Functional assessment of the collateral-dependent circulation in chronic total coronary occlusion using transthoracic Doppler ultrasound and venous adenosine infusion

The measurement of collateral flow reserve (CFR; the hyperemic/baseline collateral flow velocity ratio) in patients with chronic total coronary occlusion requires invasive and expensive techniques. Noninvasive transthoracic coronary Doppler echocardiography may be an alternative option. Fifty-one patients with chronic total coronary occlusion were evaluated by transthoracic coronary Doppler echocardiography and venous adenosine infusion to measure CFR in occluded coronary arteries (the left anterior descending artery in 44 patients and the artery supplying the posterior descending artery in 7 patients). CFR data were plotted against 3 angiographic parameters: (1) grade of the epicardial filling of the occluded artery (1=absent, 2=partial, 3=complete), (2) stenosis of the donor artery, and (3) the extent of coronary artery disease (vessels with >or=70% stenosis). Collateral flow was maintained at stress in 34 patients (CFR>or=1, range 1.0 to 2.2) but was withdrawn in 17 patients (CFR<1, range 0.25 to 0.90). CFR increased with the degree of angiographic collateral flow (grade 1: 0.73+/-0.29; grade 2: 1.16+/-0.31; grade 3: 1.34+/-0.49; F=5.31, p=0.008). A multivariate model of CFR prediction showed a direct relation with angiographic collateral grade and the number of diseased vessels and an inverse relation with stenosis of the donor artery. In conclusion, CFR measurement is feasible by transthoracic coronary Doppler echocardiography. One third of the patients with chronic total coronary occlusion had collateral flow withdrawal at stress, which occurs when collateral circulation is poor and when the donor artery is stenotic. CFR correlates with angiographic collateral grade and with the extent of coronary artery disease

AB0241 PREVALENCE OF ANXIOUS SYMPTOMS AND DEPRESSION IN A SAMPLE OF PATIENTS WITH RHEUMATOID ARTHRITIS (RA) AND OTHER CHRONIC RHEUMATIC DISEASES

Background:Clinical practice with patients suffering from chronic diseases highlights the presence of psychological symptoms of discomfort fed by biological and non-biological mechanisms linked to disease and treatment. In rheumatic diseases, literature detects the presence of anxious symptoms and depressed mood of clinical and sub-clinical importance with a multifactorial genesis1.Objectives:To detect the impact on the state of health of anxious symptoms and depressed mood in a population suffering from RA and other rheumatic diseases in order to implement the effectiveness of psychological intervention through the selection of patients who present critical levels of discomfort.Methods:Patients afferent to the Rheumatology outpatient clinic of Mauriziano Hospital have been screened from May 2018 to July 2018 with two self-administered questionnaires: HADS-A and HADS-D (Hospital Anxiety and Depression Scale), specifically developed for the evaluation of anxious and depressive symptoms in medical pathologies, and HAQ (Health Assessment Questionnaire) to explore functional disability. Data about rheumatic diagnosis and socio-demographic characteristics were also collected. Data were analyzed with descriptive statistics; the Student Test and the ANOVA test were used to evaluate prevalence and to compare the presentation of symptoms in the different diseases and the Pearson correlation coefficient was used to evaluate the relationship between symptoms and disability.Results:A total of 427 subjects were screened (317 females and 110 males), aged between 19 and 90 years (mean 60 ± 14 yrs). 156 subjects (36.5%) had a diagnosis of RA, 76 (17.8%) of psoriatic arthritis, 42 (9.8%) of ankylosing spondylitis, 14 (3.3%) of systemic lupus erythematosus and 139 (32.6%) of other rheumatic diseases (including Sjogren, osteoarthritis, fibromyalgia).A high prevalence of anxious symptoms and depressed mood has been found and the number of subjects reporting scores indicating a clinically relevant uncomfortable situation (HADS ≥ 11) was also relevant (Table 1); an increased prevalence in female patients was observed. There were no differences in the presentation of symptoms between RA and the other included pathologies (Table 2).Table 1.Prevalence of anxiety and depression according to the HADS questionnaire in rheumatic diseasesMeanSDHADS-A7.564.63HADS-D7.124.59HADS-A ScoreN%0-722452.47-108419.711-2111927.9HADS-D ScoreN%0-723154.17-109221.511-2110424.4Table 2.Comparison between RA and other rheumatic diseases in anxiety and depression symptoms presentation (ANOVA test).NMeanSDSECIHADS-ARA1562.345.200.411.52PsA762.304.470.511.28AS421.513.190.490.51SLE141.773.741.00-0.38other1392.465.080.431.61HADS-DRA1561.743.510.281.19PsA762.034.210.481.07AS420.690.540.080.52SLE140.930.680.180.54other1391.683.790.321.04There was a positive and significant correlation between anxious symptoms or depressed mood and functional disability (0.49 and 0.60 respectively, p<0,01).Conclusion:The results show a significant presence of uncomfortable situations that could evolve in a psychopathological sense. The discomfort expressed through anxious and depressive symptoms is related to the level of functional disability. Recognizing the presence of psychological distress allows to orient the treatment plan and facilitate the patient's adaptation to the disease condition.References:[1]Geenen R. et al. Best Pract Res Clin Rheumatol. 2012;26(3):305-19.Disclosure of Interests:Gloria Crepaldi Consultant of: Advisory board for Sanofi and Celgene, Speakers bureau: BMS, MSD, Mariarosaria Voci: None declared, Marta Saracco: None declared, Antonella Laezza: None declared, Paolo Santino: None declared, Maddalena Marcato: None declared, Guido Rovera: None declared, Claudia Lomater Consultant of: Advisory board for Sanofi, Novartis, Abbvi

The mantle wedge's transient 3-D flow regime and thermal structure

Arc volcanism, volatile cycling, mineralization, and continental crust formation are likely regu-lated by the mantle wedge’s flow regime and thermal structure. Wedge flow is often assumed to follow a regular corner-flow pattern. However, studies that incorporate a hydrated rheology and thermal buoyancy predict internal small-scale-convection (SSC). Here, we systematically explore mantle-wedge dynamics in 3- D simulations. We find that longitudinal ‘‘Richter-rolls’’ of SSC (with trench-perpendicular axes) commonly occur if wedge hydration reduces viscosities to ≤1 ∙ 10^19 Pa s, although transient transverse rolls (with trench-parallel axes) can dominate at viscosities of ~5 ∙ 10^18 - 1 ∙ 10^19 Pa s. Rolls below the arc and back arc differ. Subarc rolls have similar trench-parallel and trench-perpendicular dimensions of 100–150 km and evolve on a 1–5 Myr time-scale. Subback-arc instabilities, on the other hand, coalesce into elongated sheets, usually with a preferential trench-perpendicular alignment, display a wavelength of 150–400 km and vary on a 5–10 Myr time scale. The modulating influence of subback-arc ridges on the subarc system increases with stronger wedge hydration, higher subduction velocity, and thicker upper plates. We find that trench-parallel averages of wedge velocities and temperature are consistent with those predicted in 2-D models. However, lithospheric thinning through SSC is somewhat enhanced in 3-D, thus expanding hydrous melting regions and shifting dehydration boundaries. Subarc Richter-rolls generate time-dependent trench-parallel temperature variations of up to ~150 K, which exceed the transient 50–100 K variations predicted in 2-D and may contribute to arc-volcano spacing and the variable seismic velocity structures imaged beneath some arcs

Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells

AIM: To investigate in vitro the therapeutic effect and mechanisms of silybin in a cellular model of hepatic steatosis. METHODS: Rat hepatoma FaO cells were loaded with lipids by exposure to 0.75 mmol/L oleate/palmitate for 3 h to mimic liver steatosis. Then, the steatotic cells were incubated for 24 h with different concentrations (25 to 100 mol/L) of silybin as phytosome complex with Vitamin E. The effects of silybin on lipid accumulation and metabolism, and on indices of oxidative stress were evaluated by absorption and fluorescence microscopy, quantitative real-time PCR, Western blot, spectrophotometric and fluorimetric assays. RESULTS: Lipid-loading resulted in intracellular triglyceride (TG) accumulation inside lipid droplets, whose number and size increased. TG accumulation was mediated by increased levels of peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). The lipid imbalance was associated with higher production of reactive oxygen species (ROS) resulting in increased lipid peroxidation, stimulation of catalase activity and activation of nuclear factor kappa-B (NF-B). Incubation of steatotic cells with silybin 50 mol/L significantly reduced TG accumulation likely by promoting lipid catabolism and by inhibiting lipogenic pathways, as suggested by the changes in carnitine palmitoyltransferase 1 (CPT-1), PPAR and SREBP-1c levels. The reduction in fat accumulation exerted by silybin in the steatotic cells was associated with the improvement of the oxidative imbalance caused by lipid excess as demonstrated by the reduction in ROS content, lipid peroxidation, catalase activity and NF-B activation

3,5-Diiodo-L-thyronine modulates the expression of genes of lipid metabolism in a rat model of fatty liver.

Recent reports demonstrated that 3,5-diiodo-l-thyronine (T(2)) was able to prevent lipid accumulation in the liver of rats fed a high-fat diet (HFD). In this study, we investigated how the rat liver responds to HFD and T(2) treatment by assessing the transcription profiles of some genes involved in the pathways of lipid metabolism: oxidation, storage and secretion. The mRNA levels of the peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ), and of their target enzymes acyl-CoA oxidase and stearoyl-CoA desaturase were evaluated by real-time RT-PCR. Moreover, the expression of the adipose triglyceride lipase involved in lipid mobilisation, of the main PAT proteins acting in lipid droplet (LD) turnover, and of apoprotein B (apo B), the major protein component of very low-density lipoproteins (VLDLs) were analysed. Overall, our data demonstrated that T(2) administration to HFD rats counteracts most of the hepatic transcriptional changes that occurred in response to the excess exogenous fat. In particular, our results suggest that T(2) may prevent the pathways leading to lipid storage in LDs, promote the processes of lipid mobilisation from LDs and secretion as VLDL, in addition to the stimulation of pathways of lipid oxidation. In conclusion, our findings might give an insight into the mechanisms underlying the anti-steatotic ability of T(2) and help to define the potential therapeutic role of T(2) for preventing or treating liver steatosis

Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria

The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of &gt; 1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P &lt; .005) and 5-year patient survival improved (42% vs. 83%, P &lt; .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P &lt; .05) and to lower 5-year patient survival (38% vs. 78%, P &lt; .005%) in the preoperative analysis, but not in the postoperative one. The alfa-fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P &lt; .005 and P &lt; .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long-term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa-fetoprotein level may improve the selection of patients. Copyright © 2004 by the American Association for the Study of Liver Diseases

Long term effectiveness on prescribing of two multifaceted educational interventions: Results of two large scale randomized cluster trials

Introduction: Information on benefits and risks of drugs is a key element affecting doctors' prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours. Objectives: Testing the short and long-term effectiveness on general practitioners' prescribing of small groups meetings led by pharmacists. Methods: Two cluster open randomised controlled trials (RCTs) were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach - TEA, with information materials on osteoporosis or prostatic hyperplasia - and a single drug oriented approach - SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners) were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months) were also evaluated. Results: In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio -8.5%, p = 0.03). Another primary outcome (prescription of risedronate) showed a reduction at 24 and 48 months (-7.6%, p = 0.02; and -9,8%, p = 0.03), but not at six months (-5.1%, p = 0.36). In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine -9.8%, p = 0.02; prescription of prulifloxacin -11.1%, p = 0.04), which persisted or increased over time. Interpretation: These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially relevant long-term impact on prescribing habits, in particular when focusing on a single drug. National Health systems should invest in independent drug information programs. Trial Registration: Controlled-Trials.com ISRCTN05866587