Publications by Year: 2026

Through a multidisciplinary quality improvement initiative, the Pre-Immunosuppression (Pre-IS) Clinic was created at a tertiary referral institution to ensure appropriate vaccination and infectious disease screening for patients on immunosuppressive medications. Consensus guidelines on immunisation and infectious disease screening for immunosuppressed patients were created through a multidisciplinary committee. The guidelines included three sections: (1) screening recommendations for chronic/latent infections prior to immunosuppression, (2) immunisation recommendations for immunosuppressed patients and (3) recommendations for household contacts of immunosuppressed patients. The workflow to the Pre-IS Clinic was optimised. We present the vaccination guidelines and workflow as an effective example of a multidisciplinary qualitive improvement initiative.

BACKGROUND: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.

METHODS: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences in Stroke) study to identify common, rare, and structural variants associated with NT-proBNP levels. The main outcome of the study was rank-based inverse normal and standardized NT-proBNP levels. Genetic associations with NT-proBNP were examined, followed by gene prioritization, transcriptome-wide association studies, colocalization, and rare variant analyses.

RESULTS: Nine novel loci and 3 previously reported loci were identified to be associated with NT-proBNP levels. Novel structural variants were detected across 12 loci. Similar effect sizes were observed for both common and rare variants. Key genes such as BAG3 (10q26.11) and SLC39A8 (4q24) were identified through gene prioritization, with prior animal models supporting their therapeutic relevance. Rare variant analysis identified 6 masks with significant associations, specifically non-coding masks, suggesting regulatory modulation of NT-proBNP.

CONCLUSIONS: This study identifies novel common, rare, and structural variants associated with NT-proBNP levels, highlighting the contribution of both coding and regulatory non-coding variation. These findings advance our understanding of the genetic architecture of NT-proBNP and may inform future cardiometabolic therapeutic strategies.

Collagenous gastritis (CG) is a rare disease characterized by thick bands of subepithelial collagen within the stomach that presents with symptoms ranging from anemia to vomiting. Its etiology is poorly understood, and currently, there are no well-defined effective treatment options. We collected gastric and duodenal biopsies from seven patients with CG and several matched controls. Flow cytometry, histopathology, and single-cell RNA-seq (scRNA-seq) and T cell receptor (TCR)-sequencing were performed on samples to understand immune mechanisms underlying CG. Patients with CG had reduced parietal cells and enhance expression of collagen genes by fibroblasts. We identified a population of activated/exhausted lymphocytes, with increased CD4:CD8 ratios and decreased tissue-resident T cells in patients with CG compared to controls. We identified potential therapeutic targets, including integrin α4 expression (ITGA4), indicative of mucosal homing. Preventing activated T cells from entering the gastric mucosa through blockade of integrin α4 may be a useful therapeutic target for patients with CG.

Background/Objectives: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children, especially during infancy, resulting in substantial morbidity and mortality. Methods: Acknowledging the real-world evidence on RSV immunization, the College of Pediatrics, Academy of Medicine of Malaysia, has appointed an expert panel to develop a position paper on recommendations for infant and/or maternal vaccination against childhood RSV, specifically in the Malaysian context with year-round RSV activity. Results: Recognizing the potential constraints and limitations in the implementation process, the expert panel recommends targeted immunization with long-acting RSV monoclonal antibody (mAb) for high-risk infants as a pragmatic first step, with subsequent scale-up to universal immunization of infants when resources permit. Conclusions: Immunization is the most effective strategy to prevent RSV-related lower respiratory tract infection in childhood. Year-round maternal vaccination between 28 and 36 weeks' gestation, combined with immunization at six months for all infants, may potentially circumvent the unclear seasonality.

Background/Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exhibit neuroprotective properties in preclinical models of Alzheimer's disease (AD), reducing amyloid accumulation, neuroinflammation, and insulin resistance within the brain. However, clinical evidence regarding their cognitive effects in AD and mild cognitive impairment (MCI) remains inconclusive. To evaluate the effects of GLP-1 RAs on cognitive outcomes in patients with AD or MCI due to AD. Methods: A systematic review was conducted according to PRISMA 2020 and registered in PROSPERO (CRD420251143171). Although the original registry was broad, the identification of a small set of homogeneous randomized controlled trials (RCTs) during screening, prior to data extraction, allowed for a random-effects meta-analysis of cognitive outcomes. RCTs enrolling adults with clinically or biomarker-confirmed AD or MCI were included. Interventions comprised liraglutide or exenatide compared with placebo. Standardized mean differences (SMD) in global cognitive scores were pooled using a random-effects model (restricted maximum likelihood [REML] estimator with Hartung-Knapp adjustment). Results: Three randomized trials (n = 278 participants; 51% women; mean age 68 ± 7 years) met inclusion criteria. Treatment duration ranged from 26 weeks to 18 months. Pooled analysis revealed no significant effect of GLP-1 RAs on global cognition compared with placebo -0.21 (95% CI -0.81 to 0.38; I2 = 47%; τ2 = 3.77). Sensitivity analyses restricted to liraglutide or studies ≥ 12 months yielded similar results. Conclusions: Current randomized evidence does not support cognitive improvement with GLP-1 RAs in AD or MCI.

Background: Tumor-associated neutrophils (TANs) exhibit remarkable functional plasticity within tumor microenvironment (TME), with N1-like subtypes promoting anti-tumor immunity and N2-like subtypes facilitating tumor progression. Despite their critical role in cancer immunology, strategies to selectively modulate TAN polarization remain limited. Methods: We integrated transcriptomic analyses of TAN subtypes to identify potential hub molecules. Molecular docking and experimental assays were used to evaluate DHA's effect on neutrophil-like cell polarization. Results: Hub genes (TNF, IL1B, PTGS2, BCL2A1, MSR1, ACOD1, CXCL16, CLEC10A, and SOCS3) were identified, with TNF serving as a potential core regulator. Molecular docking indicated that DHA forms stable interactions hub proteins. Experimentally, DHA treatment of neutrophil-like dNB4 cells promoted N1 polarization, evidenced by upregulation of TNF, IL1B, PTGS2, BCL2A1, MSR1, ACOD1, CXCL16, and N1 markers PD-L1 and NOX2, and downregulation of N2 marker CEACAM8 and hub genes CLEC10A and SOCS3. Functional assays demonstrated that DHA-treated cells exhibited increased secretion of TNF, IL1β, ROS, and PD-L1, accompanied by enhanced cytotoxic activity against hepatocellular carcinoma cells in a co-culture system. Conclusions: These findings reveal the molecular mechanisms underlying TAN polarization, and establish DHA as a potent immunomodulatory agent capable of reshaping TANs toward an anti-tumor phenotype.

Background: Bloating, gas, and abdominal discomfort are common in healthy individuals but lack effective interventions. Probiotics can alleviate some gastrointestinal (GI) symptoms; however, evidence for their impact on bloating, gas and abdominal discomfort in otherwise healthy populations remains limited. Mechanistic studies suggest that synbiotics may influence the underlying mechanisms of bloating, including increased gas production, impaired gut motility, and visceral hypersensitivity, but there is a paucity of data from large trials evaluating clinical outcomes. Accordingly, we evaluated the effects of a multi-species synbiotic on GI symptoms. Methods: In a randomized, double-blind, placebo-controlled, decentralized trial, participants (n = 350) with self-reported bloating/indigestion received either a multi-species synbiotic (53.6 billion AFU multi-species probiotic and 400 mg pomegranate extract; DS-01) or placebo daily for 6 weeks. Outcomes included GI quality-of-life (DQLQ), bloating and gas (PROMIS-GI 13a), abdominal discomfort (PROMIS-GI 5a), constipation, regularity, mood-related symptoms, and safety. Results: The multi-species synbiotic improved GI quality-of-life compared to placebo (0.80 vs. 1.20; p < 0.05) at Week 6. Bloating and gas were reduced in the synbiotic arm compared to placebo (16.0 vs. 21.0; p < 0.01), with more participants reporting never/rarely bloating (72.3% vs. 55.9%; p < 0.001). Abdominal discomfort also decreased (8.0 vs. 10.0; p < 0.01). Additionally, there was a statistically significant improvement in constipation symptoms and regularity in the synbiotic arm relative to placebo. Conclusions: Daily supplementation with this multi-species synbiotic significantly improved GI quality-of-life, bloating, gas, abdominal discomfort, and bowel habits. This is the first synbiotic to demonstrate meaningful improvements in bloating and gas in a generally healthy, diverse, real-world population.

BACKGROUND: The role of lipid profiles in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) remains largely unexplored. This study aimed to identify lipid profile variations across geospatial lung lesions, their reflection in serum relative to disease severity and their diagnostic discriminative ability using lipidomic analysis.

METHODS: Lipidomics was performed using hydrophilic interaction liquid chromatography-tandem mass spectrometry on lung tissues and serum samples. 960 lipid species were analysed across geospatial lung lesions (cavity wall, centre of cavity, granuloma, bronchiectasis and normal lungs) and assessed in serum according to disease severity. Python-based machine-learning models in PyCaret were used to classify NTM-PD based on lipidomic signatures.

RESULTS: This study included 23 lung specimens from seven patients with NTM-PD and 332 serum samples comprising 134 patients with NTM-PD, 136 with non-NTM bronchiectasis and 62 healthy controls. Triacylglycerol (TG) levels were elevated in lung lesions affected by NTM-PD, particularly in the centre of the cavity. In serum, TG levels were higher in patients with NTM-PD than controls but decreased in patients with more severe disease, including those with acid-fast bacilli smear positivity, cavitation or higher BACES (body mass index, age, cavity, erythrocyte sedimentation rate and sex) scores. The top five models, developed using lipid species characteristically altered in NTM-PD, effectively discriminated patients with NTM-PD from healthy controls.

CONCLUSION: TG levels were elevated in lung lesions affected by NTM-PD but decreased in serum as disease severity increased, suggesting TG accumulation in lung tissues. These findings highlighted the role of lipid metabolism in the pathogenesis of NTM-PD.

Treatments for secondary and tertiary hyperparathyroidism (SHPT/THPT) remain significant challenges in patients with end-stage renal disease. Thermal ablation (TA) has emerged as a minimally invasive, safe, and effective alternative to surgical resection (SR). However, technical variations and a lack of standardization have limited its widespread adoption. To address these challenges, an international expert panel developed consensus recommendations using a modified Delphi method, integrated with a systematic literature review. As a result, sixteen recommendations were formulated, addressing diagnosis, preoperative preparation, technical procedures, postoperative management, follow-up strategies, efficacy assessment, and complications associated with TA for SHPT/THPT. These recommendations aim to promote standardized treatment protocols, improve procedural safety, and provide evidence-based guidance for clinical practice and future research in ultrasound-guided TA for SHPT/THPT management.