Search

Right-wing populist ideologies are expressed not only by politicians, party members or mass media actors but also by non-organised citizens on social media. On these platforms, political messages a...

The problem of “fake news” has received considerable attention both in public discourse and in scholarship. However, many have argued that the term should be avoided for ideological reasons or because it lacks clarity. At the same time, a growing body of literature investigates “fake news” empirically. We complement this discussion by reflecting on epistemological and methodological problems with the term “fake news” and the implications for possible solutions to the problem of disinformation such as automatic detection and increased media literacy. Based on the principle of symmetry established in the sociology of scientific knowledge, we show that a classification of messages according to the researcher’s assessment of their truthfulness can lead to biased or tautological explanations. We argue that many researchers commit themselves to the truth or falsehood of messages in cases where they should not and avoid such a commitment when it is necessary.

Abstract HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E. coli LPS-B5 and CpG-ODN-2216, we observed greater induction of IL-6/IL-1beta double-positive CD14+CD16++ monocytes as well as IFN-gamma-positive cytotoxic CD56highCD16neg NK cells in HLA-B*57- versus HLA-B*44-positive HIV patients, while TNF-alpha induction remained unchanged. Differences were not seen in the other monocyte and NK cell subsets or in HLA-matched healthy controls. Our findings show that, in virally suppressed HIV infection, HLA-B*57 is associated with enhanced responsiveness of inflammatory innate immune cells to TLR ligands, possibly contributing to increased vulnerability in sepsis. Key messages • HLA-B*57 is a host factor affecting clinical outcomes of HIV infection. • HLA-B*57 modifies inflammatory subsets of NK cells and monocytes in HIV infection. • In HLA-B*57-positive HIV patients TLR agonists induce enhanced IL-6/IL-1beta in monocytes. • NK cells from HLA-B*57 HIV patients release more IFN-gamma upon TLR costimulation. • HLA-B*57 is linked to enhanced inflammatory responsiveness to TLR ligands.

The presentation of single cases as examples for larger phenomena has a long-standing tradition in journalism. However, their usage has been viewed rather critically within the scientific community, because they are employed in a highly selective manner. Consequently, over the course of the last three decades, communication scholars from different research traditions have concerned themselves with the question of how single-case information within media content affects audience judgments. Although most publications report exemplification effects of some sort, it remains unclear which types of exemplars are effective and whether they are capable of influencing both perceptual and personal judgments. Applying a multi-level meta-regression approach, we synthesize findings across different studies and investigate potential moderators. Our results suggest overall exemplification effects that seem to be most pronounced for first-level reality judgments, such as public opinion or frequency estimates, but that are limited in their robustness when controlling for interdependence of the measurements.

Research on cooperative social structures and particular types of conflict behavior online is readily available. However, the field lacks a framework to analyze how antagonistic structures are represented on online platforms. Social structures can be represented formally (manifestly) or informally (in open verbal or visual forms) or remain latent - a distinction that has received little scholarly attention in the analysis of computermediated communication. Based on an interpretative analysis of relational structures and types of acts, we distinguish structural elements that lead us to empirical typologies of antagonistic structures and an analysis of whether and how they are represented online. We develop theses about why some structures are formally represented more often than others and theorize the consequences of this selective representation.

Immune checkpoint inhibition suggests promising progress for the treatment of advanced hepatocellular carcinoma (HCC). However, the underlying cellular mechanisms remain unclear because liver cancer cells apparently do not upregulate inhibitory checkpoint molecules. Here, we analysed whether regulatory T cells (Tregs) can alternatively trigger checkpoint inhibition pathways in HCC. Using flow cytometry we analysed expression of checkpoint molecules (PD-1, PD-L1, CTLA-4, GITR, Tim-3) on peripheral CD4+CD25+Foxp3+ Tregs and their secretion of inhibitory mediators (IL-10, IL-35, TGF-beta, galectin-9) in 116 individuals (50 patients with HCC, 41 non-tumour bearing liver disease controls, 25 healthy controls). Functional activity of Tregs on T effector cells (IFN-gamma production, cytotoxicity) was characterized in vitro using a lectin-dependent cellular cytotoxicity (LDCC) assay against checkpoint inhibitor-negative P815 target cells. Unlike liver patients without malignancy and healthy controls, the frequency of checkpoint inhibitor-positive Tregs inversely correlated to age of patients with HCC (PD-L1, p = 0.0080; CTLA-4, p = 0.0029) and corresponded to enhanced numbers of Tregs producing IL-10 and IL-35 (p

BACKGROUND & AIMS Bacterial translocation drives liver disease progression. We investigated whether functional genetic variants in toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, affect the risk for hepatocellular carcinoma (HCC). METHODS Healthy controls (n = 212), patients with alcohol abuse without liver disease (n = 382), and patients from a discovery cohort of alcohol-associated cirrhosis (n = 372 including 79 HCC cases), a validation cohort of alcohol-associated cirrhosis (n = 355 including 132 HCC cases), and a cohort of cirrhosis due to nonalcoholic steatohepatitis (NASH) (n = 145 including 62 HCC cases) were genotyped for the TLR5 rs5744174 and rs5744168 polymorphisms. Chemokine levels were measured by ELISA in patients' sera and supernatants of flagellin-stimulated healthy monocytes. RESULTS Frequency of the TLR5 rs5744174 TT genotype was similar in healthy controls (33%), controls with alcohol abuse (34%), and patients with alcohol-associated cirrhosis in the discovery (28%), validation (33%), and NASH cohort (31%). The TT genotype was enriched in patients with versus without HCC in the discovery, validation, and NASH cohort (41% vs 25%; 39% vs 29%; 40% vs 24%; p

SUMMARYThe SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,800 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

In their outstanding study, Wei et al 1 compared the intestinal microbiota (IM) of well-defined autoimmune hepatitis (AIH) patients to healthy controls. They reported significantly reduced IM alpha diversity and disparate IM compositional heterogeneity (beta diversity) with enrichment of Streptococcus , Veillonella , Klebsiella and Lactobacillus in AIH. The excellent achievement of this study is to have characterised the IM of untreated patients with AIH. However, differentiation between IM changes caused by AIH in particular and by chronic liver disease (CLD) in general was not possible because this study lacked a control group with CLD other than AIH. In a pilot study, we analysed the IM of patients with CLD of mixed aetiology in comparison to healthy controls to clarify alterations across different stages of CLD (table 1 and online supplementary data). In contrast to the study by Wei et al , patients with recent intake of antibiotics were excluded. Additionally, only patients on proton pump inhibitors (PPIs), which are frequently taken by patients with CLD, were included to avoid a bias due to mixed PPI use, because PPI can alter the IM, in particular, the abundance of Veillonellaceae and Streptococcaceae.2 Based on investigations of normalised relative reads (n-RR) per IM taxon as well as IM alpha-diversity and beta-diversity analyses, we detected Veillonella …

‘Severe Acute Respiratory Syndrome - Coronavirus-2’ (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46+n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DRhiCD11chiinflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DRtomonocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.

The perception of political messages may not only be shaped by textual information, but also by its visual appearance. An online experiment investigated how newspaper articles’ layout style and text slant affect the perception of a newspapers’ political orientation on the left-right axis. The layout versions were based on a prior analysis of correlations between design and political direction of quality newspapers. Results suggest the existence of political layout effects: a conservative layout style led to the source of a left-wing slanted text being estimated more right-wing, especially for left-wing-oriented participants. However, it had no effect when it was combined congruently with a right-wing slanted text. A progressive layout style had only an effect for participants with more knowledge on quality newspapers, leading them to locate the source more left-wing.

This article develops a theoretical classification of functions of different Internet applications and plattforms in right-wing populism. Its aim is to understand how the Internet is seen and used by populists and how it contributes to populism. Online communication by both populist leaders or organizations and non-organized actors is discussed. Main functions include the representation of the relationship between leaders and ‘the people,’ justifying the exclusion of outgroups, the conceptual elaboration of the right-wing populist ideology, developing a right-wing populist lifestyle and identity, and circumventing the traditional media.

OBJECTIVE To analyze the role of CD3(+)CD56(+) natural killer (NK)-like T cells in HIV(+) patients with acute hepatitis C. DESIGN Frequency, phenotype, and anti-hepatitis C virus (HCV) activity of CD3(+)CD56(+) NK-like T cells were studied in 36 HIV(+) patients with acute hepatitis C. As controls, 12 patients with chronic HCV/HIV coinfection, 8 HIV monoinfected patients, and 12 healthy donors were enrolled in this study. METHODS CD3(+)CD56(+) NK-like T-cell-mediated inhibition of HCV replication was analyzed using the HuH7A2HCVreplicon model. The CD3(+)CD56(+) NK-like T-cell phenotype and interferon (IFN)-γ secretion were studied by flow cytometry. RESULTS Interleukin 12/interleukin 15 stimulated CD3(+)CD56(+) NK-like T cells from healthy donors effectively block HCV replication in vitro in an IFN-γ dependent manner. Accordingly, we found that blocking of IFN-γ with a specific antibody significantly reduced the antiviral activity of CD3(+)CD56(+) NK-like T cells. However, when CD3(+)CD56(+) NK-like T cells from HIV(+) patients were studied, we found HIV infection to be associated with a significantly impaired IFN-γ production, irrespective of HCV coinfection. Accordingly, CD3(+)CD56(+) NK-like T cells from HIV(+) patients were significantly less effective in blocking HCV replication in vitro than cells from healthy individuals. CONCLUSIONS Taken together, our data indicate that HIV infection is associated with an impaired anti-HCV activity of CD3(+)CD56(+) NK-like T cells, which might represent a novel mechanism of dysregulated immune response in HIV/HCV-coinfected patients.

The value of inspiratory muscle training (IMT) in pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) is unclear. The RIMTCORE (Routine Inspiratory Muscle Training within COPD Rehabilitation) randomised controlled trial examined the effectiveness of IMT added to pulmonary rehabilitation.In total, 611 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) received a 3-week inpatient pulmonary rehabilitation, of which 602 patients were included in the intention-to-treat analyses. The intervention group (n=300) received highly intensive IMT and the control group (n=302) received sham IMT. The primary outcome was maximal inspiratory pressure (PImax). The secondary outcomes were 6-min walk distance, dyspnoea, quality of life and lung function. Outcomes were assessed pre- and post-pulmonary rehabilitation. ANCOVA was used.The intervention group showed higher effects in PImax (pIMT as an add-on to a 3-week pulmonary rehabilitation improves inspiratory muscle strength, but does not provide additional benefits in terms of exercise capacity, quality of life or dyspnoea. A general recommendation for COPD patients to add IMT to a 3-week pulmonary rehabilitation cannot be made.

It is commonly said that “there are” social structures on the Internet. But how can they exist there, how can we identify and classify them? A theoretical and methodological framework is presented that describes the relationship between data structures, algorithms, and different types of social structures. We suggest that the latter are “represented” online in different senses of the word: They are not only described, but, by manipulating data, social structures can also be constituted and modified. We then outline a methodology for the analysis of social structures on the Internet: By analyzing the practical meaning of the structures of Internet platforms, we can reconstruct their providers’ and users’ ontological commitments (i.e., what kinds of social structures they have to assume “there are”).

Objective The objective of this study was to analyse the potential role of CD27 in natural killer (NK) cell-mediated control of hepatitis C virus (HCV) infection in HIV-positive patients. Design Frequency of CD27-expressing CD56 NK cells was analysed in HIV mono-infected individuals and HIV-positive patients with acute or chronic hepatitis C. Anti-HCV activity of CD27(+) and CD27(-) NK cells was compared. Methods NK cell mediated inhibition of HCV replication was analysed using the HUH7 HCV Replicon model. NK cell phenotype and interferon (IFN) secretion was studied by flowcytometry. Results High frequency of CD27(+)CD56 NK cells is associated with spontaneous clearance of acute hepatitis C in HIV-positive patients. Accordingly, we found CD27(+)CD56 NK cells to display strong anti-HCV activity. Conclusion Our results underline the important role of NK cells in modulating outcome of HCV infection.

On the basis of a review of the literature on populism and a definition of populism in general, the concept of media populism is developed. The structural position of media organizations is analyzed regarding the opportunities and constraints when using a populist rhetoric and populist political claims. Two exemplary cases of media populism (typical elements can be found in the tabloid press and in talk radio), and its prevalence in popular culture and on the Internet are discussed. Theses on the effects of media populism are developed, based on cognitive schemata and the dynamics of climates of opinion (or perceived orthodoxies).

Mediennutzung wird hier theoretisch als strategische Praxis (im Sinne Bourdieus) gefasst, die zu langfristigen Profiten führt oder von kurzfristigen taktischen Orientierungen geleitet ist. Mittels Strategien der Mediennutzung passen sich Rezipienten der Struktur von Situationen, Medieninhalten und Technologien an; ferner sind Strategien mit der Sozialstruktur verknüpft. Die Reichweite einer Strategie (was die dabei aufgewendeten Einsätze und die Profite betrifft) kann weiter sein als ihr bewusster Anwendungsbereich, d. h. der Teil der subjektiven Realität, der im Prozess der Auswahl und Nutzung von Medien berücksichtigt wird. Auf verschiedenen Ebenen wie derjenigen der Modalität, des Fokus, der Haltung, des Stils, Repertoires und Arrangements können Handelnde Strategieelemente auswählen, um ihre Ziele zu erreichen und Gratifikationen zu erlangen. Die vorliegende praxeologische Analyse verbindet strukturelle und phänomenologische Perspektiven auf Mediennutzung.

Background A relevant proportion of human immunodeficiency virus (HIV) infected patients is co-infected with the hepatitis C virus (HCV). HCV co-infection in HIV-positive patients is associated with faster progression of liver disease in comparison to HCV mono-infection. Natural killer (NK) cells critically modulate the natural course of HCV infection. Both HIV and HCV mono-infection are associated with alterations of the NK cell pool. However, little data is available concerning phenotype and function of NK cells in HIV/HCV co-infection. Methods A total of 34 HIV/HCV co-infected, 35 HIV and 39 HCV mono-infected patients and 43 healthy control persons were enrolled into this study. All HIV-positive patients were under effective antiretroviral therapy. NK cell phenotype, IFN-γ production and degranulation were studied by flow cytometry. Results NK cell frequency in HIV/HCV co-infection was significantly lower than in healthy individuals but did not differ from HIV and HCV mono-infection. HIV/HCV co-infection was associated with significantly decreased expression of the maturation/differentiation markers CD27/62L/127 on NK cells but increased expression of CD57 compared to healthy controls. Of note, expression also differed significantly from HCV mono-infection but was similar to HIV mono-infection, suggesting a pronounced impact of HIV on these alterations. Similar findings were made with regard to the NK cell receptors NKG2A/C and NKp30. More importantly, NK cells in co-infection displayed a highly impaired functional activity with significantly lower IFN-γ production and degranulation than in healthy donors as well as HIV and HCV mono-infection, suggesting a synergistic effect of both viruses. Conclusions Our data indicate that HIV/HCV co-infection is associated with significant alterations of the NK cell pool, which might be involved in the rapid progression of liver disease in co-infected patients and which mainly reflect alterations observed in HIV mono-infection.

Software protection is a difficult task especially for managed code, which executes only on a runtime environment such as C# or Java. Applications developed in such languages can be accurately decompiled, as opposed to x86 machine code. This facilitates reverse engineering attacks, with the goal of extracting proprietary algorithms. Due to the ease of distributing software copies across different jurisdictions, software developers cannot only rely on legal means for protection against reverse engineering attacks. Therefore, they have to employ technical means for software protection such as obfuscation. This paper presents an open source tool for virtualization obfuscation of programs written in the C# language, called VOT4CS. Our tool offers several possibilities for randomization that aim to confuse attacks based on pattern recognition. An evaluation of VOT4CS is performed based on several case-studies, which show the performance-security trade-off offered by the tool.

Background: RIMTCORE study showed (ERS Congress 2015) that IMT within a 3-week-PR leads to benefits concerning PI max and FIV1 but not with respect to QoL (SGRQ, CAT) and 6MWD. This secondary analysis aims to clarify if there are subgroups with clinical benefits. Methods: RCT, 602 COPD patients GOLD grade 2-4 (IG/GC n = 300/302), intention-to-treat-analysis. Results: Significant moderator effects for gender were found in CAT (p

Background Spontaneous bacterial peritonitis (SBP) can be life-threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP. Patients and methods We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively. Results Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequency of these microorganisms were comparable for healthcare-related and nosocomial SBP (14 vs. 11%, 14 vs. 8%, 14 vs. 5% and 10 vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30 vs. 11% for piperacillin-tazobactam; p>0.05), but comparable concerning third-generation cephalosporins (30 vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n=3) and Candida albicans (n=1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; p=0.002). Conclusion Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP. This article is protected by copyright. All rights reserved.

Background Recently, we identified increased rates of CD4+ T-cell apoptosis in HCV-infected HIV-positive patients as a potential mechanism for enhanced mortality in patients with HIV/HCV coinfection. Since this effect might be attributed to changes in receptor-induced apoptosis, we studied expression and function of Fas ligand (FasL) and its death receptor Fas on CD4+ T-cells in HIV/HCV coinfection. Methods In this cross-sectional study, we simultaneously analysed surface expression of Fas and FasL on CD4+ T-cells and serum levels of soluble FasL in HCV/HIV-coinfected, HIV-monoinfected and HCV-monoinfected patients. Susceptibility to FasL-induced apoptosis was analysed by incubating isolated peripheral blood mono-nuclear cells with rhFasL followed by measuring CD4+ T-cell apoptosis. Results HIV and HCV monoinfection were associated with significantly enhanced surface expression of Fas. Highest Fas expression was detected in HIV/HCV-coinfected patients and correlated with low CD4+ T-cell counts. By contrast, elevated levels of soluble and cellular FasL were found only in patients with HIV infection, but not in patients with HCV infection. Importantly, enhanced Fas expression in HCV/HIV coinfection rendered CD4+ T-cells more susceptible towards FasL-induced apoptosis. While effective HAART normalized expression and secretion of FasL in HIV-infected and HIV/HCV-coinfected patients, expression of Fas decreased only slightly and still remained significantly elevated as compared with healthy controls. Conclusions Our findings suggest a synergistic mechanism in HIV/HCV coinfection between up-regulation of Fas expression on CD4+ T-cells and HIV-induced elevated levels of cellular and soluble FasL. Together, both effects contribute to enhanced apoptosis of CD4+ T-cells in HIV/HCV coinfection.

Background: Up to now it is unclear whether IMT as a routine add-on to PR improves clinical outcome in COPD patients. Method: We underwent a RCT with 555 COPD-patients GOLD-stage 2-4. OFEV1 = 1.42 l = 46.4% pred., O age 57,6 years, 65.1% male. The intervention group (IG; n= 278) provided 7 days/week 21 min. high intensive IMT as routine add-on to a comprehensive 3-week inpatient PR-program. The control group (CG, n = 277) underwent the same intensive PR-program (standard PR) but with a sham IMT of identical duration. There was no difference in the baseline characteristics between the two groups. Primary outcome: maximal inspiratory mouth pressure (PI,max). Secondary outcomes: Vital capacity (VC), forced expiratory and inspiratory volume in 1 second (FEV1, FIV1), 6MWD, Quality of life (SGRQ) and dyspnea (TDI). Results: First analysis of the subgroup of patients with PI, max ≤ 6 kPa didn´t show other significant differences. Discussion: Routine IMT as add-on to PR resulted in a significant increase of PI max and FIV1. But there were no additional benefits in other outcomes like QoL, exercise capacity and dyspnea in comparison to the very good short-term effects of the standard PR. Further analysis of our data will focus on subgroups and the long-term effects of the still ongoing 1 year follow-up.

Background Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52 kDa ( NDP52 ), a negative regulator of toll-like receptor (TLR) signalling and autophagy adaptor protein, might be involved. Methods Two cohorts comprising 152 (derivation cohort) and 198 patients (validation cohort) with decompensated liver cirrhosis and 168 healthy controls were genotyped for the rs2303015 polymorphism in the NDP52 gene and prospectively followed-up for spontaneous bacterial peritonitis. Results Overall, 57 (38%) patients in the derivation cohort and 77 (39%) in the validation cohort had spontaneous bacterial peritonitis. Cirrhosis was due to alcohol abuse in 57% of the derivation and 66% of the validation cohort. In patients with alcoholic cirrhosis, patients with spontaneous bacterial peritonitis had an increased frequency of the NDP52 rs2303015 minor variant in the derivation ( p = 0.04) and in the validation cohort ( p = 0.01). Multivariate analysis confirmed this minor variant (odds ratio 4.7, p = 0.002) and the TLR2 −16934 TT variant (odds ratio 2.5, p = 0.008) as risk factors for spontaneous bacterial peritonitis. In addition, presence of the NDP52 minor variant affected survival negatively. Conclusion Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.

Diagnosis of spontaneous bacterial peritonitis (SBP) is based on a differential ascites leukocyte count which does not provide prognostic information. We performed a pilot study to assess calprotectin in ascites as an alternative diagnostic and prognostic marker.We collected ascites from patients with liver cirrhosis from March 2012 to July 2013. Routine clinical and laboratory data of the patients were recorded. Ascites calprotectin levels were determined by ELISA.Overall, we collected 120 ascites samples from 100 patients with liver cirrhosis and from eight patients with malignant peritoneal effusion as disease control. Samples without infection had significantly lower calprotectin levels (median 34 ng/mL, range 5–795) than SBP samples (median 928 ng/mL, range 21–110,480; pThe ratio of ascites calprotectin to total protein may be a promising new diagnostic and prognostic marker in patients with liver cirrhosis and SBP and should be evaluated further.

The IFNL4 ss469415590 polymorphism has recently be shown to better predict treatment response in chronic hepatitis than the IL28B rs12979860 variant. However, no data exist in patients with HIV/hepatitis C virus (HCV) coinfection. Analysing 206 HCV(+)/HIV(+) and 162 HCV(+)/HIV(-) patients, we found that compared with IL28B rs12979860, IFNL4 ss469415590 was strongly associated with response to interferon/ribavirin therapy in HCV(+)/HIV(-) individuals but not in HIV(+)/HCV(+) patients. Thus, effects of the IFNL4 variant may differ in HIV(+) and HIV(-) patients.

Background Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC. Methods Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population. Results Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. DR4 variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 106 IU/ml vs. 1.81 ± 0.23 × 106 IU/ml, p = 0.049). Conclusions The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.

Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the β(2)-agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability. Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 μg q.d. (n=797) or tiotropium 18 μg q.d. (n=801) for 12 weeks. After 12 weeks, the two treatments had similar overall effects on "trough" (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01 versus 1.43; p

BackgroundAn isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC).MethodsWe compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection.ResultsPNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (pConclusionThe PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should be taken into account in future HCC prevention studies.

Beatrix Balint1, Henrik Watz2, Carolynn Amos3, Roger Owen3, Mark Higgins3, Benjamin Kramer4, On behalf of the INSURE* Study Investigators1Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza, Deszk, Hungary; 2Pulmonary Research Institute, Hospital Grosshansdorf, Grosshansdorf, Germany; 3Novartis Horsham Research Centre, Horsham, West Sussex, UK; 4Novartis Pharmaceuticals, East Hanover, NJ, USA; *Indacaterol: starting quickly and remaining effective in COPDBackground: Indacaterol is a novel, inhaled once-daily ultra-long-acting ß2-agonist for the treatment of chronic obstructive pulmonary disease (COPD).Objectives: This study compared the onset of action of single doses of indacaterol 150 and 300 µg with salbutamol 200 µg, salmeterol-fluticasone 50/500 µg, and placebo in moderate-to-severe COPD patients.Methods: This was a multicenter, randomized, double-blind, placebo-controlled crossover study. The primary variable was forced expiratory volume in one second (FEV1) at five minutes postdose.Results: Out of 89 patients randomized (mean age 62 years), 86 completed the study. At five minutes postdose, both indacaterol doses were statistically and clinically superior to placebo (P< 0.001), with treatment–placebo differences in FEV1 of 100 (95% confidence interval [CI] 70–130) mL and 120 (95% CI 90–150) mL for indacaterol 150 and 300 µg, respectively. FEV1 at five minutes postdose with both indacaterol doses was numerically higher than for salbutamol (10 and 30 mL for indacaterol 150 and 300 µg, respectively) and significantly higher than for salmeterol-fluticasone (50 mL, P = 0.003; 70 mL, P< 0.001, respectively). Moreover, both indacaterol doses showed significantly higher FEV1 than placebo (P< 0.001) at all postdose time points. The numbers of patients with an FEV1 increase of at least 12% and 200 mL at five minutes postdose were 16 (18.8%), 24 (27.6%), 20 (23.3%), 8 (9.1%), and 3 (3.4%) for indacaterol 150 and 300 µg, salbutamol 200 µg, salmeterol-fluticasone 50/500 µg, and placebo, respectively.Conclusions: Single doses of indacaterol 150 and 300 µg demonstrated a fast onset of action similar to that for salbutamol and faster than that for salmeterol-fluticasone.Keywords: indacaterol, onset of action, chronic obstructive pulmonary disease

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (p

Udgivelsesdato: 2010-Jun BACKGROUND: Indacaterol is a long-acting inhaled beta(2)-agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). In previous studies, indacaterol provided 24 h bronchodilation on once-daily dosing with a fast onset of action. This study compared the efficacy and safety of indacaterol with the twice-daily LABA formoterol and placebo over 1 year. METHODS: Patients with moderate to severe COPD were randomised to receive once-daily indacaterol 300 microg (n=437) or 600 microg (n=428), twice-daily formoterol 12 microg (n=435) or placebo (n=432) for 52 weeks in a double-blind double-dummy parallel group study. The primary efficacy variable was forced expiratory volume in 1 s (FEV(1)) measured 24 h postdose after 12 weeks (indacaterol vs placebo). Other outcomes included dyspnoea (transition dyspnoea index, TDI), use of as-needed salbutamol, symptom-based measures recorded on diary cards, exacerbations, health status (St George's Respiratory Questionnaire), BODE index (body mass index, obstruction, dyspnoea, exercise), safety and tolerability. RESULTS: Indacaterol increased 24 h postdose FEV(1) after 12 weeks by 170 ml (both doses) versus placebo and by 100 ml versus formoterol (all p