Flinders Medical Centre

BK polyomavirus (BKPyV) is a common opportunistic infection in kidney transplant recipients, typically reactivating in the context of immunosuppression. Although asymptomatic in immunocompetent individuals, reactivation in transplant recipients can cause BKPyV-associated nephropathy (BKPyVAN), a leading cause of graft dysfunction and loss. BKPyV viremia affects approximately 10%-15% of transplant recipients, and once BKPyVAN is established, the risk of graft failure can exceed 50%. The current standard of care involves immunosuppression reduction to restore virus-specific immunity, but this approach increases the risk of acute and chronic rejection. Intravenous immunoglobulin (IVIg), which contains antiviral and immunomodulatory antibodies, has been proposed as an adjunctive therapy, although evidence supporting its efficacy remains limited to small observational studies. The BEAT-BK trial is a multicenter, adaptive, randomized controlled trial comparing standard immunosuppression reduction with or without IVIg in kidney and simultaneous pancreas-kidney transplant recipients with BKPyV viremia or biopsy-confirmed BKPyVAN. The trial will enroll participants aged 2 y and older, randomizing them 1:1 to receive standard care alone or in combination with a total IVIg dose of 2 g/kg for 8 wk. An adaptive Bayesian design will permit interim analyses with the potential for early trial success or futility. The primary endpoint is a composite ordinal outcome at 12 wk, incorporating death, graft loss, estimated glomerular filtration rate decline, acute rejection, viral load, and degree of immunosuppression reduction. Secondary outcomes include viral clearance, development of BKPyVAN and donor-specific antibodies, infections, malignancy, quality of life, and cost-effectiveness. This trial will provide the first high-quality evidence on the role of IVIg in BKPyV management and inform clinical decision-making in posttransplant care.

Jack Jumper ant (JJA) venom immunotherapy (VIT) is highly efficacious but the lowest effective dose is unknown. Delta-inulin adjuvant (Advax) is known to enhance honeybee VIT immunogenicity. This phase 1/2 single-blind, randomised controlled trial aimed to compare the efficacy and safety of JJA VIT with different doses of venom ± Advax. Adults aged 18-65 with a history of immediate systemic reaction (SR) to JJA stings were randomised to receive JJA VIT at a maintenance dose of 25 mcg or 50 mcg ± Advax; participants were blinded to treatment allocation. Primary outcomes were the response to sting challenges after 12 months and venom-specific IgE and IgG4 responses to treatment. Forty-nine of 50 screened subjects met inclusion criteria and were randomised; 44 started treatment (25 mcg n = 12; 25 mcg + Advax n = 13; 50mcg n = 12, 50 mcg + Advax n = 12). Subsequently, two withdrew due to SRs to treatment, and two withdrew due to unrelated factors. The higher JJA venom maintenance dose was associated with reduced likelihood of SRs (OR 0.53 (95% CI, 0.28-0.98)), while Advax did not have an effect (OR 1.17 (95% CI, 0.59-2.32)). Forty proceeded to sting challenge, with six developing SRs. There was no difference between groups for sting challenge outcome (p = 0.98), and the ORs for 25 mcg vs. 50 mcg venom dose (0.89, 95% CI, 0.38-2.09) and Advax vs. no Advax (0.99, 95% CI 0.42-2.33) indicated no effect. There were no differences between groups for venom sIgE (p = 0.78), sIgG4 (p = 0.25), sIgE/IgG4 ratio (p = 0.42), intradermal (p = 0.77), and basophil activation test (BAT) (p = 0.69) responses to treatment. Subjects with high baseline BAT sensitivity, which reduced markedly in response to treatment, were less likely to have a positive sting challenge (p = 0.006). Challenge outcomes were similar for all groups, with no significant difference found between 25 and 50 mcg maintenance dose or between treatment with and without Advax. Further research of low dose JJA VIT is warranted to confirm its efficacy and tolerability. NCT03066986.

Survival prediction in metastatic long-bone disease is essential for surgical decision-making, yet the performance of legacy prognostic models has declined in the era of immunotherapy and molecularly targeted agents. As these systemic therapies become routine, treatment patterns themselves may influence survival in ways not captured by earlier models. We, therefore, quantified preoperative systemic therapy use over the last decade and evaluated its association with postoperative overall survival in patients undergoing surgery for long-bone metastases. We conducted a retrospective cohort study of 975 consecutive adults who underwent surgery for long-bone metastases at two affiliated tertiary centers between January 2010 and June 2022. Preoperative systemic therapy was categorized into four groups: chemotherapy only, targeted therapy only, combined chemotherapy and targeted therapy, or neither. Postoperative was defined as time from surgery to death from any cause. We described temporal uptake of therapies by calendar year and assessed associations with postoperative survival using multivariable Cox regression adjusting for demographics, ECOG performance status, Katagiri primary tumor grouping, visceral/brain metastases, and laboratory variables. Adjusted survival over calendar time was summarized via marginal standardization at fixed horizons (1, 3, 12, and 24months). Use of targeted agents including checkpoint inhibitors rose markedly, from 2% in 2015 to 43% in 2022. In multivariable Cox models, preoperative chemotherapy alone was associated with worse survival versus no preoperative systemic therapy (HR 1.41, 95% CI 1.21-1.65; p<0.01), as was combined chemotherapy plus targeted therapy (HR 1.24, 95% CI 1.05-1.47; p=0.01). In contrast, targeted therapy alone before surgery was associated with better survival (HR 0.76, 95% CI 0.58-0.99; p=0.04). Adjusted survival appeared to increase modestly across calendar years, but the pre-specified joint Wald test for the calendar year spline terms was not significant (p=0.17), indicating a non-significant trend over time. This study found that preoperative systemic therapy patterns are strongly associated with post-operative survival in metastatic long-bone disease: targeted therapy alone correlates with improved survival whereas preoperative use of chemotherapy-alone or combined with targeted agents-was associated with worse survival. These findings support incorporating contemporary treatment exposure into prognostic models and suggest that model recalibration to the immunotherapy era may be warranted.

We welcome the comment [...].

Rates of early-onset pancreatic cancer (EOPC) and early-onset colorectal cancer (EOCRC) are rising globally. Although research and clinical guidelines have sought to address the psychosocial and supportive care needs of people with colorectal and pancreatic cancers, these efforts have focused largely on older adults, meaning the experiences of individuals with EOPC and EOCRC may be poorly understood. Social media offers a source of real-time, first-hand narratives that may help address this gap. This study analyzed posts on X (formerly Twitter) to explore the lived experiences and needs of people with EOPC and EOCRC to inform more age-appropriate, person-centered care. Posts containing keywords relating to EOPC and EOCRC, shared between 2023 and 2025, were extracted. Of 7441 posts retrieved, approximately 40% were categorized automatically using predefined keywords, with the remainder manually coded. Automated coding demonstrated substantial agreement with manual coding (Cohen's κ=0.717). Most posts related to "academic and clinical" content (66.1%) or "medical advice and discussion" (13.5%). Only 11 posts (0.2%) described patient experiences, all relating to EOCRC, with none reflecting lived experiences of EOPC. These posts highlighted rising EOCRC incidence, late-stage diagnoses, advocacy for screening, survivorship themes, and peer support. X posts by people with early-onset cancers were scarce, whereas clinician- and researcher- posts dominated. This imbalance on X suggests a one-directional, paternalistic model of healthcare communication on this platform that contrasts with person-centered principles. Future research should explore alternative platforms and digital strategies to better engage younger cancer populations and support more collaborative communication.

Silicosis is a progressive fibrotic lung disease caused by chronic inhalation of crystalline silica. Increasing evidence indicates that oxidative stress plays a central role in linking silica exposure to inflammation, tissue injury, and fibrosis. We conducted a systematic review to critically appraise the current evidence on the imbalance between oxidant and antioxidant markers in patients with silicosis compared with unexposed healthy controls. A systematic literature search was conducted in PubMed, Scopus, and Google Scholar from their inception to 30 November 2025. Eligible studies assessed oxidative stress biomarkers in biological samples from patients with silicosis and non-exposed controls. Malondialdehyde (MDA) and Superoxide Dismutase (SOD) were the most frequently assessed oxidative and antioxidant markers, respectively, with MDA significantly increased and SOD decreased in patients with silicosis, highlighting amplified lipid peroxidation and impaired antioxidant defense. In addition, elevated levels of other oxidant molecules confirmed the presence of lipid, nitrosative, and DNA oxidative damage. Overall, antioxidant defenses were compromised, although some markers appeared to vary with disease stage. This review highlights the central role of oxidative stress in the pathogenesis and progression of silicosis. Future studies with larger cohorts and a broader range of biomarkers are needed to better understand oxidative imbalance and its potential utility for monitoring disease progression and assessing severity in this population.

Diabetic retinopathy incidence in Australasia is highly variable, highest in institution-based cohorts and among Indigenous Australians. HbA1c is the only determinant consistently and significantly associated with both onset and progression. Because most evidence predates modern diabetes care, future prospective cohorts should adopt standardised, multifactorial designs to generate contemporary, comparable data and reduce persistent inequities in eye-care access.

Chronic Obstructive Pulmonary Disease (COPD) poses significant public health and economic challenges and performant prognostic models may be useful to direct treatment. The purpose of this study was to develop predictive models, validate the DOSE and updated ADO predictive models, and identify predictors of future hospitalisation and mortality in contemporary Australian COPD patients. Data from 8,578 inpatients and outpatients diagnosed with COPD (via post-bronchodilator spirometry) between 2006 and 2021 at a large South Australian tertiary public hospital were analysed. Multivariate logistic models and Cox regression, utilising penalised regularisation in multiply imputed data, were used to investigate predictors of hospitalisation due to COPD exacerbation at 1-, 3-, and 5-years post-diagnosis, and COPD-specific mortality at 3- and 5-years. Haemoglobin-corrected DLCO (DLCOc) was used to extend the DOSE and updated ADO models. Locally developed models could predict COPD-specific 1-year hospitalisation risk with AUCs 0.80 (95% CI = [0.76, 0.83]) in males and 0.82 (95% CI = [0.78, 0.86]) in females on a temporally distinct hold-out set, with 3- and 5-year AUCs falling within this range. COPD-specific mortality was predicted with AUCs of 0.90 (95% CI = [0.85, 0.94]) and 0.89 (95% CI = [0.84, 0.92]) at 3 and 5 years in females, and 0.90 (95% CI = [0.86, 0.93]) and 0.88 (95% CI = [0.84, 0.92]) in males. Cox regression models predicted survival well in the test set for both females (C-index = 0.88, 95% CI = [0.85, 0.90]) and males (C-index = 0.86, 95% CI = [0.82, 0.88]). Local model performance was superior to that of the DOSE and updated ADO models for all outcomes, although not always significantly. Among the selected predictors, reduced DLCOc was strongly predictive of all outcomes. and acts as a short-term survival risk for follow-up durations less than 10 years. There was no significant difference in performance between sex, and there were differences in selected features and feature strength between sexes. Extending the extant clinical models with DLCOc significantly improved updated ADO and DOSE model fit and improved discriminatory performance, with the extended ADO index achieving AUC of 0.77 (95% CI = [0.75, 0.79]) and 0.87 (95% CI = [0.84, 0.89]) for predicting 5-year hospitalisation and mortality respectively across the full cohort. The extended DOSE index performed similarly with AUCs 0.77 (95% CI = [0.75, 0.79]) and 0.87 (95% CI = 0.83, 0.89)) for 5-year hospitalisation and mortality. Ours is the only large clinical cohort and prognostic study of Australian COPD patients to date. Locally developed models achieved greater discriminative performance than the original updated ADO and DOSE models within our cohort. Extending the ADO and DOSE models with DLCOc significantly improved model fit in our cohort. We recommend further research into the use of DLCOc as a prognostic index for COPD, and its inclusion in future modelling attempts. Retrospectively registered. Clinical trial number: Not Applicable.