A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship.

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD).

Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS.

Pain management challenges in a patient with mucopolysaccharidosis IVA.

It is important to consider all potential pain management modalities including alternative treatment on managing complex pain presentations. Acupuncture is a treatment modality that may result in reduction of pain in patients with significant medical comorbidities due to MPS IVA.

Evolution in coeliac disease diagnosis and management.

The traditional gut-centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease - well demonstrated in children - are growing for adults. Novel biomarkers such as interleukin-2 that identify the gluten-specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge.

Whole blood transcriptomics reveals granulocyte colony-stimulating factor as a mediator of cardiopulmonary bypass-induced systemic inflammatory response syndrome.

Objectives: Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS is associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, and as a result, biomarkers are lacking and treatment remains expectant and supportive. This study aimed to understand the pathophysiological mechanisms driving SIRS induced by CPB and identify novel therapeutic targets that might reduce systemic inflammation and improve patient outcomes.

Alzheimer's disease biomarker utilization at first referral enhances differential diagnostic precision with simultaneous exclusion of Creutzfeldt-Jakob disease.

Most suspected Creutzfeldt-Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1-42 (Aβ1-42), phosphorylated tau 181 (p-tau181), and total tau (t-tau) could be assessed via Elecsys immunoassays ( = 419) and NfL via enzyme-linked immunosorbent assay (ELISA;  = 161).

Utility of panenteric capsule endoscopy for the detection of small-bowel Crohn's disease in patients with a normal magnetic resonance enterography: A prospective observational pilot study.

Background And Aim: Capsule endoscopy allows the direct visualization of the small bowel. We examined the diagnostic utility of a new modality, namely panenteric Crohn's capsule endoscopy (CE), in detecting active small-bowel Crohn's disease (CD) in those with normal magnetic resonance enterography (MRE).

Methods: We prospectively recruited patients with a diagnosis of CD or suspected small-bowel CD in whom the MRE was normal.

Interventions to Attenuate Cardiovascular Calcification Progression: A Systematic Review of Randomized Clinical Trials.

Background: Cardiovascular calcification, characterized by deposition of calcium phosphate in the arterial wall and heart valves, is associated with cardiovascular morbidity and mortality and is commonly seen in aging, diabetes, and chronic kidney disease. Whether evidence-based interventions could significantly attenuate cardiovascular calcification progression remains uncertain.

Methods And Results: We conducted a systematic review of randomized controlled trials involving interventions, compared with placebo, another comparator, or standard of care, to attenuate cardiovascular calcification.

Targeting BMI-1 to deplete antibody-secreting cells in autoimmunity.

Objectives: B cells drive the production of autoreactive antibody-secreting cells (ASCs) in autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome, causing long-term organ damage. Current treatments for antibody-mediated autoimmune diseases target B cells or broadly suppress the immune system. However, pre-existing long-lived ASCs are often refractory to treatment, leaving a reservoir of autoreactive cells that continue to produce antibodies.

Impact of focused cardiac and lung ultrasound screening performed by a junior doctor during admission to the surgical ward on patients before emergency non-cardiac surgery: A pilot prospective observational study.

Purpose: To assess whether pre-operative focused cardiac ultrasound and lung ultrasound screening performed by a junior doctor can change diagnosis and clinical management of patients aged ≥65 years undergoing emergency, non-cardiac surgery.

Method: This pilot prospective observational study included patients scheduled for emergency, non-cardiac surgery. The treating team completed a diagnosis and management plan before and after focused cardiac and lung ultrasound, which was performed by a junior doctor.

His bundle combined with deep septal left bundle branch area pacing for atrial fibrillation prior to atrioventricular node ablation.

Background: To mitigate the risk of dyssynchrony-induced cardiomyopathy, international guidelines advocate His bundle pacing (HBP) with a ventricular backup lead prior to atrioventricular node ablation in treatment-refractory atrial fibrillation and normal left ventricular ejection fraction. As a result of concerns with long-term pacing parameters associated with HBP, this case series reports an adopted strategy of HBP combined with deep septal left bundle branch area pacing (dsLBBAP) in this patient cohort, enabling intrapatient comparison of the two pacing methods.

Methods And Results: Eight patients aged 72 ± 10 years (left ventricular ejection fraction 53 ± 4%) underwent successful combined HBP and dsLBBAP implant prior to AV node ablation.

The impact of training on communication quality during interpreter-mediated cognitive assessments: Study protocol for a randomized controlled trial.

Introduction: The number of Australian residents with dementia is projected to double by 2058, with 28% currently being migrants from non-Anglophone countries. There will be growing demand for professional interpreters for cognitive assessments and dementia-related health consultations in the future. Interpreting cognitive assessments can be challenging for interpreters; inaccurate interpreting can influence assessment outcomes.

Alcohol and tobacco use and risk of multiple myeloma: A case-control study.

Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population-based case-control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases.

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder characterised by reduced or absent OTC enzyme activity, resulting in the accumulation of neurotoxic ammonia. Approximately 80%-90% of the causative variants are identified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA) of the gene. A 23-year-old male with biochemical evidence of OTCD was referred for molecular analysis.

A phase 1b open-label study of sodium selenate as a disease-modifying treatment for possible behavioral variant frontotemporal dementia.

Introduction: Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioral variant frontotemporal dementia (bvFTD).

Methods: Twelve participants with bvFTD received sodium selenate (15 mg, three times a day) for 52 weeks.

Point-of-care lung ultrasound in the assessment of patients with COVID-19: A tutorial.

The adoption of point-of-care lung ultrasound for both suspected and confirmed COVID-19 patients highlights the issues of accessibility to ultrasound training and equipment. Lung ultrasound is more sensitive than chest radiography in detecting viral pneumonitis and preferred over computed tomography for reasons including its portability, reduced healthcare worker exposure and repeatability. The main lung ultrasound findings in COVID-19 patients are interstitial syndrome, irregular pleural line and subpleural consolidations.

Glucose patterns following alcohol and illicit drug use in young adults with type 1 diabetes: A flash glucose monitoring study.

Introduction: To assess the effects of alcohol and illicit drug use in young adults (age 18-35) with type 1 diabetes (T1D) on flash glucose monitor sensor glucose (SG) readings.

Methods: Twenty young adults with T1D were enrolled from a tertiary referral hospital outpatient department in Melbourne, Australia for a 6-week prospective observational study using flash glucose monitoring (FGM). Glucometrics comparing substance using days (SUEDs) to those without substance use (non-SUEDS) were analysed.

Reduction of Calciprotein Particles in Adults Receiving Infliximab for Chronic Inflammatory Disease.

Patients with chronic inflammatory diseases (CID) experience accelerated loss of bone mineral density, which is often accompanied by increased vascular calcification. These disturbances can be attenuated by therapies for inflammation, such as the tumor necrosis factor inhibitor infliximab. Calciprotein particles (CPP) are circulating colloidal aggregates of calcium and phosphate together with the mineral-binding protein fetuin-A, which have emerged as potential mediators of vascular calcification.

Adaptive immunity to human coronaviruses is widespread but low in magnitude.

Objectives: Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults.

Methods: We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals.

Evaluation of literature searching tools for curation of mismatch repair gene variants in hereditary colon cancer.

Pathogenic constitutional genomic variants in the mismatch repair (MMR) genes are the drivers of Lynch syndrome; optimal variant interpretation is required for the management of suspected and confirmed cases. The International Society for Hereditary Gastrointestinal Tumours (InSiGHT) provides expert classifications for MMR variants for the US National Human Genome Research Institute's (NHGRI) ClinGen initiative and interprets variants with discordant classifications and those of uncertain significance (VUSs). Given the onerous nature of extracting information related to variants, literature searching tools which harness artificial intelligence may aid in retrieving information to allow optimum variant classification.

Natural killer cells in inflammatory autoimmune diseases.

Natural killer (NK) cells are a specialised population of innate lymphoid cells (ILCs) that help control local immune responses. Through natural cytotoxicity, production of cytokines and chemokines, and migratory capacity, NK cells play a vital immunoregulatory role in the initiation and chronicity of inflammatory and autoimmune responses. Our understanding of their functional differences and contributions in disease settings is evolving owing to new genetic and functional murine proof-of-concept studies.

Proteomic analysis of extracellular vesicles reveals an immunogenic cargo in rheumatoid arthritis synovial fluid.

Objectives: Extracellular vesicles (EVs) from rheumatoid arthritis (RA) synovial fluid (SF) have been reported to stimulate the release of pro-inflammatory mediators from recipient cells. We recently developed a size exclusion chromatography (SEC)-based method for EV isolation capable of high-quality enrichments from human SF. Here, we employed this method to accurately characterise the SF EV proteome and investigate potential contributions to inflammatory pathways in RA.

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma.

For the reference citation '[57]' in the second paragraph of the Results section of the original article there was no corresponding entry in the References section. It should have referred to the below mentioned article by Ebrahimkhani et al. (2018).

Successful treatment of HIV-associated lupus-like glomerulonephritis with mycophenolic acid.

HIV-associated lupus-like glomerulonephritis is an uncommon but well-described entity. Treatment has traditionally focused on control of HIV viremia with some using adjuvant steroids. Mycophenolic acid may prove to be a novel, nonsteroid, therapy in patients with active glomerulonephritis despite control of the underlying infection.

Serum microRNA is a biomarker for post-operative monitoring in glioma.

Purpose: A circulating biomarker has potential to provide more accurate information for glioma progression post treatment, however no such biomarker is currently available. We aimed to discover a microRNA serum biomarker for longitudinal monitoring of glioma patients.

Methods: A prospectively collected cohort of 91 glioma patients and 17 healthy controls underwent pre and post-operative serum miRNA profiling using Nanostring®.