patients reported advantages with treatment. As compared with nonusers, CAM users were more often female (55% vs. 42%), with a higher school degree (43% vs. 36%), more frequently performing physical activity (51% vs. 41%), and reporting anxiety (45% vs. 31%). However, none of these differences were statistically significant. Three patients with previous acute pancreatitis reported the use of Serenoa repens that is potentially pancreatotoxic. DISCUSSION: The rate of CAM use in patients with pancreatic disorders is similar to those reported for other digestive diseases. CAM use seems to be more frequent in women with a higher education level and a "healthier lifestyle." Patients might not be aware of the potential pancreatotoxicity of CAM, which should be carefully considered by physician

Meaning in life: structure, sources and relations with mental and physical health

Meaning in life is a core component of human experience, and it plays a relevant role in the promotion of mental, social and physical well-being, as well as in the successful adaptation to adverse conditions, including chronic and progressive diseases. This paper provides an overview of the most recent conceptualizations of meaning in the psychological domain, specifically addressing its tripartite structure, encompassing the facets of coherence, significance and purpose. Empirical evidence will be summarized concerning the role of social relationships and self-transcendence as primary sources of meaning in life. Research findings highlighting the role of meaning as a core component of mental health,and as a resource in adaptively managing illness consequences on daily functioning and life goals will be also reported. Current research gaps and future directions for theoretical and empirical advancements will be outlined