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Sodium-glucose cotransporter2 inhibitors and associated liver-related outcomes in diabetes patients
No full text[[abstract]]Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with poorer liver-related outcomes in type 2 diabetes (T2D) patients. We compared risk of liver-related outcomes and all-cause mortality between sodium-glucose cotransporter-2 inhibitor (SGLT-2i) users and nonusers in T2D patients. Methods: We identified 282,161 T2D patients from the Taiwan National Health Insurance Research Database (2009-2020), excluding those with viral hepatitis or alcohol-related disorders. Propensity score matching created patient pairs on SGLT-2i and other antidiabetic drugs, and Cox proportional hazard models assessed outcomes. Results: Over a mean follow-up of 2.7 years, SGLT-2i use was associated with significantly lower risk of liver cirrhosis (adjusted hazard ratio [aHR] 0.78, 95 % CI: 0.70-0.87), decompensated cirrhosis (aHR 0.79, 95 % CI: 0.70-0.89), liver failure (aHR 0.78, 95 % CI: 0.68-0.89), and all-cause mortality (aHR 0.52, 95 % CI: 0.51-0.54). Compared to dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), pioglitazone, and sulfonylureas, SGLT-2i use was associated with lower risk of cirrhosis, liver failure, and allcause mortality. SGLT-2i use was associated with lower liver-related mortality than DPP-4i or GLP-1 RA use. Conclusions: This cohort study suggests that SGLT-2i may reduce the risk of liver cirrhosis, decompensated cirrhosis, liver failure, and liver-related and all-cause mortality in T2D patients
Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele
No full text[[abstract]]Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10(-)(9)), including two secondary signals. Notably, we identified and replicated a novel low-frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine
Revisiting maternal age and child health: A nationwide birth cohort study in Taiwan
No full text[[abstract]]BACKGROUND: Delayed childbearing is a growing trend globally, with Taiwan experiencing one of the steepest increases in maternal age. Advanced maternal age affects offspring health, including birth outcomes and long-term morbidity. However, its impact in Taiwan remains underexplored. This study investigates these effects using a nationwide birth cohort. METHODS: This retrospective cohort study utilized data from Taiwan's National Health Insurance Research Database (NHIRD), covering infants born from January 1, 2004, to December 31, 2014. The cohort included 2,068,672 infants, categorized into six maternal age groups: <20, 20-24, 25-29, 30-34, 35-40, and ≥40 years. Principal outcomes were stillbirth, mortality, preterm birth, congenital anomalies, neurodevelopmental outcomes, and atopic diseases. Multivariate logistic regression models adjusted for covariates to assess associations between maternal age and health outcomes. RESULTS: Among the 2,068,672 infants, stillbirth and mortality rates were highest in infants born to mothers <20 years, decreased with increasing maternal age, then rose again for mothers ≥30 years, showing a reverse J-shaped pattern. Similar trends were noted for preterm birth, congenital anomalies, and neurodevelopmental outcomes. Atopic diseases followed a nonlinear trend, peaking at maternal age 25-34 years. CONCLUSION: Maternal age significantly impacts child health, with risks associated with both younger and older maternal ages. These findings are crucial for regions experiencing delayed childbearing. Further research is needed to explore underlying mechanisms and establish causality
Silicosarcoidosis: Histologic and clinical features of an occupational granulomatous disease
No full text[[abstract]]Sarcoidosis is a multisystem inflammatory disease of unknown etiology. Growing evidence indicates that occupational exposure to respirable crystalline silica (RCS) is associated with an increased incidence of sarcoidosis. Yet a diagnosis of sarcoidosis rarely prompts investigation to identify preventable exposures. We sought to elucidate features that identify this important clinical syndrome of silicosarcoidosis. We assembled a multinational case series of workers with sarcoidosis who also reported occupational RCS exposure. We characterized clinical and histopathologic findings using a standardized instrument. We also assessed lung specimens using a novel quantitative microscopy technique to measure birefringent dust density in silicosarcoidosis cases and compared them to control groups. We identified 35 silicosarcoidosis cases (97% male, mean age 48 years) from the United States, Israel, and Taiwan who reported 21 ± 9 years of RCS exposure. On histology scoring, 25/29 (86%) had granulomas and 17/18 (94%) with evaluable lung tissue had lymphocytic inflammation and/or lymphoid aggregates. Common lung interstitial findings included silicotic nodules (39%), mixed-dust macules/nodules (44%), and birefringent dust (50%). Quantitative birefringent dust density was significantly greater (p < 0.001) in silicosarcoidosis cases compared with healthy controls (147 ± 179 vs. 12 ± 9 particles/mm(2)) but lower than in coal miners with silica-related progressive massive fibrosis (623 ± 777). We found significant differences in the frequency of histologic abnormalities in large versus small biopsy specimens, with fewer findings of RCS exposure in smaller tissue samples. The use of the term silicosarcoidosis should enhance recognition of this significant exposure-related granulomatous lung disease and will help guide clinical management that addresses exposure prevention in combination with appropriate pharmacologic treatment
Effectiveness of molnupiravir as early treatment for COVID-19 to prevent mortality and hospitalisation in high-risk adults: A systematic review and meta-analysis of randomised trials and real-world studies involving 1,612,082 patients
No full text[[abstract]]Background: The efficacy of molnupiravir for COVID-19 treatment remains controversial due to substantial heterogeneity in dosage and study settings across randomised controlled trials (RCTs). Method: We systematically searched Medline, PubMed, Embase, and the Cochrane Register of Clinical Trials up to February 3, 2025, for RCTs and real-world studies evaluating molnupiravir 800 mg twice daily as an early treatment for COVID-19 to prevent mortality and hospitalisation in high-risk adult outpatients. The primary outcomes were all-cause mortality and all-cause hospitalisation. Random-effects models were used to estimate pooled effect sizes. Results: Thirty-four studies were included, comprising 30,345 participants from 11 RCTs and 1,581,737 participants from 23 cohort studies. Molnupiravir reduced mortality risk by 55 %–65 % at 28 days (RCTs: risk ratio [RR] 0.35; 95 % CI 0.12–0.98, I2 0 %; cohort studies: RR 0.45; 95 % CI 0.27–0.73, I2 91 %). This benefit persisted at 3 months (RR 0.47; 95 % CI 0.23–0.95, I2 93 %) and 6 months (RR 0.62; 95 % CI 0.52–0.74, I2 0 %). The effectiveness in preventing 28-day hospitalisation varied by participants’ mean age in both RCTs (35–45 vs. 45–57 years: RR 0.55; 95 % CI 0.36–0.84 vs. 1.06; 95 % CI 0.81–1.39, subgroup difference P = 0.01) and cohort studies (62–74 vs. 75–85 years: RR 0.88; 95 % CI 0.77–1.01 vs. 0.56; 95 % CI 0.44–0.72, subgroup difference P < 0.01). Conclusions: Molnupiravir significantly reduces the risk of mortality. It also lowers the risk of hospitalisation in the oldest group (mean age ≥75 years) but not in younger groups (mean age 45–74 years)
Zranb1 and mib1 regulate zebrafish convergent extension via Ryk
No full text[[abstract]]Ryk, a member of receptor related tyrosine kinase, acts as a receptor for the Wnt signaling pathway through binding with Wnt3, Wnt5 and Wnt11. It plays an important role in neurogenesis, axon guidance, polarity of stereocilia hair cells in the cochlea and convergent extension during embryonic gastrulation. In zebrafish, the Wnt5b/Ryk-mediated non-canonical Wnt signaling pathway is required for convergent extension that provides a cue for directing cell migration away from Wnt5b source. Although the multiple roles of the Ryk-mediated Wnt signaling pathway have been elucidated, the regulatory mechanism is not well understood. Here, we found that deubiquitzylase zinc finger, RAN binding domain containing 1b (Zranb1b) and ubiquitin E3 ligase Mind bomb (Mib1) are involved in the regulation of the Ryk-mediated non-canonical Wnt signaling pathway in zebrafish. Our data revealed that zebrafish embryos with knockdown of zranb1b by morpholino exhibited convergent extension defects, including short trunk, wide somites and thick noto- chord, which were similar to embryos with wnt5b mutations or ryk/ wnt5b knockdown. In addition, zranb1b knockdown also slowed cell migration during zebrafish gastrulation, demonstrated by cell transplantation assay. On the other hand, overexpression of mib1 led to convergent extension defects. Both zranb1b and mib1 had genetic interaction with ryk because the defects in convergent extension caused by ryk knockdown were synergistically enhanced by zranb1b knockdown or mib1 overexpression. Moreover, Ryk was an interacting protein and common substrate of Zranb1b and Mib1. The Ryk on cell surface was reduced in embryos with zranb1b knockdown or with mib1 overexpression; in contrast, the internal- ization of Ryk to late endosomes was increased. These results suggest that balanced deubiquitylation and ubiquitylation of Ryk regulated by Zranb1b and Mib1 is required for maintaining Ryk on the cell surface to modulate the non-canonical Wnt signaling pathway during convergent extension in zebrafish
Modified citrus pectin protects aortic dissection development involving macrophage pyroptosis
No full text[[abstract]]Background Uncontrolled aortic aneurysms can progress to aortic dissection (AD), a severe vascular disorder characterized by hematoma formation in the aortic wall, with inflammation playing a crucial role. Galectin-3 (Gal-3), a 26-kDa lectin, regulates many aspects of inflammatory cell behavior. Inhibition of Gal-3 ameliorates diabetic neuroinflammation and cardiomyopathy. Modified citrus pectin (MCP) is a PH-modified dietetic supplement produced from citrus pectin. This study investigates the therapeutic potential of MCP, which has a known affinity for Gal-3, in AD. Methods A murine model of AD was induced by beta-aminopropionitrile fumarate (BAPN)/angiotensin II (Ang-II) and treated orally with either 100 mg/kg MCP or vehicle. In vitro, H2O2 treatment was applied to RAW264.7 cells to detect macrophage death and pyroptosis. Results MCP administration significantly reduced AD incidence and mortality, with decreased inflammatory cell infiltration in the aorta. MCP downregulated genes associated with inflammation and pyroptosis. In vitro, MCP mitigated macrophage death and pyroptosis induced by H2O2 treatment. The study suggests that MCP's protective effects are due to its interference with the Gal-3 and TLR4 interaction, inhibiting pyroptotic macrophage-induced inflammation. Conclusion MCP could improve patient outcomes and reduce progression to severe forms of AD. Clinically, MCP could serve as supportive therapy to prevent and delay aortic dissection, particularly during the acute stage of uncomplicated type B AD in patients with Marfan syndrome or abdominal aortic aneurysm
The resting-state EEG correlates of delusion-prone experiences in healthy young adults
No full text[[abstract]]Introduction: Delusion is a mental state of fixed false beliefs that conflict with an external reality. Delusions have been identified as one of the main symptoms in the assessment of mental illness. Previous studies investigating neurocognitive mechanisms associated with delusions have focused on patients with mental disorders, but research focusing on healthy individuals who may have delusion-prone experiences remains limited. This study aims to examine whether and how delusion-prone experiences modulate neurophysiological signals in healthy young adults using behavioral task and resting-state electroencephalogram (EEG) technique. Methods: Twelve healthy young adults (4 females, 8 males; age range 20-27 years, mean = 24 ± 1.74 years; education, 16.6 ± 1.59 years) participated in this EEG study. All participants completed the 21-item version of the Peters Delusional Inventory to assess their level of delusional ideation (Peters et al., 1999). Each item is answered with a yes or no, and participants rate their responses along three dimensions: distress (1 = not at all distressing, 5 = very distressing), preoccupation (1 = hardly ever think about it, 5 = think about it all the time), and conviction (1 = don't believe it's true, 5 = absolutely believe it's true). Based on the median yes/no score of the PDI, participants were divided into two groups: high delusional ideation group (DLE, n = 5; mean = 146.57 ± 42.94) and low delusional ideation group (NDLE, n = 7; mean = 24 ± 5.22). A behavioral task using the modified Mnemonic Similarity Task (MST) was designed to assess false memory performance (Leger et al., 2024). In the encoding phase, participants viewed 128 images of real objects and categorized them as 'inside' or 'outside'. After 30 min of rest, a surprise recognition test was administered in which participants identified 192 images as 'old' or 'new'. Resting-state EEG was recorded from each participant with a 32-electrode cap using the CURRY9 system. Each EEG recording lasted 10 minutes at a sampling rate of 1024 Hz. EEG signals were amplified, filtered, and digitized with impedances maintained below 5 kΩ. EEG data were preprocessed using EEGLAB v.2024.2.1 and analyzed for spectral power in frequency band using Fast Fourier Transform (FFT). Results: The resting-state EEG results showed that the DLE group had significantly increased resting-state EEG activity across several frequency spectrums, including theta, alpha, beta, and gamma bands. In particular, hyperactivity in the theta and gamma bands was observed in frontal, central, and occipital regions in the DLE group (Figure. 1). The analysis of the MST task followed the methods described by Stark et al. (2015), in which three d' and c response bias types (target-foil, lure-foil, and target-lure) were calculated. In the regression analysis, the P value for the lure-foil c response bias was 0.048 (p < 0.05), indicating a conservative bias towards responding "new" between lure and foil in the DLE group. All other variables had P values greater than 0.05 and did not reach statistical significance
Prognostic significance of clonal hematopoiesis in STEMI: A 10-year follow-up reveals high-risk gene mutations
No full text[[abstract]]BACKGROUND: To elucidate the extent and clinical implications of clonal hematopoiesis of indeterminate potential (CHIP) prevalence in patients with ST-segment elevation myocardial infarction (STEMI), and to evaluate its utility as a contributory factor for risk stratification in long-term outcomes. METHODS: Whole-exome sequencing was performed in a cohort of 101 patients presenting with STEMI who underwent emergency percutaneous coronary intervention. These patients were longitudinally followed for over 120 months. Their genomic data were compared with those from a control group of 706 individuals without cardiovascular events. Comparative analyses were conducted to identify patterns of CHIP between the STEMI and control cohorts. RESULTS: In our cohort, 37.6% (n = 38) of STEMI patients exhibited somatic mutations associated with CHIP at a variant allele frequency of 1% or greater, compared to 22.8% (n = 161) in the control group. The most frequently detected mutations in STEMI patients were in the ASXL1 and CREBBP genes, each present in 5.0% of this cohort. Long-term follow-up revealed that STEMI patients with CHIP had a higher incidence of major adverse cardiovascular events (MACEs), with an adjusted hazard ratio of 2.23 (95% confidence interval (CI) 1.16-4.28, p = 0.015). CONCLUSION: CHIP is prevalent in the STEMI patient cohort and is significantly correlated with adverse clinical outcomes. Incorporating CHIP status could enhance the risk stratification process, thus informing more tailored clinical management strategies for STEMI patients
2025 expert consensus recommendations on vaccinations in adults with high cardiovascular risk and cardiovascular disease: A report of the task force of the Taiwan society of cardiology and the infectious diseases society of Taiwan
No full text[[abstract]]Cardiovascular disease (CVD) is a leading cause of death worldwide, and infections often worsen the clinical condition of these patients. Respiratory infections, either bacterial or viral sources, are important causes of high morbidity and mortality in older adults. Beyond the burden of infection-related complications, they are also associated with non-infection-related complications such as cardiovascular (CV) events. For example, herpes zoster is associated with an increased risk of stroke and myocardial infarction. Vaccination is an effective preventive strategy for patients with CVD by reducing viral and bacterial infections, and minimizing systemic inflammatory responses to support plaque stability and reduce the likelihood of CV events in high-risk patients, thereby reducing the risks of CV and non-CV hospitalizations and mortality. Despite evidence on the effectiveness, safety, and benefits of vaccines and recommendations to vaccinate older patients and those with risk factors, vaccination rates remain sub-optimal in this population. The Taiwan Society of Cardiology and the Infectious Diseases Society of Taiwan recently appointed a task force to formulate a consensus on vaccinations for adults with high CV risk or CVD. Based on the most up-to-date information, the consensus provides current evidence-based important recommendations