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Background: This study aimed to determine the effectiveness of loosely regulated online quizzes in evaluating students' knowledge outcomes compared to a traditional summative examination, using Medical Bacteriology and Mycology as a model., Methods: A retrospective review of the student's academic performances was conducted (n = 320), analyzing the quiz score as well as how each student did the quizzes. Each parameter was mapped back to the students' actual summative score to evaluate the correlation., Results: There was a strong correlation between the online quiz and the summative scores (p = 0.013). An in-depth analysis also shows that students who performed well in the summative examination had the following characteristics; [1] they tried to pass the online quizzes in the early attempts (p < 0.001), [2] continued to revisit the quizzes after passing (p = 0.011) and [3] tried further to improve their quiz scores (p = 0.002)., Conclusion: Although online quizzes cannot yet replace traditional examinations, they can be an effective tool to assess student's competence, and careful monitoring of the quiz results can help identify students who may need extra attention. The results also suggest that diligence and intelligence are both important in Medical Bacteriology and Mycology., Competing Interests: Declarations. Ethics approval and consent to participate: This project was exempted by the Siriraj Institutional Review Board as a part of the course development project for the Doctor of Medicine curriculum (Protocol number 496/2566(IRB2), COA number Si 520/2023). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Premature birth poses significant health challenges, including respiratory distress syndrome (RDS). Corticosteroids reduce the incidence of RDS, but higher dexamethasone doses may lead to adverse neonatal outcomes, such as growth restriction and neurodevelopmental issues. Determining the appropriate dose is crucial to balance efficacy and safety. Dexamethasone is inexpensive and widely available in most low- and middle-income countries. This study aims to compare the efficacy and safety of 4-mg, 5-mg and 6-mg dexamethasone in preventing RDS among preterm infants. This trial aims to determine whether lower dexamethasone doses are as effective as the standard dose in preventing RDS in preterm infants. By assessing efficacy and potential adverse outcomes, this study will provide critical insights for optimizing treatment protocols and improving neonatal care., Methods: This randomized controlled trial will include pregnant women with gestational ages between 29 0 and 36 6  weeks admitted to Siriraj Hospital and three secondary centres in Thailand. The participants will be randomly assigned to receive intramuscular dexamethasone at 4 mg, 5 mg or 6 mg, which will be administered every 12 h for a total of four doses over 48 h. The same dose will be used for rescue or repeat courses. The primary outcome will be the incidence of RDS, defined by clinical criteria and confirmed by a neonatologist. The secondary outcomes will include other adverse neonatal and maternal outcomes., Results: The study requires 1,560 participants, accounting for a 15% loss to follow-up. The data will be analysed via descriptive statistics, chi-squared tests for categorical data, and one-way ANOVA or Kruskal-Wallis tests for continuous data. An independent Data Safety Monitoring Board will conduct interim analyses every 3 months to ensure participant safety and study integrity., Discussion: This trial addresses the gap in research regarding optimal dexamethasone dosing for preventing RDS in preterm infants. The study will provide evidence on whether lower doses of dexamethasone (4 and 5 mg) are as effective as the standard 6-mg dose and will examine their potential adverse outcomes. The results will guide adjustments to medical practice guidelines, aiming to align them with clinical practices while ensuring safety and efficacy. Trial registration page https://www.thaiclinicaltrials.org/export/pdf/TCTR20220511003 10/05/2022., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval has been granted by the Faculty of Medicine Siriraj Hospital (Si 480/2019). All the authors have completed the International Committee of Medical Journal Editors’ Form for Uniform Disclosure of Potential Conflicts of Interest and declare that they have nothing to disclose. All procedures involving human participants will be conducted in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent to participate: Written informed consent will be obtained from all study participants. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The incidence of colorectal cancer (CRC) in young adults has increased worldwide. Our study aimed to evaluate genomic alterations in early-onset (aged 15-39 years) sporadic CRC., Methods: Formalin-fixed, paraffin-embedded tissue samples from 90 patients with histologically confirmed colorectal adenocarcinoma with proficient mismatch repair status from Siriraj Hospital (Bangkok, Thailand) were extracted. Patients with clinically suspected familial adenomatous polyposis were excluded. A 517-gene mutational analysis was performed by next-generation sequencing using the Oncomine Comprehensive Assay Plus kit. The previously reported molecular data in adult-onset CRC from our group were used as a comparator group., Results: The five most frequently mutated genes were APC (66%), TP53 (51%), KRAS (47%), ARID1A (31%), and KMT2B (31%). When compare with adult-onset, NOTCH1 (11.1% vs. 1.9%), FBXW7 (23.3% vs. 14.8%), PIK3CA (20% vs. 12.1%), and FGFR3 (8.9% vs. 3.7%) mutations were more prevalent in early-onset. No differences were observed in other common mutations, such as TP53, EGFR, KRAS, NRAS and BRAF mutations. An increased prevalence in KRAS codon 12 mutations was also observed in early-onset patients compared to the adult-onset group (38.9% vs. 29.6%)., Conclusions: Overall, the genomic landscape between early- and adult-onset CRC appears similar. However, our study revealed the enrichment of NOTCH1, FBXW7, PIK3CA, and FGFR3 along with KRAS G12 mutations, were more frequent in early-onset compared to adult-onset cases. Further studies with a larger cohort of patients on the comprehensive analysis of genetic/epigenetic signatures are required., Competing Interests: Declarations. Ethics approval and consent to participate: The study was adhered to the Helsinki Declaration and approved by the Siriraj Institutional Review Board of the Siriraj Hospital Faculty of Medicine, Mahidol University, Bangkok, Thailand (EC1 No. 515/2561, Si 538/2018). This study is a retrospective study and does not have adverse effects on the rights and health of the participants, so the requirement of informed consent is waived. At the same time, patients’ privacy and personal identity information are protected. The preparation of the article was followed in accordance with the STROBE guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Circadian rhythms are present in almost all cells, but their existence in stem cells has remains not well established. Circadian clock appears to be closely associated with differentiated mature cells and rarely detected in immature embryonic stem cells. Recent evidence reveals the presence of circadian genes and rhythmic physiologic activities in stem cells as well as stem cell-derived extracellular vesicle (EV) characteristics. The circadian clock entails diverse physiologic and pathological mechanisms underlying cell fate. Integration of circadian rhythm to clinical applications, such as chronotherapy, chrono-biomarker, and environment modification, may facilitate therapeutic outcomes of stem cell-based regenerative medicine. Understanding circadian rhythms in stem cells can optimize stem cell-based therapies by determining the best times for harvesting and administering stem cells, thereby enhancing therapeutic efficacy. Further research into the circadian properties of stem cells will refine stem cell-based therapies, contributing to advancements in regenerative medicine., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing Interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: This study aimed to describe the characteristics and outcomes of children and adolescents with autoimmune inflammatory rheumatic diseases (AIIRD) who were admitted to the pediatric intensive care unit (PICU). The accuracy of the Pediatric Risk of Mortality (PRISM) III and Pediatric Index of Mortality (PIM) 3 scores to predict the mortality were investigated., Methods: This was a retrospective cohort study. Children and adolescents with AIIRD aged ≤ 18 years who were admitted to the PICU at the largest university-based referral center in Thailand during July 2011 to June 2021 were included., Results: There were 122 PICU admissions from 74 patients; mean age of 12.0 ± 4.3 years, 74.3% female. Majority of AIIRD were systemic lupus erythematosus (SLE) (83.8%), followed by systemic juvenile idiopathic arthritis (5.4%), juvenile dermatomyositis (JDM) (2.7%) and microscopic polyangiitis (2.7%). The main cause of admission was combined infection and disease flare (29.5%). Pneumonia was the main site of infection. Acinetobacter baumanii was the most common causative agent. Macrophage activation syndrome occurred in 8 (6.5%) admissions. The mortality rate of PICU admissions was 14.8% from 18 deaths; 17 with SLE and 1 with JDM. Mechanical ventilation (aOR 24.07, 95%CI:1.33-434.91, P= 0.031), pneumothorax (aOR 24.08, 95%CI:1.76-328.86, P = 0.017 and thrombocytopenia (aOR 8.34, 95%CI:1.31-53.73, P = 0.025) were associated with mortality. The risk of mortality rate as predicted by the PRISM III score increased with a score ≥ 9. For the PIM 3 score, the risk of mortality increased if the score ≥ 3. The area under the ROC curve for the PRISM III and PIM 3 scores was 0.741 (95%CI: 0.633-0.849), P = 0.001 and 0.804 (95%CI: 0.685-0.924), P < 0.001, respectively. The model calibration using the Hosmer-Lemeshow goodness of fit test demonstrated a chi-square of 4.335, P = 0.826 for PRISM III and 7.987, P = 0.435 for PIM 3., Conclusion: SLE was the main AIIRD that required admission to the PICU. Mechanical ventilation, pneumothorax and thrombocytopenia were associated with mortality in pediatric patients with AIIRD. The PRISM III and PIM 3 scores demonstrated good calibration, while the PIM 3 score provided better discrimination ability in the prediction of mortality for pediatric AIIRD., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol for this study received ethical approval from the Siriraj Institutional Review Board (SIRB) (COA no. Si 416/2021). Consent for publication: Not applicable. Competing interests: All authors declare no personal or professional conflicts of interest relating to any aspect of this study., (© 2025. The Author(s).)

Background: Hand-foot syndrome (HFS) is a common adverse event of capecitabine causing treatment modifications. Topical urea cream can reduce sorafenib-induced hand-foot skin reaction. However, its benefit in preventing capecitabine-associated HFS was not seen early in the course and had been unknown with long-term use. The aim of this study was to evaluate the efficacy of urea cream for HFS prophylaxis throughout capecitabine treatment., Methods: Patients with cancer who received capecitabine were randomized (1:1) to receive usual care alone or in combination with urea-based cream. The incidence and degree of HFS were assessed at each capecitabine cycle. The primary endpoint was the proportion of patients with any grade HFS. The secondary endpoints included the proportion of patients with severe (≥ grade 3) HFS, modifications in capecitabine because of HFS, and HFS onset., Results: After a median of six capecitabine cycles, any grade HFS was reported by 68 of 109 patients (62.4%) who received usual care and by 60 of 107 patients (56%) who used urea cream (p = 0.36). The patients who received usual care and urea cream had similar proportions of grade 3 HFS occurrence [52 (47.7%) vs. 44 (41.1%), respectively, p = 0.34] and needed capecitabine modification because of HFS [20 patients (18.3%) vs. 17 patients (15.9%), respectively, p = 0.89], as well as similar HFS onset., Conclusions: Urea-based cream did not prevent capecitabine-associated HFS, reduce capecitabine modification, and delay HFS onset. However, it had a tendency to lessen HFS severity, especially in the later cycles of capecitabine., Clinical Trial Registration Number: ClinicalTrials.gov Identifier: NCT05348278, registered on April 21, 2022., Competing Interests: Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Siriraj Hospital, Mahidol University (Date October 15, 2021/COA No.SI 790/2021). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The findings on mortality, rebleeding rate, and hospital stay in patients who underwent early vs. late endoscopy are conflicting. We aimed to compare in-hospital outcomes and medical resource use in patients with acute non-variceal upper gastrointestinal bleeding., Methods: We retrospectively reviewed the medical records of patients with acute non-variceal upper gastrointestinal bleeding who underwent early or late endoscopy between 2016 and 2019. The primary outcome was in-hospital mortality. The secondary outcomes were the need for packed red blood cells and number of transfusions, the proportion of lesions with high-risk stigmata, endoscopic and additional hemostasis, in-hospital rebleeding, duration of stay, and admission cost. Statistical analysis was performed using Pearson's chi-squared or Fisher's exact test for categorical variables, Student's t-test, and Wilcoxon rank-sum test for continuous variables., Results: Early and late endoscopies were performed on 451 and 279 patients, respectively. After 1:1 propensity score matching, 278 patients from each group were included, and patients' baseline characteristics were similar in the matched groups. Compared with the late group, the early group had a significantly increased rate of endoscopic hemostasis (22.7% vs. 13.7%, P = 0.006) and a low rate of packed red blood cell transfusion (53.6% vs. 61.9%, P = 0.048). Duration of stay and admission costs were significantly higher in the late group than in the early group (all P < 0.05). After adjusting for confounding factors, early endoscopy was positively associated with ulcers with high-risk stigmata (adjusted odds ratio = 1.83, P = 0.023) and endoscopic hemostasis (adjusted odds ratio = 1.97, P = 0.004). It was negatively associated with the need for packed red blood cell transfusion (adjusted odds ratio = 0.62, P = 0.017) and duration of stay (adjusted coefficient=-0.10, P < 0.001) with no impact on in-hospital mortality, rebleeding, or radiological interventions., Conclusions: The timing of endoscopy does not affect in-hospital mortality or rebleeding rate. This study supports using early endoscopy in patients with acute non-variceal upper gastrointestinal bleeding based on the potential benefits and feasibility of medical resource use., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board of Hatyai Hospital approved the study (protocol number: HYH EC 097-65-01). This study was conducted in accordance with the principles of the Declaration of Helsinki. Our Institutional Review Board deemed that no additional informed consent was required apart from the standard consent for endoscopy. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: Sarcopenia, characterized by loss of muscle mass and function, has gained importance in the evaluation of cirrhotic patients. Evidence suggests its role in adverse clinical outcomes, including minimal hepatic encephalopathy (MHE). This study aimed to investigate the association between sarcopenia and MHE in patients with cirrhosis., Methods: We prospectively enrolled outpatients with cirrhosis to assess sarcopenia using the 2019 criteria from the Asian Working Group for Sarcopenia. MHE was diagnosed through the Psychometric Hepatic Encephalopathy Score., Results: Of the 210 cirrhotic patients (57.1% male, mean age 62.7 ± 9.6 years), 54 (25.7%) had sarcopenia, with 26 (12.3%) classified as severe. Thirty-seven patients (17.6%) were diagnosed with MHE. Sarcopenia prevalence was significantly higher in patients with MHE compared to those without MHE (45.9% vs. 21.4%). MHE was significantly associated with age, education level, Mini-Mental State Examination score, and a history of hepatic decompensation. No significant associations were found regarding gender, body mass index, comorbidities, sleep quality, and the etiology of cirrhosis. Multivariable logistic regression showed that MHE was significantly associated with age (adjusted odds ratio [aOR] 1.08, 95% CI 1.02-1.13), sarcopenia (aOR 3.29, 95% CI 1.44-7.50), history of overt hepatic encephalopathy (aOR 7.40, 95% CI 1.20-45.56), and variceal bleeding (aOR 3.13, 95% CI 1.38-7.10). Severe sarcopenia was also independently associated with MHE (aOR 3.64, 95% CI 1.32-10.05)., Conclusions: Sarcopenia is prevalent in cirrhotic patients and is associated with an increased risk of MHE. Our findings emphasize the importance of assessing sarcopenia to potentially mitigate MHE risk in managing patients with cirrhosis., Competing Interests: Declarations. Ethics approval and consent to participate: The research was performed according to the Declaration of Helsinki and approved by the ethics committees of the Faculty of Medicine Siriraj Hospital. All subjects provided informed written consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The clinical characteristics, therapy, and outcome of Fournier Gangrene (FG) in patients using sodium-glucose cotransporter-2 inhibitors (SGLT2i) were examined in this systematic review., Methods: Without a publication year restriction, we searched PubMed, ScienceDirect, and Cochrane. Additionally, we manually searched bibliographies using the terms "Fournier's gangrene" and "SGLT2 inhibitors." The requirements for inclusion were the English language case reports with specific patient data and FG patients with diabetes who were using SGLT2 medication. The risk of bias was analyzed utilizing the Joanna Briggs Institute checklists., Results: A total of 78 studies were identified, and 14 of them were included in this review. The duration of SGLT2i use varied from 6 months to 6 years. The patients' age varied from 34 to 72 years, with 10 studies including male participants only and patients with obesity. All studies have discontinued SGLT2i and replaced them with other anti-diabetic drugs. Therapy options included perianal ring block, insulin, rigid sigmoidoscopy, aggressive debridement, antibiotics, fluid resuscitation, incision, drainage, surgery, hyperbaric oxygen therapy, plastic surgery, and fasciocutaneous flaps. Seven studies reported patients discharged in the range of 9-51 days., Conclusions: The incidence of FG following SGLT2i use is rare. Therapy was performed by replacing SGLT2i with other anti-diabetic drugs. The patient's outcome improved after treatment., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Objectives: To determine the prevalence of occult endometrial carcinoma in patients with endometrial intraepithelial neoplasia (EIN) post-hysterectomy and identify pre-hysterectomy risk factors predictive of occult carcinoma., Methods: This retrospective study included patients diagnosed with EIN between 2007 and 2021 who underwent hysterectomy as primary treatment. An expert gynecologic pathologist reviewed pathological slides. Data collected from medical records included demographic and gynecologic information, sonographic findings, and surgical and pathological outcomes. The prevalence of occult endometrial carcinoma was calculated. Descriptive statistics evaluated carcinoma incidence, and logistic regression analysis identified independent risk factors., Results: A total of 113 patients were evaluated. The median time to hysterectomy was 9.1 weeks (range 5.8-12.8 weeks). Post-hysterectomy, 36 patients (31.8%) were diagnosed with endometrial carcinoma, all endometrioid type. Of these, 88.9% were stage I per the International Federation of Gynecology and Obstetrics classification system, and 11.1% were at high risk for nodal metastasis. Predictive factors for occult carcinoma included the intraoperative gross lesion size (2 cm or larger and less than 2 cm) and endometrial aspiration. Adjusted odds ratios were 6.723 (95% CI 2.338 to 19.333) for lesions 2 cm or larger, 3.381 (95% CI 1.128 to 10.132) for lesions less than 2 cm, and 2.752 (95% CI 1.092 to 6.936) for endometrial aspiration., Conclusions: Occult endometrial carcinoma was identified in 31.8% of patients with a pre-hysterectomy EIN diagnosis. The significant predictors were endometrial aspiration and the presence of a gross lesion during surgery., Competing Interests: Declarations. Ethics norm or standard: The research was conducted in accordance with the principles outlined in the Declaration of Helsinki. Human ethics and consent to participate declarations: Human Ethics and Consent to Participate declarations: not applicable. Consent to participate: Since no individual participants were involved, there was no need for a consent to participate. Competing interests: The authors indicate no potential conflicts of interest., (© 2025. The Author(s).)

Background: This study aimed to develop ion-releasing and antibacterial resin-based dental sealants comprising 3 to 6 wt% monocalcium phosphate monohydrate (MCPM, M), 3 to 6 wt% bioactive glass (BAG, B), and 3 to 6 wt% polylysine (PLS, P). The physical properties, mechanical performance, cytotoxicity, and inhibition of S. mutans biofilm by these materials were subsequently evaluated., Methods: Five experimental dental sealants were formulated as follows: F1 (M6B6P6), F2 (M6B6P3), F3 (M3B3P6), F4 (M3B3P3), and F5 (M0B0P0, serving as the control). ClinproXT (CP, 3 M, Saint Paul, MN, USA) was used for commercial comparison. The degree of monomer conversion (DC) was determined using attenuated total reflectance-Fourier transform infrared spectroscopy (n = 5). The biaxial flexural strength (n = 6) and Vickers surface microhardness (n = 5) of the materials were evaluated after a 24-hour immersion in water. The element release over 4 weeks was measured using inductively coupled plasma-optical emission spectrometry (ICP-OES) (n = 3). The cell viability of mouse fibrosarcoma cells exposed to the extract was assessed via an MTT assay (n = 3). Additionally, the inhibition of S. mutans biofilm was tested (n = 3). Statistical analysis was conducted using one-way ANOVA and the Tukey HSD test., Results: The lowest DC among experimental sealants was obtained from F1 (66 ± 4%), which was significantly higher than CP (54 ± 2%, p < 0.001). The lowest biaxial flexural strength was obtained from F3 (131 ± 47 MPa). This was comparable to that of CP (140 ± 58 MPa, p = 0.992). The lowest surface microhardness among experimental materials was detected with F2 (19 ± 2 Vickers hardness number), which was higher than that of CP (12 ± 1 Vickers hardness number, p = 0.003). Furthermore, high cell viability of > 90% after exposure to extracts from the experimental materials was detected, which was similar to that observed with CP. Additionally, the experimental materials exhibited higher Ca and P release compared to CP and showed a potential trend for reducing S. mutans biofilm formation. Increasing additive concentrations exhibited minimal effects on material properties, except for enhanced elemental release and a slight reduction in BFM with higher PLS content., Conclusion: The experimental sealants provided sufficient physical and mechanical strength and maintained cell viability and bacterial inhibition with higher elemental release than the commercial product., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Anne Young has a patent on the use of MCPM in dental composites licensed to a dental company (Davis Schottlander and Davis Ltd., Letchworth Garden City, UK). The other authors declare no conflicts of interest., (© 2025. The Author(s).)

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities., Methods: To address these issues, we developed a lentiviral system to engineer T cells that secrete αB7-H3-αCD3 bispecific engager molecules (αB7-H3-αCD3 ENG-T cells). We evaluated their effectiveness against MM cells with varying B7-H3 expression levels, from B7-H3 neg to B7-H3 high ., Results: The αB7-H3-αCD3 ENG-T cells demonstrated significant anti-tumor activity against MM cell lines expressing B7-H3. SupT-1 cells (B7-H3 neg ) served as controls and exhibited minimal cytotoxicity from αB7-H3-αCD3 ENG T cells. In contrast, these engineered T cells showed dose-dependent killing of B7-H3-expressing MM cells: NCI-H929 (B7-H3 low ), L-363 (B7-H3 medium ), and KMS-12-PE (B7-H3 high ). For NCI-H929 cells, cytotoxicity reached 38.5 ± 7.4% (p = 0.0212) and 54.0 ± 9.2% (p = 0.0317) at effector-to-target (E:T) ratios of 5:1 and 10:1, respectively. Against L-363 cells, cytotoxicity was 56.6 ± 3.2% (p < 0.0001) and 71.4 ± 5.2% (p = 0.0002) at E:T ratios of 5:1 and 10:1, respectively. For KMS-12-PE cells, significant cytotoxic effects were observed even at an E:T ratio of 1:1, with 27.2 ± 3.7% (p = 0.0004), 44.4 ± 3.7% (p < 0.0001), and 68.6 ± 9.2% (p = 0.0004) cytotoxicity at E:T ratios of 1:1, 5:1, and 10:1, respectively., Conclusions: These results indicate that αB7-H3-αCD3 ENG T cells could be a promising therapy for B7-H3-positive MM. They may enhance current MM treatments and improve overall outcomes. Additional preclinical and clinical research is required to fully assess their therapeutic potential., Competing Interests: Declarations. Ethics approval and consent to participate: The research involving human participants was reviewed and approved by the Siriraj Institutional Review Board (SIRB) of the Faculty of Medicine Siriraj Hospital, Mahidol University (COA No. Si104/2022). Consent for publication: Not applicable. Competing interests: The authors disclose no conflicts of interest. Additionally, a patent application has been submitted to protect the intellectual property described in this study., (© 2024. The Author(s).)

Background: "Hospitels" are hotels that have been specially converted to healthcare facilities. Their utilization emerged as a resource-optimization strategy during the peak of the COVID-19 pandemic in Thailand. This study evaluated the clinical characteristics, outcomes, and admission costs of asymptomatic and mild-to-moderate COVID-19 patients treated in these facilities., Methods: We conducted a retrospective analysis of adult COVID-19 patients who were admitted between July and October 2021 to two hospitels in Bangkok that were affiliated with Siriraj Hospital. Patient demographics, clinical data, vaccination status, treatment modalities, outcomes, and total costs were collected and analyzed via univariable and multivariable statistical methods., Results: Of the 1729 patients, 644 (37.2%) presented with abnormal baseline chest X-rays that could imply to moderate cases. These patients were older (49.2 vs. 42.2 years, P < 0.001), had greater body weights (68.1 vs. 64.7 kg, P < 0.001) and body mass indices (26.3 vs. 24.9 kg/m 2 , P < 0.001), and more frequently presented comorbidities. They demonstrated an increased risk for severe COVID-19 (P < 0.001), lower full vaccination rates (P < 0.001), and higher hospital referral rates (P < 0.001). Symptomatology was largely comparable between patients with normal and abnormal baseline chest X-rays, with significant differences noted only for cough and fatigue. While the admission costs of both groups were similar, the total costs for referred patients were sixfold greater than those for discharged patients (70 545 vs. 12 010 Thai Baht, P < 0.001)., Conclusions: Compared with patients with normal baseline chest X-rays, COVID-19 patients with abnormal chest X-rays admitted to hospitels presented higher comorbidity rates, greater severe disease risk, and increased hospital referral rates. Referrals from the hospitels back to Siriraj Hospital substantially escalated the total costs. Vigilant monitoring of patients with initial abnormal chest X-rays in hospitels is crucial for efficient management and resource allocation., Competing Interests: Declarations. Ethical approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University (protocol code: 731/2564(IRB3); IRB certificate of approval number: Si 732/2021; approval date: March 14, 2023). Consent to participate was waived due to the retrospective nature of the study by the Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University. Clinical trial number: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Cryotherapy is a non-pharmacological option that complements drug therapy to achieve the most comprehensive multimodal analgesia. Various techniques are currently available, including the conventional gel cold pack, the cryo-cuff, and a novel mobile cold compression device (MCCD). This study aimed to evaluate and compare three cryotherapy techniques in terms of efficacy and patient satisfaction in patients undergoing total knee arthroplasty (TKA)., Methods: This prospective randomized study included 108 patients who were scheduled for primary unilateral TKA. The patients were allocated to 3 groups for postoperative cryotherapy techniques: gel cold pack, cryo-cuff, and MCCD. Scores on the visual analog scale (VAS) for pain intensity, morphine consumption, knee range of motion (ROM), knee swelling, length of hospital stay, and patient satisfaction were collected., Results: Postoperative VAS scores showed a significant difference among the groups at 8 and 72 h after surgery (P = 0.002 and 0.026, respectively). At the earliest postoperative time point, post hoc analysis demonstrated that patients in the MCCD group had lower pain scores than those in the gel cold pack (P < 0.001) and the cryo-cuff group (P = 0.030). However, cryo-cuff reduced knee swelling significantly compared to gel cold pack (P = 0.028) and MCCD (P = 0.011) at postoperative 72 h. The total satisfaction score was 86.8, 82.8, and 89.1 with gel cold pack, cryo-cuff, and MCCD, respectively., Conclusions: Cryotherapy is an adjunct to post-TKA pain control at the surgical site. MCCD has shown superior efficacy in pain reduction during the earliest postoperative period, and achieved high patient satisfaction., Trial Registration: This study was registered in the Thai Clinical Trials Registry database (no. TCTR20200517002)., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol for this study was approved by the Siriraj Institutional Review Board (no. Si289/2019) and was registered in the Thai Clinical Trials Registry (no. TCTR20200517002). Written informed consent was obtained from all study participants. All procedures involved in this study followed the ethical standards and complied with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: All authors declare that they have no competing interests related to this study., (© 2025. The Author(s).)

Background: With the increasing number of older adults, musculoskeletal disorders such as sarcopenia have become increasingly important to research because of their strong association with falls and fractures. Sarcopenia, which is characterized by reduced muscle mass, is common among older adults and significantly increases the risk of falls. This study aimed to assess the effectiveness of the SARC-F and SARC-CalF questionnaires, along with calf circumference measurements, for sarcopenia screening among Thai community-dwelling older adults, following the 2019 criteria of the Asian Working Group for Sarcopenia., Methods: This analysis drew on data from the Thai Musculoskeletal Diseases Nationwide Study, which included 2543 participants aged 60 years or older. The SARC-F, SARC-CalF, and calf circumference data were evaluated against the 2019 Asian Working Group for Sarcopenia criteria. We calculated the sensitivity, specificity, and area under the curve to determine the diagnostic performance of each tool., Results: Of the 2455 participants analyzed, 18.1% were diagnosed with sarcopenia. The SARC-F and SARC-CalF questionnaires showed limited effectiveness in diagnosing sarcopenia, with area under the curve values of 0.508 and 0.729, respectively. In contrast, calf circumference demonstrated greater diagnostic accuracy, with area under the curve values of 0.897 in males and 0.878 in females. Adjusting the cutoff points to < 33 cm for males and < 31 cm for females improved the overall diagnostic accuracy from 66.4 to 82%., Conclusions: Sarcopenia is relatively prevalent in Thailand. The SARC-F and SARC-CalF questionnaires are inadequate for diagnosing sarcopenia, while calf circumference alone is the most effective screening tool. Adding more parameters to the SARC-F questionnaire could enhance its diagnostic accuracy., Trial Registration: This study was registered at ClinicalTrials.gov (NCT06558617). Registration Date 16 August 2024., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted per the Declaration of Helsinki and received ethical approval from the Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA-715/2024). Trained research assistants obtained written informed consent from all participants before their enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Pneumonia is a potentially life-threatening respiratory tract infection. Many Early Warning Scores (EWS) were developed to detect patients with high risk for adverse clinical outcomes, but few have explored the utility of these EWS for pneumonia patients in the Emergency Department (ED) setting. We aimed to compare the prognostic utility of A-DROP, NEWS2, and REMS in predicting in-hospital mortality and the requirement for mechanical ventilation among ED patients with pneumonia., Methods: A retrospective study was conducted at the ED of Siriraj Hospital, Thailand. Adult patients diagnosed with non-COVID-19 pneumonia between June 1, 2021, and May 31, 2022, were included. We calculated and analyzed their EWS at ED arrival. The primary outcome was all-cause in-hospital mortality. The secondary outcome was mechanical ventilation., Results: We enrolled 735 patients; 272 (37%) died at hospital discharge, and 75 (10.2%) required mechanical ventilation. A-DROP had the highest discrimination capacity for in-hospital mortality (AUROC: 0.698, 95% CI 0.659-0.737) compared to NEWS2 (AUROC 0.657; 95%CI 0.617, 0.698) and REMS (AUROC 0.637; 95%CI 0.596, 0.678). A-DROP also had superior performances than NEWS2 and REMS in terms of calibration, overall model performance, and balanced diagnostic accuracy indices at its optimal cut point (A-DROP ≥ 2). No EWS could perform well in predicting mechanical ventilation., Conclusion: A-DROP had the highest prognostic utility for predicting in-hospital mortality in non-COVID-19 pneumonia patients in the ED compared to NEWS2 and REMS., Competing Interests: Declarations. Ethics approval and consent to participant: The Siriraj Institutional Review Board approved the study (certificate number Si 557/2022) and waived the need for consent to participate by the participants as per the retrospective nature of the study. The study was performed in accordance with the Good Clinical Practice (GCP) guideline and the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Evidence regarding the effect of time to neurosurgical and neuroradiological intervention on outcomes in traumatic brain injury (TBI) across Asia-Pacific region is limited. This study evaluates the quality of care and outcomes for TBI patients undergoing neurosurgical and neuroradiological procedures at different timings., Methods: Adult TBI patients who received any neurosurgical or neuroradiological interventions during the year 2015-2022 in the Pan-Asian Trauma Outcome Study database were analyzed. The time to intervention, as the main exposure, was classified into three groups (Early, Intermediate, and Delayed) using Restricted Cubic Spline (RCS) analysis. The outcomes were in-hospital mortality and unfavorable neurological outcomes. W score was utilized to compare the quality of care among exposure groups. Multivariable logistic regression analysis and interaction analysis were performed to identify the association between the exposure groups and outcomes, reported as adjusted odds ratios (AOR) with 95% confidence intervals (CI)., Results: A total of 1,780 patients were included. From the RCS analysis, patients were classified into three groups according to time to intervention: Early (< 1.9 h), Intermediate (1.9-4.1 h), and Delayed (> 4.1 h). According to the time to intervention, W score was - 8.6 in the early group, -1.1 in the intermediate group, and + 0.4 in the delayed group. Patients receiving intermediate and delayed intervention showed significantly lower mortality (AOR 0.64, 95% CI 0.47-0.86 and AOR 0.66, 95%CI 0.48-0.90, respectively)., Conclusion: Early neurosurgical and neuroradiological interventions in TBI patients in the Asia-Pacific region were associated with lower quality of care and higher mortality. The quality of care should be focused and improved during the early hours of TBI., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Siriraj Institutional Review Board (certification of approval number 179/2024). Informed consent was waived due to the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Childhood-onset systemic lupus erythematosus (cSLE) is associated with significant morbidity and mortality. Dyslipidemia and metabolic syndrome are recognized risk factors for premature atherosclerosis. This study aimed to determine the prevalence of dyslipidemia and metabolic syndrome, and to explore the relationships between lipid profiles, anthropometry, and disease status in cSLE., Methods: This cross-sectional study was conducted at a university-based tertiary referral center from April 2023-March 2024. Patients aged 10-19 years with cSLE diagnosed before 18 years and at least 1 year follow-up were enrolled, excluding those with other autoimmune disorders, chronic kidney disease, infections, receiving lipid lowering drugs prior, and pregnancy. Demographic data, metabolic laboratory tests, disease status, dietary intake, anthropometry, and body composition via bioelectric impedance analysis were evaluated. The prevalence of dyslipidemia and metabolic syndrome were documented. Variables were compared between patients with and without dyslipidemia. Correlations between lipid profiles, metabolic laboratory variables, and SLE disease-related variables were explored., Results: A total of 132 cSLE patients (94.7% female, mean age 11.6 ± 2.6 years) were included. Dyslipidemia was present in 48.5%, hypertriglyceridemia being the most common (28.8%); metabolic syndrome and hyperuricemia were present in 3.8% and 20.5%, respectively. Patients with dyslipidemia were significantly younger at cSLE diagnosis, had higher percentage of hypertension and active features of organ involvement, lower percentage of Lupus Low Disease Activity State, more use of mycophenolate mofetil and antihypertensive medications, higher uric acid level, higher waist circumference, body mass index, body mass index z-score, and fat mass (P < 0.05). Triglycerides, low-density lipoprotein cholesterol, and total cholesterol correlated positively with urine protein-to-creatinine ratio (r = 0.472, 0.469, and 0.591, respectively; P < 0.001) and negatively with serum albumin (r = -0.372, -0.506, and - 0.528, respectively; P < 0.001). Total cholesterol and low-density lipoprotein cholesterol correlated positively with cumulative prednisolone equivalent dose (rho = 0.350 and rho = 0.351, respectively, P < 0.001)., Conclusions: Nearly half of cSLE patients had dyslipidemia, especially those with younger age at diagnosis, higher body mass index, proteinuria, and suboptimal-controlled disease. Metabolic syndrome and hyperuricemia were present. Lipid profile assessment in early adolescents is recommended to identify metabolic comorbidities in cSLE., Competing Interests: Declarations. Ethical approval: This study was approved by the Siriraj Institutional Review Board (certificate of approval Si 190/2023) and was conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent and assent before participating in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The eradication of Plasmodium vivax malaria is complicated due to the presence of hypnozoites, the hidden dormant form of the parasite that is present in the liver. Currently available drug regimens are effective at killing hypnozoites but cause side effects and are difficult to administer. Studies testing drugs for liver-stage malaria remain rare and mainly rely on the use of cancerous or immortalized hepatic cells and primary hepatocytes., Methods: Organoids were used as platform to model liver-stage vivax malaria. Hepatic endoderm cells, endothelial progenitor cells and mesenchymal cells were generated from human induced pluripotent stem cells and self-assembled into liver organoids on top of Matrigel layer. Liver characteristic and maturity were examined through genes and proteins expression of liver markers, and liver functional tests before infected with Plasmodium vivax sporozoites. The infection was then verified by the detection of parasitophorous vacuole membrane proteins, Upregulated in Infectious Sporozoite 4 (UIS4), and blood-stage infection following co-culture with human reticulocytes., Results: Generated liver organoids showed upregulation of liver specific transcripts including hepatic nuclear factor 4A (HNF4A), alpha-fetoprotein (AFP), and albumin (ALB) which also confirmed by the protein expression. Furthermore, those organoids resembled mature hepatocytes in terms of albumin secretion, fat and glycogen storage and cytochrome activity. Following invasion of P. vivax sporozoites, PvUIS4 was detected and the hepatic merozoites could develop into ring-stage and early trophozoites in human reticulocytes. Moreover, differential expression patterns of genes involved in lipid and cholesterol synthesis were also detected., Conclusions: Stem cell-derived liver organoids resemble mature liver cells in terms of liver functions and are susceptible to infection with P. vivax sporozoites, paving the way for studies on the mechanism of hypnozoite formation and testing of possible hypnozoitocidal drugs., Competing Interests: Declarations. Ethics approval and and consent to participate: To generate liver organoids in this study, a human iPSC line, MUSIi001-A, established in a previous study [26], was used. Human erythrocytes were obtained from the peripheral venous blood of the subjects after obtaining informed consent. Protocols related to iPSCs, blood collection and cell preparation were approved by the Human Research Protection Unit, Faculty of Medicine Siriraj Hospital, Mahidol University (COA no. Si 953/2023, 924/2566(IRB3), and 400/2567(Exempt)). P. vivax sporozoites were used in accordance with biosafety guidelines, and the corresponding protocols were approved by the Faculty of Medicine Siriraj Hospital, Mahidol University (approval no. SI 2024–003). Consent for publications: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Evaluating myocardial function using cardiac magnetic resonance (CMR) feature tracking provides a comprehensive cardiac assessment, particularly a detailed evaluation for patients with repaired tetralogy of Fallot (rTOF). This study aimed to identify factors associated with arrhythmias in rTOF patients utilizing conventional CMR techniques, including myocardial strain measurements., Methods: This single-center, retrospective study included 245 rTOF patients who underwent CMR between 2017 and 2023. Patients were stratified based on the presence or absence of arrhythmias during follow-up. The biventricular strain was assessed using CMR-derived feature tracking. Demographic, clinical, and imaging data were collected, and statistical analyses were performed to identify factors associated with arrhythmic events., Results: The median age at surgery was 5.6 years (range 1-44 years), with the median age at CMR was 27.5 years (range 15-69 years). Over the follow-up period, 25 patients (10.2%) experienced atrial or ventricular arrhythmias. Univariate analysis revealed significant associations between arrhythmic events and older age at surgery and CMR, lower functional class, larger heart size on chest radiograph, and prolonged QRS duration (QRSd). Additionally, arrhythmias were associated with increased right ventricular (RV) volume, reduced RV and left ventricular (LV) ejection fraction (EF), and impaired strain values. Multivariate binary logistic regression, adjusting for age at surgery, NYHA class, QRSd, and cardiothoracic ratio, identified that a lower RV EF (adjusted odds ratio [aOR] 6.97), RV global radial strain (GRS) (aOR 6.68), RV global circumferential strain (GCS) (aOR 6.36), RV global longitudinal strain (GLS) (aOR 3.14), and LV GRS (aOR 3.02) were all significantly associated with arrhythmias., Conclusion: This study highlights the significant contribution of CMR-derived myocardial strain measurements in predicting arrhythmic events in patients with rTOF. In addition to conventional RV EF, strain metrics-particularly those of the right ventricle- emerged as strong, independent predictors of arrhythmias, offering valuable prognostic information for clinical management in this patient population. These findings underscore the importance of myocardial strain analysis as a complementary tool to conventional imaging in evaluating arrhythmic risk in rTOF patients., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethical approval and consent to participate, consent for publication: Electrocardiograms and chest radiographs correlated within 6 months of CMR were reviewed. The Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University approved the protocol for this study (COA no. Si 631/2023). Given the anonymous and retrospective nature of this study, written informed consent was not obtained from study subjects. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: To avoid exaggerated inflammation, innate immune cells adapt to become hypo-responsive or "tolerance" in response to successive exposure to stimuli, which is a part of innate immune memory. Polycomb repressive complex 2 (PRC2) mediates the transcriptional repression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3) but little is known about its role in lipopolysaccharide (LPS)-induced tolerance in macrophages., Result: We examined the unexplored roles of EED, a component of the PRC2, in LPS tolerant macrophages. In Eed KO macrophages, significant reduction in H3K27me3 and increased active histone mark, H3K27ac, was observed. Eed KO macrophages exhibited dampened pro-inflammatory cytokine productions (TNF-α and IL-6) while increasing non-tolerizable genes upon LPS tolerance. Pharmacological inhibition of EED also reduced TNF-α and IL-6 during LPS tolerance. Mechanistically, LPS tolerized Eed KO macrophages failed to increase glycolytic activity. RNA-Seq analyses revealed that the hallmarks of hypoxia, TGF-β, and Wnt/β-catenin signaling were enriched in LPS tolerized Eed KO macrophages. Among the upregulated genes, the promoter of Runx3 was found to be associated with EED. Silencing Runx3 in Eed KO macrophages partially rescued the dampened pro-inflammatory response during LPS tolerance. Enrichment of H3K27me3 was decreased in a subset of genes that are upregulated in Eed KO LPS tolerized macrophages, indicating the direct regulatory roles of PRC2 on such genes. Motif enrichment analysis identified the ETS family transcription factor binding sites in the absence of EED in LPS tolerized macrophages., Conclusion: Our results provided mechanistic insight into how the PRC2 via EED regulates LPS tolerance in macrophages by epigenetically silencing genes that play a crucial role during LPS tolerance such as those of the TGF-β/Runx3 axis., Competing Interests: Declarations. Ethics approval: No human samples or subjects were used in this study. All experimental procedures involving laboratory animals were approved by the Institutional Animal Care and Use Committee (IACUC) of the Faculty of Medicine, Chulalongkorn University (approval protocol No. 025/2562) and Chulalongkorn University Laboratory Animal Center (CULAC, approval protocol 2073015. All experiments were performed according to the guidelines issued by the IACUC. This study is reported in accordance with the ARRIVE guidelines. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Streptococcus suis (S. suis) is a zoonotic disease that is transmitted to humans via contact or oral route. Although the major clinical presentation of this pathogen is known to be meningitis, S. suis infective endocarditis (IE) has recently emerged as a clinical manifestation of increasing interest. Echocardiography may be an underutilized modality for evaluating patients with S. suis bacteremia., Objective: The primary objective was to estimate the prevalence of S. suis IE in patients with S. suis bacteremia. The secondary objective was to investigate the predictors, echocardiographic features, and clinical outcomes of S. suis IE in patients with S. suis bacteremia., Materials and Methods: This single-center retrospective study was conducted at Siriraj Hospital - Thailand's largest university-based tertiary referral center. Adult patients (aged > 18 years) who were admitted to our center with confirmed diagnosis of S. suis bacteremia during January 2007 to September 2023 were included. Prevalence is reported as percentage and confidence interval. Baseline characteristics and clinical manifestation were compared between the IE and non-IE groups. Factors found to be statistically significant were further analyzed using binary logistic regression analysis to identify univariate predictors of S. suis IE., Result: A total of 71 patients with S. suis bacteremia were included in this study. The prevalence of S. suis IE was 26.8% (95% confidence interval: 17.85-38.05). Perivalvular complications and significant valvular regurgitation were found in 52.6% and 80.0% of patients, respectively. Thirteen of 19 patients (68.4%) required valvular surgery according to standard guidelines. By univariate analysis, dyspnea, new murmur, immunologic phenomenon, and heart failure were predictors of S. suis IE in patients with S. suis bacteremia., Conclusion: The results of this study revealed a sizable prevalence of S. suis IE in patients with S. suis bacteremia, and there were high rates of both valvular damage and perivalvular complications. Our results strongly suggest that echocardiography may be indicated to evaluate for S. suis IE in patients diagnosed with S. suis bacteremia. Reclassification of S. suis from an atypical organism to a typical organism should be considered., Competing Interests: Declarations Ethics approval and consent to participate The protocol for this study was approved by the Siriraj Institutional Review Board (SIRB) of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. (COA no. Si935/2023). Written informed consent was not obtained from study subjects due to the retrospective and anonymity-preserving design of our study. Consent for application Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma associated with hemophagocytic lymphohistiocytosis (HLH)/HLH-like systemic illnesses and germline HAVCR2 mutations. Although previous studies suggested successful treatment of SPTCL with immunosuppressive therapy (IST) without chemotherapy, IST data in pediatric SPTCL remain scarce. To explore characteristics and therapeutic outcomes, comparing IST-based and chemotherapy-based regimens in pediatric SPTCL, in this retrospective cohort study, patients with SPTCL diagnosed at age ≤20 years during 2007-2023 were enrolled from 6 hematology/oncology centers in Thailand. HAVCR2 exon 2 sequencing was performed using DNA extracted from peripheral blood or bone marrow. Presence of HLH/HLH-like systemic illnesses, treatment outcomes, and adverse events (AEs) were reviewed and analyzed., Results: Of 22 patients with SPTCL (median age at diagnosis, 11.5 years [range, 6.0-19.0]; 63.6% males), 86.4% harbored germline HAVCR2 mutation, either homozygous (77.3%) or heterozygous (9.1%) p.Y82C variant, while 68.2% developed HLH/HLH-like systemic illnesses. Overall, 36.4% received IST as first-line treatment. Durable complete remission (CR) was achieved in 71.4% and 50.0% after first-line chemotherapy and IST, respectively (P=0.45); however, chemotherapy tended to increase any AEs compared to IST (57.1% vs. 12.5%; P=0.07). The most common AEs were hypertension (27.3%), febrile neutropenia (18.2%), and fungal infection (13.6%). Among the relapsed cases, 71.4% could reach CR after subsequent-line therapy. Fatality (4.5%) only occurred in the chemotherapy group., Conclusions: Pediatric SPTCL in Thailand frequently involves germline HAVCR2 mutations and/or HLH/HLH-like systemic illnesses. With comparable response and modest therapy-related toxicity, IST-based regimens may alternatively be considered as first-line treatment for pediatric SPTCL., Competing Interests: Declarations Ethical approval and consent to participate The study protocol was ethically approved by the Institutional Review Boards of all the study sites, including the central study site at the Faculty of Medicine, Chulalongkorn University (IRB no. 0607/65). Written informed consent forms were obtained from each patient and/or their parents/guardians prior to participation in the study, in accordance with the Declaration of Helsinki. Consent for publication Not applicable Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: The well-being of LGBTQ + medical students can be influenced by religiosity, family support, and the disclosure of their gender identity or sexual orientation. These factors have frequently been overlooked and warrant further consideration in creating a supportive environment for all students., Methods: This multicenter study investigated two main outcomes including the differences in religiosity and perceived family support between LGBTQ + and non-LGBTQ + medical students in Thailand, and the gender disclosure to family among LGBTQ + medical students. It was conducted among students from five medical schools across Thailand, using online questionnaires during the academic year 2021-2022. Data were collected on demographic characteristics, religiosity, gender identity/sexual orientation disclosure to family, and perceived family support. Comparisons between groups were conducted using chi-square test and Wilcoxon rank-sum test., Results: Of the 1,322 participants, 31.2% identified themselves as LGBTQ+, among whom 81.8% were Buddhists. The proportion of non-religious LGBTQ + students was significantly higher (vs. non-LGBTQ+; 15.0% vs. 8.4%, respectively; p = 0.001). However, there was no statistical difference in religiosity between LGBTQ + and non-LGBTQ + students as well as between LGBTQ + subgroups. Although, 74% of LGBTQ + students reported good family support, significantly more LGBTQ + students perceived poor family support (vs. non-LGBTQ+, 7.0% vs. 4.7%; p = 0.002). Regarding the disclosure of gender identity or sexual orientation to the family, the majority of LGBTQ + individuals indicated either a non-disclosure or uncertainty. There were significant associations between perceived family support and the likelihood of disclosing one's identity to family members, as better perceived support was associated with higher disclosure rates., Conclusions: No statistically significant difference in religiosity was found between LGBTQ + and non-LGBTQ + students. The majority of LGBTQ + medical students reported receiving good family support; however, among those who perceived their family's support to be lacking, there was a greater tendency to conceal their gender identity from their families. For future studies, it is crucial to investigate whether this concealment extends to other spheres of their lives and to assess the potential impact on their well-being, including mental health and quality of life., Competing Interests: Declarations Ethical approval and consent to participate This study was approved by Institutional Review Boards at each site: Mahidol University (167/2022), Chulalongkorn University (0006/2022), Khon Kaen University (HE651083), Prince of Songkla University (65-085-3-1), and Chiang Mai University (PSY-2565-08832). Informed consent to participate in the study was obtained from all participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Conflict of interest The authors report no conflicts of interest with respect to the research, authorship, or publication of this article., (© 2024. The Author(s).)

Background: Osteoporotic vertebral compression fractures (OVF) are prevalent and substantially impact healthcare systems and patients' quality of life. The osteoporotic fracture treatment score (OF score), developed by the German Society of Orthopedics and Trauma (DGOU), guides surgical decisions, but its reliability and validity are underexplored. This study assessed the OF score's inter- and intraobserver reliability, validated its treatment recommendations, and investigated intermediate outcomes of different DGOU-recommended surgical strategies for OVF., Methods: A retrospective cohort study was conducted. Inter- and intraobserver reliability of the OF score and its subcomponents were analyzed using clinical and radiographic data. Validity was assessed by comparing the OF score's recommended treatments with actual treatments received. Outcomes at the final follow-up were back pain visual analog scale, Oswestry Disability Index, EQ-VAS, EQ-5D-5 L, adjacent fracture incidence, local kyphotic angle, and reoperation rates. Patients with at least 1-year follow-up were included., Results: A total of 157 patients (84.7% female; mean age 74.2 ± 10.5 years) were evaluated. The most frequent osteoporotic fracture (OF) types were OF4 (49.0%) and OF3 (40.8%). The OF score demonstrated good interobserver reliability (ICC = 0.77, 95% CI: 0.65-0.86) and intraobserver reliability (ICC = 0.83, 95% CI: 0.72-0.90). Kappa values for subcomponents ranged from 0.57 to 0.89. Excluding patients with indeterminate recommendations (OF score = 6), 82.9% received treatments concordant with OF score recommendations. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 (95% CI: 0.67-0.86); an OF score cutoff > 6.5 predicted actual treatment with 87.9% sensitivity and 61.0% specificity. All surgical treatments showed comparable improvements in clinical outcomes. However, patients treated with stand-alone cement augmentation (CA) had less local kyphotic angle correction (P = 0.004) and greater postoperative kyphotic progression (P < 0.001) than those undergoing short-segment (SS-PI) or long-segment instrumentation (LS-PI). No significant differences in adjacent fractures or complications were observed., Conclusions: The OF score is a reliable and valid system with good discriminative ability for surgical decision-making in OVF patients. CA, SS-PI, and LS-PI are viable options with comparable functional outcomes. However, in OF3 or OF4 fractures, caution is advised due to lesser kyphosis correction and greater kyphotic progression with CA compared to SS-PI or LS-PI, as recommended by the DGOU., Competing Interests: Declarations Ethics approval and consent to participate The protocol for this study was approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 864/2022). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Adoptive immunotherapy using natural killer (NK) cells has attracted considerable interest in numerous clinical trials targeting both hematological and solid tumors. Traditionally, NK cells are primarily derived from either peripheral blood (PB) or umbilical cord blood (UCB). However, these methods can lead to variability and heterogeneity within the NK cell population. In contrast, induced pluripotent stem cell (iPSC)-derived NK (iNK) cells provide a more controlled and uniform cellular population, suitable for large-scale clinical applications. This makes iNK cells a promising option for developing "off-the-shelf" immunotherapeutic products. Nevertheless, current NK cell differentiation protocols, which rely on embryoid body (EB) cultures, are labor-intensive and susceptible to unwanted heterogeneity during differentiation. Here, we developed a more efficient approach for generating iNK cells by employing a monolayer and feeder-free differentiation protocol, alongside optimized culture media., Methods: The iNK cells were generated using a two-step in vitro monolayer feeder-free system following NK cell development. To evaluate their maturity, phenotypic analysis was performed using flow cytometry, comparing with PB-NK cells and the NK-92 cell line. Additionally, single-cell RNA sequencing was performed to examine their transcriptomic profiles. The cytotoxic activity of the iNK cells was evaluated by co-culturing with cholangiocarcinoma (CCA) and breast cancer (BCA) cell lines in both monolayer (2D) and tumor spheroid (3D) co-culture systems., Results: We successfully differentiated iPSCs into mesoderm (ME), hematopoietic stem/progenitor cells (HSPCs), and NK cells. The resulting iNK cells exhibited typical NK cell markers such as CD45, CD56, and CD16, and expressed key functional proteins, including both activating and inhibitory receptors. Single-cell RNA sequencing confirmed that the transcriptomic profile of our iNK cells closely resembles that of PB-NK cells. Importantly, our iNK cells demonstrated strong cytotoxic abilities against various CCA and BCA cell lines, surpassing the NK-92 cell line in both monolayer cultures and tumor spheroid cultures., Conclusion: This study highlights the potential of iPSCs as an effective alternative cell source for generating NK cells. Using a two-step in vitro monolayer feeder-free system, we successfully generated iNK cells that not only expressed key NK cell markers and their receptors but also displayed a transcriptomic profile closely resembling PB-NK cells. Furthermore, iNK cells exhibited cytotoxicity against CCA and BCA cell lines comparable to that of PB-NK cells. This approach could pave the way for off-the-shelf NK cell products, potentially enhancing the effectiveness of adoptive NK cell therapy., Competing Interests: Declarations Ethics approval and consent to participate The use of peripheral blood samples in this study was approved by the Siriraj Institutional Review Board, Thailand (Si 320/2021) on May 5, 2021, in accordance with the Helsinki Declaration of 1975. This research was part of the project titled” Generation of “off-the-shelf” iPSC-derived natural killer (NK) cells as a prototype for cell-based therapy”. Each patient was given an information sheet explaining the study and provided written informed consent. Consent for publication All authors have contributed to, read, and approved the manuscript for submission. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Cholangiocarcinoma (CCA) presents a formidable therapeutic challenge due to its extensive heterogeneity and plasticity, which inevitably lead to acquired resistance to current treatments. However, recent evidence suggests that acquired drug resistance is associated with a fitness cost resulting from the myriad of acquired alterations under the selective pressure of the primary treatment. Consequently, CCA patients with acquired resistance are more susceptible to alternative therapies that are ineffective as monotherapies. This phenomenon, termed "acquired vulnerability," has garnered significant interest in drug development, as the acquired alterations could potentially be exploited therapeutically. This review elucidates the modes of acquired vulnerability, methods for identifying and exploiting acquired vulnerabilities in cancer (particularly in CCA), and strategies to enhance the clinical efficacy of drug combinations by leveraging the principle of acquired vulnerability. Identifying acquired vulnerabilities may pave the way for novel drug combinations to effectively treat highly heterogeneous and adaptable malignancies such as CCA., (© 2024. The Author(s).)

Objective: Atrial cardiomyopathy is closely associated with atrial fibrillation (AF), and some patients exhibit no dysfunction at rest but demonstrate evident changes in left atrial (LA) function and LA volume during exercise. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF)., Methods: A prospective cohort of 1055 patients in SR was enrolled across 12 centers. The main study cohort was divided into two groups: the modeling group (n = 513) and the verification group (n = 542). All patients underwent ESE, which included B-lines, LA volume index (LAVi), and LA strain of the reservoir phase (LASr)., Results: Age, resting and stress LAVi and LASr, and B-lines were identified as a combination of detectors for PAF in both groups. In the entire cohort, aside from resting and stress LAVi and LASr, additional parameters differentiating PAF and non-PAF patients were the presence of systemic hypertension, exercise E/e' > 7, worse right ventricle (RV) contraction during exercise (∆ tricuspid annular plane systolic excursion < 5 mm), a lower left ventricular contractile reserve (< 1.6), and a reduced chronotropic reserve (heart rate reserve < 1.64). The composite score, summing all 9 items, yielded a score of > 4 as the best sensitivity (79%) and specificity (65%)., Conclusion: ESE can complement rest echocardiography in the identification of previous PAF in patients with SR through the evaluation of LA functional reservoir and volume reserve, LV chronotropic, diastolic, and systolic reserve, and RV contractile reserve., (© 2024. The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression., Objective: To assess the efficacy of improving type 2 diabetes (T2DM)., Study Design: This randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes., Methods: All subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A 1c, β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention., Results: After 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA 1c (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001., Conclusions: A 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial., Trial Registration: Thai clinical trials regentrify no.20140303003., (© 2024. The Author(s).)

Background: Total knee arthroplasty (TKA) demands precision in achieving optimal alignment and soft tissue balance, especially in cases of medial compartment osteoarthritis where the need for medial soft tissue release is critical yet challenging to ascertain., Objective: This study aims to systematically investigate the relationship between preoperative data, initial knee conditions and the necessity for deep collateral ligament (MCL) release in adjusted mechanical alignment total knee arthroplasty., Methods: We conducted a retrospective study involving 61 TKA patients who underwent adjusted mechanical alignment robotic-assisted procedures. Soft tissue release was carried out when clinically indicated. We collected and statistically analyzed patient demographics, initial knee conditions, and surgical details., Results: Among the patients, 52% required deep MCL release. Notably, patients without soft tissue release exhibited lower initial hip-knee-ankle (HKA) angles, reduced varus-valgus stress test angles, and a greater range of flexion. We identified a predictive threshold HKA angle of 6.250 degrees, demonstrating high sensitivity and specificity for determining the need for deep MCL release., Conclusion: This study underscores the significance of the initial HKA angle and varus-valgus stress tests in predicting deep MCL release during TKA. The established HKA angle threshold simplifies surgical decision-making, reducing the likelihood of unnecessary soft tissue release., (© 2024. The Author(s).)

Background: Medical students with sexual and gender diversity (SGD) often face challenges in educational performance and encounter more education-related problems, potentially due to discrimination in medical schools. This study aimed to compare academic difficulties, education-related issues, and experiences of discrimination among medical students with SGD versus those identifying as non-SGD., Methods: This was a cross-sectional study. Participants included a convenient sample of medical students aged at least 18 from five Thai medical schools, all recruited during the 2021 academic year. General demographic data, academic difficulties, education-related problems, and both positive and negative aspects of medical education, encompassing physical aspects, supporting systems, and discrimination, were assessed. The descriptive data and comparison between SGD and non-SGD medical students were performed. Binary logistic regression was adopted to evaluate the association between characteristics of discrimination in each categorized type of gender diversity., Results: Among 1322 medical students, 412 (31.2%) described themselves as having SGD. There was no significant difference in academic performance between SGD and non-SGD students. However, SGD students reported higher dropout thoughts (39.8% vs. 23.1%, p < 0.001) and self-perceived burnouts (84.2% vs. 74.9%, p < 0.001). The SGD group perceived lower support from medical staff and higher inadequate financial support (30.3% vs. 22.1%, p < 0.01; 11.2% vs. 23.1%, p < 0.01, respectively). 64.44% of students reported witnessing at least one form of discrimination. Lesbian students were more likely to report witnessing discrimination (OR = 3.85, [1.05-14.16]). Gay students were significantly associated with experiencing sexist remarks (OR = 6.53 [3.93-10.84]) and lower selectively prohibited educational opportunities (OR = 0.36 [0.21-0.63])., Conclusions: While academic performance did not differ between medical students with SGD and their non-SGD peers, SGD students reported more academic difficulties and perceived less support from medical staff and financial support. They also reported a higher incidence of discrimination. The need for specific interventions to address these issues should be further explored., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC), known for its aggressiveness and limited treatment options, presents a significant challenge. Adoptive cell transfer, involving the ex vivo generation of antigen-specific T cells from peripheral blood mononuclear cells (PBMCs), emerges as a promising approach. The overexpression of mesothelin (MSLN) and nucleolin (NCL) in TNBC samples underscores their potential as targets for T cell therapy. This study explored the efficacy of multi-peptide pulsing of PBMCs to generate MSLN/NCL-specific T cells targeting MSLN + /NCL + TNBC cells., Methods: TNBC patient samples were confirmed for both MSLN and NCL expression via immunohistochemistry. Synthesized MSLN and NCL peptides were combined and administered to activate PBMCs from healthy donors. The cancer-killing ability of the resultant T cells was assessed using crystal violet staining, and their subtypes and cytotoxic cytokines were characterized through flow cytometry and cytokine bead array., Results: Findings showed that 85.3% (127/149) of TNBC cases were positive for either MSLN or NCL, or both; with single positivity rates for MSLN and NCL of 14.1% and 28.9%, respectively. MSLN and NCL peptides, with high binding affinity for HLA-A*02, were combined and introduced to activated PBMCs from healthy donors. The co-pulsed PBMCs significantly induced T EM and T EMRA CD3 + /CD8 + T cells and IFN-γ production, compared to single-peptide pulsed or unpulsed conditions. Notably, MSLN/NCL-specific T cells successfully induced cell death in MSLN + /NCL + MDA-MB-231 cells, releasing key cytotoxic factors such as perforin, granzymes A and B, Fas ligand, IFN-γ, and granulysin., Conclusions: These findings serve as a proof-of-concept for using multiple immunogenic peptides as a novel therapeutic approach in TNBC patients., (© 2024. The Author(s).)

Background: Multimodal analgesia is crucial for effective postoperative pain management in minor hand surgeries, enhancing patient satisfaction. The use of local wound infiltration with Ketorolac as an adjuvant pain management strategy is proposed for open trigger finger release surgery. This study aims to compare pain scores and functional outcomes between local wound infiltration with Ketorolac and oral non-steroidal anti-inflammatory drugs., Methods: This study is a double-blind, parallel design, randomized controlled trials. Sixty-nine patients underwent trigger finger surgery between December 2021 and October 2022 were randomized into one of three groups: oral Ibuprofen alone group, local Ketorolac alone group and local Ketorolac with oral Ibuprofen group. The assessment included postoperative numeric rating scale (NRS) pain score, Disabilities of the Arm, Shoulder, and Hand (DASH) score, grip strength, mobility of proximal interphalangeal (PIP) joint. and complications., Results: NRS pain scores during movement of the operated fingers were significantly lower at 6 h in local Ketorolac alone group and local Ketorolac with oral Ibuprofen group compared to oral Ibuprofen alone group. However, there were no significant differences between the groups in postoperative DASH scores, grip strength, mobility of PIP joints, and complications., Conclusions: Local infiltration of Ketorolac as an adjunct in postoperative pain management has been shown to provide superior analgesia during finger movement within the initial 6 h following trigger finger surgery, in comparison to oral NSAIDs., Clinical Trial Registration: Thaiclinicaltrials.org identifier: TCTR20210825002. Registered 25/08/2021. https://www.thaiclinicaltrials.org/show/TCTR20210825002., (© 2024. The Author(s).)

Background: Lactobacillus acidophilus is a commensal urinary bacterium found more abundantly in healthy individuals than in stone patients. Hence, it has been proposed to play an inhibitory role in kidney stone disease (KSD) but with unclear mechanisms. We therefore investigated the direct effects of L. acidophilus on calcium oxalate (CaOx) stone development compared with Escherichia coli, which is known to promote CaOx stone formation., Results: L. acidophilus at 1 × 10 3 CFU/ml  significantly reduced the abundance of newly formed crystals, enlargement and aggregation of seeded crystals, and crystal adhesion on renal cell membranes. By contrast, E. coli at 1 × 10 3 CFU/ml significantly enhanced crystal growth and aggregation but did not affect crystallization and crystal-cell adhesion. Oxalate consumption assay showed that neither L. acidophilus nor E. coli significantly reduced the remaining oxalate level after 1 - 3 h incubation. However, both of them adhered to CaOx crystals. Surface component detection revealed that only L. acidophilus expressed S-layer protein, whereas only E. coli exhibited flagella on their surfaces. Removal of L. acidophilus S-layer protein and E. coli flagella completely abolished the inhibitory and promoting effects of L. acidophilus and E. coli, respectively., Conclusions: L. acidophilus inhibits CaOx stone development by hampering crystallization, growth, aggregation and cell-adhesive ability of CaOx. By contrast, E. coli enhances CaOx stone development by promoting CaOx growth and aggregation. Their contradictory effects are most likely from differential surface components (i.e., S-layer protein on L. acidophilus and flagella on E. coli) not from oxalate-degrading ability. Video Abstract., (© 2024. The Author(s).)

Background: Pregnant women are more likely to have a higher severity of illness after being infected with coronavirus disease 2019 compared with the general population, particularly in the hyperinflammatory phase. However, immunomodulatory drugs are contraindicated and have been associated with an increased risk of fetal abnormalities. Therefore, we are reporting our experience with the use of HA330 hemoperfusion in combination with standard therapy in severe to critical coronavirus disease 2019 cases among pregnant patients., Case Presentation: From January 2020 to December 2021, four pregnant Thai women were treated with hemoperfusion using a cytokine adsorptive technique. The patients' ages ranged from 21 to 36 years old, and their gestational ages at the time of admission ranged from 18 to 38 weeks. Two patients required intubation. Extracorporeal blood purification with an adsorptive cartridge (HA330 ® , Jafron, China) was applied as an adjunctive strategy to standard therapy approximately one week after the onset of symptoms, and most patients received three sessions of hemoperfusion. The baseline C-reactive protein level was greater than 80 mg/dL. The results showed that hemoperfusion could decrease the C-reactive protein level by approximately 80% and improve oxygenation. The newborns were delivered by Cesarean section without complications. Neither mortality nor serious adverse events related to hemoperfusion occurred., Conclusion: This report may help ensure the use of the hemoperfusion strategy in pregnant patients during a cytokine storm. However, a larger cohort is needed to confirm its safety and efficacy., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has significantly impacted individuals with chronic conditions. This investigation assessed the quality of care provided to pediatric and adolescent patients with juvenile idiopathic arthritis (JIA) during the pandemic in Thailand., Methods: This cross-sectional analysis enrolled JIA patients aged ≤ 18 years at an academic tertiary care facility from April 2022 to March 2023. Retrospective reviews were performed, complemented by patient and caregiver questionnaires to assess the pandemic's impact on care quality., Results: Seventy JIA patients (37 males, 33 females) with a mean age of 13.5 ± 3.1 years were included. A total of 41.4% of the caregivers reported negative impacts on JIA care due to the pandemic and the lockdown, and 31.4% of the patients experienced pandemic-related anxiety. A comparison between the pandemic and prepandemic periods revealed a higher incidence of active disease, although the difference was statistically nonsignificant (37.1% vs 14.2%, p = 0.106). Nonadherence significantly predicted active disease status (adjusted OR 15.04, 95% CI 2.48-91.15, p = 0.03). COVID-19 vaccinations were administered to 85.7% of patients; 52.8% of whom contracted mild COVID-19. Most patients (71.4%) postponed clinic visits; 36% due to lockdowns and 28% due to concerns about COVID-19 exposure in healthcare settings. The majority of patients received telephone JIA management advice from rheumatologists during the lockdown (91.4%)., Conclusions: The COVID-19 pandemic and associated lockdown measures affected the care of JIA patients, impacting both physical and mental health. Nonadherence was a critical factor in disease flare-ups. Telemedicine is indispensable for patient care., (© 2024. The Author(s).)

Background: Enthesitis-related arthritis (ERA) is a subtype of juvenile idiopathic arthritis with high disease burden. The objectives of this study were to explore the prevalence of HLA-B27, clinical characteristics, and treatment outcomes in children with ERA and compare the differences between HLA-B27 positive and negative patients., Methods: A retrospective cohort study at a pediatric rheumatology clinic in a tertiary referral hospital in Bangkok, Thailand, including ERA patients with at least 6 months of follow-up (July 2011-April 2022) was performed. Data were collected from medical records from diagnosis to recent follow-up, assessing disease activity and treatment outcomes, with an analysis comparing HLA-B27 positive and negative patients. Descriptive statistics were used for data analysis., Results: There were 59 ERA patients with mean age ± SD at diagnosis 11.2 ± 2.5 years, 53 males (89.8%), and positive HLA-B27 in 38 patients (64.4%). The HLA-B27 positive group had significantly higher levels of inflammatory markers at initial diagnosis (p = 0.001), lower baseline hemoglobin (p = 0.001) and hematocrit (p = 0.002), higher disease activity assessed by the Juvenile Spondyloarthritis Disease Activity score at 6 and 12 months of follow-up (p = 0.028 and 0.040, respectively), increased utilization of bridging systemic corticosteroids (60.5% vs. 14.3%, p = 0.001) and anti-TNF (39.5% vs. 9.5%, p = 0.018), and longer duration of methotrexate (median[IQR] 1.7[1.1-3.1] vs. 1.3[0.6-1.9] years, p = 0.040). The HLA-B27 negative group had more prevalent hip arthritis than the positive group at initial diagnosis (66.7% vs. 28.9%, p = 0.005) and during the course of the disease (71.4% vs. 36.8%, p = 0.011)., Conclusion: Most of the ERA patients tested positive for HLA-B27. Throughout the follow-up period, these patients demonstrated greater disease activity, greater use of corticosteroids and anti-TNF, and longer duration of methotrexate to control the disease., (© 2024. The Author(s).)

Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological and pathological processes. They play crucial roles in immune modulation and tissue regeneration but are also involved in pathogenic conditions like inflammation and degenerative disorders. EVs have heterogeneous populations and cargo, with numerous subpopulations currently under investigations. EV therapy shows promise in stimulating tissue repair and serving as a drug delivery vehicle, offering advantages over cell therapy, such as ease of engineering and minimal risk of tumorigenesis. However, challenges remain, including inconsistent nomenclature, complex characterization, and underdeveloped large-scale production protocols. This review highlights the recent advances and significance of EVs heterogeneity, emphasizing the need for a better understanding of their roles in disease pathologies to develop tailored EV therapies for clinical applications in neurological disorders., (© 2024. The Author(s).)

Background: Test enhancing learning (TEL) had shown a significant effect in promoting the learning of many learning contents. However, its effect on the postgraduate medical level was unclear. This study aimed to investigate the effect of TEL in 1st year anesthesiology residents learning neuroanesthesia., Method: The residents were randomized to either group A, which was assigned to do the intervention exam (exam A) for two times during learning in neuroanesthesia, or group B, which studied in the same environment without doing the exam. All participants were assigned to do the assessment exam (exam B) at one month after the end of the rotation. All of the exams were ten multiple choice questions (MCQ). Since the anesthesia residents rotated to neuroanesthesia for two weeks twice during the first year, we conducted the experiments twice, using exams that covered both basic science (BS) and clinical science (CS) topics., Results: There was no significant difference in mean ± SD of the scores for assessment exams asking about the basic science topic (BS&#95;B) [group A (5.25 ± 2.05) VS group B (4.90 ± 1.80); p = 0.570] and the clinical science topic (CS&#95;B) [group A (6.30 ± 1.26) VS group B (5.95 ± 1.61); p = 0.448]., Conclusion: This study showed null findings on the effect of TEL on learning in residents of the first year of anesthesiology. More studies on TEL were required to confirm the effect of TEL and find the appropriate test format that could enhance learning for post-graduate medical trainees., (© 2024. The Author(s).)

Background: The adoption of robot-assisted total knee arthroplasty (TKA) aims to enhance the precision of implant positioning and limb alignment. Despite its benefits, the adoption of such technology is often accompanied by an initial learning curve, which may result in increased operative times. This study sought to determine the learning curve for the ROSA (Robotic Surgical Assistant) Knee System (Zimmer Biomet) in performing TKA and to evaluate the accuracy of the system in executing bone cuts and angles as planned. The hypothesis of this study was that cumulative experience with this robotic system would lead to reduced operative times. Additionally, the ROSA system demonstrated reliability in terms of the accuracy and reproducibility of bone cuts., Methods: In this retrospective observational study, we examined 110 medical records from 95 patients who underwent ROSA-assisted TKA performed by three surgeons. We employed the cumulative summation methodology to assess the learning curves related to operative time. Furthermore, we evaluated the accuracy of the ROSA Knee System in performing TKA by comparing planned versus validated values for femoral and tibial bone cuts and angles., Results: The learning curve for the ROSA Knee System spanned 14, 14, and 6 cases for the respective surgeons, with operative times decreasing by 22 min upon reaching proficiency (70.8 vs. 48.9 min; p < 0.001). Significant discrepancies were observed between the average planned and validated cuts and angles for femoral bone cuts (0.4 degree ± 2.4 for femoral flexion, 0.1 degree ± 0.6 for femoral coronal alignment, 0.3 mm ± 1.2 for distal medial femoral resection, 1.4 mm ± 8.8 for distal lateral femoral resection) and hip-knee-ankle axis alignment (0.3 degree ± 1.9 )(p < 0.05) but not for tibial bone cuts. Differences between planned and validated measurements during the learning and proficiency phases were nonsignificant across all parameters, except for the femoral flexion angle (0.42 degree ± 0.8 vs. 0.44 degree ± 2.7) (p = 0.49)., Conclusion: The ROSA Knee System can be integrated into surgical workflows after a modest learning curve of 6 to 14 cases. The system demonstrated high accuracy and reproducibility, particularly for tibial bone cuts. Acknowledging the learning curve associated with new robot-assisted TKA technologies is vital for their effective implementation., (© 2024. The Author(s).)

Background: Childhood-onset systemic lupus erythematosus (c-SLE) is a multifaceted autoimmune disorder predominantly affecting the musculoskeletal (MSK) system. This investigation delineated the spectrum and sequelae of MSK involvement in c-SLE patients., Methods: This retrospective analysis included SLE patients aged ≤ 18 years treated at a tertiary center between 2009 and 2019. Data were extracted from electronic health records., Results: The cohort comprised 321 SLE patients (mean age 13.2 ± 2.5 years, 91.3% female). MSK manifestations were observed in 134 (41.7%) individuals, with joint pain universally present, followed by joint swelling in 32.1% and morning stiffness in 9.7%. Arthritis was documented in 52 (38.8%) patients, whereas 82 (61.2%) had arthralgia. Symmetrical joint involvement was observed in 96 (71.7%) subjects. The knees, wrists, and fingers were most commonly affected, with incidences of 43.3%, 40.3%, and 33.6%, respectively. Neither erosive arthritis nor Jaccoud's arthropathy was detected. MSK symptoms were significantly correlated with older age at diagnosis, the presence of non-scarring alopecia, neuropsychiatric manifestations, and elevated SLE disease activity index scores at diagnosis. Over a median follow-up of 53.6 months (IQR 26.1-84.6), five patients developed septic arthritis or osteomyelitis, and avascular necrosis was identified in 16 (4.9%) patients., Conclusions: Nearly half of c-SLE patients demonstrated MSK manifestations, chiefly characterized by symmetrical involvement of both large and small joints without evidence of erosive arthritis or Jaccoud's arthropathy. Avascular necrosis is a critical concern and warrants close monitoring., (© 2024. The Author(s).)

Background: The current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 -) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib., Methods: This multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 - ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events., Results: Of the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55-1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29-1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%)., Conclusion: This preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 - ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted., (© 2024. The Author(s).)

Introduction: Within the Thai medical curriculum, its rigorous education framework, demanding schedules and high academic standards can contribute to psychological distress. Regular physical activity has consistently shown positive effects on mental health. The aim of the study was to investigate the association between exercise and psychological well-being, including depression, anxiety, and burnout, in Thai medical students, and factors related to insufficient exercise and depression., Methods: The cross-sectional study was conducted among medical students in the university hospital during 2020-2021. Participants completed self-administered questionnaires consisting of demographic data, Godin-Shephard Leisure-Time Physical Activity Questionnaire, depression screening (9Q), Thai General Health Question-28 (4 domains: somatic symptoms, anxiety and insomnia, social dysfunction, severe depression), and Maslach burnout inventory (Emotional exhaustion (EE), Depersonalization (DP), Reduced Personal Achievement (rPA)., Results: Of the 404 participants, 50.5% were women, the mean age (SD) was 21.06 (1.8) years, and 52% were in clinical years. The prevalence of insufficient exercise was 59.6%, depression (30.2%), somatic symptoms (27.7%), anxiety (30.7%), insomnia (89.4%), social dysfunction (89.4%), high level of EE (32.4%), DP (21%), and rPA (56.7%). Insufficient exercise was associated with moderate to severe depression (OR 2.89, 95% CI 1.16-7.25), anxiety and insomnia (OR 1.56, 95% CI 1.01-2.43), social dysfunction (OR 2.51, 95% CI 1.31-4.78), burnout in part due to high rPA (OR 2.4, 95% CI 1.4-4.13), and study in clinical years (OR 1.91, 95% CI 1.28-2.87). After adjusted significant factors, only studying in the clinical year, social dysfunction, and burnout in part of rPA were related to insufficient exercise., Conclusions: High rates of insufficient exercise, psychological challenges, and burnout were prevalent among medical students. To effectively address these issues, medical school should advise students to participate in regular exercise, promoting mental well-being and healthier lifestyles., (© 2024. The Author(s).)

Purpose: To compare the postoperative pain score, opioid consumption, and blood loss in knee osteoarthritis patients who underwent unilateral primary total knee arthroplasty with and without intraoperative cold solution irrigation., Method: In total, 70 knee osteoarthritis patients were randomly included in the study and allocated into 2 groups. The first group was irrigated intraoperatively with a cold solution and the second group was irrigated intraoperatively with a room-temperature solution., Results: The cold solution group showed significantly lower pain scores (numerical rating scale, NRS) at 28 h postoperatively (p = 0.047). There were no significant differences in opioid consumption or blood loss between the groups., Conclusions: Intraoperative cold solution irrigation in unilateral primary total knee arthroplasty patients may provide the benefit of early postoperative pain reduction for up to 28 h but has no effect in terms of reducing opioid consumption or blood loss., Trial Registration: The trial was registered in the Thai Clinical Trials Registry (TCTR) Trial registration number ID: TCTR20200706001 on 06/07/2020., (© 2024. The Author(s).)

Background: Rheumatic mitral stenosis (MS) remains a common and concerning health problem in Asia. Percutaneous balloon mitral valvuloplasty (PBMV) is the standard treatment for patients with symptomatic severe MS and favorable valve morphology. However, studies on the incidence and predictors of adverse cardiac outcomes following PBMV in Asia have been limited. This study aims to evaluate the incidence and predictors of adverse outcomes in patients with rheumatic MS following PBMV., Methods: A retrospective cohort study was conducted on patients with symptomatic severe MS who underwent successful PBMV between 2002 and 2020 at a tertiary academic institute in Thailand. Patients were followed up to assess adverse outcomes, defined as a composite of cardiac death, heart failure hospitalization, repeat PBMV, or mitral valve surgery. Univariable and multivariable analyses were performed to identify predictors of adverse outcomes. A p-value of < 0.05 was considered statistically significant., Results: A total of 379 patients were included in the study (mean age 43 ± 11 years, 80% female). During a median follow-up of 5.9 years (IQR 1.7-11.7), 74 patients (19.5%) experienced adverse outcomes, with an annualized event rate of 2.7%. Multivariable analysis showed that age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.008-1.05, p = 0.006), significant tricuspid regurgitation (HR 2.17, 95% CI 1.33-3.56, p = 0.002), immediate post-PBMV mitral valve area (HR 0.39, 95% CI 0.25-0.64, p = 0.01), and immediate post-PBMV mitral regurgitation (HR 1.91, 95% CI 1.18-3.07, p = 0.008) were independent predictors of adverse outcomes., Conclusions: In patients with symptomatic severe rheumatic MS, the incidence of adverse outcomes following PBMV was 2.7% per year. Age, significant tricuspid regurgitation, immediate post-PBMV mitral valve area, and immediate post-PBMV mitral regurgitation were identified as independent predictors of these adverse outcomes., (© 2024. The Author(s).)

Background: Despite advances in surgical techniques, the incidence of stroke following acute type A aortic dissection (ATAAD) repair remains markedly high, with substantial immediate and long-term adverse outcomes such as elevated mortality, extended hospital stays, and persistent neurological impairments. The complexity of managing ATAAD extends beyond the operation itself, highlighting a crucial gap in research concerning modifiable preoperative patient conditions and perioperative anesthetic management strategies., Objectives: This investigation aimed to elucidate the incidence, consequences, and perioperative determinants of stroke following surgical intervention for acute type A aortic dissection (ATAAD)., Methods: In a multicenter retrospective analysis, 516 ATAAD surgery patients were evaluated. The data included demographic information, clinical profiles, surgical modalities, and outcomes. The primary endpoint was postoperative stroke incidence, with hospital mortality and other complications serving as secondary endpoints., Results: Postoperative stroke occurred in 13.6% of patients (70 out of 516) and was associated with significant extension of the ICU (median 10 vs. 5 days, P < 0.001) and hospital stay (median 18 vs. 12 days, P < 0.001). The following key independent stroke risk factors were identified: modified Frailty Index (mFI) ≥ 4 (odds ratio [OR]: 4.18, 95% confidence interval [CI]: 1.24-14.1, P = 0.021), common carotid artery malperfusion (OR: 3.76, 95% CI: 1.23-11.44, P = 0.02), pre-cardiopulmonary bypass (CPB) hypotension (mean arterial pressure ≤ 50 mmHg; OR: 2.17, 95% CI: 1.06-4.44, P = 0.035), ≥ 20% intraoperative decrease in cerebral regional oxygen saturation (rSO 2 ) (OR: 1.93, 95% CI: 1.02-3.64, P = 0.042), and post-CPB vasoactive-inotropic score (VIS) ≥ 10 (OR: 2.24, 95% CI: 1.21-4.14, P = 0.01)., Conclusions: Postoperative stroke significantly increases ICU and hospital durations in ATAAD surgery patients. These findings highlight the critical need to identify and mitigate major risks, such as high mFI, common carotid artery malperfusion, pre-CPB hypotension, significant cerebral rSO 2 reductions, and elevated post-CPB VIS, to improve outcomes and reduce stroke prevalence., Trial Registration: Thai Clinical Trials Registry (TCTR20230615002). Date registered on June 15, 2023. Retrospectively registered., (© 2024. The Author(s).)

Objective: Patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) can present with diabetic ketoacidosis (DKA) as the first manifestation. Differentiating types of newly diagnosed diabetes could provide appropriate long-term management. Therefore, we conducted this study to compare clinical characteristics and outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with DKA., Materials and Methods: A retrospective study was conducted on adult patients who presented with DKA as the first diagnosis of diabetes in our tertiary hospital between January 2005 and December 2019. Demographic data, precipitating causes, laboratory investigations, treatment, and outcomes were obtained by chart review. The primary outcome was to compare the clinical characteristics of initially diagnosed patients with T1DM and T2DM who presented with DKA., Results: A total of 100 initially diagnosed diabetic patients who presented with DKA were analyzed (85 T2DM patients and 15 T1DM patients). Patients with T1DM were younger than patients with T2DM (mean age 33 ± 16.2 vs. 51 ± 14.5 years, p value < 0.001). Patients with T2DM had a higher body mass index, family history of diabetes, precipitating factors, plasma glucose, and lower renal function than those with T1DM. There was no difference in resolution time or DKA management between T1DM and T2DM patients. The overall mortality rate of DKA was 4%., Conclusion: In this population, most adult patients who presented with DKA had T2DM. Older age, obesity, a family history of diabetes, and the presence of precipitating factors were strong predictors of T2DM. We can implement the same clinical management for DKA in both T1DM and T2DM patients. However, T2DM patients had longer hospitalization than T1DM patients. After DKA resolution for 12 months, more than half of patients with T2DM could discontinue insulin. Therefore, the accurate classification of the type of diabetes leads to appropriate treatment., (© 2024. The Author(s).)

Introduction: International medical trainees, including residents and fellows, must cope with many challenges, such as differences in cultural hierarchical systems, languages, and acceptance. Nonetheless, the need for adjustment perpetuates even after training is completed abroad. When some international trainees return to their countries of origin, they continue to face adjustment challenges due to reverse culture shock. Others must make many further readjustments. This study presents an exploration of the adjustment and coping strategies of international medical learners after returning to their countries of origin upon completion of their programs., Method: This study employed a qualitative approach grounded in interpretivism and utilised inductive thematic analysis following Braun and Clarke's method. Semi-structured, in-depth individual interviews were employed to explore the participants' coping strategies. Participants included international medical learners who were (1) international medical graduates who had already returned to their countries of origin, (2) non-Canadian citizens or nonpermanent residents by the start of the programs, and (3) previously enrolled in a residency or fellowship training programme at the University of Toronto, Ontario, Canada., Results: Seventeen participants were included. Three main themes and seven subthemes were created from the analysis and are represented by the Ice Skater Landing Model. According to this model, there are three main forces in coping processes upon returning home: driving, stabilising, and situational forces. The sum and interaction of these forces impact the readjustment process., Conclusion: International medical learners who have trained abroad and returned to their countries of origin often struggle with readjustment. An equilibrium between the driving and stabilising forces is crucial for a smooth transition. The findings of this study can help stakeholders better understand coping processes. As healthy coping processes are related to job satisfaction and retention, efforts to support and shorten repatriation adjustment are worthwhile., (© 2024. The Author(s).)