Spectrum of WAS gene mutations in Vietnamese patients with Wiskott-Aldrich syndrome.

BACKGROUND: WAS gene mutational analysis is crucial to establish a definite diagnosis of Wiskott-Aldrich syndrome (WAS). Data on the genetic background of WAS in Vietnamese patients have not been reported. METHODS: We recruited 97 male, unrelated patients with WAS and analyzed WAS gene mutation using Sanger sequencing technology. RESULTS: We identified 36 distinct hemizygous pathogenic mutations, with 17 novel variants, from 38 patients in the entire cohort (39.2%). The mutational spectrum included 14 missense, 12 indel, five nonsense, four splicing, and one non-stop mutations. Most mutations appear only once, with the exception of c.37C>T (p.R13X) and c.374G>A (p.G125E) each of which occurs twice in unrelated patients. CONCLUSION: Our data enrich the mutational spectrum of the WAS gene and are crucial for understanding the genetic background of WAS and for supporting genetic counseling.

Three new chromanes and one new flavone C-glycoside from Mallotus apelta.

Three new chromanes, malloapeltas J-L (1-3), and one new flavone C-glycoside, malloflavoside (4), together with four known compounds, apigenin 6-C-ß-D-xylopyranosyl-8-C-α-L-arabinopyranoside (5), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (6), apigenin 7-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (7), and acantrifoside E (8) were isolated from the methanol extract of the leaves of Mallotus apelta. Their chemical structures were determined using spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS methods. All the isolated compounds were evaluated their cytotoxic activity against human prostate cancer (PC-3) and human breast cancer (MCF-7) cells, but none of them showed cytotoxicities on both human cancer cell lines.

Allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database.

WHAT IS KNOWN AND OBJECTIVE: Allopurinol, the first-line medication for hyperuricemia is well-known for its association with severe cutaneous adverse reactions, especially Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol-induced SJS/TEN in Vietnam from 2010 to 2019. METHODS: Signal generation was assessed using the case/non-case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated. RESULTS: Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830-6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508-16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. WHAT IS NEW AND CONCLUSION: The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness.

Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta.

Mallotusapelta(Lour.) Müll.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (1-6) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M.apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovariancancer cell line (TOV-21G). Compounds 1-5 and 7 exhibited significant growth and viability inhibitory effects with GI50 values ranging from 0.06 to 10.39 µM and IC50 values ranging from 1.62 to 10.42 µM on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-κB signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-κB activity.

Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3-6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 µM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

Systemic and Local Metabolic Alterations in Sleep-Deprivation-Induced Stress: A Multiplatform Mass-Spectrometry-Based Lipidomics and Metabolomics Approach.

Sleep deprivation (SD) is known to be associated with metabolic disorders and chronic diseases. Complex metabolic alterations induced by SD at omics scale and the associated biomarker candidates have been proposed. However, in vivo systemic and local metabolic shift patterns of the metabolome and lipidome in acute and chronic partial SD models remain to be elucidated. In the present study, the serum, hypothalamus, and hippocampus CA1 of sleep-deprived rats (SD rats) from acute and chronic sleep restriction models were analyzed using three different omics platforms for the discovery and mechanistic assessment of systemic and local SD-induced dysregulated metabolites. We found a similar pattern of systemic metabolome alterations between two models, for which the area under the curve (AUC) of receiver operating characteristic curves was AUC = 0.847 and 0.930 with the pseudotargeted and untargeted metabolomics approach, respectively. However, SD-induced systemic lipidome alterations were significantly different and appeared to be model-dependent (AUC = 0.374). Comprehensive pathway analysis of the altered lipidome and metabolome in the hypothalamus indicated the abnormal behavior of eight metabolic and lipid metabolic pathways. The metabolic alterations of the hippocampus CA1 was subtle in two SD models. Collectively, these results extend our understanding of the quality of sleep and suggest metabolic targets in developing diagnostic biomarkers for better SD control.

High-Throughput Omics and Statistical Learning Integration for the Discovery and Validation of Novel Diagnostic Signatures in Colorectal Cancer.

The advancement of bioinformatics and machine learning has facilitated the discovery and validation of omics-based biomarkers. This study employed a novel approach combining multi-platform transcriptomics and cutting-edge algorithms to introduce novel signatures for accurate diagnosis of colorectal cancer (CRC). Different random forests (RF)-based feature selection methods including the area under the curve (AUC)-RF, Boruta, and Vita were used and the diagnostic performance of the proposed biosignatures was benchmarked using RF, logistic regression, naïve Bayes, and k-nearest neighbors models. All models showed satisfactory performance in which RF appeared to be the best. For instance, regarding the RF model, the following were observed: mean accuracy 0.998 (standard deviation (SD) < 0.003), mean specificity 0.999 (SD < 0.003), and mean sensitivity 0.998 (SD < 0.004). Moreover, proposed biomarker signatures were highly associated with multifaceted hallmarks in cancer. Some biomarkers were found to be enriched in epithelial cell signaling in Helicobacter pylori infection and inflammatory processes. The overexpression of TGFBI and S100A2 was associated with poor disease-free survival while the down-regulation of NR5A2, SLC4A4, and CD177 was linked to worse overall survival of the patients. In conclusion, novel transcriptome signatures to improve the diagnostic accuracy in CRC are introduced for further validations in various clinical settings.

A systematic review on metabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer.

INTRODUCTION: Metabolomics is an emerging approach for early detection of cancer. Along with the development of metabolomics, high-throughput technologies and statistical learning, the integration of multiple biomarkers has significantly improved clinical diagnosis and management for patients. OBJECTIVES: In this study, we conducted a systematic review to examine recent advancements in the oncometabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for relevant studies published before September 2017. We examined the study designs, the metabolomics approaches, and the reporting methodological quality following PRISMA statement. RESULTS AND CONCLUSION: The included 25 studies primarily focused on the identification rather than the validation of predictive capacity of potential biomarkers. The sample size ranged from 10 to 8760. External validation of the biomarker panels was observed in nine studies. The diagnostic area under the curve ranged from 0.68 to 1.00 (sensitivity: 0.43-1.00, specificity: 0.73-1.00). The effects of patients' bio-parameters on metabolome alterations in a context-dependent manner have not been thoroughly elucidated. The most reported candidates were glutamic acid and histidine in seven studies, and glutamine and isoleucine in five studies, leading to the predominant enrichment of amino acid-related pathways. Notably, 46 metabolites were estimated in at least two studies. Specific challenges and potential pitfalls to provide better insights into future research directions were thoroughly discussed. Our investigation suggests that metabolomics is a robust approach that will improve the diagnostic assessment of pancreatic cancer. Further studies are warranted to validate their validity in multi-clinical settings.

The Dominant Role of Forkhead Box Proteins in Cancer.

Forkhead box (FOX) proteins are multifaceted transcription factors that are significantly implicated in cancer, with various critical roles in biological processes. Herein, we provide an overview of several key members of the FOXA, FOXC, FOXM1, FOXO and FOXP subfamilies. Important pathophysiological processes of FOX transcription factors at multiple levels in a context-dependent manner are discussed. We also specifically summarize some major aspects of FOX transcription factors in association with cancer research such as drug resistance, tumor growth, genomic alterations or drivers of initiation. Finally, we suggest that targeting FOX proteins may be a potential therapeutic strategy to combat cancer.

Metabolic phenotyping combined with transcriptomics metadata fortifies the diagnosis of early-stage Hepatocellular carcinoma.

INTRODUCTION: The low sensitivity of alpha-fetoprotein (AFP) renders it unsuitable as a stand-alone marker for early hepatocellular carcinoma (eHCC) surveillance. Therefore, additional blood-based biomarkers with enhanced sensitivities are required. OBJECTIVES: In light of the metabolic changes that are distinctive to eHCC development, the current study presents a panel of serum metabolites that may serve as noninvasive diagnostic indicators for patients with eHCC. METHODS: Serum samples obtained from normal control (NC), cirrhosis, and eHCC patients were analyzed by four different metabolomic platforms. A meta-analysis of very early-stage HCC transcriptomic datasets retrieved from public sources supports the integrated interpretation with metabolic changes. RESULTS: A total of 94 metabolites were significantly correlated with a progressive disease status. Integrated analysis of the significant metabolites and differentially expressed genes from meta-analysis emphasized metabolic pathways including bile acid biosynthesis, phenylalanine and tyrosine metabolism, and butanoate metabolism. The 11 metabolites associated with these pathways were compiled into a metabolite panel for use as diagnostic signatures. With an accuracy of 81.8%, compared with 45.4% for a model trained solely on AFP, the model enhanced its ability to differentiate between the three groups by incorporating a metabolite panel and AFP. Upon examining the trained models using receiver operating characteristic curves, the AFP and metabolite panel combined model exhibited greater area under the curve values in comparisons between NC and eHCC (1.000 versus 0.810) and cirrhosis and eHCC (0.926 versus 0.556). The result was consistent in an independent validation cohort. CONCLUSION: This study emphasizes the role of circulating metabolite markers in the diagnosis of eHCC.

Clinical evaluation of AI-assisted muscle ultrasound for monitoring muscle wasting in ICU patients.

Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n = 10) or non-AI (n = 10). Muscle loss during ICU stay was similar for both methods: 26 ± 15% for AI and 23 ± 11% for the non-AI, respectively (p = 0.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998-0.999 vs. 0.982 95% CI 0.962-0.993) and lower Bland Altman limits of agreement (± 1.9% vs. ± 6.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9-21.7) to 9.4 min (IQR 7.2-11.7) compared to when using the AI tool (p < 0.001). AI-assisted muscle ultrasound removes the need for manual tracing, increases reproducibility and saves time. This system may aid monitoring muscle size in ICU patients assisting rehabilitation programmes.

Spinal cord ischemia after transcatheter artery chemoembolization for hepatocellular carcinoma: A case-report.

INTRODUCTION: Transarterial hepatic chemoembolization (TACE) has been used to treat unresectable hepatocellular carcinoma and has gained widespread acceptance as a treatment for both primary and secondary hepatic malignancies. CASE REPORT: We report a case of 78-year-old male patient with chronic hepatitis B, diagnosed with HCC. He underwent the second TACE, and right after the procedure, the patient abruptly developed bilateral lower extremities motor weakness and sensory impairment below the T10 dermatome. Spinal magnetic resonance imaging showed T2-weighted scans showed increased intramedullary signal strength at the T1-T12 level. The patient received supportive care, ongoing rehabilitation, and steroid pulse therapy. The motor strength remained unchanged, but the sensory deficiencies practically disappeared. CLINICAL DISCUSSION: The hepatic artery injury or decreased flow at the prior TACE site, which causes collateral recruitment, can explain why spinal cord injury following TACE typically happens after the second or third session. It can occasionally result from accidental embolized spinal branches originating from intercostal or lumbar collateral arteries. In our case, we hypothesize the embolism caused the infarction to the spinal cord travel through the connection between the lateral branches of the right inferior phrenic artery and the intercostal arteries, which supply the spinal cord through the anterior spinal artery. CONCLUSIONS: TACE in rare case can have severe complications. A tailored therapeutic strategy, including consideration of a shunt and selection of the vessels utilized for the Lipiodol infusion prior to TACE, is crucial to achieving an optimal end outcome to avert these significant consequences.

Unveiling potentially convergent key events related to adverse outcome pathways induced by silver nanoparticles via cross-species omics-scale analysis.

The adverse effects of silver nanoparticles (AgNPs) have been studied in various models. However, there has been discordance between molecular responses across the literature, attributed to methodological biases and the physicochemical variability of AgNPs. In this study, a gene pathway meta-analysis was conducted to identify convergent and divergent key events (KEs) associated with AgNPs and explore common patterns of these KEs across species. We performed a cross-species analysis of transcriptomic data from multiple studies involving various AgNPs exposure. Pathway enrichment analysis revealed a set of pathways linked to oxidative stress, apoptosis, and metabolite and lipid metabolism, which are considered potentially conserved KEs across species. Subsequently, experiments confirmed that oxidative stress responses could be early KEs in both Caenorhabditis elegans and HepG2 cells. Moreover, AgNPs preferentially impaired the mitochondria, as evidenced by mitochondrial fragmentation and dysfunction. Furthermore, disruption of amino acids, nucleotides, sulfur compounds, glycerolipids, and glycerophospholipids metabolism were in good agreement with gene pathway shreds of evidence. Our findings imply that, although there may be organism-specific responses, potentially conserved events could exist regardless of species and physicochemical factors. These results provide valuable insights into the development of adverse outcome pathways of AgNPs across species and the regulatory toxicity of AgNPs.

Molecular and Metabolic Phenotyping of Hepatocellular Carcinoma for Biomarker Discovery: A Meta-Analysis.

Identifying and translating hepatocellular carcinoma (HCC) biomarkers from bench to bedside using mass spectrometry-based metabolomics and lipidomics is hampered by inconsistent findings. Here, we investigated HCC at systemic and metabolism-centric multiomics levels by conducting a meta-analysis of quantitative evidence from 68 cohorts. Blood transcript biomarkers linked to the HCC metabolic phenotype were externally validated and prioritized. In the studies under investigation, about 600 metabolites were reported as putative HCC-associated biomarkers; 39, 20, and 10 metabolites and 52, 12, and 12 lipids were reported in three or more studies in HCC vs. Control, HCC vs. liver cirrhosis (LC), and LC vs. Control groups, respectively. Amino acids, fatty acids (increased 18:1), bile acids, and lysophosphatidylcholine were the most frequently reported biomarkers in HCC. BAX and RAC1 showed a good correlation and were associated with poor prognosis. Our study proposes robust HCC biomarkers across diverse cohorts using a data-driven knowledge-based approach that is versatile and affordable for studying other diseases.

The dehiscence process in Panax ginseng seeds and the stigmasterol biosynthesis pathway in terms of metabolomics.

Background: Ginseng, officially known as Panax ginseng Meyer, has been traditionally used as a medicinal herb, particularly in Asia. Ginseng is propagated from seeds; however, seed germination is challenging, especially in its natural environment on farms. The seeds typically exhibit morphophysiological dormancy and require release from both morphological and physiological dormancy before germination. Although some studies have proposed methods for increasing seed germination rates, the underlying mechanisms of its dormancy release process remain unclear. Here, we investigated metabolic alterations during dehiscence in P. ginseng to determine their potential roles in dormancy release. Methods: We compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes. Results: After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated. Conclusion: Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of P. ginseng germination processes and promotes further research of its germination and cultivation.

Caenorhabditis elegans deep lipidome profiling by using integrative mass spectrometry acquisitions reveals significantly altered lipid networks.

Lipidomics coverage improvement is essential for functional lipid and pathway construction. A powerful approach to discovering organism lipidome is to combine various data acquisitions, such as full scan mass spectrometry (full MS), data-dependent acquisition (DDA), and data-independent acquisition (DIA). Caenorhabditis elegans (C. elegans) is a useful model for discovering toxic-induced metabolism, high-throughput drug screening, and a variety of human disease pathways. To determine the lipidome of C. elegans and investigate lipid disruption from the molecular level to the system biology level, we used integrative data acquisition. The methyl-tert-butyl ether method was used to extract L4 stage C. elegans after exposure to triclosan (TCS), perfluorooctanoic acid, and nanopolystyrene (nPS). Full MS, DDA, and DIA integrations were performed to comprehensively profile the C. elegans lipidome by Q-Exactive Plus MS. All annotated lipids were then analyzed using lipid ontology and pathway analysis. We annotated up to 940 lipids from 20 lipid classes involved in various functions and pathways. The biological investigations revealed that when C. elegans were exposed to nPS, lipid droplets were disrupted, whereas plasma membrane-functionalized lipids were likely to be changed in the TCS treatment group. The nPS treatment caused a significant disruption in lipid storage. Triacylglycerol, glycerophospholipid, and ether class lipids were those primarily hindered by toxicants. Finally, toxicant exposure frequently involved numerous lipid-related pathways, including the phosphoinositide 3-kinase/protein kinase B pathway. In conclusion, an integrative data acquisition strategy was used to characterize the C. elegans lipidome, providing valuable biological insights into hypothesis generation and validation.

Metabolic and Cardiovascular Benefits of Apple and Apple-Derived Products: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Quantitative evidence of the metabolic and cardiovascular effects of apples (Malus domestica) is lacking in interventional studies. This study aimed to summarize the available evidence of the beneficial effects of apples and apple-derived products (ADPs) on metabolic and cardiovascular markers. Methods: Peer-reviewed randomized controlled trials (RCTs) were identified from four databases on May 3, 2021 and regularly updated until the end of May 2021. Demographic characteristics, intervention types, and evaluation parameters were extracted. A meta-analysis on the mean difference of change scores was conducted on commonly presented outcomes in the RCTs. Results: The metabolic and cardiovascular effects of diverse regimens, including whole apple, apple extract, and apple juice, were examined in 18 eligible RCTs. Nine common evaluation outcomes were eventually introduced to the meta-analysis, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, glucose, insulin, C-reactive protein, and systolic/diastolic blood pressures. The levels of TC (-2.69 mg/dL; 95% CI: -5.43, 0.04 mg/dL) and LDL (-2.80 mg/dL; 95% CI: -5.78, 0.17 mg/dL) showed a non-significant decreasing tendency after at least a week of apple consumption. Further subgroup analysis, particularly, a comparison with placebo as a control, showed a significant reduction in TC and LDL levels. When stratified by the baseline level, subjects with high TC and LDL level were shown to have more benefits from the apple intake. Intriguingly, apple and ADPs significantly reduced HDL levels to a small extent (-1.04 mg/dL; 95% CI: -1.79, -0.29 mg/dL). The other markers were mostly unaffected by the intervention. Conclusion: Our investigation revealed that apples could improve blood cholesterol levels. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020215977].

Effects of Oats (Avena sativa L.) on Inflammation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Oat and its compounds have been found to have anti-inflammatory effects. Through this systematic review and meta-analysis, we aimed to determine an evidence-based link between oat consumption and inflammatory markers. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. By the end of April 2021, we included randomized controlled trials (RCTs) that investigated the anti-inflammatory effect of oat and oat-related products through screening PubMed, Embase, Web of Science, ClinicalTrial.gov, and CENTRAL. Meta-analysis was conducted with a random-effect model on the standardized mean difference (SMD) of the change scores of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Subgroup analyses were conducted to stratify confounding variables. The risk of bias was evaluated using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to report the quality of evidence. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021245844). Results: Systematic screening of five databases yielded 4,119 studies, of which 23 RCTs were finally selected. For the four systemic inflammatory markers analyzed, no significant alterations were found after oat consumption. However, oat intake was found to significantly decrease CRP levels in subjects with one or more health complications (SMD: -0.18; 95% CI: -0.36, 0.00; P = 0.05; I 2 = 10%). Furthermore, IL-6 levels were significantly decreased in subjects with dyslipidemia (SMD = -0.34; 95% CI: -0.59, -0.10; P = 0.006; I 2 = 0%). These beneficial effects might be attributed to the effects of avenanthramide and ß-glucan. Conclusions: Overall evidence supporting the alleviation of inflammatory response by oat intake was poor, calling for future studies including a larger sample size to confirm the findings.

Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis.

INTRODUCTION: The prevalence of gene mutations in hemophagocytic lymphohistiocytosis (HLH) varied between studies. Thus far, data on the genetic background of HLH in Vietnamese patients are limited. METHODS: We recruited 94 HLH patients and analyzed for the 4 genes using Sanger sequencing technology. RESULTS: Pathogenic variants were observed in 36 (38.29%) patients, including 27 in UNC13D, 5 in STXBP2, 3 in PRF1, and 2 in STX11 (one patient with digenic variants in both UNC13D and STX11). Monoallelic variants accounted for 77.8% of all cases with mutation. A total of 23 different types of pathogenic variants were documented in the 4 genes tested, including 15 in UNC13D, 3 in PRF1, 3 in STXBP2, and 2 in STX11. Interestingly, the novel splicing variant c.3151G>A in UNC13D was recurrently identified in 8 unrelated patients. CONCLUSION: Vietnamese patients with HLH showed a distinct genetic variant spectrum, in which UNC13D is the predominant genetic lesion associated with HLH.

Active surveillance for adverse events in patients on longer treatment regimens for multidrug-resistant tuberculosis in Viet Nam.

OBJECTIVE: Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. METHOD: We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. RESULTS: Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91-37.42]), renal dysfunction (HR = 8.46 [1.91-37.42]), alcoholism (HR = 13.28 [5.04-34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14-1.43]). CONCLUSION: While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.