Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening condition that remains under-recognised in Malaysia. Although disease-modifying therapies are available, their high cost and limited accessibility contribute to delays in diagnosis, compounded by gaps in clinical awareness, differences in diagnostic tool availability and disparities in healthcare resources. While international guidelines offer a comprehensive framework for diagnosing and managing ATTR-CM, local adaptation is essential to ensure their relevance and feasibility within the Malaysian healthcare system. This expert consensus provides practical, locally relevant recommendations to assist Malaysian clinicians in the timely identification and management of ATTR-CM. A multidisciplinary panel of clinicians from cardiology, haematology, nuclear medicine and other related specialties convened to develop tailored recommendations for national practice, drawing on international guidance, current evidence and local clinical practices. The guidance outlines key clinical features to raise early suspicion, proposes a diagnostic algorithm adaptable to different levels of care and offers recommendations on appropriate use of diagnostic tests-including imaging, laboratory investigations, tissue biopsy, and genetic testing when indicated-while emphasising the distinction between ATTR-CM and amyloid light chain amyloidosis, optimising non-invasive diagnostic approaches and fostering multidisciplinary collaboration across the care continuum. These consensus recommendations aim to enhance diagnostic accuracy, reduce variability in clinical practice and support earlier identification of ATTR-CM. By bridging global standards with local healthcare practices, this guidance equips clinicians to deliver timely, effective care for an underdiagnosed and often overlooked condition.

Epidemiological studies have shown that lower activity of the cholesteryl ester transfer protein (CETP) correlates with reduced Alzheimer's disease (AD) risk. While small-molecule CETP inhibitors like evacetrapib have previously been assessed for cardiovascular diseases, their involvement in AD has not been investigated. Here, we establish CETP as a novel pharmacological target for AD treatment. Using CETP transgenic mice crossed to a mouse model of amyloidosis and administering evacetrapib, we provide evidence that CETP inhibition maintained memory independent of classic AD markers, likely through maintained vascular health, while increasing hippocampal cholesterol and altering plasma lipoproteins. Using proteomic data of cerebrospinal fluid (CSF) from cognitively unimpaired individuals at risk for AD in the PResymptomatic EValuation of Experimental or Novel Treatments for AD (PREVENT-AD) cohort, we confirm that our mouse model reflects physiological changes in pre-symptomatic human subjects. We propose the repurposing of CETP inhibitors as an effective therapeutic strategy to delay or prevent cognitive impairment in AD.

This review examines cardiovascular complications of multiple myeloma and anti-myeloma therapy, emphasising integrated systems-based cardiovascular management and the institutional model developed at the University College London Hospital Cardio-Oncology (CO) Centre of Excellence.

A 74-year-old man presented with leg edema and was found to have nephrotic-range proteinuria. Renal biopsy revealed AL amyloidosis. Subsequent bone marrow examination demonstrated an increase in monoclonal plasma cells accounting for 13% of nucleated cells. Right-sided pleural effusion developed and was confirmed to be chylothorax. Although treatment with daratumumab, lenalidomide, and dexamethasone (DLd regimen) was initiated, the pleural effusion continued to increase. Lymphangiography using ethiodized oil identified a leakage point in the anterior mediastinum. A chest drain was inserted on the following day, and approximately 4 l of chylous fluid was drained. The tube was removed one week later, and pleural effusion did not recur thereafter. Although a hematologic response was achieved, the nephrotic syndrome persisted, and the patient ultimately died. Chylothorax associated with AL amyloidosis is rare and difficult to treat. This case suggests that lymphangiography using ethiodized oil may be both diagnostic and therapeutic.

The optimal choice between sedating histamine H1 antagonists (sAHs) and non-sedating histamine H1 antagonists (nsAHs) for preventing infusion-related reactions (IRRs) during daratumumab subcutaneous (DARA-SC) therapy remains unclear. Here, we aimed to compare the efficacy and safety of nsAH and sAH as premedication for DARA-SC therapy. Patients with multiple myeloma or light-chain amyloidosis who received DARA-SC therapy at eight hospitals were enrolled in this prospective, multicenter, observational study. Patients were categorized into nsAH and sAH groups based on their premedication. IRRs and drowsiness were assessed using patient-reported questionnaires, including the Stanford Sleepiness Scale (SSS) and the Japanese Epworth Sleepiness Scale (JESS), at baseline, post-administration (Q2), and before bedtime (Q3). Overall, 104 patients (nsAH, n = 49; sAH, n = 55) were analyzed. No significant differences were observed in the IRR incidence between the nsAH and sAH groups at Q2 (8.2 vs. 9.1%) or Q3 (13 vs. 17%). Conversely, the incidence of new-onset drowsiness at Q2 was significantly lower in the nsAH group (13%) than in the sAH group (32%, p < 0.05). Additionally, the increase in SSS from baseline to Q2 was significantly lower in the nsAH group than in the sAH group (p < 0.05). No significant differences were observed in JESS scores. Thus, nsAH was associated with reduced early post-administration drowsiness and there were no statistically significant differences in IRR preventive effects compared to that for sAH, suggesting that nsAH may reduce sedation without a significant increase in the incidence of IRRs; however, these hypothesis-generating findings warrant verification through future prospective comparative trials.

Tracheobronchial amyloidosis (TBA) is an extremely rare and localized form of amyloidosis. Effective curative therapies for amyloidosis are lacking, and no standardized guidelines exist. Here, we report a 64-year-old female with a 20-year history of Sjögren's syndrome (SS) and 30-year history of type 2 diabetes mellitus (T2DM) who presented with progressive dyspnea. Chest computed tomography (CT) revealed tracheal and bronchial stenosis. Bronchoscopy showed submucosal nodular shadows and luminal narrowing, initially suspected as lung cancer. Biopsy confirmed TBA. Bronchoscopic interventions including argon plasma coagulation (APC) and mechanical debulking alleviated symptoms. Three-month follow-up showed significant improvement. This case highlights diagnostic challenges of TBA due to nonspecific manifestations and underscores the importance of considering TBA in SS patients with airway lesions. Congo red staining remains the diagnostic gold standard.

Proteolysis, the irreversible, hydrolytic cleavage of peptide bonds by proteases, is essential for life. The plasminogen system, one of the central proteolytic systems, regulates diverse physiological pathways, including fibrinolysis, inflammation, wound healing, and tissue remodelling. Beyond its proteolytic functions, the plasminogen system serves as a hub for crosstalk to maintain homeostasis. Yet, its dysregulation, misuse, or hijacking by pathogens can drive pathologies such as hereditary disorders, tumour dissemination, bacterial invasion, and viral priming. This review explores its evolution, structural aspects, activation mechanisms, regulatory pathways, and pharmacological modulation of the plasminogen system, synthesising decades of research with recent advances. We highlight the multifaceted nature of the plasminogen system-as both a guardian of physiological balance and a potential driver of disease-and discuss its components as therapeutic targets and tools.

AL amyloidosis is characterized by extracellular deposition of immunoglobulin light-chain fibrils, frequently leading to kidney involvement and progressive organ dysfunction. We report a case of kidney AL amyloidosis secondary to multiple myeloma in which daratumumab-based chemotherapy combined with autologous peripheral blood stem cell transplantation resulted in marked improvement, as confirmed by sequential kidney biopsy. The initial biopsy revealed vascular-dominant amyloid deposition, whereas the second biopsy obtained 2 years later demonstrated a marked reduction in amyloid burden, particularly within the vascular compartments. This histopathological improvement corresponded with hematologic remission and stabilization of kidney function. The observed reduction in tissue amyloid deposits was presumed to result from suppression of amyloidogenic light chains, leading to inhibition of new fibril formation and subsequent tissue remodeling. Our findings provide direct pathological evidence that daratumumab-based combination therapy, through immune-mediated plasma cell depletion, may indirectly promote the regression of amyloid deposits and contribute to functional recovery.

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