Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Objective: To validate the analytical performance, operational performance, and process control measures of a domestic fully automatic nucleic acid testing (NAT) system, thereby ensuring an efficient and orderly blood screening workflow. Methods: The concordance rate and sensitivity of WanTag-Vortex Plus system were verified using WHO standard reference panels of HIV-1, HCV and HBV, while precision was assessed using weak positive samples of HIV-1, HCV and HBV. As for its operational performance evaluation, cross-contamination resistance was assessed using strong positive samples, and throughput and stress testing were conducted using negative samples. Reagent stability was verified using weak positive samples, and inter-system performance consistency was assessed using verification panels. In addition, the process control measures were verified using the laboratory quality control demand scale. Results: 1) Verification of concordance rate: The detection results of negative and positive samples of HIV-1, HCV and HBV by WanTag-Vortex Plus system were all consistent with expectations, and the concordance rate was 100%. 2) Precision verification: the repeatability and intermediate precision were extremely high, and the coefficient of variation was less than 5%. 3) Verification of analytical sensitivity: The detection limit of 95% for standard strains of HIV-1, HCV and HBV by WanTag-Vortex Plus system in our laboratory was consistent with the analytical sensitivity provided by reagent manufacturers. 4) Verification of cross-contamination resistance: Five strong positive samples and 87 negative samples were placed according to the actual working conditions and equipment operation design, and the test results were consistent with expectations, with no cross-contamination in the testing system. 5) Throughput and stress testing: Each system completed the individual donor-nucleic acid amplification testing (ID-NAT) of 276 samples in three batches within 12 hours, and successfully completed the ID-NAT test of 828 samples in three consecutive days. 6) Verification of reagent stability: After extreme storage (unsealed storage for 1 week with 4 freeze-thaw cycles), the reagents maintained 100% detection rate in the weak positive samples of HIV-1, HCV, and HBV, showing no significant differences from the control group (Kappa=1). 7) Verification of inter-system performance consistency: The system has stable operation performance, and the performance comparison results across the four devices were consistent (Kappa=1). 8) Process control measures: WanTag-Vortex Plus system software accurately controlled the equipment operation process with strict quality control measures, and correctly interpreted and safely reported the test results. Conclusion: The analytical and operational performance of the WanTag-Vortex Plus system complies with manufacturer design standards and essential laboratory workflow requirements. Integrated with laboratory information system (LIS), the system's control software meets standard process control requirements, yet requires further improvement.

Objective: To validate the analytical performance, operational performance, and process control measures of a domestic fully automatic nucleic acid testing (NAT) system, thereby ensuring an efficient and orderly blood screening workflow. Methods: The concordance rate and sensitivity of WanTag-Vortex Plus system were verified using WHO standard reference panels of HIV-1, HCV and HBV, while precision was assessed using weak positive samples of HIV-1, HCV and HBV. As for its operational performance evaluation, cross-contamination resistance was assessed using strong positive samples, and throughput and stress testing were conducted using negative samples. Reagent stability was verified using weak positive samples, and inter-system performance consistency was assessed using verification panels. In addition, the process control measures were verified using the laboratory quality control demand scale. Results: 1) Verification of concordance rate: The detection results of negative and positive samples of HIV-1, HCV and HBV by WanTag-Vortex Plus system were all consistent with expectations, and the concordance rate was 100%. 2) Precision verification: the repeatability and intermediate precision were extremely high, and the coefficient of variation was less than 5%. 3) Verification of analytical sensitivity: The detection limit of 95% for standard strains of HIV-1, HCV and HBV by WanTag-Vortex Plus system in our laboratory was consistent with the analytical sensitivity provided by reagent manufacturers. 4) Verification of cross-contamination resistance: Five strong positive samples and 87 negative samples were placed according to the actual working conditions and equipment operation design, and the test results were consistent with expectations, with no cross-contamination in the testing system. 5) Throughput and stress testing: Each system completed the individual donor-nucleic acid amplification testing (ID-NAT) of 276 samples in three batches within 12 hours, and successfully completed the ID-NAT test of 828 samples in three consecutive days. 6) Verification of reagent stability: After extreme storage (unsealed storage for 1 week with 4 freeze-thaw cycles), the reagents maintained 100% detection rate in the weak positive samples of HIV-1, HCV, and HBV, showing no significant differences from the control group (Kappa=1). 7) Verification of inter-system performance consistency: The system has stable operation performance, and the performance comparison results across the four devices were consistent (Kappa=1). 8) Process control measures: WanTag-Vortex Plus system software accurately controlled the equipment operation process with strict quality control measures, and correctly interpreted and safely reported the test results. Conclusion: The analytical and operational performance of the WanTag-Vortex Plus system complies with manufacturer design standards and essential laboratory workflow requirements. Integrated with laboratory information system (LIS), the system's control software meets standard process control requirements, yet requires further improvement.

INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a significant cause of disease morbidity. One-third of patients with ASUC are steroid refractory. Rescue therapy may not successfully induce remission, necessitating colectomy. We aimed to identify predictors of rescue therapy and colectomy in ASUC assessed within 24 h of admission for early risk stratification. METHODS: We conducted a retrospective cohort study of 58 admissions for ASUC among 47 patients from August 2002 to January 2022. Serum biomarkers assessed were measured on admission. Primary outcomes were the need for rescue therapy during the same admission and colectomy within 1 year of admission. RESULTS: Rescue therapy (all with infliximab) was given in 20 (34.5%) of the admissions. Colectomy was done within 1 year for nine (15.5%) of the admissions. An elevated C-reactive protein (CRP) of >30 mg/L (relative risk [RR] 1.63), a CRP-albumin ratio of >0.85 (RR 1.63), and a composite factor of both CRP > 30 mg/L and age ≥60 years (RR 2.37) were significantly associated with the need for rescue therapy. Hypoalbuminaemia ≤ 25 g/L (RR 4.35) and the use of biologics at presentation (RR 1.54) were significantly associated with colectomy within 1 year of admission, while a CRP of ≥ 80 mg/L was a significant protective factor (RR 0.70). CONCLUSION Patients with ASUC who have elevated CRP or CRP-albumin ratio on admission should be considered at risk for steroid-refractory disease. Those with hypoalbuminaemia on admission and using biologics at presentation are more likely to require colectomy in the first year after admission for ASUC.
Humans ; Colitis, Ulcerative/therapy* ; Colectomy ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult ; C-Reactive Protein/metabolism* ; Infliximab/therapeutic use* ; Biomarkers/blood* ; Acute Disease ; Aged ; Severity of Illness Index ; Treatment Outcome

Environmental damage affects many aspects of healthcare, from extreme weather events to evolving population disease. Singapore's healthcare sector has the world's second highest healthcare emissions per capita, hampering the nation's pledge to reduce emissions by 2030 and achieve net zero emissions by 2050. In this review, we provide an overview of the impact environmental damage has on healthcare, including facilities, supply chain and human health, and examine measures to address healthcare's impact on the environment. Utilising the 'R's of sustainability - rethinking, reducing/refusing, reusing/repurposing/reprocessing, repairing, recycling and research - we have summarised the opportunities and challenges across medical disciplines. Awareness and advocacy to adopt strategies at institutional and individual levels is needed to revolutionise our environmental footprint and improve healthcare sustainability. By leveraging evidence from ongoing trials and integrating sustainable practices, our healthcare system can remain resilient against environment-driven challenges and evolving healthcare demands while minimising further impacts of environmental destruction.
Humans ; Climate Change ; Delivery of Health Care ; Singapore ; Conservation of Natural Resources ; Sustainable Development ; Environment

INTRODUCTION: Degenerative mitral stenosis (DMS) is frequently cited as increasing in prevalence in the developed world, although comparatively little is known about DMS in comparison to rheumatic mitral stenosis (RMS). METHOD: A retrospective observational study was conducted on 745 cases of native-valve mitral stenosis (MS) with median follow-up time of 7.25 years. Clinical and echocardiographic parameters were compared. Univariate and multivariate Cox regression analyses were performed for a composite of all-cause mortality and heart failure hospitalisation. RESULTS: Patients with DMS compared to RMS were older (age, mean ± standard deviation: 69.6 ± 12.3 versus [vs] 51.6 ± 14.3 years, respectively; P<0.001) and a greater proportion had medical comorbidities such as diabetes mellitus (78 [41.9%] vs 112 [20.0%], P<0.001). The proportion of cases of degenerative aetiology increased from 1.1% in 1991-1995 to 41.0% in 2016-2017. In multivariate analysis for the composite outcome, age (hazard ratio [HR] 95% confidence interval [CI] of 1.032 [1.020-1.044]; P<0.001), diabetes mellitus (HR 1.443, 95% CI 1.068-1.948; P=0.017), chronic kidney disease (HR 2.043, 95% CI 1.470-2.841; P<0.001) and pulmonary artery systolic pressure (HR 1.019, 95% CI 1.010- 1.027; P<0.001) demonstrated significant indepen-dent associations. The aetiology of MS was not independently associated with the composite outcome. CONCLUSION DMS is becoming an increasingly common cause of native-valve MS. Despite numerous clinical differences between RMS and DMS, the aetiology of MS did not independently influence a composite of mortality or heart failure hospitalisation.
Humans ; Mitral Valve Stenosis/etiology* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Rheumatic Heart Disease/mortality* ; Echocardiography ; Hospitalization/statistics & numerical data* ; Heart Failure/epidemiology* ; Singapore/epidemiology* ; Proportional Hazards Models ; Diabetes Mellitus/epidemiology*

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries