Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

Purpose: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions.

Methods: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575).

Systemic Outcomes of (Pyr)-Apelin-13 Infusion at Mid-Late Pregnancy in a Rat Model with Preeclamptic Features.

Preeclampsia is a syndrome with diverse clinical presentation that currently has no cure. The apelin receptor system is a pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. We established the systemic outcomes of (Pyr)-apelin-13 administration in rats with preeclamptic features (TGA-PE, female transgenic for human angiotensinogen mated to male transgenic for human renin).

Anxiety of myoma patients: results of standardized interviews with the State Trait Anxiety Inventory and the Kessler 10 questionnaire.

The aim of this study was to explore a possible relation between myoma-related anxieties and general state or trait anxiety or psychological distress, to get a better understanding of the impact of anxiety on the patients. This prospective study was conducted at the myoma clinic of a large university hospital in a major European city from November 2016 to February 2017. Patients completed standardized questionnaires on myoma-related fears, the State Trait Anxiety Inventory (STAI), and the Kessler 10.

Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group.

Background: Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors (ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown.

Methods: The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set.

Correlation between SFRP1 expression and clinicopathological parameters in patients with triple-negative breast cancer.

Breast cancer is a heterogeneous disease with distinct molecular and clinical behavior demanding reliable biomarkers, especially in triple-negative breast cancer (TNBC). This study seeks to improve the understanding of SFRP1 as a potential biomarker in breast cancer focusing on TNBC. SFRP1 expression was investigated via immunohistochemistry with two anti-SFRP1-antibodies on tissue-microarrays of 376 invasive breast cancers.

The Deubiquitinase Inhibitor b-AP15 and Its Effect on Phenotype and Function of Monocyte-Derived Dendritic Cells.

The ubiquitin-proteasome system is elementary for cellular protein degradation and gained rising attention as a new target for cancer therapy due to promising clinical trials with bortezomib, the first-in class proteasome inhibitor meanwhile approved for multiple myeloma and mantle cell lymphoma. Both bortezomib and next-generation proteasome inhibitors mediate their effects by targeting the 20S core particle of the 26S proteasome. The novel small molecule inhibitor b-AP15 affects upstream elements of the ubiquitin-proteasome cascade by suppressing the deubiquitinase activity of both proteasomal regulatory 19S subunits and showed promising anticancer activity in preclinical models.

Clinical Validation of the BREAST-Q Breast-Conserving Therapy Module.

Background: The BREAST-Q is a patient-reported outcome measure to evaluate satisfaction and health-related quality of life (HRQOL) after breast surgery. The aim of this study is to test the acceptability, reliability, and validity of the most recently developed BREAST-Q module for breast-conserving therapy (BCT) in a prospective clinical cohort.

Methods: The BREAST-Q BCT module was translated into German according to international guidelines.

Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior.

Background: Heterozygous deletion of the TSHZ3 gene, encoding for the teashirt zinc-finger homeobox family member 3 (TSHZ3) transcription factor that is highly expressed in cortical projection neurons (CPNs), has been linked to an autism spectrum disorder (ASD) syndrome. Similarly, mice with Tshz3 haploinsufficiency show ASD-like behavior, paralleled by molecular changes in CPNs and corticostriatal synaptic dysfunctions. Here, we aimed at gaining more insight into "when" and "where" TSHZ3 is required for the proper development of the brain, and its deficiency crucial for developing this ASD syndrome.

Explaining the unexplainable: discrepancies in results from the CALGB/SWOG 80405 and FIRE-3 studies.

We propose a working hypothesis that integrates data from the CALGB/SWOG 80405 and FIRE-3 studies to explain apparent discrepancies in their results. Both trials assessed the combination of either cetuximab or bevacizumab with a different chemotherapy backbone: irinotecan in all patients in the FIRE-3 study, or oxaliplatin in 75% of the patients in the CALGB/SWOG 80405 study. The hypothesis is divided into three parts.

Identifying unmet needs in long-term stroke care using in-depth assessment and the Post-Stroke Checklist - The Managing Aftercare for Stroke (MAS-I) study.

Introduction: Detailed data on the long-term consequences and treatment of stroke are scarce. We aimed to assess the needs and disease burden of community-dwelling stroke patients and their carers and to compare their treatment to evidence-based guidelines by a stroke neurologist.

Methods: We invited long-term stroke patients from two previous acute clinical studies ( = 516) in Berlin, Germany to participate in an observational, cross-sectional study.

Surgical Techniques for Myasthenia Gravis: Robotic-Assisted Thoracoscopic Surgery.

Robotic-assisted thoracoscopic surgery (RATS) creates an extended approach for thymectomy in terms of locating contralateral phrenic nerve and upper poles of the thymus. RATS thymectomy is indicated in all non-thymomatous myasthenia gravis (MG) patients and thymomatous MG patients with resectable thymoma, typically Masaoka-Koga I and II. Left-sided RATS thymectomy is superior for anatomic reasons and in the special care patients with MG.

Undifferentiated connective tissue disease: state of the art on clinical practice guidelines.

The term 'undifferentiated connective tissue disease' (UCTD) is generally used to describe clinical entities characterised by clinical and serological manifestations of systemic autoimmune diseases but not fulfilling the criteria for defined connective tissue diseases (CTDs). In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the ERN ReCONNET project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. No specific CPG on UCTD were found, potential areas of intervention are absence of a consensus definition of UCTD, need for specific monitoring and therapeutic protocols, stratification of UCTD based on the risk of developing a defined CTD and preventive measure for the future development of a more severe condition.

Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines [corrected].

Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ' and clinicians' unmet needs not covered by CPGs.

Results of Robotic Thymectomy Performed in Myasthenia Gravis Patients Older Than 60 Years at Onset.

Background: Data are limited on the safety and efficacy of robotic thymectomy in patients with myasthenia gravis (MG) older than 60 years at onset.

Methods: Patients older than 60 years at MG onset who underwent robotic thymectomy in Charite Universitaetsmedizin Berlin between 2003 and 2017 were potentially eligible for inclusion. The main outcomes were perioperative complications and clinical outcome according to the Myasthenia Gravis Foundation of America Post-Intervention Status.

IL-6 Plasma Levels Correlate With Cerebral Perfusion Deficits and Infarct Sizes in Stroke Patients Without Associated Infections.

We aimed to investigate several blood-based biomarkers related to inflammation, immunity, and stress response in a cohort of patients without stroke-associated infections regarding their predictive abilities for functional outcome and explore whether they correlate with MRI markers, such as infarct size or location. We combined the clinical and radiological data of patients participating in two observational acute stroke cohorts: the PREDICT and 1000Plus studies. The following blood-based biomarkers were measured in these patients: monocytic HLA-DR, IL-6, IL-8, IL-10, LBP, MRproANP, MRproADM, CTproET, Copeptin, and PCT.

Validation of a Nomogram Predicting Non-Sentinel Lymph Node Metastases among Patients with Breast Cancer after Primary Systemic Therapy - a transSENTINA Substudy.

Background: Prediction of non-sentinel lymph node (SLN) status after primary systemic therapy (PST) may allow tailored axillary staging. The aim of this analysis was to compare established nomograms from i) the primary operative (n = 6) and ii) the neoadjuvant (n = 1) setting with an optimized nomogram to predict non-SLN status in patients after PST.

Methods: 181 patients converting from cN1 prior to PST to ycN0 but found to have a histologically positive SLN in the SENTINA trial were analyzed.

DNA methylation profiling reliably distinguishes pulmonary enteric adenocarcinoma from metastatic colorectal cancer.

Pulmonary enteric adenocarcinoma is a rare non-small cell lung cancer subtype. It is poorly characterized and cannot be distinguished from metastatic colorectal or upper gastrointestinal adenocarcinomas by means of routine pathological methods. As DNA methylation patterns are known to be highly tissue specific, we aimed to develop a methylation-based algorithm to differentiate these entities.

Pressurized intraperitoneal aerosol chemotherapy and its effect on gastric-cancer-derived peritoneal metastases: an overview.

This manuscript aspires to portray a review of the current literature focusing on manifest peritoneal metastasis (PM) derived from gastric cancer and its treatment options. Despite the development of chemotherapy and multimodal treatment options during the last decades, mortality remains high worldwide. After refreshing important epidemiological considerations, the molecular mechanisms currently accepted through which PM occurs are revised.

Accelerated progression of IDH mutant glioma after first recurrence.

Background: Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct subtype, reflected in the World Health Organization (WHO) 2016 revised diagnostic criteria. To inform IDH-targeting trial design, we sought to characterize outcomes exclusively within IDH mutant gliomas.

Methods: We retrospectively analyzed 275 IDH mutant glioma patients treated at our institution.

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia.

Background: Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes of B cell acute lymphoblastic leukemia (BCP-ALL) have not yet been investigated. Here, we assess to what extent lncRNA expression and DNA methylation is driving the progression of relapsed BCP-ALL subtypes and we determine if the expression and DNA methylation profile of lncRNAs correlates with established BCP-ALL subtypes.

Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts.

The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes (rs12794714, rs10741657) and (rs12785878, rs11234027), were combined in two allelic scores.

Need for psychological support in intensive care : A survey among members of the German Society of Medical Intensive Care and Emergency Medicine.

A high incidence of care-relevant psychological problems in critical care medicine has been reported among patients, their families and professional care givers. International guidelines give appropriate recommendations for such care. What is unclear, however, is just how the care and support are provided in day-to-day practice and, in particular, which service providers are responsible for this support.