Guideline adherence in the use of coronary angiography in patients presenting at the emergency department without myocardial infarction - Results from the German ENLIGHT-KHK project.

Background: For patients with acute myocardial infarction (AMI), direct coronary angiography (CA) is recommended, while for non-AMI patients, the diagnostic work-up depends on clinical criteria. This analysis provides initial prospective German data for the degree of guideline-adherence (GL) in the use of CA on non-AMI patients presenting at the emergency department (ED) with suspected acute coronary syndrome (ACS) according to the 2015 ESC-ACS-GL. Furthermore the implications of the application of the 2020 ESC-ACS-GL recommendations were evaluated.

Evaluation of the guideline-adherence of coronary angiography in patients with suspected chronic coronary syndrome - Results from the German prospective multicentre ENLIGHT-KHK project.

Background: With 900'000 coronary angiographies (CA) per year, Germany has the highest annual per capita volume in Europe. Until now there are no prospective clinical data on the degree of guideline-adherence in the use of CA in patients with suspected chronic coronary syndrome (CCS) in Germany.

Methods: Between January 2019 and August 2021, 458 patients with suspected CCS were recruited in nine German centres.

Health economic consequences of optimal vs. observed guideline adherence of coronary angiography in patients with suspected obstructive stable coronary artery in Germany: a microsimulation model.

Aims: While the number of patients with stable coronary artery disease (SCAD) is similar across European countries, Germany has the highest per capita volume of coronary angiographies (CA). This study evaluated the health economic consequences of guideline-non-adherent use of CA in patients with SCAD.

Methods And Results: As part of the ENLIGHT-KHK trial, a prospective observational study, this microsimulation model compared the number of major adverse cardiac events (MACE) and the costs of real-world use of CA with those of (assumed) complete guideline-adherent use (according to the German National Disease Management Guideline 2019).

The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.

Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours.

ISCOMATRIX vaccines mediate CD8+ T-cell cross-priming by a MyD88-dependent signaling pathway.

Generating a cytotoxic CD8(+) T-cell response that can eradicate malignant cells is the primary objective of cancer vaccine strategies. In this study we have characterized the innate and adaptive immune response to the ISCOMATRIX adjuvant, and the ability of vaccine antigens formulated with this adjuvant to promote antitumor immunity. ISCOMATRIX adjuvant led to a rapid innate immune cell response at the injection site, followed by the activation of natural killer and dendritic cells (DC) in regional draining lymph nodes.

An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells.

Antibodies to cell-surface antigens trigger activatory Fcγ receptor (FcγR)-mediated retrograde signals in leukocytes to control immune effector functions. Here, we uncover an FcγR mechanism that drives antibody-dependent forward signaling in target cells. Agonistic antibodies to death receptor 5 (DR5) induce cancer-cell apoptosis and are in clinical trials; however, their mechanism of action in vivo is not fully defined.

Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients.

Purpose: Despite multimodal aggressive treatment glioblastoma patients still face a rather poor prognosis. Recent data indicate that certain molecular markers, in particular MGMT promoter hypermethylation, are associated with response to alkylating chemotherapy and longer survival. The clinical significance of other glioblastoma-associated molecular aberrations and their relationship to MGMT promoter hypermethylation is still poorly understood.

The ubiquitin E3 ligase Cbl-b in T cells tolerance and tumor immunity.

The implication of the immune system in tumor surveillance is proven and widely accepted. However, anti-cancer immunotherapy is still difficult due to insufficient activation, immune suppression and tolerance induction. The ubiquitin E3 ligase Cbl-b, is a member of the Cbl (casitas B-lineage lymphoma) protein family and was identified as a key dominant "tolerogenic" factor in T cells that directly regulates T-cell activation by controlling activation thresholds and the requirement for co-stimulation.

Spontaneous tumor rejection by cbl-b-deficient CD8+ T cells.

The concept of tumor surveillance implies that specific and nonspecific components of the immune system eliminate tumors in the early phase of malignancy. Understanding the biochemical mechanisms of tumor immunosurveillance is of paramount significance because it might allow one to specifically modulate spontaneous antitumor activity. We report that inactivation of the E3 ligase Casitas B cell lymphoma-b (Cbl-b) confers spontaneous in vivo rejection of tumor cells that express human papilloma virus antigens.

Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b.

The family of the Casitas B-lineage Lymphoma (Cbl) proteins, c-Cbl, Cbl-b, and Cbl-3, function as E3 ubiquitin ligases and molecular adaptors. In particular, Cbl-b acts as a gatekeeper in T cell activation that controls activation thresholds and the requirement for co-stimulation. Loss of Cbl-b expression renders animals susceptible to antigen-triggered autoimmunity suggesting that Cbl-b is a key autoimmunity gene.

Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin.

Pilocytic astrocytomas (PAs) are the most common glioma in children. Whereas many PAs are slow-growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. To identify genetic signatures that might predict PA clinical behavior, we did gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1).

Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells.

Regulatory CD4(+)CD25(+) T cells are important in suppressing immune responses. The requirements for the maintenance of peripheral CD4(+)CD25(+) T cells remain incompletely understood. Receptor activator of NF-kappaB (RANK) and its ligand (RANKL; also known as CD254, OPGL and TRANCE) are key regulators of bone remodeling, mammary gland formation, lymph node development and T-cell/dendritic cell communication.

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03.

Purpose: To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM).

Patients And Methods: Thirty-one adult patients (median Karnofsky performance score 90; median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity.

Results: A median of five courses (range, one to six courses) were delivered.