Since the publication of the Taiwan Headache Society's 2022 Guidelines for the Acute Treatment of Migraine Attacks, advances in headache medicine and the approval of new drugs in Taiwan have necessitated an update. To address clinical needs, the Guideline Committee of the Taiwan Headache Society reviewed evidence for pharmacological and non-pharmacological acute treatments using evidence-based principles. Drawing from the latest European, American, and international guidelines, and through expert consensus, this revision updates treatment roles, grades of recommendation, efficacy, and adverse-effect profiles. Currently, a broad range of medications is available in Taiwan for acute migraine management, categorised into "specific" and "non-specific" agents. Specific treatments include oral and intranasal triptans, and gepants, i.e., oral calcitonin gene-related peptide (CGRP) receptor antagonists. Non-specific agents include acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs: diclofenac, ibuprofen, naproxen). Injectable prochlorperazine is also strongly recommended. Ergotamine/caffeine combinations are less effective and are second-line agents, while high-dose aspirin is limited by gastrointestinal risk. Considering the potential risk of dependency, tramadol or tramadol/paracetamol combinations should be reserved until all other agents fail, and should be limited to oral forms. Other opioids, such as morphine, butorphanol, etc., lack evidence and are not recommended. Treatment should follow the principle of stratified care: oral NSAIDs for mild disability, with combination analgesics or parenteral NSAIDs as alternatives, and oral or intranasal triptans for moderate to severe disability, ideally administered early. Antiemetics may be added, and combining triptans with NSAIDs enhances efficacy. Rimegepant can be considered a first-line therapy, particularly for patients who are unresponsive or intolerant to triptans, have cardiovascular contraindications, or are at risk of developing medication overuse. In status migrainosus, parenteral corticosteroids with intravenous fluids are advised. Acetaminophen remains first-line for children and pregnant women. To prevent medication-overuse headache, acute treatments, including NSAIDs, acetaminophen, triptans, ergot derivatives, and combination analgesics, should not exceed two days per week, probably with the exception of rimegepant.
Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that can progress to non-alcoholic steatohepatitis (NASH), in which lipotoxicity, oxidative stress, apoptosis, and impaired autophagy contribute to liver injury. 14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive diterpenoid from Andrographis paniculata, has shown anti-inflammatory and antioxidant activities, but its role in NASH-associated lipotoxicity remains unclear. This study investigated the protective effects and underlying mechanisms of deAND using palmitic acid (PA)-treated AML12 hepatocytes and a choline-deficient, L-amino acid-defined, high-fat-diet (CDAHFD)-induced mouse model of NASH. In AML12 cells, PA impaired autophagic flux and reduced the expression of the mitophagy-associated proteins PINK1 and Parkin and increased p62, LC3-II, reactive oxygen species production, and apoptotic signaling. deAND treatment restored autophagic flux and increased PINK1 and Parkin expression, enhanced antioxidant defense-related proteins, including HO-1, GCLM, and GPX2, and reduced oxidative stress and apoptosis. The protective effects of deAND were attenuated by autophagy inhibitors, supporting the involvement of autophagy regulation. In CDAHFD-fed mice, deAND reduced hepatic steatosis, inflammation, fibrosis, apoptosis, and autophagy dysregulation. These findings suggest that deAND alleviates lipotoxic liver injury by restoring autophagic homeostasis and reducing oxidative stress.
Objectives:This study aimed to evaluate the prognostic implications and optimal timing for assessing left ventricular ejection fraction (LVEF) trajectory in patients with heart failure (HF) and an LVEF < 50%. Methods:The Taiwan Society of Cardiology HF Registry 2020 is a prospective, multicenter registry of hospitalized HF patients in Taiwan. This study included patients with an LVEF < 50% during their index HF hospitalization, and at least one follow-up echocardiogram within 2 years. HF with improved EF (HFimpEF) was defined as an absolute increase in LVEF > 10% from baseline. The primary endpoints were all-cause mortality and HF hospitalization at 2 years. Predictors of an improvement in LVEF trajectory were also evaluated. Results:A total of 1478 patients were enrolled, with 873 in the HFimpEF group and 605 in the non-HFimpEF group. HFimpEF was associated with a lower risk of mortality (hazard ratio: 0.41 [0.27-0.62], p < 0.001) and reduced HF hospitalizations (8.6% vs. 24.4%, p < 0.001) at 2 years follow-up. Subgroup analysis showed that survival benefits diverged at an LVEF improvement > 10%, emerging as early as 6 months and persisting beyond 12 months. Lower baseline LVEF was paradoxically associated with better survival. Neither maximal guideline-directed medical therapy (GDMT) score nor revascularization correlated with LVEF trajectory. However, HFimpEF patients received higher doses of renin-angiotensin system inhibitors and beta-blockers in the first year. Conclusions:LVEF trajectory at 6 months appears to be a valuable prognostic tool, and higher-dose fundamental HF therapy was more important than achieving a higher overall GDMT score.
Angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is critical for viral entry and pulmonary homeostasis, yet its regulation during infection remains unclear. Using SARS-CoV-2 single-round infectious particles (SRIPs), we found that ACE2 protein and mRNA were markedly reduced in human alveolar (A549) and bronchial (Calu-3) cells. This effect was reproduced by expression of the viral main protease (Mpro). Notably, ACE2 suppression was independent of Mpro enzymatic activity, as the catalytically inactive mutant (Mpro_C145A) downregulated ACE2 comparably to wild-type Mpro, and inhibition with nirmatrelvir or MG132 failed to restore expression. Mechanistically, Mpro enhanced STAT1 phosphorylation while suppressing STAT3 Tyr705 phosphorylation, impairing STAT3 nuclear localization and transcriptional activity. Overexpression of STAT3, but not STAT1, restored ACE2 expression in both Mpro-expressing and SARS-CoV-2-infected cells. Moreover, Mpro activated ERK1/2 through TRAF6-TAK1 signaling, which facilitated STAT3 interaction with the tyrosine phosphatase MEG2, leading to dephosphorylation of STAT3 at Tyr705. ERK1/2 inhibition restored STAT3 activity and ACE2 expression, while JNK inhibition had no effect. In infected cells, ERK1/2 inhibition increased ACE2 but also enhanced viral replication. These findings identify a non-enzymatic role of Mpro in suppressing ACE2 through the ERK1/2-MEG2-STAT3 axis, highlighting a mechanism that regulates host receptor availability and influences SARS-CoV-2 pathogenesis.
Background and Aims Pediatric obesity is linked to many metabolic complications and has limited treatment options. We evaluated the safety and effectiveness of GLP-1 receptor agonist (liraglutide) in adolescents with obesity in clinical practice in Taiwan. Methods We conducted a prospective study (NCT06283641) across 14 hospitals and clinics from February 2024 to March 2025 evaluating adolescents receiving liraglutide at baseline, week 13, and week 26. Demographics, and safety and effectiveness outcomes, including incidence proportions of adverse events and adverse drug reactions, and changes in body weight and body mass index, were assessed. Results Among 41 participants, 22 (53.7%) were male, with mean age (±standard deviation) 13.9 ± 1.8 years, body weight (BW) 88.5 ± 19.3 kg, and body mass index (BMI) 33.4 ± 5.1 kg/m2. Nineteen (46.3%) had medical history of hepatic impairment. Mean daily and maximum doses were 1.4 ± 0.5 mg/day and 1.8 ± 0.7 mg/day, respectively, throughout 128.3 ± 56.0 days; 14.4% escalated to 3.0 mg/day. Overall respective incidence proportions of adverse events and adverse drug reactions were 19.5% (8/41; all mild) and 9.8% (4/41; 6 events), respectively. Gastrointestinal events were most frequent, followed by injection site-related events. No treatment discontinuation resulted from intolerance. Mean respective losses in BW, BMI, and BMI standard deviation score at weeks 13 and 26 were −2.7 ± 3.8 kg (p = 0.0003), −1.3 ± 1.4 kg/m2 (p < 0.0001), and −0.2 ± 0.2 (p < 0.0001); and −4.4 ± 5.7 kg (p = 0.0015), −1.9 ± 2.1 kg/m2 (p = 0.0004), and −0.4 ± 0.3 (p < 0.0001), respectively. Conclusion In adolescents with obesity in Taiwan, liraglutide at doses below 3.0 mg/day was well-tolerated, and reductions in BW, BMI, and BMI standard deviation score were observed.
