The effect of increased vascular afterload measures on flow rate and survival in severe aortic stenosis.

Aims: Although an association between the systemic circulation and transaortic flow rate (TFR) is frequently hypothesized in patients with aortic stenosis (AS), it has not been demonstrated previously. We sought to explore the relationship between blood pressure (BP), vascular afterload measures, clinical history of hypertension, TFR, and survival in patients with severe AS (aortic valve area ≤ 1 cm²).

Methods And Results: We studied 323 patients ≥ 65 years (110 prospective, 213 registry analysis) who underwent transcatheter aortic valve replacement over a 5-year period.

Machine learning approaches for risk prediction after percutaneous coronary intervention: a systematic review and meta-analysis.

Aims: Accurate prediction of clinical outcomes following percutaneous coronary intervention (PCI) is essential for mitigating risk and peri-procedural planning. Traditional risk models have demonstrated a modest predictive value. Machine learning (ML) models offer an alternative risk stratification that may provide improved predictive accuracy.

Advanced electrocardiography heart age: a prognostic, explainable machine learning approach applicable to sinus and non-sinus rhythms.

Aims: An explainable advanced electrocardiography (A-ECG) Heart Age gap is the difference between A-ECG Heart Age and chronological age. This gap is an estimate of accelerated cardiovascular aging expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG Heart Age requires sinus rhythm.

The tumor immune microenvironment in primary cutaneous melanoma.

Melanoma is an immunogenic tumor. The melanoma tumor immune microenvironment (TIME) is made up of a heterogenous mix of both immune and non-immune cells as well as a multitude of signaling molecules. The interactions between tumor cells, immune cells and signaling molecules affect tumor progression and therapeutic responses.

Portrait of a Cerebral Killer.

: Primary amebic meningoencephalitis (PAM) caused by is a rare and devastating infection of the central nervous system, often diagnosed late, due to its rapid progression and nonspecific symptoms. We report one of the youngest documented pediatric Vietnamese cases of PAM in a 10-month-old girl from the Mekong Delta, Vietnam. The diagnosis was confirmed through multiplex real-time PCR (MPL-rPCR), microscopy, and sequencing.

Use of Cardioprotective Adjuncts in Type 1 Diabetes.

Type 1 diabetes is associated with excess cardiovascular risk, even after accounting for traditional cardiovascular risk factors, including glycaemia. Hence, there is an urgent need to document the metabolic abnormalities that contribute to the cardiovascular mortality gap in type 1 diabetes, and to examine whether cardioprotective type 2 diabetes medications prevent premature morbidity and mortality in this population.

Biomimetic Proteoglycans for Intervertebral Disc (IVD) Regeneration.

Intervertebral disc degeneration, which leads to low back pain, is the most prevalent musculoskeletal condition worldwide, significantly impairing quality of life and imposing substantial socioeconomic burdens on affected individuals. A major impediment to the development of any prospective cell-driven recovery of functional properties in degenerate IVDs is the diminishing IVD cell numbers and viability with ageing which cannot sustain such a recovery process. However, if IVD proteoglycan levels, a major functional component, can be replenished through an orthobiological process which does not rely on cellular or nutritional input, then this may be an effective strategy for the re-attainment of IVD mechanical properties.

Opioid-induced respiratory depression: clinical aspects and pathophysiology of the respiratory network effects.

Important insights and consensus remain lacking for risk prediction of opioid-induced respiratory depression (OIRD), reversal of respiratory depression (RD), the pathophysiology of OIRD, and which sites make the most significant contribution to its induction. The ventilatory response to inhaled carbon dioxide is the most sensitive biomarker of OIRD. To accurately predict respiratory depression (RD), a multivariant RD prospective trial using continuous capnograph and oximetry examining 5 independent variables: age ≥60, sex, opioid naivety, sleep disorders, and chronic heart failure (PRODIGY trial), was undertaken.

Machine learning and SHAP value interpretation for predicting comorbidity of cardiovascular disease and cancer with dietary antioxidants.

Objective: To develop and validate a machine learning model incorporating dietary antioxidants to predict cardiovascular disease (CVD)-cancer comorbidity and to elucidate the role of antioxidants in disease prediction.

Methods: Data were sourced from the National Health and Nutrition Examination Survey. Antioxidants, including vitamins, minerals, and polyphenols, were selected as key features.

A technology-enabled collaborative learning model (Project ECHO) to upskill primary care providers in best practice pain care.

Background The South Australian (SA) Chronic Pain Extension for Community Healthcare Outcomes (ECHO) Network was established to upskill primary care providers in best practice pain care aligned to a patient-centred, biopsychosocial approach using didactic and case-based virtual mentoring sessions. The aims of this study were to assess: (a) participation, satisfaction (relevance, satisfaction with format and content, perceptions of the mentorship environment), learning (perceived knowledge gain, change in attitudes), competence (self-confidence) and performance (intention to change practice, perceived practice change) of the ECHO Network clinician participants; and (b) self-perceived barriers at the clinical, service and system level to applying the learnings. Methods A mixed methods, participatory evaluation approach was undertaken.

Second Generation I-Body AD-214 Attenuates Unilateral Ureteral Obstruction (UUO)-Induced Kidney Fibrosis Through Inhibiting Leukocyte Infiltration and Macrophage Migration.

Kidney fibrosis is the common pathological pathway in progressive chronic kidney disease (CKD), and current treatments are largely ineffective. The C-X-C chemokine receptor 4 (CXCR4) is crucial to fibrosis development. By using neural cell adhesion molecules as scaffolds with binding loops that mimic the shape of shark antibodies, fully humanized single-domain i-bodies have been developed.

Adjuvant Radiation Therapy in Macroscopic Regional Nodal Melanoma.

Adjuvant radiation therapy (ART) for macroscopic regional nodal cutaneous melanoma has evolved. A significant step was the discovery of targeted therapies, particularly towards V600E-mutated melanoma, and immunotherapy under its different kinds. Prior to this, the defining trial was the Australia and New Zealand Melanoma Trials Group (ANZMTG) 01.

Disparities in Lung Cancer Death Among People with Chronic Lower Respiratory Diseases in the United States.

Purpose: Patients with chronic lower respiratory diseases (CLRD) are at a higher risk of lung cancer. Less is known regarding how the risk of CLRD-associated lung cancer death might have changed on a national scale over the past 20 years across demographic and regional groups.

Methods: We calculated age-adjusted mortality rates (AAMR) for lung cancer death among people with CLRD using 1999-2020 data from the CDC WONDER multiple cause of death database.

Optimizing Antitumor Effect of Triple-Negative Breast Cancer via Rosmarinic Acid-β-Cyclodextrin Inclusion Complex.

: Rosmarinic acid (ROS) has gained notable attention for its anticancer potential; however, its limited aqueous solubility hinders its effective delivery and application in pharmaceutical formulations. : To overcome this limitation, an inclusion complex of ROS with β-cyclodextrin (β-CD) was prepared using the recrystallization method. The resultant ROS-β-CD complex was comprehensively characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM).

Characteristics of Inherited Metabolic Disorders Following Kidney Transplantation: A 13-Year Observational Study.

Inherited metabolic disorders (IMDs), primarily cystinosis, Fabry disease, and methylmalonic acidemia (MMA), are genetic conditions that typically result in multi-organ disease manifestations. Kidney function progressively deteriorates in many cases, with patients eventually reaching end-stage kidney disease (ESKD) and requiring renal replacement therapy. Kidney transplantation has been deemed the optimal renal replacement therapy option to achieve long-term survival in patients with IMD.

MuscleMap: An Open-Source, Community-Supported Consortium for Whole-Body Quantitative MRI of Muscle.

Disorders affecting the neurological and musculoskeletal systems represent international health priorities. A significant impediment to progress in trials of new therapies is the absence of responsive, objective, and valid outcome measures sensitive to early disease changes. A key finding in individuals with neuromuscular and musculoskeletal disorders is the compositional changes to muscles, evinced by the expression of fatty infiltrates.

Adolescent behavioural intentions: Secondary outcomes from a cluster randomized controlled trial of the Health4Life school-based lifestyle modification intervention.

Intervention: Health4Life: a school-based eHealth intervention targeting multiple health behaviour change (MHBC).

Research Question: Does Health4Life impact secondary outcomes of self-reported intentions regarding six lifestyle behaviours in adolescents (alcohol use, tobacco smoking, screentime, physical activity, discretionary beverage consumption, and sleep)?

Methods: We implemented a cluster randomized controlled trial within secondary schools across three Australian states. Schools were randomly assigned (1:1) to receive either the Health4Life intervention, which consisted of a six-module, web-based program and accompanying smartphone app, or an active control (standard health education).

Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma.

Background: In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI.

Patients And Methods: This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy.

Medication shortage behaviour change with multidisciplinary clinician-designed digital notification intervention.

Objectives: To evaluate the effect of a clinician-designed digital notification system on the use of intravenous paracetamol during a medication shortage.

Methods: An in-house digital notification platform was designed through multidisciplinary collaboration. A 4-week pre- and post-implementation methodology was employed to evaluate the effect of the intervention.

Diet and Disease Development: Mechanisms, Prevention, and Treatment.

The overall aims of this Special Issue "Diet and Disease Development: Mechanisms, Prevention and Treatment" are to describe and emphasise the importance of diet in disease development; understand the mechanism(s) whereby an unhealthy diet can induce various diseases; examine the potential effects of natural compounds or extracts on disease prevention or treatment; and determine whether nutrients and their metabolites can be used as biomarkers to diagnose certain diseases [...

Evaluating Alternative Registration Planes in Imageless, Computer-Assisted Navigation Systems for Direct Anterior Total Hip Arthroplasty.

(1) Background: Imageless computer navigation systems have the potential to improve the accuracy of acetabular cup position in total hip arthroplasty (THA). Popular imageless navigation methods include locating the patient in a three-dimensional space (registration method) while using a baseline to angle the acetabular cup (reference plane). This study aims to compare the accuracy of different methods for determining postoperative acetabular cup positioning in THA via the direct anterior approach.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol.

Background: Fluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3-4 (≥ G3) toxicities that require hospital-based management ± intensive care admission.

Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.

Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms.