A mixed-methods pilot study of domiciliary nasal high-flow therapy for breathlessness in people with chronic obstructive pulmonary disease who do not qualify for domiciliary long-term oxygen therapy.

Background: High-flow nasal oxygen (HFNO) therapy delivers humidified, heated air with flow rates of up to 60 L/min with oxygen entrained. HFNO has advantages over conventional oxygen therapy, including precise and reliable fraction of inspired oxygen delivery, therefore is recommended as first-line treatment for people with acute hypoxaemic respiratory failure.

Objectives: This pilot study aimed to determine the feasibility and acceptability of domiciliary nasal high flow (NHF) without entrained oxygen for people with chronic obstructive pulmonary disease (COPD) and severe breathlessness.

Challenges with cancer pain management: novel opioid shortages and cancer trials restrictions.

Patients with advanced cancer often experience bothersome symptoms requiring specialist palliative care input. Oncology clinical trials commonly include a list of prohibited medications while on trial, to avoid potential drug interactions with the investigational product. This case series illustrates how recent opioid shortages combined with prohibited opioids in clinical trials significantly impacted cancer pain control and quality of life.

Validation of a Prediction Model From Quantitative Coronary Angiography to Detect Ischaemic Lesions as Evaluated by Invasive Fractional Flow Reserve.

Aim: Physician visual assessment (PVA) in invasive coronary angiography (ICA) is clinically used to determine stenosis severity and guide coronary intervention. However, PVA provides limited information regarding the haemodynamic significance of stenosis. This prospective study aimed to develop a model combining visual diameter stenosis (DS) and quantitative coronary angiography (QCA)-derived parameters to diagnose ischaemic lesions using invasive fractional flow reserve (FFR) with pharmacologically induced maximal hyperaemia as the gold standard.

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?

Aims: To examine the associations between and polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.

Patients & Methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.

Widespread Impact of Natural Genetic Variations in CRISPR-Cas9 Outcomes.

The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) is a genome editing tool widely used in biological research and clinical therapeutics. Natural human genetic variations, through altering the sequence context of CRISPR-Cas9 target regions, can significantly affect its DNA repair outcomes and ultimately lead to different editing efficiencies. However, these effects have not been systematically studied, even as CRISPR-Cas9 is broadly applied to primary cells and patient samples that harbor such genetic diversity.

Influence of (rs4680) and (rs1799971) on Cancer Pain, Opioid Dose, and Adverse Effects.

The influence of pharmacogenomics on opioid response, particularly with (rs4680) and (rs1799971) variants, has been studied individually and in combination. However, most studies are in a noncancer context and not all their possible variant combinations have been examined. This study examined (rs4680) and (rs1799971), and their allele combinations, in advanced cancer to examine associations with pain scores, opioid dose, and adverse effects.

Ischemia-reperfusion responses in human lung transplants at the single-cell resolution.

Ischemia-reperfusion is an unavoidable step of organ transplantation. Development of therapeutics for lung injury during transplantation has proved challenging; understanding lung injury from human data at the single-cell resolution is required to accelerate the development of therapeutics. Donor lung biopsies from 6 human lung transplant cases were collected at the end of cold preservation and 2-hour reperfusion and underwent single-cell RNA sequencing.

Different Sensory Information Is Used for State Estimation when Stationary or Moving.

The accurate estimation of limb state is necessary for movement planning and execution. While state estimation requires both feedforward and feedback information, we focus here on the latter. Prior literature has shown that integrating visual and proprioceptive feedback improves estimates of static limb position.

IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells.

Wound healing in response to acute injury is mediated by the coordinated and transient activation of parenchymal, stromal, and immune cells that resolves to homeostasis. Environmental, genetic, and epigenetic factors associated with inflammation and aging can lead to persistent activation of the microenvironment and fibrosis. Here, we identify opposing roles of interleukin-4 (IL-4) cytokine signaling in interstitial macrophages and type II alveolar epithelial cells (ATIIs).

Cognitive neuropsychological and neuroanatomic predictors of naturalistic action performance in left hemisphere stroke: a retrospective analysis.

Individuals who have experienced a left hemisphere cerebrovascular accident (LCVA) have been shown to make errors in naturalistic action tasks designed to assess the ability to perform everyday activities such as preparing a cup of coffee. Naturalistic action errors in this population are often attributed to limb apraxia, a common deficit in the representation and performance of object-related actions. However, naturalistic action impairments are also observed in right hemisphere stroke and traumatic brain injury, populations infrequently associated with apraxia, and errors across all these populations are influenced by overall severity.

A Rapid Human Lung Tissue Dissociation Protocol Maximizing Cell Yield and Minimizing Cellular Stress.

The human lung is a complex organ that comprises diverse populations of epithelial, mesenchymal, vascular, and immune cells, which gains even greater complexity during disease states. To effectively study the lung at a single-cell level, a dissociation protocol that achieves the highest yield of viable cells of interest with minimal dissociation-associated protein or transcription changes is key. Here, we detail a rapid collagenase-based dissociation protocol (Col-Short) that provides a high-yield single-cell suspension that is suitable for a variety of downstream applications.

Diffusion tensor MRI is sensitive to fibrotic injury in a mouse model of oxalate-induced chronic kidney disease.

Chronic kidney disease (CKD) is characterized by inflammation and fibrosis in the kidney. Renal biopsies and estimated glomerular filtration rate (eGFR) remain the standard of care, but these endpoints have limitations in detecting the stage, progression, and spatial distribution of fibrotic pathology in the kidney. MRI diffusion tensor imaging (DTI) has emerged as a promising noninvasive technology to evaluate renal fibrosis in vivo both in clinical and preclinical studies.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention.

Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore.

Sodium salicylate improves detection of amplitude-modulated sound in mice.

Salicylate is commonly used to induce tinnitus in animals, but its underlying mechanism of action is still debated. We therefore tested its effects on the firing properties of neurons in the mouse inferior colliculus (IC). Salicylate induced a large decrease in the spontaneous activity and an increase of ∼20 dB SPL in the minimum threshold of single units.

Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

Background And Aims: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure?

Methods: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death.

Results: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .