The Evolution of Percutaneous Mitral Valve Repair Therapy Lessons Learned and Implications for Patient Selection

AbstractMitral regurgitation (MR) is the most common valve disease in the United States. However, a significant number of patients are denied surgery due to increased age, poor ventricular function, or associated comorbidities, putting them at high risk for adverse events. Moreover, the benefit of surgery for MR is unclear in patients with functional (secondary) MR. Recently, percutaneous repair of the mitral valve with a particular device (MitraClip, Abbott, Menlo Park, California) has emerged as a novel therapeutic option for patients with secondary MR or those deemed to be high risk for surgery. We review data from its initial concept through clinical trials and current data available from several registries. We focused on lessons learned regarding adequate patient selection, along with current and future perspectives on the use of device therapy for the treatment of MR

Intersystem Collaboration: A Statewide Initiative to Support Families

The study described in this paper utilized a qualitative case study method to assess the processes involved in inter-system collaboration in the context of one state\u27s system change initiative. The collaborative experience is described from the perspective of participating service system professionals and family members. The major themes of collaboration that emerged from the study included changes in communication across systems, changes in inter-system relationships, changes in attitudes, changes in interactions with families, and changes in the ways services are delivered. Lessons learned and practice implications of each theme are discussed

Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine

Objective Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques. Methods and results Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet. Arterial remodeling and local endothelial shear stress (ESS) were assessed using intravascular ultrasound, coronary angiography and computational fluid dynamics at weeks 23 and 30. Coronary arteries were harvested and 142 arterial subsegments were analyzed using histomorphologic staining, immunostaining and real time PCR. Heparanase staining and activity was increased in arterial segments with low ESS, in lesions with thin cap fibroatheroma (TCFA) morphology and in lesions with severely degraded internal elastic laminae. In addition, heparanase staining co-localized with staining for CD45 and MMP-2 within atherosclerotic plaques. Dual staining with gelatinase zymography and heparanase immunohistochemical staining demonstrated co-localization of matrix metalloprotease activity with heparanase staining. A heparanase enzymatic activity assay demonstrated increased activity in TCFA lesions, subsegments with low ESS and in macrophages treated with oxidized LDL or angiotensin II. Conclusions Taken together, our results support a critical role for heparanase in the development of vulnerable plaques and suggest a novel therapeutic target for the treatment of atherosclerosis.Novartis (Firm)Boston Scientific CorporationNational Institutes of Health (U.S.) (Grant R01 GM49039

Influenza sequence and epitope database

Influenza epidemics arise through the acquisition of viral genetic changes to overcome immunity from previous infections. An increasing number of complete genomes of influenza viruses have been sequenced in Asia in recent years. Knowledge about the genomes of the seasonal influenza viruses from different countries in Asia is valuable for monitoring and understanding of the emergence, migration and evolution of strains. In order to make full use of the wealth of information from such data, we have developed an integrated user friendly relational database, Influenza Sequence and Epitope Database (ISED), that catalogs the influenza sequence and epitope information obtained in Asia. ISED currently hosts a total of 13 020 influenza A and 2984 influenza B virus sequence data collected in 17 countries including 9 Asian countries, and a total of approximately 545 amantadine-resistant influenza virus sequences collected in Korea. ISED provides users with prebuilt application tools to analyze sequence alignment and different patterns and allows users to visualize epitope-matching structures, which is freely accessible at http://influenza.korea.ac.kr and http://influenza.cdc.go.kr

Variable and value elimination in binary constraint satisfaction via forbidden patterns

Variable or value elimination in a constraint satisfaction problem (CSP) can be used in preprocessing or during search to reduce search space size. A variable elimination rule (value elimination rule) allows the polynomial-time identification of certain variables (domain elements) whose elimination, without the introduction of extra compensatory constraints, does not affect the satisfiability of an instance. We show that there are essentially just four variable elimination rules and three value elimination rules defined by forbidding generic sub-instances, known as irreducible existential patterns, in arc-consistent CSP instances. One of the variable elimination rules is the already-known Broken Triangle Property, whereas the other three are novel. The three value elimination rules can all be seen as strict generalisations of neighbourhood substitution.Comment: A full version of an IJCAI'13 paper to appear in Journal of Computer and System Sciences (JCSS

Augmented Expression and Activity of Extracellular Matrix-Degrading Enzymes in Regions of Low Endothelial Shear Stress Colocalize With Coronary Atheromata With Thin Fibrous Caps in Pigs

Background—The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. : Methods and Results—Intravascular ultrasound–based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation. : Conclusions—Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.Novartis Pharmaceuticals CorporationBoston Scientific CorporationHellenic Heart FoundationHellenic Atherosclerosis SocietyAlexander S. Onassis Public Benefit FoundationPropondis FoundationHellenic Harvard FoundationA.G. Leventis FoundationPhilip Morris International. External Research ProgramAmerican Heart Association (Scientist Development Grant)National Institutes of Health (U.S.) (Grant NIHR01 GM49039

Twenty articles that critical care clinicians should read about COVID-19

Infection with the severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) was first identified in December 2019 and has since become a worldwide pandemic, challenging and sometimes overwhelming healthcare systems as well as causing more than a million deaths thus far. In just 10 months, over 80,000 indexed publications have appeared that reference SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19). In this article, we highlight 20 papers that are of particular relevance to the critical care clinician. The papers are divided into four broad topics: manifestations of severe COVID- 19 disease, pharmacological therapy for COVID-19, ventilatory support for COVID-19 acute respiratory distress syndrome (ARDS), and healthcare system and worker stress. This list is not designed to be comprehensive but rather to give the reader an overview of important early papers and their findings.info:eu-repo/semantics/publishedVersio

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Signs and symptoms of acute mania: a factor analysis

<p>Abstract</p> <p>Background</p> <p>The major diagnostic classifications consider mania as a uni-dimensional illness. Factor analytic studies of acute mania are fewer compared to schizophrenia and depression. Evidence from factor analysis suggests more categories or subtypes than what is included in the classification systems. Studies have found that these factors can predict differences in treatment response and prognosis.</p> <p>Methods</p> <p>The sample included 131 patients consecutively admitted to an acute psychiatry unit over a period of one year. It included 76 (58%) males. The mean age was 44.05 years (SD = 15.6). Patients met International Classification of Diseases-10 (ICD-10) clinical diagnostic criteria for a manic episode. Patients with a diagnosis of mixed bipolar affective disorder were excluded. Participants were evaluated using the Young Mania Rating Scale (YMRS). Exploratory factor analysis (principal component analysis) was carried out and factors with an eigenvalue > 1 were retained. The significance level for interpretation of factor loadings was 0.40. The unrotated component matrix identified five factors. Oblique rotation was then carried out to identify three factors which were clinically meaningful.</p> <p>Results</p> <p>Unrotated principal component analysis extracted five factors. These five factors explained 65.36% of the total variance. Oblique rotation extracted 3 factors. Factor 1 corresponding to 'irritable mania' had significant loadings of irritability, increased motor activity/energy and disruptive aggressive behaviour. Factor 2 corresponding to 'elated mania' had significant loadings of elevated mood, language abnormalities/thought disorder, increased sexual interest and poor insight. Factor 3 corresponding to 'psychotic mania' had significant loadings of abnormalities in thought content, appearance, poor sleep and speech abnormalities.</p> <p>Conclusions</p> <p>Our findings identified three clinically meaningful factors corresponding to 'elated mania', 'irritable mania' and 'psychotic mania'. These findings support the multidimensional nature of manic symptoms. Further evidence is needed to support the existence of corresponding clinical subtypes.</p