Combining SKY92 gene expression profiling and FISH (according to R2-ISS) defines ultra-high-risk Multiple Myeloma.

The definition of high-risk (HR) multiple myeloma (MM) is still a matter of debate. We prospectively evaluated the HR detection using FISH in combination with SKY92 gene expression profiling in 258 MM patients (newly diagnosed [ND] MM:  = 109; relapsed/refractory [RR] MM:  = 149). HR SKY92 was significantly enriched in RRMM (57/121, 47.

Nephrectomy in Autosomal Dominant Polycystic Kidney Disease: A consensus statement of the ERA Genes & Kidney Working Group.

A substantial number of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) undergo a nephrectomy, especially in work-up for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD.

Advanced Automated Model for Robust Bone Marrow Segmentation in Whole-body MRI.

Rationale And Objectives: To establish an advanced automated bone marrow (BM) segmentation model on whole-body (WB-)MRI in monoclonal plasma cell disorders (MPCD), and to demonstrate its robust performance on multicenter datasets with severe myeloma-related pathologies.

Materials And Methods: The study cohort comprised multi-vendor, multi-protocol imaging data acquired with varying field strength across 8 different centers. In total, 210 WB-MRIs of 207 MPCD patients were included.

Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.

Background: Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement.

Allergic Rhinitis and its Impact on Asthma (ARIA) Classes in MASK-air Users.

Background And Objectives: The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify rhinitis as "intermittent" or "persistent" and "mild" or "moderate-severe". To assess ARIA classes in a real-world study in terms of phenotypic differences and their association with asthma.

Methods: We performed a cross-sectional real-world study based on users of the MASK-air® app who reported data for at least 3 different months.

Muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis.

Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.

Association of sodium-glucose cotransporter-2 inhibitors with mortality across the spectrum of myocardial infarction: a systematic review and meta-analysis.

Background: The impact of sodium-glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit.

Nursing staff and supervisors perceptions on stress and resilience: a qualitative study.

Background: Supervisor-subordinate relationship is high relevant in dealing with work-related stress and providing a compassionate, high-quality, and safe nursing care while meeting the needs of the hospital. Our aim was to assess the predisposing risk and resilience factors of the stress of nursing staff as well as to explore the common and distinctive perceptions of these factors between nurses without a managerial position (nursing staff) and employees in a supervising position (nurse managers, ward nurses).

Design: Generic qualitative study using half-standardized interviews.

Measuring the impact of hospitalisation for infectious diseases on the quality of life of older patients in four European countries: the AEQUI longitudinal matched cohort study (2020-2023).

Objectives: To evaluate the impact of hospitalisation for infectious diseases on the Health-Related Quality of life (HRQOL), multidimensional frailty, and functioning of older patients, we conducted a longitudinal matched cohort study in four European countries.

Methods: HRQOL, frailty, and functioning were assessed using validated questionnaires at inclusion, at discharge, and up to six months later (M6) in patients aged over 65 years hospitalised for severe acute respiratory or bloodstream infections, and matched controls hospitalised for non-infectious conditions. Comparative analyses employed multilevel mixed-effect linear or logistic models to assess changes from inclusion.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response.

The DNA-damaging agent Gemcitabine (GEM) is a first-line treatment for pancreatic cancer, but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs, including kinase inhibitors, but the experimental evidence for such rationale is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines.

TRAF2 and RIPK1 redundantly mediate classical NFκB signaling by TNFR1 and CD95-type death receptors.

This study suggests a modified model of TNFR1-induced complex I-mediated NFκB signaling. Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. TRAF2 deficiency inhibited death receptor-induced classical NFκB-mediated production of IL-8 only in a subset of cell lines and only partly.

The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency.

Introduction: Human Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance and variable disease expressivity, suggesting the presence of disease modifiers that trigger the disease onset and severity. Various genetic and non-genetic potential triggers have been analyzed in CTLA-4 insufficiency cohorts, however, none of them have revealed a clear association to the disease. Multiple HLA haplotypes have been positively or negatively associated with various autoimmune diseases and inborn errors of immunity (IEI) due to the relevance of MHC in the strength of the T cell responses.

Exercise-induced dynamic mitral regurgitation is associated with outcomes in patients with ischaemic cardiomyopathy.

Aims: Ischaemic mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular remodelling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the haemodynamic relevance of MR and is recommended by current guidelines. We aimed to assess the prevalence, haemodynamic consequences, and prognostic impact of dynamic MR using isometric handgrip exercise.

Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE.

Aims: Despite receiving guideline-directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH-LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long-acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile.

Trajectory of Cardiogenic Dementia: A New Perspective.

The functions of the heart and brain are closely linked and essential to support human life by the heart-brain axis, which is a complex interconnection between the heart and brain. Also, cardiac function and cerebral blood flow regulate the brain's metabolism and function. Therefore, deterioration of cardiac function may affect cognitive function and may increase the risk of dementia.

Protocol for generating protein profiles and distance-based network analysis of murine tissue slices.

We introduce a protocol for spatial proteomics using thin cryotome sections of mouse skeletal muscle tissue. We describe steps for preparing muscle sections and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses to generate spatial protein profiles along the longitudinal skeletal muscle axis. We detail procedures for scanning longitudinal protein profiles and replacing missing data using a sliding window approach.

Cerebrovascular risk in rheumatoid arthritis patients: insights from carotid artery atherosclerosis in the Paracelsus 10,000 study.

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation. While RA primarily affects the joints, its systemic effects may lead to an increased cerebro- and cardiovascular risk. Atherosclerosis of the carotid arteries is a significant risk factor for cerebrovascular events and serves as a surrogate marker for cardiovascular risk.