Dose reduced preoperative chemotherapy in older patients with resectable gastroesophageal cancer: A real-world data study.

Introduction: Older patients with gastroesophageal (GE) cancer are at increased risk of low treatment tolerability and poor outcome. Dose reduced chemotherapy has been shown to improve tolerability without compromising efficacy in advanced GE cancer. However, the impact of reduced dose preoperative chemotherapy in the curative setting of older patients is unknown.

An Automated Machine Learning-Based Quantitative Multiparametric Approach for Mitral Regurgitation Severity Grading.

Background: Considering the high prevalence of mitral regurgitation (MR) and the highly subjective, variable MR severity reporting, an automated tool that could screen patients for clinically significant MR (≥ moderate) would streamline the diagnostic/therapeutic pathways and ultimately improve patient outcomes.

Objectives: The authors aimed to develop and validate a fully automated machine learning (ML)-based echocardiography workflow for grading MR severity.

Methods: ML algorithms were trained on echocardiograms from 2 observational cohorts and validated in patients from 2 additional independent studies.

Effect of Qualifying Atherosclerotic Cardiovascular Disease Diagnosis Proximity on Cardiovascular Risk and Benefit of Empagliflozin in the EMPA-REG OUTCOME Trial.

Background: In patients with type 2 diabetes mellitus (T2DM), a history of an ischemic event is associated with increased risk for cardiovascular (CV) disease. Whether patients with T2DM and a recent atherothrombotic diagnosis benefit from early intervention with a sodium-glucose co-transporter 2 inhibitor is unknown.

Methods: This study is a secondary analysis of the gliflozin Cardiovascular Event Trial in Type 2 Diabetes Mellitus Patients-emoving xcess lucose (EMPA-REG OUTCOME), which compared empagliflozin to placebo in adults with T2DM and atherosclerotic CV disease (ASCVD).

Effect of empagliflozin on total myocardial infarction events by type and additional coronary outcomes: insights from the randomized EMPA-REG OUTCOME trial.

Background: The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized.

Methods: This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years.

Impact of empagliflozin on first and recurrent events leading to or prolonging hospitalisation in the EMPA-REG OUTCOME trial.

In EMPA-REG OUTCOME, empagliflozin reduced the composite of total events leading to/prolonging hospitalisation for any cause and all-cause mortality by 24 % versus placebo in patients with T2DM and ASCVD, with 67.7 events prevented/1000 patient-years and a low NNT. Effects were sustained and were consistent regardless of the reason for hospitalisation.

Reactivity and mechanism of the reactions of 4-methylbenzoquinone with amino acid residues in β-lactoglobulin: A kinetic and product investigation.

Quinones, produced by the oxidation of phenolic compounds, covalently bind to nucleophilic groups on amino acids or proteins. In this study, the reactions of 4-methylbenzoquinone (4MBQ) with β-lactoglobulin (β-LG) and amino acids at neutral pH were investigated. LC-MS analysis revealed that Cys121 was likely the most modified residue in β-LG.

Cardiometabolic risk management: insights from a European Society of Cardiology Cardiovascular Round Table.

Metabolic comorbidities are common in patients with cardiorenal disease; they can cause atherosclerotic cardiovascular disease (ASCVD), speed progression, and adversely affect prognosis. Common comorbidities are Type 2 diabetes mellitus (T2DM), obesity/overweight, chronic kidney disease (CKD), and chronic liver disease. The cardiovascular system, kidneys, and liver are linked to many of the same risk factors (e.

Uranium and lanthanum in Norwegian drinking water - Is there cause for concern?

Due to natural conditions such as geology, topography, and climate, and historical features such as resource utilization, land use, and settlement patterns, the drinking water supply in Norway is separated into many public and private water supply systems. This survey sheds light on whether the Drinking Water Regulation's limit values provide a sufficient basis for ensuring safe drinking water for the Norwegian population. Participating waterworks, both private and public, were spread throughout the country, in 21 municipalities with different geological conditions.

Optimizing outcomes in heart failure: 2022 and beyond.

Although the development of therapies and tools for the improved management of heart failure (HF) continues apace, day-to-day management in clinical practice is often far from ideal. A Cardiovascular Round Table workshop was convened by the European Society of Cardiology (ESC) to identify barriers to the optimal implementation of therapies and guidelines and to consider mitigation strategies to improve patient outcomes in the future. Key challenges identified included the complexity of HF itself and its treatment, financial constraints and the perception of HF treatments as costly, failure to meet the needs of patients, suboptimal outpatient management, and the fragmented nature of healthcare systems.

Temperature affects the kinetics but not the products of the reaction between 4-methylbenzoquinone and lysine.

Quinones are electrophilic compounds that can undergo Michael addition or Schiff base reaction with nucleophilic amines, but the effect of temperature has not been systematically studied. The aim of this study was to characterize how temperature affects the reaction mechanism and kinetics of 4-methylbenzoquinone (4MBQ) with lysine (Lys), N-acetyl Lys or N-acetyl Lys. The products were identified and characterized by LC-MS/MS, which revealed formation of Michael addition products, Schiff base, and a di-adduct in Lys and N-acetyl Lys-containing reaction mixtures.

Real-world comparative effectiveness of ARNI versus ACEi/ARB in HF with reduced or mildly reduced ejection fraction.

Aims: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF).

Methods: Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016-31 December 2020).

Heart Failure Drug Treatment-Inertia, Titration, and Discontinuation: A Multinational Observational Study (EVOLUTION HF).

Background: Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. Understanding GDMT use is critical to improving clinical practice.

Objectives: This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.

Covalent bonding between polyphenols and proteins: Synthesis of caffeic acid-cysteine and chlorogenic acid-cysteine adducts and their quantification in dairy beverages.

Protein-polyphenol interactions affect the structure, stability, and functional properties of proteins and polyphenols. Oxidized polyphenols (o-quinones) react rapidly with the sulfhydryl group of cysteine (Cys) residues, inducing covalent bonding between proteins and polyphenols. However, quantitative data on such reactions remain elusive, despite the importance of depicting the significance of such interactions on food structure and function.

Covalent bonding of 4-methylcatechol to β-lactoglobulin results in the release of cysteine-4-methylcatechol adducts after in vitro digestion.

Protein-polyphenol adducts are formed upon covalent bonding between oxidized polyphenols and proteins. 4-Methylcatechol (4MC) is a polyphenol with origin in coffee and is oxidized to 4-methylbenzoquinone (4MBQ) under conditions used during food processing. The present study characterizes 4MBQ-induced covalent modifications on β-lactoglobulin (β-LG) from bovine milk, (henceforth β-LQ) and the effect on protein digestibility.

Fluorescent tracking identifies key migratory dendritic cells in the lymph node after radiotherapy.

Radiation therapy generates extensive cancer cell death capable of promoting tumor-specific immunity. Within the tumor, conventional dendritic cells (cDCs) are known to carry tumor-associated antigens to the draining lymph node (TdLN) where they initiate T-cell priming. How radiation influences cDC migration is poorly understood.

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.

Background: Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events.

Methods: SODIUM-HF is an international, open-label, randomised, controlled trial that enrolled patients at 26 sites in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand).

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars with magnetic fields up to around 10 gauss, luminosities of approximately 10-10 ergs per second and rotation periods of about 0.3-12.0 s.