Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.

Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches.

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is the most frequent and most aggressive brain tumour in adults. The brain is an immunopriviledged organ, and the blood-brain barrier shields the brain from immune surveillance. In this review, we discuss the composition of the immunosuppressive tumour micromilieu and potential immune escape mechanisms in GBM.

Prognosis of Patients With Primary Melanoma Stage I and II According to American Joint Committee on Cancer Version 8 Validated in Two Independent Cohorts: Implications for Adjuvant Treatment.

Purpose: The first randomized trial of adjuvant treatment with checkpoint inhibitor in stage II melanoma reported a significant reduction in risk of tumor recurrence. This study evaluates two independent data sets to further document survival probabilities for patients with primary stage I and II melanoma.

Patients And Methods: The Central Malignant Melanoma Registry (CMMR) in Germany evaluated 17,544 patients with a primary diagnosis of stage I and II melanoma from 2000 to 2015.

Auditory stimulation in-phase with slow oscillations to enhance overnight memory consolidation in patients with schizophrenia?

Sleep-dependent memory consolidation is disturbed in patients with schizophrenia, who furthermore show reductions in sleep spindles and probably also in delta power during sleep. The memory dysfunction in these patients is one of the strongest markers for worse long-term functional outcome. However, therapeutic interventions to normalise memory functions, e.

Analysis of the Seasonal Fluctuation of γδ T Cells and Its Potential Relation with Vitamin D.

In addition to its role in bone metabolism, vitamin D exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity.

A Ménage à Trois of Cytotoxic Effector Cells: γδ T Cells Suppress NK Cells but Not CTLs.

Three types of cytotoxic effector cells can kill tumor cells: innate natural killer (NK) cells, CD8+ CTL, and γδ T cells. In this issue, Walwyn-Brown and colleagues report new insights into the interplay between these three cell types that are integral to antitumor immunity, finding that γδ T cells can specifically suppress NK cells but not CD8+ CTLs. These results are relevant in view of the so far limited efficacy of γδ T-cell immunotherapy.

New aspects in deriving health-based guidance values for bromate in swimming pool water.

Bromate, classified as a EU CLP 1B carcinogen, is a typical by-product of the disinfection of drinking and swimming pool water. The aim of this study was (a) to provide data on the occurrence of bromate in pool water, (b) to re-evaluate the carcinogenic MOA of bromate in the light of existing data, (c) to assess the possible exposure to bromate via swimming pool water and (d) to inform the derivation of cancer risk-related bromate concentrations in swimming pool water. Measurements from monitoring analysis of 229 samples showed bromate concentrations in seawater pools up to 34 mg/L.

Anxiety, Depression and Quality of Life in Patients with Neuroendocrine Neoplasia After Surgery.

Background: Neuroendocrine neoplasia (NEN) are rare and complex, with surgery as key therapy even in cases with metastasis. Little is known regarding the quality of life, prevalence of depression, anxiety and the impact of surgery.

Methods: This prospective, follow-up study included 90 consecutively recruited patients with NEN after surgery in a university hospital.

The ALSTER-FLX Registry: 3-Month outcomes after left atrial appendage occlusion using a next-generation device, a matched-pair analysis to EWOLUTION.

Background: The new-generation WATCHMAN FLX (Boston Scientific) device for left atrial appendage occlusion has been modified in various aspects to improve procedural results. No comparison of the WATCHMAN FLX device with the previous WATCHMAN device is available.

Objective: We aimed to compare procedural results with WATCHMAN FLX in patients on dual antiplatelet therapy at ∼3 months with data with WATCHMAN (EWOLUTION [Registry on WATCHMAN Outcomes in Real-Life Utilization]).

A scattered landscape: assessment of the evidence base for 71 patient decision aids developed in a hospital setting.

Background: Recent publications reveal shortcomings in evidence review and summarization methods for patient decision aids. In the large-scale "Share to Care (S2C)" Shared Decision Making (SDM) project at the University Hospital Kiel, Germany, one of 4 SDM interventions was to develop up to 80 decision aids for patients. Best available evidence on the treatments' impact on patient-relevant outcomes was systematically appraised to feed this information into the decision aids.

Dynamic monitoring of fracture healing process in response to magnesium implant with multimodal imaging: pilot longitudinal study in a rat external fixation model.

Rodent models are commonly used in pre-clinical research of magnesium (Mg)-based and other types of biomaterials for fracture treatment. Most studies selected unstable fixation methods, and there is a lack of multimodal longitudinal monitoring of bone healing. The purpose of this study is to develop a rat femoral fracture model stabilized by external fixation with intra-medullary Mg implant, and to investigate the dynamic bone union process with several imaging techniques offering complementing insights into the process.

Tissue Engineered Transcatheter Pulmonary Valved Stent Implantation: Current State and Future Prospect.

Patients with the complex congenital heart disease (CHD) are usually associated with right ventricular outflow tract dysfunction and typically require multiple surgical interventions during their lives to relieve the right ventricular outflow tract abnormality. Transcatheter pulmonary valve replacement was used as a non-surgical, less invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly developing over the past years. Despite the current favorable results of transcatheter pulmonary valve replacement, many patients eligible for pulmonary valve replacement are still not candidates for transcatheter pulmonary valve replacement.

Biodegradable Poly-ε-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves.

Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM.

Chemotherapy after immune checkpoint inhibitor failure in metastatic melanoma: a retrospective multicentre analysis.

Introduction: Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown.

Complete response of advanced cutaneous squamous cell and basal cell carcinomas with sequential cemiplimab and sonidegib therapy.

A 78-year-old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep-infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging.

Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacle to precision medicine.

Background: Cancer is a somatic evolutionary disease and adenocarcinomas of the stomach and gastroesophageal junction (GC) may serve as a two-dimensional model of cancer expansion, in which tumor subclones are not evenly mixed during tumor progression but rather spatially separated and diversified. We hypothesize that precision medicine efforts are compromised when clinical decisions are based on a single-sample analysis, which ignores the mechanisms of cancer evolution and resulting intratumoral heterogeneity. Using multiregional whole-exome sequencing, we investigated the effect of somatic evolution on intratumoral heterogeneity aiming to shed light on the evolutionary biology of GC.

NF1-mutated melanomas reveal distinct clinical characteristics depending on tumour origin and respond favourably to immune checkpoint inhibitors.

Background: NF1-mutated tumours represent a small subset (10-15%) of melanomas, not sufficiently analysed in large clinical cohorts. This study investigated the largest multicentre collection of NF1-mutated melanomas to date.

Methods: This study analysed a multicentre tumour tissue sample cohort from 266 patients with NF1-mutated melanoma.

Ecology impacts the decrease of Spirochaetes and Prevotella in the fecal gut microbiota of urban humans.

Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets - especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis.

The Microbiome Tumor Axis: How the Microbiome Could Contribute to Clonal Heterogeneity and Disease Outcome in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. It is characterized by a poor prognosis with a 5-year survival rate of only around 10% and an ongoing increase in death rate. Due to the lack of early and specific symptoms, most patients are diagnosed at an advanced or even metastasized stage, essentially limiting curative treatment options.

Postoperative Outcomes of Tangential Segmental Resection and End-to-end Reconstruction of the Superior Mesenterico-Portal Vein During Pancreatoduodenectomy for Pancreatic Adenocarcinoma: A Single-Center Experience.

Background/aim: The impact of venous resections and reconstruction techniques on morbidity after surgery for pancreatic cancer (PDAC) remains controversial.

Patients And Methods: A total of 143 patients receiving pancreatoduodenectomy (PD) for PDAC between 2013 and 2018 were identified from a prospective database. Morbidity and mortality after PD with tangential resection versus end-to-end reconstruction were assessed.

How COVID-19 kick-started online learning in medical education-The DigiMed study.

Background: The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts.