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.

Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study.

Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.

Approach to the Diagnosis and Management of Complex Fascicular Ventricular Tachycardias.

Complex ventricular tachycardias involving the fascicular system (fascicular ventricular tachycardias [FVTs]) can be challenging. In this review, we describe our approach to the diagnosis and ablation of these arrhythmias with 10 illustrative cases that involve (1) differentiation from supraventricular tachycardia; (2) assessment for atypical bundle branch reentry and other interfascicular FVTs; (3) examination of P1/P2 activation sequences in sinus rhythm, pacing, and tachycardia; and (4) entrainment techniques to establish the tachycardia mechanism and aid circuit localization. To summarize, 5 cases had prior ablation with 2 previously misdiagnosed as supraventricular tachycardia.

BNC210, an α7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder.

Background: Post-traumatic stress disorder (PTSD) is a serious, debilitating, and prevalent psychiatric condition occurring in people who are traumatized and experience intense, disturbing thoughts and feelings that persist. BNC210 is a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator developed to treat PTSD.

Methods: ATTUNE was a randomized, double-blind, phase 2b, placebo-controlled trial.

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.

Development and Initial Validation of the Novel Scleroderma Clinical Trials Consortium Activity Index.

Objective: Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant clinical challenge. The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index (AI) Working Group (WG) to develop a novel measure of disease activity (SCTC-AI).

Methods: Using consensus methodology, we developed a conceptual definition of disease activity.

Supporting best practice in the management of chronic diseases in primary health care settings: a scoping review of training programs for Indigenous Health Workers and Practitioners.

Background To improve diabetes management in primary health care for the Aboriginal and Torres Strait Islander peoples population, training programs that are culturally and contextually relevant to the local context are required. Using a scoping review methodology, the aim of this review was to describe the characteristics of chronic disease management training programs for Aboriginal Health Workers and Practitioners, their effectiveness on knowledge and skills, and client-related outcomes, and the enablers, barriers to delivery and participation. Methods Following protocol parameters, a systematic search was conducted in relevant databases and grey literature.

Outcomes of Patients With Diffuse Systemic Sclerosis Eligible for Autologous Stem Cell Transplantation Treated With Conventional Therapy.

Objective: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT.

Methods: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed.

Metastatic colorectal cancer- third line therapy and beyond.

Introduction: The outcome of patients with metastatic colorectal cancer (mCRC) has improved significantly in the last few decades. Metastatic colorectal cancer is a highly heterogenous cancer. Beyond second line chemotherapy, treatment decisions are often based on molecular testing.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

Objective: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time.

Methods: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH).

Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a Two-Year, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial.

Objective: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN).

Methods: We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022.

Methotrexate for juvenile idiopathic arthritis.

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used disease-modifying antirheumatic drug (DMARD). This is an update of a 2001 Cochrane review.

Inflammatory Arthritis in Systemic Sclerosis: Its Epidemiology, Associations, and Morbidity.

Objective: To describe the epidemiology, associations, and impact of inflammatory arthritis (IA) in systemic sclerosis (SSc).

Methods: Patients with SSc prospectively enrolled in the Australian Scleroderma Cohort Study were included. IA was defined clinically as the presence of synovitis on examination.

Structural and electro-anatomical characterization of the equine pulmonary veins: implications for atrial fibrillation.

Introduction/objectives: Spontaneous pulmonary vein (PV) activity triggers atrial fibrillation (AF) in humans. Although AF frequently occurs in horses, the origin remains unknown. This study investigated the structural and electro-anatomical properties of equine PVs to determine the potential presence of an arrhythmogenic substrate.

Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial.

Background: Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study.

Anticipatory anxiety and participation in cancer screening. A systematic review.

Objectives: To synthesize current evidence on the association between anticipatory anxiety, defined as apprehension-specific negative affect that may be experienced when exposed to potential threat or uncertainty, and cancer screening to better inform strategies to maximize participation rates.

Methods: Searches related to cancer screening and anxiety were conducted in seven electronic databases (APA PsycINFO, Scopus, Web of Science, Embase, Cochrane Library, PubMed, CINAHL), with potentially eligible papers screened in Covidence. Data extraction was conducted independently by multiple authors.

What Therapeutic Biomarkers in Gastro-Esophageal Junction and Gastric Cancer Should a Pathologist Know About?

Malignancies of upper gastrointestinal tract are aggressive, and most locally advanced unresectable and metastatic cancers are managed by a combination of surgery and neoadjuvant/adjuvant chemotherapy and radiotherapy. Current therapeutic recommendations include targeted therapies based on biomarker expression of an individual tumor. All G/gastro-esophageal junction (GEJ) cancers should be tested for HER2 status as a reflex test at the time of diagnosis.

Impact of the COVID-19 Pandemic on Health Care Access and Diagnosis of Pulmonary Arterial Hypertension Among Patients With Systemic Sclerosis.

Objective: Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH.

Methods: South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc.