Prince of Wales Hospital

To provide recommendations for the most appropriate endovascular intervention of femoropopliteal (FP) arterial disease based on plaque characterization. A panel of 22 physicians from multiple disciplines participated in a modified Delphi consensus, leveraging the RAND/UCLA Appropriateness Method. Panelists engaged in 2 rounds of voting, following a literature review, with an in-person discussion prior to the second round of voting. A rigorous statistical approach was used to analyze the points of agreement and disagreement. Consensus-based recommendations on the most appropriate endovascular approaches for treating patients with FP lesions, stratified by lesion morphology, were generated. Overall, 490 individual items were included in the voting, 458 (93%) of which achieved consensus and 32 (7%) were nonconsensus items, based on a priori criteria under the following categories: (a) recommendations on method for determining plaque morphology, (b) preferred endovascular devices for vessel preparation and definitive treatment stratified by (i) plaque morphology and (ii) Tosaka classification of in-stent restenosis, and (c) vessel preparation device safety-related considerations. This international, multidisciplinary consensus provides evidence- and expert-informed recommendations for vessel preparation and definitive treatment of FP arterial disease, tailored to plaque morphology. These consensus recommendations aim to support clinical decision making and promote best interventional practices by serving as an expert opinion supplement to existing guideline-based care pathways.

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.

Some patients exhibit characteristics of both asthma and COPD (asthma-COPD overlap [ACO]). There is no gold standard for diagnosing ACO, and limited prospective data exist on the medium-term outcomes of these patients based on the Global Initiative for Asthma (GINA) definition compared to those with asthma or COPD alone. This study assessed the clinical characteristics and risk factors for acute exacerbations (AEs) in ACO patients versus those with COPD or asthma over 3 years. Subjects aged over 40 years with a history of asthma and COPD, diagnosed by GINA and Global Obstructive Lung Disease (GOLD) guidelines, were recruited and followed for 3 years. Baseline assessments included a clinical history, symptoms, lung function, a 6-minute walk test (6MWT), blood eosinophil levels, and immunoglobulin E levels. ACO patients were identified per GINA 2017 criteria. AEs were recorded, and risk factors were assessed using Cox regression. Of 538 patients (299 asthma, 239 COPD), 78 (14.5%) were classified as ACO. Post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted (mean ± SD) was 83.1 ± 19.0% for asthma, 48.0 ± 19.0% for COPD, and 63.0 ± 22.2% for ACO (p < 0.001). Over 3 years, all AEs occurred in 59/272 (21.7%) asthma, 90/188 (47.9%) COPD, and 28/78 (35.9%) ACO patients, while severe AEs requiring hospitalization occurred in 24/272 (8.8%), 79/188 (42.0%), and 20/78 (25.6%), respectively. Compared to asthma patients, ACO patients had a significantly higher risk of first severe AE requiring hospitalization (p < 0.0001) but a lower risk compared to COPD patients (p = 0.014). Risk factors for AEs (all or severe) were: for asthma, prior AE history, shorter 6MWT distance, and lower lung function; for COPD, prior AE history, lower lung function, higher eosinophil count, and being underweight; for ACO, prior AE history and lower lung function. In this 3-year prospective study using the GINA definition, ACO patients showed an intermediate risk of severe AEs requiring hospitalization compared to asthma (higher) and COPD (lower), with prior exacerbation history and lower lung function as common risk factors across groups. gov registration number NCT03272932 (registration date: 9 Jan 2017).

The optimal sequencing of radiotherapy (RT) combined with immunotherapy (iRT) and the value of chemotherapy remain undefined for advanced non-small cell lung cancer (NSCLC), where randomized data are limited. To compare real-world overall survival (OS) between sequential and concurrent iRT in newly diagnosed advanced NSCLC, assess the effect of immune checkpoint inhibitor (ICI) maintenance after RT in refractory disease, and evaluate the association of chemotherapy with survival. This is a territory-wide study (OCEANUS) based on the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System (more than 90% population coverage). Patients with NSCLC diagnosed from January 1, 2010, to December 31, 2021, who subsequently received iRT for advanced or refractory disease were included. Overlap weighting was the primary propensity score-weighted method, with inverse probability of treatment weighting used for sensitivity analysis. Data were analyzed from December 2024 to April 2025. Sequential vs concurrent iRT for newly diagnosed advanced NSCLC; RT with vs without ICI maintenance for refractory NSCLC; receipt of chemotherapy. The primary outcome was real-world OS after landmark, estimated with weighted Kaplan-Meier and Cox models. When proportional hazards were violated (per Schoenfeld residuals), treatment effects were summarized using restricted mean survival time. Of 3522 patients who received ICIs, 335 received RT, including 155 with newly diagnosed advanced and 180 with refractory NSCLC. Of these, 247 (73.7%) were male, and the median (range) age was 64 (34-90) years. In newly diagnosed NSCLC, patients treated with sequential iRT had significant longer real-world OS than those treated with concurrent iRT (median, 20.3 months [95% CI, 13.3 to not reached] vs 16.0 months [95% CI, 8.3-30.0]; adjusted hazard ratio, 0.68; 95% CI, 0.47-0.99; P = .045). Chemotherapy was also associated with longer survival in patients with newly diagnosed advanced NSCLC. In refractory NSCLC, RT with ICI maintenance was associated with a numerically longer median real-world OS (11.2 months [95% CI, 7.9-20.6] vs 6.7 months [95% CI, 4.4-17.4]; P = .20). Addition of chemotherapy was not significant for real-world OS. Inverse probability of treatment weighting analyses produced similar estimates. In this cohort study, sequential iRT was associated with longer survival than concurrent iRT in patients with newly diagnosed advanced NSCLC, and chemotherapy was associated with longer survival. In patients with refractory NSCLC who survived at least 90 days, RT with ICI maintenance resulted in nonsignificantly longer survival and an unclear association with chemotherapy. These findings are hypothesis generating and support prospective randomized studies to define optimal sequencing of iRT and use of systemic treatment partners.

Ligament tension balance is essential for successful and long-term implant survival of total knee arthroplasty (TKA). Conventional manual tensioning methods are subjective and vary with the surgeon experience. This study evaluated the inter- and intra-rater reliability of pre-resection ligament tension assessments using an imageless robotic-assisted TKA system. In this prospective study, 24 patients (30 knees) with end-stage knee osteoarthritis underwent CORI-assisted TKA from September 2024 to February 2025. Three specialist and three trainee surgeons each performed three repeated varus and valgus stress assessments across flexion and extension. Each medial and lateral gap measurement was recorded. Intraclass correlation coefficients (ICCs) were calculated with a two-way mixed-effects and two-way random-effects model. Both specialists and trainees demonstrated excellent intra- and inter- rater reliability (ICC > 0.90) for medial and lateral gaps in extension and medial gap in flexion. Flexion lateral reliability was good-to-excellent for trainees (ICC = 0.873, 95% CI: 0.784-0.933) and moderate-to-excellent for specialists (ICC = 0.838, 95% CI: 0.729-0.913). Pre-resection ligament tension assessment with an imageless robotic system yields high inter- and intra-rater reliability, reducing variability linked to surgeon experience. Digital tensioners may standardize soft tissue balancing in TKA, potentially improving surgical outcomes and reproducibility. Level III, prospective quasi-experimental study.

Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to treatment, with mortality rates largely unchanged despite advances in cancer therapies. For ∼80% of borderline, non-resectable, or metastatic cases, chemotherapy is predominantly palliative, underscoring the need for improved drug delivery approaches. This study presents the development, characterization and in vivo evaluation of a novel polymeric implant loaded with 5-fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Scanning electron microscopy of FIRINOX implants showed internal microstructure was preserved upon drug loading, while micro-CT and X-ray imaging revealed valuable insights into the morphology and degradation of implants retrieved from in vivo experiments. In murine PDAC models, dose-escalation identified 4 × FIRINOX implants as the maximum tolerated dose, while 2 × implants achieved significant therapeutic efficacy at lower doses than IV administration, without compromising animal safety. In healthy pigs, 20 × FIRINOX implants were well-tolerated, as confirmed by histopathology and blood analysis. Finally, laser ablation-inductively coupled plasma-mass spectrometry imaging and microbiome analysis confirmed localized drug perfusion within tissues, and minimal off-target effects, including preservation of gut microbiota diversity. These findings support the potential of this implantable platform to improve outcomes in borderline or non-resectable PDAC and enhance tolerability of cytotoxic chemotherapy through localized, controlled delivery, addressing a key gap where current treatment options are limited.

Primary aldosteronism (PA) has been linked with reduced health-related quality of life (QoL) and increased prevalence of anxiety and depression. While most studies compared patients with PA to healthy subjects, this study focused on comparison with hypertensive patients without PA to identify PA-specific effects. Furthermore, the impact of targeted therapy on QoL and mental health was evaluated. Mental and physical health-related QoL, anxiety and presence of depressive and panic symptoms were assessed using the SF-12, GAD-7 and PHQ questionnaires in 925 patients with arterial hypertension tested for PA in a prospective, multi-center international prospective cohort study. Questionnaires were assessed at baseline as well as 3-6 months after initiation of targeted therapy. Amongst 833 of 925 patients who completed the necessary diagnostic procedures, 211 were diagnosed with PA. 98 of 116 patients with unilateral PA received unilateral adrenalectomy. At baseline, QoL, anxiety and mental health scores did not differ in patients with PA vs patients with hypertension without PA. At outcome assessment, SF-12 mental and physical component summaries as well as GAD-7 specifically improved in patients with unilateral PA after adrenalectomy (mean Δ = 4.2, p = 0.018, Δ = 3.6, p = 0.038 and Δ = -1.9, p = 0.006, respectively) in contrast to no improvement in patients with PA on MRA treatment. There was no difference in health-related QoL, anxiety and mental health in patients with hypertension with versus without PA. Unilateral adrenalectomy but not medical therapy improved health-related QoL and decreased anxiety in patients with PA.