Development of a novel immunocompetent murine tumor model for urothelial carcinoma using in vivo electroporation.

A lack of advanced preclinical mouse tumor models impedes the progress in urothelial carcinoma research. We present here a novel fast, robust, reliable, and highly reproducible model for the genetic induction of bladder cancer in immunocompetent mice. Different sets of oncogenic transposons (Cmyc, Kras) and Cre drivers were transfected into the murine bladder wall of two different genetic backgrounds (Trp53 and Braf, Pten, Ctnnb1).

Guideline-recommended basic parameter adherence in neurocritical care stroke patients: Observational multicenter individual participant data analysis.

Introduction: Neurocritical care patients with neurovascular disease often face poor long-term outcomes, highlighting the pivotal role of evidence-based interventions. Although International Guidelines emphasize managing basic physiological parameters like temperature, blood glucose, blood pressure, and oxygen levels, physician adherence to these targets remains uncertain. This study aimed to assess adherence to guideline-based treatment targets for basic physiological parameters in neurocritical care.

The Healthcare Workforce Shortage of Nurses and Physicians: Practice, Theory, Evidence, and Ways Forward.

The healthcare sector is ubiquitously plagued by workforce shortages in economies around the globe. The fragility of this structural shortage becomes apparent when external shocks, such as the COVID-19 pandemic, exacerbate the lack of workers in clinical practice. In this article, we summarize current trends in healthcare workforce development across the globe, review theoretical concepts of workforce shortages, and discuss policies to address them.

You are safe here: A flyer with re-orientating messages for families of patients with delirium in the intensive care unit.

Patients in delirium require trustful communication and re-orientation. We developed a flyer with positive, re-orientating suggestions for families of delirious patients in intensive care units. Suggestions include creating a safe environment, interpreting unusual behaviours positively and fostering mental resilience.

Quantifying the 'distance to LDC-goal' in patients at very high cardiovascular risk with hyperlipidaemia in Germany: a retrospective claims database analysis.

Background And Objectives: This study quantified the 'distance to LDL-C goal' in patients at very high cardiovascular risk with uncontrolled hyperlipidaemia. 'Distance to LDL-C goal' was defined as the percentage by which low-density lipoprotein cholesterol (LDL-C) levels needed to be reduced to achieve the LDL-C goals specified in the 2016 or 2019 European Society of Cardiology/European Atherosclerosis Society guidelines.

Design And Methods: This retrospective analysis using data from the IQVIA Disease Analyzer database included patients who were predominantly treated by a primary care physician, diabetologist or cardiologist between 2014 and 2018, with a diagnosis of hyperlipidaemia and an initial LDL-C measurement (index event) and one or more cardiovascular risk factors.

Phosphoproteomics-directed manipulation reveals SEC22B as a hepatocellular signaling node governing metabolic actions of glucagon.

The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmacotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little regarding how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we performed in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes.

Irradiation alters extracellular vesicle microRNA load in the serum of patients with leukaemia.

Purpose: Recent data suggest an impact of extracellular vesicles (EVs) and their micro(mi)RNA cargo on cell-cell interactions to contribute to pathophysiology of leukaemia and radiation response. Here, we investigated differential miRNA cargo of EVs from serum derived from patients with leukaemia (n = 11) before and after total body irradiation with 2 × 2 Gy as compared to healthy donors (n = 6).

Methods: RNA was isolated from EVs and subjected to next generation sequencing of miRNAs.

Revisiting voltage-coupled H secretion in the collecting duct.

Experimental studies have shown that V-type ATPase-driven H secretion is dependent on transepithelial voltage. On this basis, the "voltage hypothesis" of urinary acidification by the collecting duct was derived. Accordingly, it has been supposed that the lumen-negative potential created by the reabsorption of Na via the epithelial Na channel (ENaC) enhances electrogenic H secretion via V-type H-ATPase.

Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price.

Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.

Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000-2023). Data were collected from FDA labels, clinicaltrials.

On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.

Background: Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies.

Methods: On-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto).

The prognostic relevance of full-thickness burns on ABSI.

Introduction: The Abbreviated Burn Severity Index (ABSI) by Tobiasen, which is commonly used to estimate the mortality risk of severely burned patients, calculates an additional point for the existence of full-thickness (third-degree) burns. [1] However, the score does not consider the extent of the body surface affected by third-degree burns. To understand whether there is a way to improve ABSI prediction power, this study aims to determine the influence of full-thickness burns on survival rates and how it affects the predictive precision of the ABSI.

International expert consensus statement: surgical failure in obstructive sleep apnea.

Purpose: Upper airway (UA) surgery is commonly employed in the treatment of patients with obstructive sleep apnea (OSA). The intricate pathophysiology of OSA, variability in sites and patterns of UA collapse, and the interaction between anatomical and non-anatomical factors in individual patients may contribute to possible surgical failures. This clinical consensus statement aims to identify areas of agreement among a development group comprising international experts in OSA surgery, regarding the appropriate definition, predictive factors in patients, and management of surgical failure in OSA treatment.

Videodistraction to reduce agitation in elderly patients in the emergency department: an open label parallel group randomized controlled trial.

Background And Importance: Agitation of elderly patients in the emergency department (ED) often complicates workup and therapy.

Objective: In this study, we investigated if agitation in the ED can be reduced by showing calming video sequences in elderly agitated patients.

Designs: Prospective randomized intervention study.

Incremental value of blood-based markers of liver fibrosis in cardiovascular risk stratification.

Aims: Non-alcoholic fatty liver disease (NAFLD) with advanced liver fibrosis is associated with cardiovascular disease (CVD). To examine if markers of vascular injury mediate the link between liver fibrosis non-invasive tests (LFNITs) and CVD events, and to compare the incremental predictive value of LFNITs over established CVD risk scores.

Methods: Consecutively recruited individuals (n=1,692) with or without clinically overt coronary artery disease (CAD) from the Athens Cardiometabolic Cohort, were analysed.

De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Background: Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated.

Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.

Programmed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cancer cell-intrinsic PD-1 functional regulation is not well understood.

The ESMO Tumour-Agnostic Classifier and Screener (ETAC-S): a tool for assessing tumour-agnostic potential of molecularly guided therapies and for steering drug development.

Background: Advances in precision oncology led to approval of tumour-agnostic molecularly guided treatment options (MGTOs). The minimum requirements for claiming tumour-agnostic potential remain elusive.

Methods: The European Society for Medical Oncology (ESMO) Precision Medicine Working Group (PMWG) coordinated a project to optimise tumour-agnostic drug development.

Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: Pooled analysis of the CAO/ARO/AIO-12 and the OPRA randomized phase 2 trials.

Background: Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate.

Methods: We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS).