Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity.

Local delivery of mRNA-based immunotherapy offers a promising avenue as it enables the production of specific immunomodulatory proteins that can stimulate the immune system to recognize and eliminate cancer cells while limiting systemic exposure and toxicities. Here, we develop and employ lipid-based nanoparticles (LNPs) to intratumorally deliver an mRNA mixture encoding the cytokines interleukin (IL)-21 and IL-7 and the immunostimulatory molecule 4-1BB ligand (Triplet LNP). IL-21 synergy with IL-7 and 4-1BBL leads to a profound increase in the frequency of tumor-infiltrating CD8 T cells and their capacity to produce granzyme B and IFN-γ, leading to tumor eradication and the development of long-term immunological memory.

Inflammation-Related Genes Are Differentially Expressed in Lipopolysaccharide-Stimulated Peripheral Blood Mononuclear Cells after 3 Months of Resistance Training in Older Women.

Recently, we showed that three months of resistance exercise significantly alters 18 canonical pathways related to chronic inflammation in PBMCs of older adults. In this exploratory sub-study, the aim is to explore whether resistance exercise enhances the PBMCs stress response by mimicking an acute infection through in vitro LPS stimulation. Women (≥65 years) were randomly divided into intensive strength training (IST), strength endurance training (SET), or flexibility training (as control group, CON) groups.

Implementation of guideline-directed medical therapy for heart failure patients with reduced ejection fraction in Belgium: a Delphi panel approach.

Background: The 2021 European Society of Cardiology (ESC) guidelines recommended a shift from a traditional hierarchical treatment for heart failure with reduced ejection fraction (HFrEF) to a four-pillar medical therapy strategy intended for near-simultaneous initiation. However, practical guidance for implementation in clinical practice is lacking. To address this, a Delphi Panel of 12 Belgian heart failure experts aimed to obtain consensus on integrating guideline-directed medical therapy (GDMT) in HFrEF patients in Belgian clinical practice, considering local specificities, including reimbursement criteria.

The Challenge of Adherence to a Complex Antiretroviral Therapy Regimen in an Individual With Multidrug-Resistant HIV.

Limited therapeutic options are available for patients with multidrug-resistant HIV. This report describes a 38-year-old female who was perinatally infected with HIV-1 and treated with 14 different antiretroviral regimens over 27 years, gradually leading to 4-class drug resistance. Despite various attempts to obtain sustained viral suppression, including the off-label administration of intravenous foscarnet and enfuvirtide, and thorough follow-up with 16 viral genotyping/phenotyping from 1999 to 2021, viral control was not maintained.

The Evolution in Non-Alcoholic Fatty Liver Disease Patients' Profile and the Associated Sustainable Challenges: A Multidisciplinary Perspective.

The prevalence and incidence of NAFLD is rising due to the obesity pandemic, caused by the widespread availability of ultra-processed foods and the decrease of physical activity. Factors such as socioeconomic status (SES), ethnicity and geographical location are associated with NAFLD, with lower SES correlating with higher incidence, particularly in regions like America or Europe. Beside the quality of food, the quantity also plays a crucial role.

Therapeutical strategies in cavitary legionnaires' disease, two cases from the field and a systematic review.

Background: Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD.

Methods: A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022.

High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer.

A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRAS .

Genomic monitoring of SARS-CoV-2 variants using sentinel SARI hospital surveillance.

Background: To support the COVID-19 pandemic response, many countries, including Belgium, implemented baseline genomic surveillance (BGS) programs aiming to early detect and characterize new SARS-CoV-2 variants. In parallel, Belgium maintained a sentinel network of six hospitals that samples patients with severe acute respiratory infections (SARI) and integrated SARS-CoV-2 detection within a broader range of respiratory pathogens. We evaluate the ability of the SARI surveillance to monitor general trends and early signals of viral genetic evolution of SARS-CoV-2 and compare it with the BGS as a reference model.

Post-ICU nutrition: the neglected side of metabolic support.

Purpose Of This Review: This review will focus on the neglected side of metabolic support in ICU survivors: nutritional therapy after critical illness. Knowledge of the evolution of the metabolism of patients that survived critical illness will be bundled, and current practices will be investigated. We will discuss some studies conducted to determine resting energy expenditure in ICU survivors and which identified barriers that cause interruptions in the feeding process based on published data between January 2022 and April 2023.

Comparison of Omentum and Subcutis as Implant Sites for Device-Encapsulated Human iPSC-Derived Pancreatic Endoderm in Nude Rats.

Subcutaneous implants of device-encapsulated stem cell-derived pancreatic endoderm (PE) can establish a functional beta cell mass (FBM) with metabolic control in immune-compromised mice. In a study with human-induced pluripotent stem cell-PE, this outcome was favored by a preformed pouch which allowed lesion-free insertion of devices in a pre-vascularized site. This was not reproduced in nude rats, known to exhibit a higher innate reactivity than mice and therefore relevant as preclinical model: a dense fibrotic capsule formed around subcutis (SC) implants with virtually no FBM formation.

EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial).

Background & Aims: Several studies have compared primary endoscopic ultrasound (EUS)-guided biliary drainage to endoscopic retrograde cholangiopancreatography (ERCP) with insertion of metal stents in unresectable malignant distal biliary obstruction (MDBO) and the results were conflicting. The aim of the current study was to compare the outcomes of the procedures in a large-scale study.

Methods: This was a multicenter international randomized controlled study.

Stent appearance in a novel silicon-based photon-counting CT prototype: ex vivo phantom study in head-to-head comparison with conventional energy-integrating CT.

Background: In this study, stent appearance in a novel silicon-based photon-counting computed tomography (Si-PCCT) prototype was compared with a conventional energy-integrating detector CT (EIDCT) system.

Methods: An ex vivo phantom was created, consisting of a 2% agar-water mixture, in which human-resected and stented arteries were individually embedded. Using similar technique parameters, helical scan data was acquired using a novel prototype Si-PCCT and a conventional EIDCT system at a volumetric CT dose index (CTDI) of 9 mGy.

Energy Guidance Using Indirect Calorimetry for Intestinal Failure Patients with Home Parenteral Nutrition: The Right Bag Right at the Start.

Intestinal failure is defined as the inability to absorb the minimum of macro and micronutrients, minerals and vitamins due to a reduction in gut function. In a subpopulation of patients with a dysfunctional gastrointestinal system, treatment with total or supplemental parenteral nutrition is required. The golden standard for the determination of energy expenditure is indirect calorimetry.

Artificial intelligence for diagnosing neoplasia on digital cholangioscopy: development and multicenter validation of a convolutional neural network model.

Background: We aimed to develop a convolutional neural network (CNN) model for detecting neoplastic lesions during real-time digital single-operator cholangioscopy (DSOC) and to clinically validate the model through comparisons with DSOC expert and nonexpert endoscopists.

Methods: In this two-stage study, we first developed and validated CNN1. Then, we performed a multicenter diagnostic trial to compare four DSOC experts and nonexperts against an improved model (CNN2).

Features of post-obstructive pneumonia in advanced lung cancer patients, a large retrospective cohort.

Background: Post-obstructive pneumonia refers to an infection of the lung parenchyma distal to a bronchial obstruction. Previous experience-based studies reported a high prevalence of this infection among patients with a medical history of advanced lung neoplasia, up to 40-55%.

Objectives: The current study was designed to investigate the features of post-obstructive pneumonia in lung cancer, including its predictors and the discriminants for 30-day mortality.

EACVI SIMULATOR-online study: evaluation of transoesophageal echocardiography knowledge and skills of young cardiologists.

Aims: To assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists.

Methods And Results: A European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9-12 December 2021 and 10-13 April 2022). All young cardiologists eligible to participate (<40 years) across the world were invited to participate.

Veno-venous extra-corporeal membrane oxygenation in a COVID-19 patient with cold-agglutinin haemolytic anaemia: A case report.

Overview: The use of extra-corporeal membrane oxygenation (ECMO) therapy to treat severe COVID-19 patients with acute respiratory failure is increasing worldwide. We reported herein the use of veno-venous ECMO in a patient with cold agglutinin haemolytic anaemia (CAHA) who suffered from severe COVID-19 infection.

Description: A 64-year-old man presented to the emergency department (ED) with incremental complaints of dyspnoea and cough since one week.

Magmaris Resorbable Magnesium Scaffold Versus Conventional Drug-Eluting Stent in ST-Segment Elevation Myocardial Infarction: 1-Year Results of a Propensity-Score-Matching Comparison.

Magmaris® (Biotronik AG, Switzerland) is the first RMS and early experience has shown promising results in stable coronary artery disease. Acute coronary syndromes have been hypothesized as a potential target group for bioresorbable scaffolds, but the efficacy and safety of RMS has not been extensively studied in ST-segment elevation myocardial infarction (STEMI). BEST-MAG is a prospective multicenter trial designed to evaluate optical coherence tomography (OCT-)guided implantation of resorbable magnesium scaffold (RMS) in STEMI.

Novel 15-mm-long lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections located ≥10 mm from the luminal wall.

Background: Endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) by cautery-enhanced lumen-apposing metal stents (LAMS) has largely been limited to collections located < 10 mm from the luminal wall. We present outcomes of the use of a novel 15-mm-long cautery-enhanced LAMS for drainage of PFCs located ≥ 10 mm away.

Methods: This international, multicenter study analyzed all adults with PFCs located ≥ 10 mm from the luminal wall who were treated by EUS-guided drainage using the 15-mm-long cautery-enhanced LAMS.