Refine
Year of publication
Document Type
- Article (18)
- Working Paper (1)
Has Fulltext
- yes (19)
Is part of the Bibliography
- no (19)
Keywords
- cirrhosis (2)
- 8 weeks (1)
- APRI (1)
- Anti platelet therapy (1)
- Antiretroviral therapy (1)
- Antiretrovirals (1)
- Antithrombotic therapy (1)
- Arrhythmia/all (1)
- Atrial fibrillation (1)
- Cardiac (1)
- Cirrhosis (1)
- Clinical trials (1)
- Data sharing (1)
- Direct Acting Antivirals (DAA) (1)
- Dual therapy (1)
- FGFR (1)
- FIB-4 (1)
- General clinical cardiology (1)
- HBV (1)
- HIV (1)
- HIV-1 (1)
- Hepatitis C (1)
- Hepatitis C virus (1)
- Liver diseases (1)
- Liver transplantation (1)
- PD-L1 (1)
- Percutaneous coronary intervention (1)
- Pharmacology (1)
- Stroke prevention (1)
- Sustained virological response (SVR) (1)
- Thrombosis/hypercoagulable states (1)
- Triple therapy (1)
- acoustic radiation force impulse imaging (1)
- antiviral therapy (1)
- catheterization/diagnostic interventional (1)
- chronic viral hepatitis (1)
- fibrotest (1)
- glecaprevir (1)
- global change (1)
- habitat destruction (1)
- hepatitis C virus (1)
- hepatitis c (1)
- immune checkpoint inhibitor (ICI) (1)
- immunohistochemistry (1)
- immunotherapy (1)
- land use (1)
- management (1)
- non-invasive fibrosis assessment (1)
- pibrentasvir (1)
- point shear wave elastography (1)
- shortening of treatment (1)
- stopping rule (1)
- transient elastography (1)
- tyrosine kinase inhibitor (TKI) (1)
- гепатит С (1)
- правила прекращения лечения (1)
- противовирусные препараты прямого действия (ПППД) (1)
- сокращение лечения (1)
- устойчивый вирусологический ответ (УВО) (1)
Institute
Objectives: The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively.
Methods: When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)).
Results: Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up.
Conclusion: DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.
Background: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection.
Methods: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L).
Results: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05).
Conclusion: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.
Am 26.02.2002 hat die von der Bundesministerin der Justiz auf Empfehlung der Regierungskommission Corporate Governance eingesetzte Kodex-Kommission den Deutschen Corporate Governance Kodex (im folgenden: DCG-Kodex/Kodex) vorgelegt. Mit Inkrafttreten des Transparenz- und Publizitätsgesetzes4, voraussichtlich im August 2002, werden Vorstand und Aufsichtsrat börsennotierter Aktiengesellschaften künftig jährlich zu erklären haben, ob sie den Empfehlungen des Kodex folgen, und, soweit dies nicht der Fall ist, Abweichungen offen zu legen haben. Im folgenden ist zunächst das Kodex-Konzept, das dem angelsächsischen Rechtskreis entstammt, zu erläutern und die mit dem DCG-Kodex verfolgte Zielsetzung vorzustellen (dazu B.). Dem schließt sich ein Überblick über Regelungstechnik und Inhalt des DCG-Kodex sowie dessen gesetzliche „Flankierung“ durch das TransPuG an (dazu C.). Sodann werden die Entsprechens-Erklärung (dazu D.) sowie Haftungsfragen im Zusammenhang mit dem DCG-Kodex (dazu E.) behandelt.
Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and Methods: Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results: PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
Nuclear resonance fluorescence experiments with linearly polarized bremsstrahlung were performed to determine parities of strong dipole transitions in 40Ar. A total of 14 transitions—ten of them previously unknown—in the energy range from 4.7 to 10.2 MeV could be identified. From this experiment it is evident that the main dipole strength to bound states is due to E1 excitations. An upper limit of B(M1) [up arrow] <0.5 µN2 was found for individual magnetic dipole excitations in 40Ar in the energy region below neutron threshold.
Nuclear resonance fluorescence measurements with linearly polarized bremsstrahlung were performed to determine parities of bound dipole transitions in 206Pb. A new 1+ level at 5800 keV was found, which has almost the same strength as the isoscalar M1 transition in 208Pb. Twenty-four further dipole states in 206Pb below 7.6 MeV possess negative parity.
Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ∼ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.
Aims: Of patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population.
Methods and results: A systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36–0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48–1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms.
Conclusion: Compared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI.
Background: Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.
Methods: Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n = 11), placebo (n = 13) or PEG-IFNa-2a alone (n = 6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.
Results: Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load.
Conclusions: PEG-IFNa activates NK cells possibly contributing to virological responses independently of RBV. The role of NK cells during future IFN-free combination therapies including RBV remains to be determined.
Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.
Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).
Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.
Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.
Trial registration number NCT0209966.