Outcomes in patients receiving palliative chemotherapy for advanced biliary tract cancer.

Background & Aims: Advanced biliary tract cancer (ABTC) is associated with a poor prognosis. Real-world data on the outcome of patients with ABTC undergoing sequential chemotherapies remain scarce, and little is known about treatment options beyond the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX. This study aimed to evaluate the outcome of patients with regard to different oncological therapies and to identify prognostic factors.

Monitoring Gait Complexity as an Indicator for Running-Related Injury Risk in Collegiate Cross-Country Runners: A Proof-of-Concept Study.

Dynamical systems theory suggests that studying the complexity of biological signals could lead to a single gait metric that reliably predicts risk of running-related injury (RRI). The purposes of this pilot study were to examine center of mass (COM) acceleration complexity at baseline, prior to RRI, and the change between timepoints between collegiate runners who developed RRI during a competitive season and those who remained uninjured, and to determine if complexity at these timepoints was associated with increased odds of RRI. Twenty-two collegiate runners from the same cross-country team wore a waist-mounted triaxial accelerometer (100 Hz) during easy-intensity runs throughout the competitive season.

Functional inhibition of Oct leads to HNF4α upregulation.

Organic cation transporters (human, OCT; mouse, Oct) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. The OCT1 gene SLC22A1 (human; mouse, Scl22a1) is transactivated by hepatocyte nuclear factor 4α (human, HNF4α; mouse, Hnf4α). HNF4α is a master regulator of hepatocyte differentiation and is frequently associated with hepatocellular carcinoma (HCC).

Urinary ethyl glucuronide (uEtG) as a marker for alcohol consumption in liver transplant candidates: a real-world cohort.

Background:  In order to reduce alcohol relapse after liver transplantation (LT), the German national guidelines for waiting-list maintenance and organ allocation demand a minimum 6-month period of alcohol abstinence pre-LT, confirmed by measuring urinary ethyl glucuronide (uEtG).

Methods:  Between January 2015 and June 2016, uEtG was measured at least once in 339 cirrhotic patients with an indication for LT at the University Medical Center Mainz. uEtG was measured with an enzyme-linked immunosorbent assay (ELISA) screening test (cutoff value: 500 µg/L).

A universal approach to investigate circRNA protein coding function.

Circular RNAs (circRNAs) are an emerging class of RNA molecules that have been linked to human diseases and important regulatory pathways. Their functional roles are still under investigation, often hampered by inefficient circRNA formation in and ex vivo. We generated an intron-mediated enhancement (IME) system that-in comparison to previously published methods-increases circRNA formation up to 5-fold.

Long-term observation of hepatocellular carcinoma recurrence after liver transplantation at a European transplantation centre.

Background: The recurrence of hepatocellular carcinoma (HCC) is the strongest survival-limiting factor after liver transplantation (LT) in patients with HCC. In the face of donor organ shortage, it is necessary to identify factors associated with HCC recurrence in order to maximize the utility of the available grafts.

Objective: To study the phenomenon of HCC recurrence after LT at a European transplantation centre over the past 20 years.

Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ.

Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout (; ) and wild-type (WT; ) mice were subject to escalating doses of carbon tetrachloride (CCl) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis.

Cirrhosis risk score of the donor organ predicts early fibrosis progression after liver transplantation.

Background And Aims: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient's seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts.

Expression and prognostic significance of insulin‑like growth factor-2 receptor in human hepatocellular carcinoma and the influence of transarterial chemoembolization.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies, the incidence of which is growing worldwide. The prognosis of HCC is very poor and it is often accompanied by a high rate of recurrence. Conventional chemotherapeutic approaches are largely inefficient.

Progression of transthyretin (TTR) amyloidosis in donors and recipients after domino liver transplantation-a prospective single-center cohort study.

Liver transplantation (LT) is the first-line therapy in patients with transthyretin (TTR) amyloidosis and progressive familial amyloid polyneuropathy (FAP). Explanted organs from these patients can be used for domino liver transplantation (DLT). After DLT, de novo amyloidosis may develop in domino recipients (DR).

Loss of organic cation transporter 3 (Oct3) leads to enhanced proliferation and hepatocarcinogenesis.

Background: Organic cation transporters (OCT) are responsible for the uptake of a broad spectrum of endogenous and exogenous substrates. Downregulation of OCT is frequently observed in human hepatocellular carcinoma (HCC) and is associated with a poor outcome. The aim of our current study was to elucidate the impact of OCT3 on hepatocarcinogenesis.

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation.

Background: Cardiovascular disease is a serious problem of liver transplant (LT) recipients because of increased cardiovascular risk due to immunosuppressive therapy, higher age, intraoperative risk and comorbidities (such as diabetes and nicotine abuse). Reported frequency of cardiovascular events after LT shows a high variability between different LT cohorts. Our aim was to analyze a cohort of LT recipients from a single center in Germany to evaluate frequency of the cardiovascular endpoints (CVE) myocardial infarction and/or cardiac death after LT and to investigate correlations of CVE post LT with pretransplant patient characteristics.

Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat patients with recurrent hepatitis C virus infection after liver transplantation: a real-world cohort.

Background: Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has been a frequent and relevant problem in the past two decades. This analysis evaluated the efficacy and safety of new interferon (IFN)-free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV patients after LT.

Methods: We retrospectively analyzed a cohort of 157 patients infected with HCV who underwent deceased donor LT between 1997 and 2014.

Atrial fibrillation and gastroesophageal reflux disease: the cardiogastric interaction.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Multiple conditions like hypertension, heart failure, diabetes, sleep apnoea, and obesity play a role for the initiation and perpetuation of AF. Recently, a potential association between gastroesophageal reflux disease (GERD) and AF development has been proposed due to the close anatomic vicinity of the oesophagus and the left atrium.

Organic Cation Transporter 1 (OCT1) mRNA expression in hepatocellular carcinoma as a biomarker for sorafenib treatment.

Background: The polyspecific organ cation transporter 1 (OCT1) is one of the most important active influx pumps for drugs like the kinase inhibitor sorafenib. The aim of this retrospective study was the definition of the role of intratumoral OCT1 mRNA expression in hepatocellular carcinoma (HCC) as a biomarker in systemic treatment with sorafenib.

Methods: OCT1 mRNA expression levels were determined in biopsies from 60 primary human HCC by real time PCR.

Efficacy and safety of a conversion from the original tacrolimus and mycophenolate mofetil to the generics Tacpan and Mowel after liver transplantation.

Background: Expensive pharmaceuticals are a major reason for cost intensive health care systems. Long-term immunosuppressive therapy plays a relevant role after organ transplantation. Patents of original drugs have expired and cheaper products are available.

The Impact of Childhood Acute Otitis Media on Parental Quality of Life in a Prospective Observational Cohort Study.

Background And Objectives: Acute otitis media (AOM) not only affects childhood quality of life (QoL), but can also affect parental QoL. We adapted a previously published questionnaire on the effect of childhood recurrent ear, nose and throat infections on parental QoL for use with AOM and used it in an observational, multicentre, prospective study of children with AOM.

Methods: The AOM-specific parental QoL questionnaire grouped 15 items into emotional, daily disturbance, total and overall parental QoL impact scores.

Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population.

Background: Conventional smallpox vaccines based on replicating vaccinia virus (VV) strains (e.g. Lister Elstree, NYCBOH) are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication.

Safety and immunogenicity of modified vaccinia Ankara as a smallpox vaccine in people with atopic dermatitis.

Background: Following vaccination with traditional smallpox vaccines or after exposure to vaccinated individuals, subjects with atopic dermatitis (AD) can develop eczema vaccinatum, a severe disease with disseminated eruption of pustular contagious lesions. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need.

Methods: An open-label controlled Phase I clinical trial was conducted to investigate the safety and immunogenicity of modified vaccinia Ankara (MVA) in 15 healthy subjects compared to 45 subjects with either mild allergic rhinitis, a history of AD or presenting with mild active AD.

Incidence and clinical presentation of acute otitis media in children aged <6 years in European medical practices.

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK.

[Mechanics and effects of European reference pricing for vaccines in Germany according to §130a Abs. 2 SGB V: an analysis using the example of influenza vaccines].

Objectives: On 01 January 2011 the bill for the reorganisation of the pharmaceutical market became effective. Since that time there is a European reference pricing (ERP) system for vaccines in order to bring down the German vaccine prices to an assumed lower European level. This study describes the implementation, functioning and effect of this new system.

Identifying brain systems for gaze orienting during reading: fMRI investigation of the Landolt paradigm.

The Landolt reading paradigm was created in order to dissociate effects of eye movements and attention from lexical, syntactic, and sub-lexical processing. While previous eye-tracking and behavioral findings support the usefulness of the paradigm, it remains to be shown that the paradigm actually relies on the brain networks for occulomotor control and attention, but not on systems for lexical/syntactic/orthographic processing. Here, 20 healthy volunteers underwent fMRI scanning while reading sentences (with syntax) or unconnected lists of written stimuli (no syntax) consisting of words (with semantics) or pseudowords (no semantics).