👤 Han W Tun

Apolipoprotein B [apoB] and lipoprotein(a) [Lp(a)] concentrations are the two prime lipoprotein indices recommended by some expert consensus to assess and manage cardiovascular risk. However, their distributions, associations, inter-relationships, and clinical relevance remain un-investigated in the majority of Asian populations, particularly among healthcare workers. The distributions and relationships of serum Lp(a), apoB, and other lipid biomarker concentrations in 1,927 Asian consenting healthcare workers across ethnicities, sexes, and body mass index (BMI) were analysed. The percentage of apoB content of Lp(a) relative to apoB particle concentrations (Lp(a)-to-apoB proportion) was calculated. Participants’ mean age was 39.4 years, mostly females (79.7%). Ethnicities were Chinese (57.2%), Malay (16.9%), Indian (9.2%), Filipino (12.8%) and others (3.8%). Distribution of Lp(a) was positively skewed to the right for all ethnicities. The median Lp(a) was 16.4 nmol/L (IQR 7.9, 41.8) and ranged between < 7 to 470 nmol/L. The proportion of participants with Lp(a) ≥ 75 nmol/L was 13.9%, and with Lp(a) ≥ 125 nmol/L was 7.8%. Multivariable linear regression analysis showed that being female, older age, and Indian ethnicity were associated with higher Lp(a) levels, whereas being male, older age, Indian ethnicity, and higher BMI were associated with higher mean apoB levels. In this cohort, 11.4% of individuals had Lp(a)-to-apoB proportion > 5%, whilst 3.3% had Lp(a)-to-apoB proportion of > 10%. Among individuals with Lp(a) ≥ 250 nmol/L, the median Lp(a)-to-apoB proportion was 14.9% (IQR 12.6,19.7). Across Lp(a) deciles, the Lp(a)-to-apoB proportions were inversely correlated with LDL-C, non-HDL-C, remnant cholesterol, and triglyceride concentrations. Abnormal Lp(a) (≥ 75 nmol/L) was found in 13.9% of a predominantly female Asian healthcare cohort. In individuals with Lp(a) ≥ 250 nmol/L, Lp(a) particles contributed to the circulating apoB levels by a median of 15%. These findings support the notion that Lp(a) should be integrated into routine lipid assessment in Asian populations, including healthcare workers. clinicaltrial.gov NCT06304415. The online version contains supplementary material available at 10.1186/s12944-026-02912-7. Show less

In early childhood, individuals with Prader-Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: "PWS" AND "therapy" OR "[drug name]"; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long-term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off. Show less

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is usually diagnosed based on the presence of immature lymphoid marker terminal deoxynucleotidyl transferase (TdT), and T-cell specific markers, specifically CD3, by immunohistochemistry (IHC) staining on bone marrow and/or extramedullary tissue. We present a novel, TdT and CD3 negative, aggressive early T-cell precursor LBL (ETP-LBL) initially misdiagnosed as a high grade B-cell lymphoma due to expression of CD79a and the erroneous detection of BCL2/IGH fusion. The patient was eventually evaluated using molecular diagnostic techniques, including fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) assays that demonstrated PICALM-MLLT10 fusion and a NOTCH1 mutation in the absence of BCL2/IGH fusion. The use of NGS, specifically mate-pair sequencing (MPseq), subsequently confirmed an in-frame PICALM-MLLT10 fusion. Our retrospective analysis showed that PICALM-MLLT10 fusion has no association with CD3/TdT negativity, as 6/49 T-ALL/LBL cases from Mayo Clinic database (01/1998-09/2018), including this case, were noted to have PICALM-MLLT10 fusion; however, none of the other cases were associated with CD3/TdT negativity. We emphasize the importance of a comprehensive hematopathologic evaluation including multiple molecular studies for the appropriate interrogation and classification of a difficult acute leukemia diagnosis, and to prevent potential diagnostic errors of clinical significance. Show less