Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: meta-analysis of 5 trials.

Background & Aims: HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials resulting in limited data to guide their management. We performed a meta-analysis of well-compensated cirrhotic patients from five Phase 3 trials.

Methods: Patients received P/R (peginterferon/ribavirin; 4 weeks) followed by BOC (boceprevir)/P/R or P/R for 24, 32, or 44 weeks.

Can autism spectrum disorders and social anxiety disorders be differentiated by the social responsiveness scale in children and adolescents?

Autism spectrum disorder (ASD) as well as social phobia (SP), and selective mutism (SM) are characterised by impaired social interaction. We assessed the validity of the Social Responsiveness Scale (SRS) to differentiate between ASD, and SP/SM. Raw scores were compared in 6-18 year old individuals with ASD (N = 60), SP (N = 38), SM (N = 43), and typically developed (N = 42).

Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial.

Background & Aims: Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV.

Methods: We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66).

Purpura fulminans after therapeutic hypothermia in an asphyxiated neonate with streptococcemia.

Objective: Therapeutic hypothermia is an established therapeutic regimen in severely asphyxiated term neonates. The amount of cerebral injury is reduced resulting in an improved neurologic outcome. Therapeutic hypothermia-induced side effects mostly affect the circulatory system, kidney, and liver.

Platelet factor 4-positive thrombi adhering to the ventricles of a ventricular assist device in patients with heparin-induced thrombocytopenia type II.

Background: Thromboembolism is a major complication in patients with ventricular assist devices (VADs). Drug anticoagulation and the use of biocompatible surfaces, such as coating with heparin, aim to reduce thromboembolism in these patients. Administration of heparin can lead to heparin-induced thrombocytopenia (HIT) type II, mainly through heparin/platelet factor 4 (PF4) antibodies.

Validity of the social responsiveness scale to differentiate between autism spectrum disorders and disruptive behaviour disorders.

Autism spectrum disorder (ASD) as well as oppositional defiant (ODD) and conduct disorder (CD) is characterised by difficulties in social interaction with peers. The Social Responsiveness Scale (SRS) measures reciprocal social behaviour in children and adolescents and was originally developed as a quantitative measure of autistic traits. In the present study, we compare parent-rated SRS scores in children with ODD, CD, and ASD and examine the diagnostic validity of the SRS alone and in combination with additional questionnaires to differentiate between groups.

Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results.

Background: Faldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting antiviral agents under development for the treatment of chronic HCV infection. This article describes the final results of the Phase Ib SOUND-C1 study that evaluated the interferon-free oral combination of faldaprevir, deleobuvir and ribavirin in 32 treatment-naive patients infected with HCV genotype 1.

Methods: Patients were randomized to receive deleobuvir 400 mg (n=15) or 600 mg (n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks.

Effects of hepatic impairment on the pharmacokinetics of everolimus: a single-dose, open-label, parallel-group study.

Background: Although the pharmacokinetics of everolimus, an oral mammalian target of rapamycin inhibitor, have been characterized in patients with moderate hepatic impairment, they have not been assessed in those with mild or severe hepatic impairment.

Objective: The goal of this study was to assess the pharmacokinetics and safety of everolimus in healthy volunteers with normal hepatic function and patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment in otherwise good health to inform dosing in the clinical setting.

Methods: A multicenter, open-label, Phase I study in which all enrollees received a single, 10-mg, oral everolimus dose was conducted.

Radiation dose and image quality of X-ray volume imaging systems: cone-beam computed tomography, digital subtraction angiography and digital fluoroscopy.

Objective: Radiation dose and image quality estimation of three X-ray volume imaging (XVI) systems.

Methods: A total of 126 patients were examined using three XVI systems (groups 1-3) and their data were retrospectively analysed from 2007 to 2012. Each group consisted of 42 patients and each patient was examined using cone-beam computed tomography (CBCT), digital subtraction angiography (DSA) and digital fluoroscopy (DF).

The choice of the intravenous fluid influences the tolerance of acute normovolemic anemia in anesthetized domestic pigs.

Introduction: The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O₂) supply during acute normovolemic anemia has not been investigated so far.

Methods: Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit).

Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis.

Acoustic Radiation Force Impulse (ARFI) imaging is a novel ultrasound-based elastography method that is integrated in a conventional ultrasound machine enabling the exact localization of measurement site. It might present an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. At present, studies with small patient population have shown promising results.

Mixing and matching drugs: what makes sense?

The introduction and ongoing development of directly acting antiviral agents (DAAs) and drugs targeting host cell structures will change the management of patients with chronic hepatitis C virus (HCV) infection. The concomitant use of the protease inhibitors telaprevir or boceprevir with the standard of care, a combination of pegylated interferon (PegIFN) and ribavirin, will represent the new standard for the treatment of HCV genotype 1 infection. Contraindications and side effects limit the applicability of interferon-based therapies and motivate the investigation of PegIFN-sparing regimens.

Antiviral activity of danoprevir (ITMN-191/RG7227) in combination with pegylated interferon α-2a and ribavirin in patients with hepatitis C.

Background: Current therapy options for patients with chronic hepatitis C virus (HCV) infection genotype 1 are effective in <50%. Danoprevir (ITMN-191/RG7227) is a potent, selective, and orally active inhibitor of the HCV NS3/4A serine protease.

Methods: The safety and antiviral efficacy of danoprevir was examined over 14 days in combination with pegylated interferon α-2a (180 μg once weekly) and ribavirin (1000-1200 mg/day) in a double-blind, placebo-controlled, phase 1b, multiple ascending dose study consisting of 6 dose cohorts (400 mg, 600 mg, and 900 mg twice daily and 100 mg, 200 mg, and 300 mg 3 times daily).

Emergency airway management in trauma patients using laryngeal tube suction.

Background: Endotracheal intubation (ETI) is considered to be the "gold standard" of prehospital airway management of trauma patients. However, ETI requires substantial technical skills and ongoing experience. Because failed prehospital ETI is common and associated with a higher mortality, reliable airway devices are needed to be used by rescuers who are less experienced in ETI.

Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients.

Introduction: Systemic inflammation (for example, following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum.

Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis.

Background: FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminal propeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1). While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers.

Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 1.

Background & Aims: The current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b.

Methods: In the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 μg every week, or albIFN 900 or 1200 μg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day.

Seroepidemiology of parvovirus B19 in the Frankfurt am Main area, Germany: evaluation of risk factors.

Background: Parvovirus B 19 is a virus that is distributed by respiratory droplets. It is known to be an initiator of erythema infectiosum (children's fifth disease), with erythroblasts being the target cells of infection. In case of vertically transmission, hydrops fetalis has been documented.

Intracerebral mass bleeding in a term neonate: manifestation of hereditary protein S deficiency with a new mutation in the PROS1 gene.

Background: Vitamin K deficiency is the major cause of coagulopathy-induced intracranial bleeding in term neonates and is considered first in any term neonate with severe hemorrhage. The most common manifestation of hereditary prothrombotic disorders during the neonatal period is thrombosis of the A. cerebri media or sinus thrombosis.

Heparin-induced non-necrotizing skin lesions: rarely associated with heparin-induced thrombocytopenia.

Summary Background: Recently, there has been an increasing number of reports regarding adverse skin reactions to subcutaneous heparin administration. Case series have implied that heparin-induced skin lesions are predominantly associated with life-threatening heparin-induced thrombocytopenia (HIT) in at least 22% of patients. Skin lesions, therefore, have been included in clinical scores for HIT.

Real-time elastography and contrast-enhanced ultrasound for the assessment of thyroid nodules.

Objective: Work-up of thyroid nodules remains challenging. Recent technologies enable determination of tissue elasticity and perfusion using ultrasound devices. The aim of the present study was to evaluate real-time elastography (RTE) and contrast-enhanced ultrasound with Sonovue (CEUS) for the differentiation of benign and malignant thyroid nodules.

Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients.

Unlabelled: Boceprevir is a hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor that is currently being evaluated in combination with peginterferon alfa-2b and ribavirin in phase 3 studies. The clinical resistance profile of boceprevir is not characterized in detail so far. The NS3 protease domain of viral RNA was cloned from HCV genotype 1-infected patients (n = 22).