Royal North Shore Hospital

Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. The Asian Thoracic Oncology Research Group (ATORG) convened a multidisciplinary panel of 27 experts to develop a consensus statement on the clinical application of circulating tumor DNA-based MRD testing in early stage resected NSCLC, using a structured Delphi methodology. Statements were organized into the following broad thematic domains: assay validity and standardization; harmonization in research and trials; clinical application; challenges in implementation; consensus recommendations; infrastructure for regional MRD adoption; and roadmap for pragmatic trials. A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling time points and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. Although current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building, and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

BackgroundPreservation of normal-quality infrapatellar fat pads (IPFP) during total knee arthroplasty (TKA) has been proposed, and IPFP of abnormal quality are recommended for resection.MethodsIn this trial, patients with knee osteoarthritis (OA) undergoing TKA were stratified by IPFP status on magnetic resonance imaging (Group 1 with normal IPFP [signal intensity score ≤1; ranging from 0 to 3]; Group 2 with abnormal IPFP [signal intensity score ≥2]) and randomly assigned in a 1:1 ratio to IPFP preservation or IPFP resection. The primary outcome was 12-month change in the mean of five Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales (KOOS5), which range from 0 (worst) to 100 (best).ResultsIn Group 1, 179 participants were randomly allocated to IPFP preservation (n=90) and IPFP resection (n=89), and 198 participants were randomly assigned to IPFP preservation (n=101) and IPFP resection (n=97) in Group 2. The increases in KOOS5 score were 38.1 and 36.1 in Group 1 and were 39.2 and 37.5 in Group 2 in IPFP preservation and IPFP resection groups, respectively, resulting in between-group differences of 1.9 (95% confidence interval [CI], −1.7 to 5.6) in Group 1 and 1.6 (95% CI, −1.3 to 4.6) in Group 2. Adverse events were predominantly nonserious musculoskeletal or skin-related events (three vs. two in Group 1 and eight vs. two in Group 2).ConclusionsResection of abnormal IPFP and preservation of normal IPFP did not improve postoperative outcomes 12 months after TKA. (Funded by National Key Research & Development Program of China, Clinical Research Startup Program of Southern Medical University, and National Natural Science Foundation of China; ClinicalTrials.gov number, NCT03763448.)

Standard modifiable risk factors (SMuRFs) are associated with increased risk of acute myocardial infarction (AMI). Patients with AMI in the absence of standard modifiable risk factors (SMuRF-less) have demonstrated excess mortality. The study aims to forecast trends in prevalence and case fatality of SMuRF-less AMI in Singapore and United Kingdom. Data from the Singapore Myocardial Infarction Registry and the UK Myocardial Ischemia National Audit Project were used to construct Poisson regression models to predict the prevalence and case fatality rate of SMuRF-less AMI from 2025 to 2040. From 2025 to 2040, SMuRF-less AMI cases are expected to contribute to larger proportions of total AMI cases in Singapore (5.8% [95% CI: 5.2%-6.4%] to 8.5% [95% CI: 6.2%-10.8%]) and United Kingdom (13.8% [95% CI: 13.0%-14.6%] to 16.9% [95% CI: 15.1%-18.7%]). The proportion of SMuRF-less AMI mortality of the total AMI mortality is set to decrease in the United Kingdom (11.3% [95% CI: 10.5%-12.1%] to 9.5% [95% CI: 7.7%-11.4%]), but increase in Singapore (6.3% [95% CI: 5.7%-6.9%] to 13.3% [95% CI: 10.9%-15.6%]). Men continue to bear the majority of SMuRF-less AMI prevalence, with the most rapid rise in young adults in Singapore (8.1%; 95% CI: 7.5%-8.7%) and middle-aged adults in the United Kingdom (2.3%; 95% CI: 1.5%-3.1%). The increase in SMuRF-less AMI prevalence is set to be more rapid in the overweight/obesity population (3.9%; 95% CI: 3.3%-4.5%). By 2040, SMuRF-less AMI will expand to a larger proportion of the AMI census in Western and Eastern populations. SMuRF-less AMI vulnerability will shift toward a younger, male-dominant demographic, with overweight/obesity as a dominant risk factor.

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.

Risperidone has modest efficacy for behaviours and psychological symptoms of dementia and is associated with many adverse events. Current guidelines limit its use to no longer than 12-16 weeks. This study aims to evaluate adverse outcomes over time, identify key predictors, and examine high-risk subgroups to inform safer prescribing. A one-stage individual participant data meta-analysis of six randomised controlled trials (risperidone: n = 1009; placebo: n = 712) was conducted. Mixed-effect generalised linear models and proportional hazards mixed-effects models estimated treatment effects, predictors, and subgroup differences for adverse outcomes over varying time periods. Risperidone was associated with increased risks of cerebrovascular (hazard ratio [HR] 4.11; 95% confidence interval [CI] 1.77-9.51; p = 0.001) and major cardiovascular events (HR 2.00; 95% CI 1.23-3.26; p = 0.006), with median (interquartile range) onset at 4.3 (5.9) and 4.8 (6.8) weeks of treatment, respectively. Somnolence occurred consistently during treatment, whereas upper respiratory tract infections (odds ratio [OR] 2.31; 95% CI 1.24-4.32; p = 0.009) and extrapyramidal symptoms emerged (OR 2.93; 95% CI 1.68-5.08; p < 0.001) after week 4. Older age, male sex, and baseline cardiac pharmacotherapy use predicted serious adverse outcomes. Most adverse effects occur after 4 weeks of treatment. Attention to baseline risk factors is essential to minimise harm. Risk-benefit calculators may guide individualised prescribing.