St Vincent's Hospital Sydney

Artificial intelligence programs were not used in the provision of this article. The authors declare no conflicts of interest. Research data are not shared. Table S1: MOAHFLA (% male patients; % occupational dermatitis; % with atopic dermatitis; % hand dermatitis; % leg dermatitis; % face dermatitis; % age > 40 years) characteristics for individuals with alkyl glucoside (AG) allergic contact dermatitis (ACD) compared to those tested to AG without a relevant reaction from a retrospective study from 1st January 2016 to 31st December 2024. Analysis was made with χ2 test with Yate's continuity correction unless otherwise specified. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ABSTRACT Introduction Overweight and obesity are increasing rapidly in most countries. Underweight body mass index (BMI), though much less common, is also associated with adverse health outcomes. There is poor understanding of the implications of BMI in lymphoma patients. Recent international guidelines indicate that curative‐intent cancer treatment should not be modified for obesity alone, with no specific recommendations for low BMI patients. Our aim was to examine the impact of BMI on outcomes in a contemporary cohort of lymphoma patients. Methods We examined BMI in relation to baseline clinical features and outcomes in an Australasian cohort of 4686 lymphoma cases from the national registry. Results Patients with an overweight or obese BMI had no significant decrement in overall survival (OS) or progression free survival (PFS) compared to those with a normal BMI for any of the histological subtypes examined in this study. However, the minority of patients with underweight BMI demonstrated inferior OS for Hodgkin lymphoma (adjHR = 2.55, 95% CI = 1.05–6.19, p = 0.04) and OS (adjHR = 1.54, 95% CI = 1.02–2.32, p = 0.04) in diffuse large B‐cell lymphoma compared to patients with a normal BMI. Conclusion These findings support continued standard dosing in overweight and obese patients and identify poor outcomes requiring careful management in underweight populations. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Haemorrhage and blood product usage are common in venoarterial extracorporeal membrane oxygenation (VA ECMO) and associated with increased mortality. A prospective, investigator-initiated, longitudinal observational cohort study on major haemorrhagic events in 12 ECMO centres from 3 continents for three predefined subgroups (VA ECMO initiated during cardio-pulmonary resuscitation (ECPR), after cardiothoracic surgery (CTS), for cardiogenic shock (CS)). The aim was to describe haemorrhagic complications as well as transfusion practice and anticoagulation for the whole population as well as the subgroups. In addition, independent baseline predictors for red blood cell (RBC) transfusions were evaluated. 545 prospective patients were included between 2019 and 2022 (ECPR 149, CTS 169, CS 227). Hospital mortality was 46%. Over 2796 days 406 major haemorrhage events in 286 (52%) patients were recorded. CTS and ECPR patients had more frequent events occurring earlier in their course. 88% received RBC transfusions (1.27 (95%CI 1.22 – 1.31) units/day) with significantly more transfusions for CTS and ECPR patients. Platelet transfusion rates were highest in the CTS group (0.58 (95%CI 0.53–0.64) units/day). Haemoglobin and platelet count prior to transfusion were independent of subgroups and averaged (78 g/L (IQR 73, 84), 58 × 10^9/L (IQR 37, 85), respectively). However, platelet count prior transfusion was only marginally higher on days with major haemorrhage (74 × 10^9/L (IQR 50, 104). Systemic anticoagulation was started within the first 24 h in 83% (95% CI 80–87%) of patients, most frequently in CS patients (90%, CI 85–95%). Independent baseline predictors for RBC transfusion were ECPR (IRR 1.50, 95%CI 1.19–1.89) and prior use of antiplatelets (IRR: 1.43, 95%CI 1.13–1.80). Myocarditis and pulmonary embolism were associated with a lower rate of transfusion when compared to myocardial infarct (IRR: 0.57 (0.37–0.89), IRR: 0.67 (0.45–1.00, respectively). Haemorrhagic complications differ in clinical subgroups and RBC transfusion exposure is by far higher than in other critically unwell populations. We identified ECPR and antiplatelet therapy as additional predictors. Transfusion practice for RBC and platelets is variable and does not always follow international guidelines.

17 Background: VIR-5500, a dual-masked, PSMA-targeted bispecific T-cell engager, is designed to be specifically activated in the tumor microenvironment where protease activity is dysregulated relative to healthy tissues, potentially expanding the safety margin and therapeutic index. Methods: VIR-5500 was administered IV weekly (QW) and every 3 weeks (Q3W) at doses of 30 - 4000 ug/kg to eligible participants (pts) with progressive mCRPC after receiving SOC. Objectives were to characterize safety, pharmacokinetics (PK) profiles, anti-tumor activity, and determine the dose(s)/regimen(s) for expansion (NCT05997615). Results: As of 23 September 2025, 51 heavily pretreated mCRPC pts (~95% post-taxane) received ≥ 1 dose of VIR-5500. No dose limiting toxicities (pre-defined toxicities occurring during cycle 1) were reported. The incidence of related Grade ≥ 3 AEs was low and CRS was mostly limited to grade 1 and 2 (see Table). PSA declines were noted in all pts dosed at ≥ 3000 ug/kg Q3W, including clinically significant and deep PSA reductions (91% PSA 50 and 55% PSA 90 ). Preliminary evidence of durable PSA responses lasting over one year was noted in select patients undergoing intrapatient dose escalation. An objective response rate of 67% was observed in 4 out of 6 RECIST-evaluable patients treated at doses ≥ 3000 µg/kg Q3W, including one confirmed partial response and three additional partial responses pending confirmation. PSMA-PET imaging confirmed anti-tumor activity, demonstrating strong concordance with PSA 90 responses. Evidence of T-cell activation and target engagement included increased on-treatment CD3+ T-cell tumor infiltration and serum IFN-γ, including minimal elevation of IL-6 levels, consistent with generally low-grade CRS. Preliminary analyses indicated PK was dose-proportional for VIR-5500, with a half-life of approximately 8-10 days and minimal systemic unmasking to the fully unmasked metabolite. Dose escalation continues with both QW and Q3W regimen, and updated data will be provided at the time of the presentation. Conclusions: Pending further clinical validation, available data are suggestive of a generally favorable safety profile, with evidence of meaningful anti-tumor activity, including RECIST responses, and preliminary evidence of durable benefit in a heavily pretreated population with substantial disease burden. Clinical trial information: NCT05997615 . All Participants(n/N, %) ≥ 3000 ug/kg Q3W(n/N, %) Gr 1 CRS 24/51, 47% 9/15, 60% Gr 2 CRS 4/51, 8% 1/15, 7% Gr ≥ 3 CRS 1/51, 2% 0/15, 0% Related Gr ≥ 3 TEAE 8/51, 16% 3/15, 20% Any PSA Decline 34/45, 76% 11/11, 100% PSA 50 24/45, 53% 10/11, 91% PSA 90 11/45, 24% 6/11, 55% Objective Response Rate 4/22, 18% 4/6, 67%

Introduction Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease involving injury and a dysregulated repair response of an ageing epithelium. Here we investigate the contribution of senescence and telomere shortening to bleomycin-induced injury in alveolar epithelial cells (EpCs) derived from lung parenchymal tissue of patients with pulmonary fibrosis (PF), predominantly IPF, in vitro . Methods Injury responses of EpCs in air liquid interface (ALI) culture were assessed by ELISA, qPCR and/or immunofluorescence at 48 and 96 h post-bleomycin (30 μg·mL −1 ) treatment. Telomere length was evaluated by qPCR and corroborated by fluorescence in situ hybridisation (FISH). Results Bleomycin treatment increased markers of inflammation ( i.e. interleukin-6 and −36γ) and senescence ( i.e. p16 and p21) in EpCs from PF patients (PF-EpCs) ( p <0.05); responses markedly higher than control EpCs (Ctrl-EpCs). Conversely, the effects of bleomycin on the expression of type I and type II alveolar EpC markers were supressed or down-regulated in cultures of PF-EpCs (when compared to Ctrl-EpCs), whereas the percentage of keratin 17 positive type I and II intermediate EpCs were increased ( p <0.05). Telomere length was also significantly shorter in PF- than Ctrl-EpCs at baseline and further reduced post-bleomycin treatment ( p <0.05). Induction of telomere shortening by cell passaging augmented bleomycin-induced PF-EpC injury, whereas pharmacological telomerase activation and selected senotherapeutics were protective. Conclusion This study provides evidence that senescence-associated telomere shortening increases the susceptibility of IPF-lung EpCs to injury. Our cell-based lung epithelial injury model has utility as a pre-clinical tool for drug discovery and the evaluation of potential senotherapeutics for IPF treatment.

Multiparametric flow cytometry (MFC) enables rapid and sensitive quantification of measurable residual disease (MRD) in patients with acute myeloid leukaemia (AML), providing valuable prognostic information and guiding post-remission therapeutic strategies. Given the clinical utility of MFC AML MRD assessment and its inherent technical and analytical complexity, inter-laboratory standardisation is essential to ensure consistency of practice, diagnostic accuracy and reproducibility of results. However, limited options for external quality assessment exist. Representatives from all diagnostic laboratories in Australia and New Zealand currently performing AML MRD testing were invited to attend an in-person workshop to review site-specific practices and develop harmonisation processes. All six participating laboratories demonstrated a high level of concordance with respect to pre-analytical testing; however, greater variation was observed in post-analytical reporting, and a number of consensus recommendations were formulated for harmonisation. Ongoing meetings have also been established to promote continued sharing of expertise between AML MRD laboratories, align analytical strategies and enhance assay validation in accordance with regulatory requirements. These collaborative efforts provide guidance to existing MRD laboratories and those seeking to establish a new MRD service, facilitating sustainable provision of a high-quality regional MFC AML MRD testing network to meet current and anticipated increases in clinical demand.