The Incidence and Management of Moderate to Severe Head Injury.

Background: The comprehensive expansion of the Trauma Register of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie; TR-DGU) now enables, for the first time, studies on traumatic brain injury (TBI) with special attention to care processes, clinical course, and outcomes of treatment on discharge or transfer from the acute-care hospital.

Methods: Retrospective analysis of patients documented in the TR-DGU in the period 2013-2017 who had moderate to severe head injury as defined by the Abbreviated Injury Scale (AIS).

Results: In the period 2013-2017, 41 101 patients with moderate to severe TBI were treated in TR-DGU-associated hospitals in Germany (n = 605 hospitals), corresponding to 8220 cases per year and thus to a population-wide incidence of 10.

Addressing Profiles of Systemic Inflammation Across the Different Clinical Phenotypes of Acutely Decompensated Cirrhosis.

Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up.

JNJ-4178 (AL-335, Odalasvir, and Simeprevir) for 6 or 8 Weeks in Hepatitis C Virus-Infected Patients Without Cirrhosis: OMEGA-1.

The combination of three direct-acting antiviral agents (AL-335, odalasvir, and simeprevir: JNJ-4178 regimen) for 6 or 8 weeks demonstrated good efficacy and safety in a phase IIa study in chronic hepatitis C virus (HCV) genotype (GT)-1-infected patients without cirrhosis and has now been evaluated in a larger phase IIb study, OMEGA-1. This multicenter, randomized, open-label study (NCT02765490) enrolled treatment-naïve and interferon (±ribavirin) treatment-experienced patients with HCV GT1, 2, 4, 5, or 6 infection. Patients with HCV GT3 infection and/or liver cirrhosis were excluded.

Use of Antiplatelet Agents Is Inversely Associated With Liver Fibrosis in Patients With Cardiovascular Disease.

Platelets participate in the development of liver fibrosis in animal models, but little is known about the benefit of antiplatelet agents in preventing liver fibrosis in humans. We therefore explored the relationship between the use of antiplatelet agents and liver fibrosis in a prospective cohort study of patients at high risk of liver fibrosis and cardiovascular events. Consecutive patients undergoing elective coronary angiography at the University Hospital Frankfurt were prospectively included in the present study.

Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis.

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known.

Direct-acting antivirals-based therapy decreases hepatic fibrosis serum biomarker microfibrillar-associated protein 4 in hepatitis C patients.

Background/aims: An estimated 80 million people worldwide are infected with viremic hepatitis C virus (HCV). Even after eradication of HCV with direct acting antivirals (DAAs), hepatic fibrosis remains a risk factor for hepatocarcinogenesis. Recently, we confirmed the applicability of microfibrillar-associated protein 4 (MFAP4) as a serum biomarker for the assessment of hepatic fibrosis.

Comparison of strain elastography, point shear wave elastography using acoustic radiation force impulse imaging and 2D-shear wave elastography for the differentiation of thyroid nodules.

Purpose: The aim of the study was to compare three different elastography methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave Elastography (2D-SWE), in the same study population for the differentiation of thyroid nodules.

Materials And Methods: All patients received a conventional ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI-Imaging. Cytology/histology of thyroid nodules was used as a reference method.

Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.

Objective: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse.

Design: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis.

Patatin-like phospholipase domain containing 3 variants differentially impact metabolic traits in individuals at high risk for cardiovascular events.

Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin-like phospholipase domain containing 3 () gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss-of-function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well-established associations, the relationship of the rs738409 variant with other metabolic traits is incompletely understood.

Differential modulation of hepatitis C virus replication and innate immune pathways by synthetic calcitriol-analogs.

Background And Aims: Vitamin D signaling is involved in infectious and non-infectious liver diseases, yet the natural vitamin D metabolites are suboptimal therapeutic agents. In the present study, we therefore aimed to explore the potential and mechanism of selected calcitriol analogs to regulate the hepatocellular transcriptome and to inhibit hepatitis C virus (HCV) in comparison with calcitriol.

Methods: Human hepatoma cell lines and primary human macrophages were stimulated with calcitriol and selected calcitriol analogs.

Immunosuppression Is Associated With Clinical Features and Relapse Risk of B Cell Posttransplant Lymphoproliferative Disorder: A Retrospective Analysis Based on the Prospective, International, Multicenter PTLD-1 Trials.

Background: Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors, and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear.

Methods: This is a retrospective analysis of immunosuppression, patient baseline characteristics, and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by cyclophosphamide (CHOP-21 chemotherapy) 750 mg/m intravenously [IV] day (d) 1, doxorubicin 50 mg/m IV d1, vincristine 1.

Increased Small Intestinal Permeability during Severe Acute Exacerbations of COPD.

Background: Disturbances of intestinal integrity, manifested by increased gastro-intestinal (GI) permeability, have been found in chronic obstructive pulmonary disease (COPD) patients during physical activity, often associated with intermittent hypoxic periods. Evidence about extrapulmonary organ disturbances, especially of the GI tract, during hospitalised acute exacerbation of COPD (AE-COPD) with hypoxaemic respiratory failure (RF) is lacking.

Objective: The aim was to assess changes in GI permeability in patients with AE-COPD and during recovery 4 weeks later.

Safety and Effectiveness of Ledipasvir and Sofosbuvir, With or Without Ribavirin, in Treatment-Experienced Patients With Genotype 1 Hepatitis C Virus Infection and Cirrhosis.

Background & Aims: We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET).

Methods: We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel.

Evaluation of 2D- Shear Wave Elastography for Characterisation of Focal Liver Lesions.

Background And Aim: This is a prospective study for evaluation of 2D-shear wave elastography (2D-SWE) for characterisation and differentiation of benign und malignant focal liver lesions (FLLs).

Methods: The patients referred to our ultrasound unit were prospectively included. B-mode ultrasound and 2D-SWE (Aixplorer® France) were performed for one FLL in each patient.

Pan-intestinal capsule endoscopy in patients with postoperative Crohn's disease: a pilot study.

Background: Patients are at increased risk of disease recurrence after surgical treatment of Crohn's disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown.

Methods: This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease.

EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version).

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts.

EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Short Version).

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed.

Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival.

The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment.

Treatment Options in Hepatitis C.

Background: Among patients with chronic hepatitis C, 20-30% develop hepatic cirrhosis and its complications within 30 years. The antiviral treatment of hepatitis C, previously interferon-based, has recently become inter - feron-free, with resulting improvements in sustained virological response rates, safety, and tolerability and a shorter duration of treatment.

Methods: This review is based on relevant publications retrieved by a selective literature search, and particularly on studies and reviews concerning the course and treatment of hepatitis C.

Prognostic value of the neutrophil-to-lymphocyte ratio in the ARQ 197-215 second-line study for advanced hepatocellular carcinoma.

The ARQ 197-215 study randomized patients to tivantinib or placebo and pre-specified efficacy analyses indicated the predictive value of MET expression as a marker of benefit from tivantinib in hepatocellular carcinoma (HCC). We aimed to explore the neutrophil-to-lymphocyte ratio (NLR) in 98 ARQ 197-215 patients with available absolute neutrophil count and absolute lymphocyte count at baseline. The cut-off value used to define high versus low NLR was 3.

Diagnosis and treatment of anemia in patients with inflammatory bowel disease.

Anemia represents one of the most frequent complications in inflammatory bowel disease (IBD) and severely impairs the quality of life of affected patients. The etiology of anemia in IBD patients can be multifactorial, often involving a combination of iron deficiency (ID) and anemia of chronic disease (ACD). Although current guidelines recommend screening for and treatment of anemia in IBD patients, current observational data suggest that it still remains underdiagnosed and undertreated.