Thanh Van Ta

Background/Objectives: Host genetic variation contributes to the heterogeneous clinical outcomes of coronavirus disease 2019 (COVID-19), yet evidence from Southeast Asian populations remains limited. Methods: We investigated host genetic factors associated with COVID-19 severity in Vietnamese patients infected with the SARS-CoV-2 Delta variant using whole-exome sequencing. A total of 48 unvaccinated patients were enrolled. During sample-level quality control, one sample was excluded because the genetically inferred sex was discordant with the information recorded in the clinical medical record, leaving 47 samples (23 severe/critical and 24 mild/asymptomatic) for downstream genetic analyses. Gene-based association analysis was performed using MAGMA, followed by functional enrichment and interaction network analyses with Metascape and GeneMANIA. Results: Population structure analysis showed that the study participants clustered closely with the East Asian (EAS) reference population. No individual variant reached the prespecified multiple-testing-adjusted threshold, and no gene-level association survived Benjamini–Hochberg correction. Using a nominal MAGMA gene-based p < 0.01 threshold solely for exploratory prioritization, 44 genes were selected for downstream functional analyses. Functional enrichment highlighted RNA processing and mRNA maturation, together with mitochondrial, metabolic, immune-regulatory, and cellular homeostasis pathways. Network topology analysis further identified several highly connected genes, including CPSF4, MRPS34, ATP5MF, BUD31, SNRPD3, and HDAC1. Conclusions: These hypothesis-generating findings are consistent with a potentially polygenic contribution to severe COVID-19 and provide an exploratory systems-level framework for understanding host genetic susceptibility in the Vietnamese population, while identifying biologically plausible candidate genes and pathways for future validation.

Objectives: This study aimed to assess the effectiveness of the COVID-19 vaccine on the outcomes of patients in three hospitals in Vietnam. Methods: An observational study involved 3102 confirmed COVID-19 patients from Vietnam. Participants were classified into unvaccinated, partially vaccinated (one dose) (PV), fully vaccinated (two doses) (FV), and boosted (three doses) groups. We used a regression model to assess the relationship between vaccine status and disease outcome, including mortality, persistent symptoms after treatment, and hospital duration. Results: The proportions of unvaccinated, PV, FV, and boosted groups were 43.39%, 4.63%, 43.93%, and 8.05%, respectively, and 48% of the participants had at least one comorbidity. The proportion of severe clinical disease was significantly higher in the unvaccinated compared with the vaccinated. Biomarkers of cellular injury and organ failure, e.g., aspartate aminotransferase (AST), ferritin, troponin T, proBNP, D-dimer, and urea plasma concentration were significantly higher in unvaccinated and PV patients compared with FV and boosted patients. Age was the most crucial predictor of critical illness, followed by vaccine status, hypertension, diabetes, heart disease, and chronic kidney disease. The unvaccinated group had the highest proportion of deaths (5.2% vs. 1.4% and 0.3% in FV and boosted groups, respectively). Conclusions: Vaccination reduced mortality and both hospitalization length and disease severity in COVID-19 survivors, especially the older and patients with chronic comorbidities.

Background and Objectives: Hyperornithinemia–hyperammonemia–homocitrullinuria syndrome (HHH; OMIM 238970) is one of the rare urea cycle disorders. Ornithine carrier 1 deficiency causes HHH syndrome, characterized by failure of mitochondrial ornithine uptake, hyperammonemia, and accumulation of ornithine and lysine in the cytoplasm. The initial presentation and time of diagnosis in HHH highly varies. Genetic analysis is critical for diagnosis. Materials and Methods: This study encompassed retrospective and prospective analyses of four unrelated Vietnamese children diagnosed with HHH syndrome. Results: The age of diagnosis ranged from 10 days to 46 months. All four cases demonstrated hyperornithinemia and prolonged prothrombin time. Three out of four cases presented with hyperammonemia, elevated transaminases, and uraciluria. No homocitrulline was detected in the urine. Only one case depicted oroticaciduria. Genetic analyses revealed three pathogenic variants in the SLC25A15 gene, with the c.535C>T (p.Arg179*) variant common in Vietnamese patients. The c.562_564del (p.Phe188del) and c.408del (p.Met137Cysfs*10) variants were detected in one case. The latter variant has yet to be reported in the literature on HHH patients. After intervention with a protein-restricted diet, ammonia-reducing therapy, and L-carnitine supplementation, hyperammonemia was not observed, and liver enzyme levels returned to normal. Conclusions: Our results highlighted the clinical and biochemical heterogeneity of HHH syndrome and posed that HHH syndrome should be considered when individuals have hyperammonemia, elevated transaminase, and decreased prothrombin time.

October 17, 2024 Dear Prof. Dr. Rizzo and Dr. Oshiro, Prof. Dr. Rizzo: Editor-in-Chief of the Endocrinology section. Dr. Oshiro: Guest Editor of the “Advances in Clinical Diabetes, Obesity, and Metabolic Diseases” special Issue. I would like to submitt the manuscript entitled “Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome in Vietnamese Patients” by Khanh Ngoc Nguyen et al. to be considered for publication as an article in the “Advances in Clinical Diabetes, Obesity, and Metabolic Diseases” of the “Medicina” journal. This study included retrospective and prospective analyses of four unrelated Vietnamese children diagnosed with Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. HHH syndrome is one of the rarest urea cycle disorders and is characterized by failure of mitochondrial ornithine uptake, hyperammonemia, and accumulation of ornithine and lysine in the cytoplasm. Genetic analysis is key for diagnosis. In this study, we report the phenotype, genotype, treatment, and outcome of the four patients. To our best knowledge, this study is the first report of HHH patients in Vietnam. A diverse onset age and delayed diagnosis were observed. All four cases showed hyperornithinemia and prolonged prothrombin time. Three out of four cases presented with hyperammonemia, elevated transaminases, and uraciluria. No homocitrulline was detected in the urine. Genetic analyses identified three pathogenic variants in the SLC25A15 gene. The c.535C>T (p.Arg179*) variant is a common variant in Vietnamese patients. The c.562_564del (p.Phe188del) and c.408del (p.Met137Cysfs*10) variants were found in one case. The latter variant has yet been reported in the HHH patients in the literature. After intervention with a protein-restricted diet, ammonia-reducing therapy, and L-carnitine supplementation, no case had hyperammonemia and liver enzyme levels returned to normal range. Our results high-lighted clinical and biochemical heterogeneity of HHH syndrome and suggested that HHH syndrome should be considered when individuals present with hyperammonemia, elevated transaminase, and decreased prothrombin time. We believe these findings will be of interest to the readers of Medicina. We confirm that neither the manuscript nor any parts of its content are currently under consideration for publication with or published in another journal. All authors approved the final version of the manuscript and agree with its submission to Medicina. Thank you for your time and effort. We look forward to hearing from you regarding our submission. Yours sincerely, Chi Dung Vu (PhD., Assoc. Prof.) Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi, Vietnam Email: dungvu@nch.gov.vn. Tel: +84-246-2747643

Background: Unexplained recurrent pregnancy loss (URPL) is a significant obstetric challenge affecting maternal health and well-being. Genetic factors, including mutations in the methylenetetrahydrofolate reductase (MTHFR) gene and elevated homocysteine levels, are increasingly recognized as contributors to URPL, though their precise roles remain complex. This study aimed to comprehensively explore these factors. Objectives: This study examines the links between MTHFR gene polymorphisms (C677T and A1298C), plasma homocysteine levels, and URPL. It also aims to create a predictive model for URPL based on these factors. Design: A case-control study with Vietnamese women who had at least one pregnancy between January 2017 and June 2020, recruited from Medlatec Hospital and Hanoi Medical University. Participants included URPL cases ( n = 128) and controls ( n = 126). Methods: Participants were selected based on specific criteria. Main analyses identified the optimal multivariable logistic regression model for predicting URPL using Bayesian Model Averaging, with the optimal model chosen based on the highest Area Under the Curve (AUC) and posterior probability. A nomogram for clinical risk prediction was developed based on parameters from the optimal model. Results: URPL cases exhibited significantly higher plasma homocysteine levels (11.73 ± 6.08 µmol/L) compared to controls (7.64 ± 1.78 µmol/L), correlating with increased URPL risk (OR: 1.64, 95% confidence interval (CI): 1.41–1.96; p < 0.001). The MTHFR C677T variant showed strong associations with URPL, particularly the CT genotype (OR: 6.07, 95% CI: 3.00–12.93; p < 0.001) and TT genotype (OR: 14.62, 95% CI: 2.85–114.77; p = 0.003). Similarly, the A1298C variant demonstrated elevated URPL risk with the AC genotype (OR: 2.73, 95% CI: 1.34–5.78; p = 0.007) and CC genotype (OR: 12.43, 95% CI: 3.17–64.22; p = 0.001). Conclusion: This study provides insights into the complex interplay of MTHFR gene mutations, elevated homocysteine levels, and URPL. Genetic testing and biomarker assessment may play a crucial role in customizing risk assessment and management strategies for women at risk of URPL.

Background/Aim: Although the expression of mucin 1(MUC1) and prostate stem cell antigen (PSCA) genes is correlated with gastric cancer development and progression, the utility of these two genes as biomarkers of gastric cancer prognosis still needs to be confirmed in clinical practice. This study aimed to develop a model predictive of gastric cancer that integrates several significant single nucleotide polymorphisms (SNPs) of MUC1 and PSCA genes, and some health-risk behavior factors in a Vietnamese population. Patients and Methods: A total of 302 patients with primary gastric carcinoma and 304 healthy persons were included in a case–control study. The generalized linear model was used with the profile of age, sex, history of smoking and using alcohol, personal and family medical history of stomach diseases, and the SNPs of MUC1 and PSCA. The prognostic value of the model was assessed by the area under a receiver operating characteristic curve (AUC) and Akaike Information Criterion (AIC) values. Results: In male participants, the final model, consisting of age, sex, history of smoking and using alcohol, personal and family medical history of stomach diseases and SNP MUC1 rs4072037, provided acceptable discrimination, with an AUC of 0.6374 and the lowest AIC value (539.53). In female participants, the predictive model including age, sex, history of smoking and using alcohol, personal and family medical history of stomach diseases, SNPs MUC1 rs4072037 and rs2070803 had an AUC of 0.6937 and AIC of 266.80. The calibration plots of the male model approximately fitted the ideal calibration line. Conclusion: The predictive model based on age, sex, medical history, and genetic and health-risk behavior factors has a high potential in determining gastric cancer. Further studies that elucidate other genetic variants should be carried out to define high-risk gastric cancer groups and propose appropriate personalized prevention.

Multisystem inflammatory syndrome is associated with COVID-19 and can result in reduced food intake, increased muscle catabolism, and electrolyte imbalance. Therefore COVID-19 patients are at high risk of being malnourished and of refeeding syndrome. The present study aimed to determine the prevalence and correlates of malnutrition and refeeding syndrome (RS) among COVID-19 patients in Hanoi, Vietnam. This prospective cohort study analyzed data from 1207 patients who were treated at the COVID-19 hospital of Hanoi Medical University (HMUH COVID-19) between September 2021 and March 2022. Nutritional status was evaluated by the Global Leadership Initiative on Malnutrition (GLIM) and laboratory markers. GLIM-defined malnutrition was found in 614 (50.9%) patients. Among those with malnutrition, 380 (31.5%) and 234 (19.4%) had moderate and severe malnutrition, respectively. The prevalence of risk of RS was 346 (28.7%). Those with severe and critical COVID symptoms are more likely to be at risk of RS compared to those with mild or moderate COVID, and having severe and critical COVID-19 infection increased the incidence of RS by 2.47 times, compared to mild and moderate disease. There was an association between levels of COVID-19, older ages, comorbidities, the inability of eating independently, hypoalbuminemia and hyponatremia with malnutrition. The proportion of COVID-19 patients who suffered from malnutrition was high. These results underscore the importance of early nutritional screening and assessment in COVID-19 patients, especially those with severe and critical infection.

INTRODUCTION: The purpose of the study was to determine (a) the overall preclinical character; (b) the cumulative cutoff values and the risk ratio, and (c) the factors associated with severity by a unidimensional and multidimensional analysis on 2173 Sars-Cov2 patients. METHODS: The machine learning study population consisted of 2173 patients (1587 mild and non symptoms patients, 377 moderate patients, 209 severe patients). The status of the patients was recorded from September 2021 to March 2022. RESULTS: The Covid19 Severity directly links with a significant correlation to Age, Score index of the chest X-ray, percentage and quantity of neutrophils, Albumin, C reactive protein, and ratio of Lymphocytes. Their important cut off values (from regression analysis) respectively are: 77.56 years old (the mild-moderate group), 5.53 (the mild-moderate group) and 10.51 (the moderate-severe group), 84.80% (the mild-moderate group) and 87.74%(the moderate-severe group), 11.77G/L (the moderate-severe group), 29.73g/L (the moderate-severe group), 7.46mg/dL (the mild-moderate group), 6.32% (the moderate-severe group). Their significant (p<0.0001) R score correlation with the severity of Covid19, are: 0.44, 0.52 and 0.52, 0.33 and 0.44, 0.42, -0.43, 0.40, -0.41. Their significant risk ratio (p<0.00001) from the meta-analysis, respectively are: 4.19 [3.58-4.95], 3.29 [2.76-3.92] and 3.03 [2.4023;3.8314], 3.18 [2.73-3.70] and 3.32 [2.6480;4.1529], 3.15 [2.6153;3.8025], 3.4[2.91-3.97], 0.46 [0.3650;0.5752] (p<0.00001), 0.34 [0.2743;0.4210]. The pair ALT – Leucocytes and Transferrin – Anion Chloride get the most important correlation shift. ALT – Leucocytes show the important negative link (R=-1, p<0.00001) in the mild group to the significant positive correlation in the moderate group (R=1, p<0.00001). Transferrin–anion Chloride has an important positive association (R=1, p<0.00001) in the mild group with a significant negative correlation in the moderate group (R=-0.59, p<0.00001). The network map and HCA show that in the mild-moderate group, the closest neighbors with the Covid19 severity are ferritins, Age. Then there is C-reactive protein, SI of X-ray, Albumin, and Lactate dehydrogenase, which are the next close neighbors of these three factors. In the moderate-severe group, the closest neighbors with the Covid19 severity are Ferritin, Fibrinogen, Albumin, the quantity of Lymphocytes, SI of X-ray, white blood cells count, Lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: Complete multidimensional study in 2173 Covid19 patients in Vietnam shows the whole picture of all the preclinical factors, which may become the clinical reference marker for surveillance and diagnostic management

(1) Background: Individuals with BRCA1/2 gene mutations are at increased risk of breast and ovarian cancer. The prevalence of BRCA1/2 mutations varies by race and ethnicity, and the prevalence and the risks associated with most BRCA1/2 mutations has not been unknown in the Vietnamese population. We herein screen the entire BRCA1 and BRCA2 genes for breast and ovarian cancer patients with a family history of breast cancer and ovarian cancer, thereby, suggesting a risk score associated with carrier status and history for aiding personalized treatment; (2) Methods: Between December 2017 and December 2019, Vietnamese patients who had a pathological diagnosis of breast and epithelial ovarian cancer were followed up, prospectively, after treatment from two large institutions in Vietnam. Blood samples from 33 Vietnamese patients with hereditary breast and ovarian cancers (HBOC) syndrome were collected and analyzed using Next Generation Sequencing; (3) Results: Eleven types of mutations in both BRCA1 (in nine patients) and BRCA2 (in three patients) were detected, two of which (BRCA1:p.Tyr1666Ter and BRCA2:p.Ser1341Ter) have not been previously documented in the literature. Seven out of 19 patient’s relatives had BRCA1/2 gene mutations. All selected patients were counselled about the likelihood of cancer rising and prophylactic screening and procedures. The study established a risk score associated with the cohorts based on carrier status and family history; (4) Conclusions: Our findings suggested the implications for the planning of a screening programme for BRCA1 and BRCA2 genes testing in breast and ovarian cancer patients and genetic screening in their relatives. BRCA1/2 mutation carriers without cancer should have early and regular cancer screening, and prophylactic measures. This study could be beneficial for a diverse group in a large population-specific cohort, related to HBOC Syndrome.