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71.
Julia Dietz Olga V. Kalinina Johannes Vermehren Kai‐Henrik Peiffer Katrin Matschenz Peter Buggisch Claus Niederau Jrn M. Schattenberg Beat Müllhaupt Sabine Yerly Marc Ringelhan Roland M. Schmid Christoph Antoni Tobias Müller Julian Schulze zur Wiesch Felix Piecha Darius Moradpour Katja Deterding Heiner Wedemeyer Christophe Moreno Thomas Berg Christoph P. Berg Stefan Zeuzem Christoph Welsch Christoph Sarrazin 《Journal of viral hepatitis》2020,27(10):974-986
Data on the prevalence of resistance‐associated substitutions (RASs) and their implications for treatment with direct‐acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4‐infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA‐naïve patients (5%) and the number of NS5A RASs was significantly higher in subtype 4r compared to 4a or 4d (median three RASs vs no or one RAS, respectively, P < .0001). RASsL28V, L30R and M31L pre‐existed in subtype 4r and were maintained after NS5Ai failure. Typical subtype 4r RASs were located in subdomain 1a of NS5A, close to membrane interaction and protein‐protein interaction sites that are responsible for multimerization and hence viral replication. Retreatment of 37 DAA failure patients was highly effective with 100% SVR in prior SOF/RBV, PI/SOF and PI/NS5Ai failures. Secondary virologic failures were rare (n = 2; subtype 4d and 4r) and only observed in prior NS5Ai/SOF failures (SVR 90%). In conclusion, subtype 4r harboured considerably more RASs compared to other subtypes. A resistance‐tailored retreatment using first‐ and second‐generation DAAs was highly effective with SVR rates ≥90% across all subtypes and first‐line treatment regimens. 相似文献
72.
Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke. 相似文献
73.
Mar González-Franco Tabitha C. Peck Antoni Rodríguez-Fornells Mel Slater 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2014,232(3):875-887
We report an experiment where participants observed an attack on their virtual body as experienced in an immersive virtual reality (IVR) system. Participants sat by a table with their right hand resting upon it. In IVR, they saw a virtual table that was registered with the real one, and they had a virtual body that substituted their real body seen from a first person perspective. The virtual right hand was collocated with their real right hand. Event-related brain potentials were recorded in two conditions, one where the participant’s virtual hand was attacked with a knife and a control condition where the knife only struck the virtual table. Significantly greater P450 potentials were obtained in the attack condition confirming our expectations that participants had a strong illusion of the virtual hand being their own, which was also strongly supported by questionnaire responses. Higher levels of subjective virtual hand ownership correlated with larger P450 amplitudes. Mu-rhythm event-related desynchronization in the motor cortex and readiness potential (C3–C4) negativity were clearly observed when the virtual hand was threatened—as would be expected, if the real hand was threatened and the participant tried to avoid harm. Our results support the idea that event-related potentials may provide a promising non-subjective measure of virtual embodiment. They also support previous experiments on pain observation and are placed into context of similar experiments and studies of body perception and body ownership within cognitive neuroscience. 相似文献
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77.
Augustin S González A Badia L Millán L Gelabert A Romero A Segarra A Martell M Esteban R Guardia J Genescà J 《Hepatology (Baltimore, Md.)》2012,56(2):706-714
Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. Conclusions: After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes. 相似文献
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79.
Dalmases M Lucena CM Cano-Jiménez E Xaubet A Agustí C 《Archivos de bronconeumología》2012,48(7):258-260
Endobronchial metastases (EBM) secondary to extrapulmonary primary tumours are rare. The most common solid malignant tumours associated with EBM are breast, renal and colorectal carcinomas. This case report describes the first documented case of EBM from anal canal carcinoma. This neoplasm constitutes less than 1% of colorectal tumours. The clinical presentation of this entity is variable, being asymptomatic in more than 50% of cases. Generally, EBM are diagnosed in advanced stages and the survival after the diagnosis is poor. It is therefore an exceptional clinical manifestation in which bronchoscopy has an important role in the diagnosis and the treatment. 相似文献
80.
José R. González-Juanatey José Álvarez-Sabin José M. Lobos Antoni Martínez-Rubio Joan C. Reverter Itziar Oyagüez Nuria González-Rojas Virginia Becerra 《Revista espa?ola de cardiología》2012