INTRODUCTION: Glaucoma is a leading cause of permanent blindness, often going undetected in its early, asymptomatic stages, especially in older age groups. In Malaysia, glaucoma is a growing public health issue due to an increase in the ageing population. While screening is essential for early glaucoma detection, the most suitable strategy for Malaysia's healthcare system remains unclear. This study explored the perspectives of eye healthcare professionals on the most suitable glaucoma screening strategies for Malaysia. MATERIAL AND METHODS: This qualitative study used semi-structured interviews with 19 eye health professionals (ophthalmologists, optometrists, nurses, ophthalmic technicians, and assistant medical officers) practicing in the Klang Valley. The interviews were conducted face-to-face in their workplace or via a video conferencing platform. All interviews were recorded, transcribed, and analysed using thematic analysis. RESULTS: Six major themes were identified: types of glaucoma screening programmes, accessible screening locations, target screening population, instruments and use of digital technology, trained personnel, and referral criteria. Opportunistic case finding and population-based programmes were identified as the glaucoma screening programmes in which trained personnel conducted screening at accessible locations. Glaucoma screening for high-risk individuals was recommended, focusing on visual acuity testing, tonometry, anterior chamber angle assessment, funduscopy, perimetry, and retinal nerve fibre assessment. A lack of clear referral criteria due to low awareness and poor implementation of existing guidelines was observed. CONCLUSION: Further investigations are required to identify the best combination of components for glaucoma screening. This will enable policymakers to develop an effective glaucoma screening programme in Malaysia.

Introduction: This study aimed to develop an innovative bilayer tablet formulation of dapagliflozin and vildagliptin to increase therapeutic outcomes and patient compliance in diabetes management. Methods: By employing wet granulation, immediate-release, and sustained-release layers were formulated using various super-disintegrating and release-retarding agents, respectively. Several pre-compression parameters were utilized, such as Carr’s index, Hausner ratio, physical attributes (weight variations, friability, hardness), and disintegration time. Drug-excipient interactions were determined through employing FTIR, SEM, DSC, and TGA. In-vitro dissolution studies were performed to assess the release kinetics of these formulations. Results: For immediate-release dapagliflozin, our earlier study demonstrated that the formulations showed Carr’s index (23.5-33.3), physical attributes (weight (145–155 mg), thickness (4.42 ± 0.04 -4.46 ± 0.05 mm), hardness (3.7-5.6 kg/cm2), friability (<1%), and optimized rapid dissolution (F1: 80.50% ± 5.2 in 30 minutes). For sustained-release vildagliptin, the formulations showed Carr’s index (10.48-20), physical attributes (weight (194-203 mg), thickness (3.32 ± 0.06-3.33±0.04 mm), hardness (4.8 ± 0.1-7.6 ± 0.2 kg/cm2), friability (<1%)), and optimized controlled release (A5: 81.76% ± 2.4 in 360 minutes). The results found that F1 and A5 were the optimum formulation for the immediate release of dapagliflozin, and the sustained release of vildagliptin, respectively, and BT-1 was the optimum bilayer tablet because of its rapid onset of action for dapagliflozin (84.23% within 60 minutes) and sustained release for vildagliptin (80.026% within 360 minutes). Conclusion: Based on these data, the optimized bilayer tablet holds the potential to be a convenient and effective treatment option. Further, in-vivo assays are necessary to confirm its efficacy and safety.

Background: s/Aims: The role of surgery for pancreatic ductal adenocarcinoma (PDAC) with synchronous liver metastases remains controversial. Previous studies assessing the outcomes of combined surgery for primary PDAC and liver metastases have been limited by the inconsistent application of neoadjuvant chemotherapy (NAC). Methods: We identified patients with PDAC and fewer than three liver metastases who received at least six months of NAC and underwent simultaneous pancreas and liver resection between January 2018 and March 2023 at a single institution. Additionally, we queried the National Cancer Database (NCDB) from 2010 to 2019 to identify patients with synchronous metastatic PDAC to the liver who received NAC before simultaneous resection, serving as a comparison group. Results: Ten patients met the inclusion criteria for the institutional case series, with seven ultimately undergoing simultaneous resection. Among 224 patients in the NCDB who underwent simultaneous pancreas and liver resection, 70 patients (31.2%) received NAC.After a median follow-up of 59 months in the institutional cohort, five patients experienced recurrence, resulting in a median disease-free survival of four months (95% confidence interval [CI] 3, not reached). After controlling for confounding factors in the NCDB cohort, the administration of NAC was associated with improved survival (hazard ratio: 0.44, 95% CI 0.29–0.65, p < 0.001) compared to those who underwent upfront surgery. Conclusions Neoadjuvant therapy followed by simultaneous liver and pancreas resection for metastatic PDAC is safe and feasible, and it may provide a survival benefit in carefully selected patient populations.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Introduction: Leydig cells (LCs) are the principal source of testosterone in males, underpinning male reproductive health and androgendependent physiology. Precise isolation of viable human LCs is essential for mechanistic steroidogenesis research and cell-based therapeutic development. Existing protocols rely on density-gradient centrifugation, which is technically demanding and often compromises yield and viability. Here, we describe a simplified density-gradient-free approach using differential adhesion to enrich functional human LCs from testicular tissue. Methodology: Human testicular fragments (~5 mm³) were minced and enzymatically digested with collagenase IV (2 mg/mL) at 37°C for 20 min under gentle agitation (100 RPM). The suspension was filtered (45 µm) and plated onto poly-L-lysine-coated T25 flasks. After 24 hours, non-adherent cells were removed by PBS washing. Viability exceeded 90% by trypan blue exclusion. Cells were maintained in DMEM/F12 with 10% FBS, 1% Antibiotic-Antimycotic, and 10 ng/mL luteinizing hormone (LH) to preserve the mature LC phenotype. Characterization employed immunofluorescence and flow cytometry using antibodies against SF-1, StAR, LHCGR, PDGFRA, and TEM-1. Testosterone secretion was quantified by ELISA under basal conditions and LH-stimulated conditions (10 ng/mL). Results: The protocol yielded ~1.25 × 10⁶ LCs per gram of tissue with >80% purity. Adherent HLCs displayed dense cytoplasmic lipid granules and intercellular networks consistent with active steroidogenesis. Flow cytometry confirmed 84.7% StAR⁺ cells, indicative of a robust steroidogenic population. A distinct progenitor subpopulation (PDGFRα⁺/TEM-1⁺) comprising ~28% of primary cultures, suggests retention of regenerative capacity. Basal testosterone secretion averaged 8.88 ng/mL per 24 hours, confirming preserved functional activity post-isolation. Conclusion This differential-adhesion protocol efficiently isolates functional human LCs without density-gradient media. Multimodal validation integrating immunofluorescence, flow cytometry, and ELISA confirms both phenotypic identity and steroidogenic competence, providing a reproducible and accessible platform for LC research and translational applications in male hypogonadism and androgen replacement.
Leydig Cells

Introduction: Capivasertib is a selective oral AKT inhibitor approved for hormone receptor-positive, HER2-negative advanced breast cancer with AKT pathway mutations. As AKT is integral to insulin signaling, its inhibition predisposes patients to hyperglycemia. We report a case of severe capivasertib-induced hyperglycemia with profound insulin resistance in a non-diabetic patient. Case: A 56-year-old female with metastatic breast cancer (ER/ PR-positive, HER2-negative, AKT1- and ESR1-mutated, TMB-high) presented with severe hyperglycemia following capivasertib initiation. She had no prior diabetes history, with a baseline hemoglobin A1c of 5.6%. Her first cycle (200 mg twice daily, 7 April 2025) was uncomplicated metabolically. The second cycle was escalated to 400 mg twice daily on 21 April 2025. By Day 3, blood glucose rose significantly. Premixed insulin 20 units failed to achieve glycemic control, necessitating intravenous insulin infusion. Despite escalation to 30 units per hour, euglycemia could not be achieved. Notably, there was no biochemical evidence of diabetic ketoacidosis or hyperosmolar hyperglycemic state, and the patient remained hemodynamically stable. No corticosteroids or other contributing medications were administered. Blood glucose normalized spontaneously approximately 36 hours after the last capivasertib dose, and all insulin was weaned and discontinued by 26 April 2025. She remained euglycemic without antidiabetic therapy thereafter. The patient and family opted for palliative care, and she passed away on 6 May 2025. Conclusion Capivasertib can precipitate severe, insulin-resistant hyperglycemia even in non-diabetic patients, without progression to overt hyperglycemic crisis. Spontaneous resolution upon drug cessation supports a direct drugmediated mechanism via AKT-disrupted insulin signaling. Clinicians should monitor glucose closely during therapy and consider drug cessation in refractory cases. Further studies are warranted to guide optimal glycemic management.
capivasertib ; Hyperglycemia ; Insulins

Introduction: Fulvestrant, a selective estrogen receptor degrader widely used in hormone receptor-positive breast cancer, can cause significant analytical interference with estradiol immunoassays due to structural similarity with 17β-estradiol. This interference may result in falsely elevated estradiol measurements, potentially leading to diagnostic confusion and inappropriate clinical interventions. We report a case demonstrating this clinically significant analytical interference and emphasize the importance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in hormone monitoring for patients receiving fulvestrant therapy. Case: A 31-year-old female with metastatic hormone receptorpositive breast cancer receiving combination therapy (fulvestrant, letrozole, ribociclib, and goserelin) presented with inappropriately elevated serum estradiol levels of 566 pmol/L (early follicular phase 200–500 pmol/L), measured by chemiluminescence immunoassay. Despite effective gonadotrophin suppression evidenced by low luteinizing hormone (0.2 IU /L) and follicle-stimulating hormone (4.1 IU/L) levels and clinical amenorrhea, the discordant estradiol elevation raised suspicion of assay interference. Confirmatory testing with LC-MS/MS revealed an estradiol concentration of <36 pmol/L, consistent with expected hormonal suppression and confirming immunoassay cross-reactivity with fulvestrant. The case demonstrates significant fulvestrant interference with estradiol immunoassays, resulting in a greater than 15- fold overestimation compared to LC-MS/MS measurement. The clinical presentation was consistent with effective endocrine therapy, supported by suppressed gonadotropin levels, clinical amenorrhea, and stable disease on imaging. LC-MS/MS provided accurate estradiol measurement, avoiding potential diagnostic confusion and unnecessary clinical interventions. Conclusion Clinicians should be aware of potential fulvestrant interference with estradiol immunoassays when interpreting hormone levels in breast cancer patients. Discordant laboratory findings, particularly elevated estradiol despite clinical evidence of effective hormonal suppression, should prompt consideration of LC-MS/MS confirmation. This case underscores the clinical importance of analytical method selection in hormone monitoring and highlights the need for improved laboratory-clinical communication to optimize patient care in oncology practice.
Fulvestrant ; Immunoassay

Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol abundant in green tea, has garnered significant attention for its diverse therapeutic applications, ranging from antioxidant and anti-inflammatory effects to potential anticancer properties. Despite its immense promise, the practical utilization of EGCG in therapeutic settings as a medication has been hampered by inherent limitations of this drug, including poor bioavailability, instability, and rapid degradation. This review comprehensively explores the current challenges associated with the application of EGCG and evaluates the potential of nanoparticle-based formulations in addressing these limitations. Nanoparticles, with their unique physicochemical properties, offer a platform for the enhanced stability, bioavailability, and targeted delivery of EGCG. Various nanoparticle strategies, including polymeric nanoparticle, micelle, lipid-based nanocarrier, metal nanoparticle, and silica nanoparticle, are currently employed to enhance EGCG stability and pharmacological activity. This review concludes that the particle sizes of most of these formulated nanocarriers fall within 300 nm and their encapsulation efficiency ranges from 51% to 97%. Notably, the pharmacological activities of EGCG-loaded nanoparticles, such as antioxidative, anti-inflammatory, anticancer, and antimicrobial effects, are significantly enhanced compared to those of free EGCG. By critically analyzing the existing literature and highlighting recent advancements, this article provides valuable insights into the promising prospects of nanoparticle-mediated EGCG formulations, paving the way for the development of more effective and clinically viable therapeutic strategies.
Animals ; Humans ; Anti-Inflammatory Agents/administration & dosage* ; Antineoplastic Agents/administration & dosage* ; Antioxidants/administration & dosage* ; Biological Availability ; Catechin/analogs & derivatives* ; Micelles ; Particle Size ; Nanoparticle Drug Delivery System/chemistry*

Epigallocatechin-3-gallate (EGCG), a prominent plant-based catechin predominantly derived from Camellia sinensis and widely available on the market as a health supplement, has garnered significant attention for its potential therapeutic benefits, particularly in the context of type 2 diabetes mellitus (T2DM). This review explores the multifaceted role of EGCG in addressing the "ominous octet"-the 8 core pathophysiological defects associated with T2DM. The literature search was carried out using key terms "EGCG" OR "epigallocatechin-3-gallate" OR "epigallocatechin gallate" AND "diabetes" OR "insulin resistance" OR "hyperglycemia" in the PubMed and Scopus databases. The search was constrained to articles published between January 2018 and April 2024, focusing on the document type. Full-text articles published in English and relevant to EGCG that featured a single active ingredient, included clearly explained diabetes relief mechanism, and included ominous octet aspects were included in the final review. The outcomes of the included studies were reviewed and categorized based on 8 core pathophysiological defects, collectively referred to as the ominous octet in T2DM. This review concludes that EGCG is a potent hypoglycemic agent that has beneficial effects against the ominous octet in addition to its pharmacological activities in modulating gut microbiota dysbiosis, carbohydrate digestion and metabolism, glucose transporter-mediated intestinal glucose-uptake, endothelial dysfunction, and renal damage that are significantly associated with pathogenesis of T2DM. This extensive scientific evidence suggests that EGCG may offer a novel approach to traditional antidiabetic therapies, potentially improving glycemic control and mitigating complications associated with T2DM. The inhibitory effects of EGCG on sodium-glucose transport proteins and their role in reducing renal glucose reabsorption remain unexplored, highlighting a significant research gap. Future research should also aim to broaden the scope by investigating the "egregious eleven," which comprise a more comprehensive range of diabetic pathophysiological features. This review underscores the therapeutic promise of EGCG for managing T2DM and encourages ongoing research to fully elucidate its clinical applications. Please cite this article as: Wong CN, Lim YM, Liew KB, Chew YL, Chua AL, Lee SK. A review on mechanistic actions of epigallocatechin-3-gallate in targeting the ominous octet of type 2 diabetes mellitus. J Integr Med. 2025; 23(4): 344-356.
Diabetes Mellitus, Type 2/physiopathology* ; Humans ; Catechin/therapeutic use* ; Hypoglycemic Agents/therapeutic use* ; Animals ; Insulin Resistance

OBJECTIVE

Previous studies have indicated that clinical hypogonadism is common among males with type 2 diabetes mellitus (T2DM). However, the reported prevalence varies due to the diverse diagnostic criteria used in these studies. This study aims to determine the prevalence of clinical hypogonadism among Malaysian T2DM males and their associated factors.

A total of 360 participants who fulfilled the inclusion criteria were included in this study. Their socio-demographic and clinical parameters were documented and a total testosterone level was sampled from a morning fasting serum. Patients with serum total testosterone of 8-12 nmol/L had their serum total testosterone repeated and their symptoms assessed with the Aging Male Symptoms (AMS) scale. Clinical hypogonadism was diagnosed with total testosterone 26.

The prevalence of clinical hypogonadism among Malaysian T2DM males was 17.5% (n = 63), with 55.6% of them having hypogonadotropic hypogonadism. There is a significant association between clinical hypogonadism with waist circumference > 94 cm (p < 0.001), obesity (p < 0.001), hypertension (p = 0.010), coronary artery disease (p = 0.014) and peripheral artery disease (p = 0.022). There is a significant difference in the weight (p = 0.001), BMI (p < 0.001), waist circumference P < 0.001), serum HDL-C levels (p < 0.001), serum triglycerides levels (p = 0.001) and serum TyG index (p < 0.001). Diabetic males with increasing age (adjusted OR = 1.070, 95% CI 1.004-1.146, p = 0.038), presence of coronary artery diseases (adjusted OR = 2.08, 95% CI 1.220-10.219, p = 0.020) and low total testosterone (adjusted OR = 2.451, 95% CI 1.908-3.155, p < 0.001) are at higher risk of developing clinical hypogonadism.

This study is the first in the Asian region to use stricter criteria for diagnosing hypogonadism. Despite these stringent criteria, the prevalence of hypogonadism remains significantly high among Malaysian T2DM males. It is particularly common in diabetic males over 35 years old with coronary artery disease, regardless of A1c control and the duration of diabetes.