Atherosclerosis is a complex vascular disorder driven by oxidative stress, inflammation, and platelet activation. Agents capable of targeting multiple atherogenic pathways may provide improved therapeutic benefits. In this study, we evaluated the anti-atherogenic effects of chrysotoxine, a bibenzyl compound isolated from Dendrobium pulchellum, using in vitro models relevant to atherogenesis. Chrysotoxine significantly suppressed hemin-induced LDL oxidation by reducing lipid peroxidation and apolipoprotein modification. In an endothelial-monocyte co-culture model, chrysotoxine markedly attenuated lipopolysaccharide-induced monocyte adhesion, indicating inhibition of endothelial inflammatory activation. Chrysotoxine also inhibited platelet aggregation induced by arachidonic acid, ADP, and collagen in a concentration-dependent manner, with the strongest effects observed against arachidonic acid-mediated responses, suggesting modulation of the thromboxane pathway. Molecular docking analyses and cyclooxygenase activity assays further indicated that chrysotoxine may interact with both COX-1 and COX-2, exhibiting inhibitory activity in the low micromolar range. Collectively, these findings demonstrate that chrysotoxine modulates multiple key processes involved in atherogenesis, including oxidative LDL modification, vascular inflammation, and platelet activation. Although further in vivo studies are required, chrysotoxine represents a promising plant-derived candidate for the development of multi-target strategies against atherosclerotic disease.

Clonal hematopoiesis (CH) is associated with cardiovascular disease (CVD), inflammation, and increased mortality. However, its prevalence and clinical impact in patients with cytopenia and chronic kidney disease (CKD) remain unclear. We conducted a retrospective cohort study of patients with cytopenia and CKD who underwent targeted sequencing to evaluate the association between CH, CKD progression, and overall mortality. A total of 67 patients were included (mean age 75.7 ± 10.5 years; 58.2

White blood cell (WBC) classification assists in assessing immune health and diagnosing various diseases, yet manual classification is labor-intensive and prone to inconsistencies. Recent advancements in deep learning have shown promise over traditional methods; however, challenges such as data imbalance and the computational demands of modern technologies, such as Transformer-based models which do not scale well with input size, limit their practical application. This paper introduces a novel framework that leverages Mamba models integrated with ensemble learning to improve WBC classification. Mamba models, known for their linear complexity, provide a scalable alternative to Transformer-based approaches, making them suitable for deployment in resource-constrained environments. Additionally, we introduce a new WBC dataset, Chula-WBC-8, for benchmarking. Our approach not only validates the effectiveness of Mamba models in this domain but also demonstrates their potential to significantly enhance classification efficiency without compromising accuracy. The source code can be found at https://github.com/LewisClifton/Mamba-WBC-Classification.

Background: Unusual site venous thromboembolism (USVTE) presents therapeutic challenges. Direct oral anticoagulants (DOACs) are increasingly prescribed despite limited evidence from clinical trials. Objectives: This cross-sectional analysis aimed to describe DOAC prescription patterns and rationale for choosing DOACs for USVTE treatment in real-life clinical practice. Methods: The Direct oral anticoagulants in Unusual Site venous Thromboembolism study (NCT03778502) is an international, multicenter, prospective, observational registry. Adult patients with objectively diagnosed USVTE (years 2018-2023) treated with DOACs were included. Information was collected on patient characteristics, USVTE location, anticoagulant treatment, and rationale for starting DOACs. Results: In total, 349 patients were included from 23 centers in 9 countries. The most common USVTE were splanchnic vein thrombosis (n = 219, 62.8%) and cerebral vein thrombosis (n = 103, 29.5%). The most prescribed DOACs were apixaban (n = 186, 53.3%) and rivaroxaban (n = 101, 28.9%). The median delay between USVTE diagnosis and DOAC initiation was 24 days, with 219 patients (62.8%) starting DOACs >14 days after diagnosis. Indeed, 320 (91.7%) patients received other anticoagulants before switching to DOACs (mainly low-molecular-weight heparin, n = 217, 67.8%). The main reasons for prescribing DOACs were oral administration (145/336, 43.2%), no need for blood monitoring (131/336, 39.0%), favorable safety profile (116/336, 34.5%), and prescriber-reported patient’s preference (96/336, 28.6%). Apixaban was the most prescribed DOAC in splanchnic vein thrombosis (133/219, 60.7%), while dabigatran was the most prescribed DOAC in cerebral vein thrombosis (38/103, 36.9%). Conclusion: DOACs are increasingly prescribed for USVTE owing to their ease of use and perceived safety, but mainly after initial treatment with parenteral anticoagulation. Further evidence is still needed to support their use in the acute phase.

AIMS:Measurable residual disease (MRD) is a key prognostic marker for patient survival. This study evaluated concordance between 10-color flow cytometry and next-generation sequencing (NGS)-based immunoglobulin heavy chain (IGH) gene assays for MRD detection and to assess prognostic significance in adult B-cell acute lymphoblastic leukemia (B-ALL). METHODS:This multicenter prospective study enrolled 51 patients with newly diagnosed B-ALL. Bone marrow samples were obtained at diagnosis, post-induction (1 month), and post-early consolidation (3 months). Flow cytometry and NGS-IGH were performed at three timepoints to assess MRD B-ALL. RESULTS:Patients were classified as high risk according to white blood cell count and cytogenetic features in 37.3% and 64.7% of patients, respectively. Treatment protocols included pediatric-inspired regimens (41.2%), adult-ALL protocols (52.9%), and low-intensity chemotherapy. All 16 Philadelphia chromosome-positive patients received tyrosine kinase inhibitors. Twenty patients underwent allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR). Median relapse-free survival (RFS) and overall survival were 19 and 39 months, respectively. MRD negativity at 3 months by either method correlated with significantly superior RFS. Allogeneic HCT also conferred RFS benefit. MRD positive patients without HCT had the worst RFS. Flow cytometry MRD positivity at 3 months independently predicted inferior RFS (HR 3.81; 95% CI 1.01-14.43). The overall concordance between flow cytometry and NGS was 80.7%. CONCLUSION:MRD positivity at 3 months post-treatment strongly predicted relapse, supporting its use to guide therapeutic modifications of B-ALL. Apart from NGS-based IGH clonality assays, 10-color flow cytometry offers an alternative in resource-limited settings.

Background: International guidelines recommend that patients with Immune thrombocytopenia (ITP) presenting platelets > 30x109/L should be followed-up without treatment. However, data on clinical courses and risk factors are limited. Objective: To determine the natural history and prognostic factors of untreated ITP. Materials and Methods: This retrospective cohort included adult ITP patients (platelet count 30-149 x109/L) at King Chulalongkorn Memorial Hospital from January 2015 to October 2022. Treatments were provided only to patients with platelet counts < 30x109/L and/or major bleeding. Results: A total of 73 patients were included. The mean age was 62 ± 16.64 years, and 56% were female. The median follow-up time was 3 years, comprising 272.48 patient-years. Seventeen patients (23.3%) subsequently required treatments, with an incidence rate of 6.24% per year (95% Confidence interval [CI], 3.88-10.0%). In multivariate analysis, risk factors for requiring treatment were age < 35 years (adjusted hazard ratio [aHR] 3.93; 95%CI, 1.27-12.22, P = 0.018) and a maximum-minimum platelet count during follow-up (excluding counts at treatment initiation) ≥ 70x109/L (aHR 2.89; 95%CI, 1.02-8.23, P = 0.047). Baseline platelet count did not predict outcomes, but persistently maintaining platelet counts >100 x 109/L for more than 3 or 6 months was associated with better prognosis. No severe bleeding related to thrombocytopenia was observed. The spontaneous recovery rate was 10% with an incidence of 2.57% per year (95%CI, 1.22-5.93%). Conclusions: The majority of untreated ITP patients had a good prognosis. Adverse risk factors included younger age and wide fluctuations in platelet counts.

Anticoagulant prophylaxis for high-risk patients is strongly recommended in standard clinical practice guidelines worldwide. However, there is a recognized gap between these international mandates and actual practice in East and Southeast Asia. This narrative review summarizes the underlying factors contributing to this underutilization of venous thromboembolism (VTE) thromboprophylaxis among countries in this region. Firstly, the baseline VTE incidence in general Asian population is lower than that of Western population. While historical VTE rates after major orthopedic surgery in Asia aligned with those reported in the West, recent data demonstrate that absolute event rates have decreased significantly following the adoption of modern surgical techniques, early ambulation and mechanical prophylaxis. Similarly, in general surgery, VTE disease burden is notably lower in Asian cohorts at equivalent Caprini scores compared to Western demographics. Furthermore, while Western VTE risk assessment models are available, they lack rigorous validation and calibration specifically for Asian medical patients. Regarding the safety concern, Asians show higher baseline incidence of spontaneous intracranial hemorrhage and carry a greater risk of major bleeding after warfarin administration at the same intensity. Together, these data shift the risk-benefit ratio of routine pharmacological thromboprophylaxis in Asian patients. Finally, the economic burden of routine anticoagulants for all patients at risk remains high in developing countries. We propose that, as an initial effort, institutions should establish their own consensus-based VTE prevention protocols, prioritizing at least the universal implementation of non-pharmacological prophylaxis. Ultimately, more large-scale research specifically targeting Asians is needed to formulate robust evidence-based regional recommendations.

Background: Hemoglobin (Hb) Hekinan is a prevalent α-globin variant frequently missed in thalassemia screening centers using high-performance liquid chromatography (HPLC) or capillary electrophoresis. This study aims to investigate the hematological and molecular characteristics of Hb Hekinan in a large cohort.Methods: Hb variants were identified using isoelectric focusing (IEF) and HPLC. Hb Hekinan was confirmed by direct DNA sequencing. Additional genetic determinants, including α-thalassemia, β-thalassemia and other variants, were detected using multiplex GAP-PCR, ARMS-PCR or direct DNA sequencing as appropriate.Results: Among 61,997 Hb typing samples, 149 cases of Hb Hekinan were identified in Thai individuals and classified into 8 genotypic groups. These included 104 Hb Hekinan heterozygotes, 10 Hb Hekinan coexisting with α+-thalassemia, 3 Hb Hekinan with non-deletional α-variants, 6 Hb Hekinan with α0-thalassemia, 21 double heterozygote for Hb Hekinan and HbE, 3 Hb Hekinan with β-thalassemia trait, 1 triple heterozygotes (Hb Hekinan/α0-thalassemia/Hb E) and 1 quadruple heterozygote for Hb Hekinan/α+-thalassemia/Hb E/Hb Hope. Hb Hekinan was well-separated from Hb A using IEF but was frequently missed with HPLC. On HPLC, Hb Hekinan could only be identified when coexisting with α0-thalassemia. All cases presented with either normal Hb levels or mild anemia.Conclusions: Hb Hekinan is a prevalent α-globin variant that is often undetected by HPLC but reliably identified using IEF. These findings highlight the importance of incorporating IEF for accurate diagnosis of Hb Hekinan. Most cases are clinically benign, even when interacting with other thalassemia syndromes or Hb variants.

In Myanmar, Russell's viper (Daboia siamensis) bite is a significant public health problem. In this study, we expend upon our previous RNA-sequencing approach to characterize candidate toxin genes encoding D. siamensis toxins. The mRNA was extracted from Myanmar Russell's viper venom glands. The RNAseq was performed using Illumina next-generation sequencing. Subsequently, candidate toxin transcripts were recognized by the Venomix pipeline. This study focused on 29 unique cDNA sequences representing eight newly identified venom gene families with low-to-moderate expression levels. These transcripts represented 0.088% of the total number of transcripts in the dataset. The translated protein sequences were analyzed for their conserved motifs and domains to predict their functions. They were neprilysins (bioactive peptide inactivators), cystatins (protease inhibitors with anti-metastatic activities), waprin and vipericidin (antimicrobial peptides), veficolin (platelet and complement activation), vespryns and three-finger toxins (elapid toxin homologs causing neurotoxic activity and tissue damage), and endothelial lipases (unknown function). Their functional activities should be further investigated for potential therapeutic applications, for example, in cancer or antibiotic-resistant infections.

Clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations, which are also found in Myelodysplastic syndrome (MDS), have been linked to increased cardiovascular disease (CVD), but the burden of CVD in MDS remains unclear. We evaluated the frequency of CVD and its associated risk factors, including CHIP mutations, in patients with MDS and related disorders. Patients with unexplained cytopenia, MDS, or MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasms) who underwent targeted next-generation sequencing between 2015 and 2025 were included, excluding those with therapy-related MDS. The primary outcome was composite cardiovascular events (myocardial infarction, ischemic stroke, and cardiovascular death). Secondary outcomes included the identification of risk factors associated with cardiovascular events. Among 196 individuals, 77.2% had MDS and 26% experienced CVD, higher than the 17–20% reported in the age-matched general population. Independent risk factors for CVD included age >70 years at diagnosis (adjusted OR[aOR] 2.99, 95%CI 1.01-8.85, p=0.048), anemia (aOR 4.23, 95%CI 1.22–14.55, p=0.022), and smoking history (aOR 5.32, 95%CI 1.18-23.92, p=0.029). TET2 mutations were also associated with an increased CVD risk (OR 2.38, 95%CI 1.01-5.60, p=0.046). Patients with CVD had significantly shorter overall survival compared with those without CVD (median, 27 vs. 56 months, p=0.006). These findings highlight CVD as a major comorbidity in MDS driven by both clinical and genetic factors support integrating cardiovascular risk assessment into routine MDS management.

In Thailand, stem cell transplantation and horse antithymocyte globulin (ATG) are not accessible for most adult aplastic anemia (AA) patients. Alternative therapies are required. We conducted a cohort study of 110 adult AA patients treated with oxymetholone alone for at least 30 days from 2013 to 2023. Response at month 6 and prognostic factors were evaluated. The mean age was 63.4 years old and 58.2

ABSTRACT Introduction The causes of nonsyndromic platelet storage pool disease are still unclear, and whether they are of genetic or acquired origin remains to be defined. The study aimed to describe the characteristics and natural history of this disorder. Methods This mostly retrospective cohort enrolled adults presenting with bleeding from platelet dysfunction. Platelet glycoprotein defects, von Willebrand disease, syndromic inherited platelet disorders and known acquired platelet dysfunctions were excluded. Available patients were retested by lumiaggregometry (Chrono‐Log) over 1 year after the initial diagnosis. Results There was a total of 56 patients; 91% female, with a median diagnostic age of 28 years (interquartile range [IQR]: 24.5–38.5). The subnormal responses to ADP, epinephrine, collagen, and arachidonate were found in 91%, 82%, 55%, and 34%, respectively. Nineteen patients had von Willebrand factor levels measured. Twenty‐three subjects underwent repeat tests. Twenty‐one of them were female (91%), with a median age and follow‐up time of 37 years (IQR: 28–55) and 6 years (IQR: 3–12), respectively. Median ISTH‐BAT bleeding scores at diagnosis and follow‐up were 5 (IQR: 3–8) and 1 (IQR: 0–2), respectively. The common abnormalities were reduced responses to ADP combined with other agonists (83%). Twelve (52%) and five (22%) showed complete and partial platelet function recovery, respectively. None of the partial and non‐recovery groups had a bleeding score over 4 at follow‐up. Conclusions Idiopathic mild platelet dysfunction was female‐predominant and showed spontaneous symptom resolution after a long follow‐up. Platelet function recovery was observed in most cases. Exogenous factors triggering this condition remain to be identified.

Background For hospitalized patients with clinically suspected venous thromboembolism (VTE; pulmonary embolism—PE or organ thrombosis), a clinical criteria-adjusted D-dimer cutoff level can be used to define a negative result that minimizes the burden of imaging usage. However, the limitation of this clinical probability test among hospitalized patients infected with coronavirus disease 2019 (COVID-19) is underestimated. Methods We explored the data of the patients admitted with COVID-19 infection and used the conventional D-dimer test as the reference. The proportion of patients with COVID-19 infections with a negative D-dimer result and the negative predictive value and sensitivity of three adjusted D-dimer tests for initial VTE were compared. Results Of the 151 patients with COVID-19 infections who were admitted, 31 patients had intermediate clinical probability, with more presenting with immobilization and intensive care unit (p < 0.001). Of 131 patients, 86.8% with COVID-19 infections showed negative D-dimer results, and seven had VTE (sensitivity, 65.0%). Age-adjusted cutoff level increased the number of patients with COVID-19 infections with VTE that could be ruled out from 132 to 151 patients (87.4%), with a sensitivity of 60.0%. Among the YEARS algorithm and Wells-adjusted cutoff values, 82.8% and 71.5% showed negative results, with a sensitivity of 60.0% and 71.5%, respectively. Conclusion Conventional YEARS algorithm showed a high number of patients with COVID-19 infections with VTE, which could be considered a rule-out with a higher accuracy than other clinically adjusted D-dimer tests.

The role of antibacterial prophylaxis in non-Hodgkin lymphoma (NHL) patients undergoing Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisolone (R-CHOP) chemotherapy with granulocyte-colony stimulating factor (G-CSF) support remains uncertain. This study evaluates the efficacy of levofloxacin in preventing febrile episodes in these patients. A randomized, single-blind, placebo-controlled trial was conducted, enrolling NHL patients receiving R-CHOP every 21-day cycle between January 2023 and June 2024. Patients were randomized to receive levofloxacin 500 mg once daily or placebo from day 1 to day 7 post-chemotherapy. All patients received G-CSF support. The primary outcome was the occurrence of febrile episodes within 120 days. Eighty participants were equally randomized into two groups. The median age was 64 years. In the intention-to-treat analysis, the first febrile episode was documented in 3 (7.5%) and 12 (30%) participants in the levofloxacin and placebo groups, respectively (P = 0.010). Levofloxacin prophylaxis significantly reduced febrile neutropenia (2.5% vs. 20%, P = 0.029) and the composite of febrile episodes, septic shock, all-cause mortality and chemotherapy dose reduction (10% vs. 30%, P = 0.025). The hazard ratio (HR) for fever-free survival with levofloxacin prophylaxis was 0.23 (95% CI 0.06-0.80; P = 0.012). Multivariate analysis showed levofloxacin was associated with a lower risk of febrile episodes (adjusted HR 0.17, 95% CI, 0.05-0.66; P = 0.01). No differences in mortality or serious adverse events were observed. Levofloxacin prophylaxis is an effective, well-tolerated strategy to reduce febrile episodes, febrile neutropenia and composite adverse outcomes after R-CHOP chemotherapy, despite concurrent G-CSF support. Long-term antibiotic resistance monitoring is warranted. Trial registration: This trial is registered at Thai Clinical Trials Registry (TCTR), number TCTR20230719005.

This study aimed to assess the discriminant factors and determine the cutoff value which can predict or classify the group of prescribed and non-prescribed biosimilar among Thai physicians. The online surveys were distributed to physicians via major three medical associations in Thailand. Five psychological variables were obtained from the surveys (familiarity, attitude toward biosimilar medication, attitude toward biosimilar practice scenarios, attitude toward naming biosimilars in prescriptions, and attitude toward pricing of biosimilar). The point-based system was used to score all variables and transformed to percentage. The assumptions were tested before using discriminant function analysis (DFA). Total 82 respondents were analyzed. Data of all variables met the assumptions of DFA. Familiarity was the most influential factor to differentiate the group of physicians, followed by attitude toward biosimilar medication. The cutoff value for group differences was -0.600. The accuracy rate of discriminant function equations was 82.9% overall for the stepwise method. The study concluded that the psychological factors such as familiarity with biosimilars and attitude toward biosimilars would play a significant role to classify between prescribed and non-prescribed biosimilar groups.

BACKGROUND:Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a distinctive syndrome characterized by unusual site thrombosis accompanied by thrombocytopenia following adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2. Platelet-activating anti-platelet factor 4-dependent antibodies (anti-PF4 Abs) have been identified as pathogenic antibodies in almost all patients. OBJECTIVE:We proposed an immunological mechanism of VITT independent of anti-PF4 Abs. METHODS:Case report. RESULTS:A 68-year-old Thai woman developed pulmonary embolism and deep vein thrombosis with thrombocytopenia one week after the second ChAdOx1 nCoV-19 vaccination with undetectable anti-PF4 Abs. The platelet count responded rapidly to intravenous immunoglobulin and steroids. Therefore, the high clinical suspicion is essential for early recognition and prompt management irrespective of anti-PF4 Ab results. CONCLUSIONS:We hypothesize that platelet and endothelial activation following ChAdOx1 nCoV-19 vaccination may lead to generation of pathogenic antibodies which account for VITT independent of anti-PF4 Abs.