Bumrungrad International Hospital

Article 1: Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here, we report a screen for de novo mutations in patients with 2 classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in 4 patients, and ALG13, with the same de novo mutation in 2 patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR, and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders. Article 2: Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here, we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate 7 individual genes, 3 gene sets and 4 copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies and generalized and focal epilepsies, whereas most other gene discoveries are subtype specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single-nucleotide/short insertion and deletion variants, copy number variants and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies. Article 3: Background: The epilepsies are highly heritable conditions that commonly follow complex inheritance. While monogenic causes have been identified in rare familial epilepsies, most familial epilepsies remain unsolved. We aimed to determine (1) whether common genetic variation contributes to familial epilepsy risk, and (2) whether that genetic risk is enriched in familial compared with nonfamilial (sporadic) epilepsies. Methods: Using common variants derived from the largest epilepsy genome-wide association study, we calculated polygenic risk scores (PRS) for patients with familial epilepsy (n = 1818 from 1181 families), their unaffected relatives (n = 771), sporadic patients (n = 1182), and population controls (n = 15,929). We also calculated separate PRS for genetic generalized epilepsy (GGE) and focal epilepsy. Statistical analyses used mixed-effects regression models to account for familial relatedness, sex, and ancestry. Findings: Patients with familial epilepsies had higher epilepsy PRS compared to population controls (OR 1·20, padj = 5 × 10-9), sporadic patients (OR 1·11, padj = 0.008), and their own unaffected relatives (OR 1·12, padj = 0.01). The top 1% of the PRS distribution was enriched 3.8-fold for individuals with familial epilepsy when compared to the lowest decile (padj = 5 × 10-11). Familial PRS enrichment was consistent across epilepsy type; overall, polygenic risk was greatest for the GGE clinical group. There was no significant PRS difference in familial cases with established rare variant genetic etiologies compared to unsolved familial cases. Interpretation: The aggregate effects of common genetic variants, measured as PRS, play an important role in explaining why some families develop epilepsy, why specific family members are affected while their relatives are not, and why families manifest specific epilepsy types. Polygenic risk contributes to the complex inheritance of the epilepsies, including in individuals with a known genetic etiology.

324 Background: Multidisciplinary Tumor Boards (MTBs) are integral to quality cancer care, promoting evidence-based treatment through collaborative decision-making. While benefits are well established in Western settings, data from Southeast Asian tertiary hospitals serving diverse patients remain limited. This study evaluates the impact of a comprehensive tumor board program at a private tertiary hospital in Bangkok, Thailand. Methods: A retrospective review was conducted of all cases discussed at institutional tumor boards from January 2021–December 2025. The program includes four boards: Multidisciplinary Tumor Boards (MDT), Molecular Tumor Boards (MTB), Bumrungrad Lung Cancer Consortium (BLCC), and Palliative Oncology Tumor Board (POTB). Data included patient demographics, cancer type, stage, board category, treatment recommendations, compliance, and reasons for non-compliance. Tumor board impact was classified as no change, assisted treatment decision, altered treatment, further diagnostic workup, or de novo treatment planning. Results: A total of 1,391 cases were reviewed over five years. The population comprised 55% international patients, 32% Thai nationals, and 13% expatriates. Major malignancies were lung (20.9%), breast (10.7%), colon (7.1%), hepatobiliary (6.2%), rectal (4.7%), prostate (4.2%), and pancreatic (4.2%) cancers, with over 60 cancer types represented. Most cases were stage IV (54.2%) or stage III (10.1%). Distribution by board: MDT 75.5%, MTB 18.2%, BLCC 3.6%, and POTB 2.7%. Annual utilization was consistent (212–313 cases/year). Among 171 evaluable cases, tumor board impact showed clinical significance—38.6% led to actionable changes: altered treatment (7.0%), aided decisions (14.0%), or required further diagnostics (17.0%); 0.6% were fully directed by board recommendations. No change was noted in 61.4%, validating prior management. Compliance with recommendations was high (87.1%). Among non-compliant cases (12.9%), main reasons were loss to follow-up (69.5%), treatment elsewhere (13.8%), management abroad (3.4%), and refusal of proposed treatment (6.3%). Conclusions: This 5-year analysis demonstrates that a structured tumor boards in a Southeast Asian tertiary setting enhance multidisciplinary decision-making, influencing management in nearly 40% of cases and achieving strong treatment compliance. Specialized tumor boards (molecular, lung consortium, palliative) complement general MDT functions, addressing complex genomic, disease-specific, and end-of-life care needs. Non-compliance was mainly patient related factor rather than disagreement with recommendations. These findings support the value of comprehensive MTBs in Southeast Asian tertiary care settings managing diverse cancer populations with high disease burden and rare cancers.

[This corrects the article DOI: 10.3389/fcimb.2026.1751074.].

BackgroundCOVID-19 has been associated with persistent metabolic disturbances; however, the magnitude, consistency, and underlying mechanisms of post-infection alterations in glucose regulation remain incompletely characterized.MethodsWe conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. PubMed and Embase were searched on December 18, 2024, for studies published from 2020 onward. Eligible studies included observational cohort and cross-sectional designs assessing metabolic outcomes at least three months after recovery from COVID-19.ResultsSixteen studies met inclusion criteria. Pooled analysis suggested a 41% increased risk of new-onset diabetes among COVID-19 survivors compared with non-infected individuals (RR 1.41, 95% CI: 1.38–1.44); however, this estimate was predominantly driven by a single large-scale study. Quantitative synthesis demonstrated higher HbA1c (SMD 1.44, 95% CI: 0.36–2.52) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD 0.96, 95% CI: 0.33–1.58), consistent with impaired glycemic control and increased insulin resistance. In contrast, fasting blood glucose (FBG) findings were inconsistent and highly heterogeneous (SMD 0.77, 95% CI: −0.40–1.94). Substantial heterogeneity was observed across outcomes.ConclusionCOVID-19 may be associated with an increased risk of incident diabetes and persistent metabolic dysregulation. However, the limited number of studies contributing to pooled risk estimates and the influence of large registry-based data warrant cautious interpretation. These findings support consideration of metabolic monitoring and longitudinal follow-up in post-COVID care, particularly among individuals at elevated cardiometabolic risk.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42025630971.