Publications by authors named "K R Chien"

Article Synopsis
  • A study explored whole-exome sequencing (WES) to better understand severe hypertriglyceridemia by identifying genes linked to high triglyceride levels through a genome-wide association study (GWAS).
  • The GWAS involved over 120,000 participants and found that the APOA5 locus on chromosome 11 has the strongest association with triglyceride levels, alongside other significant genes like BUD13, GCKR, and LPL.
  • WES conducted on 29 patients with extreme hypertriglyceridemia identified additional genes such as ALDH1A2 and APOC1, highlighting both known and novel genetic factors that may influence lipid metabolism and open up possibilities for new treatments.
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Background: Patients with diabetes kidney disease (DKD) are at risk of developing frailty, leading to functional impairment and poor outcomes. Medications are potential modifiers of such risk. Ketoanalogues have been shown to delay dialysis initiation in DKD patients.

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For the primary prevention of atherosclerotic cardiovascular disease (ASCVD), the recommended treatment target for each modifiable risk factor is as follows: reducing body weight by 5-10%; blood pressure < 130/80 mmHg (systolic pressure < 120 mmHg in high-risk individuals); low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL in high-risk individuals, LDL-C < 115 mg/dL in moderate-risk individuals, LDL-C < 130 mg/dL in low-risk individuals, and LDL-C < 160 mg/dL in those with a minimal; complete and persistent abstinence from cigarette smoking; hemoglobin A1C < 7.0%; fulfilling recommended amounts of the six food groups according to the Taiwan food guide; and moderate-intensity physical activity 150 min/wk or vigorous physical activity 75 min/wk. For the primary prevention of ASCVD by pharmacological treatment in individuals with modifiable risk factors/clinical conditions, statins are the first-line therapy for reducing LDL-C levels; some specific anti-diabetic drugs proven to be effective in randomized controlled trials for the primary prevention of ASCVD are recommended in patients with type 2 diabetes mellitus; pharmacological treatment is recommended to assist in weight management for obese patients with a body mass index ≥ 30 kg/m (or 27 kg/m who also have at least one ASCVD risk factor or obesity-related comorbidity); an angiotensin-converting enzyme inhibitor, a glucagon-like peptide-1 receptor agonist, a sodium-dependent glucose cotransporter-2 inhibitor, and finerenone can be used in diabetic patients with chronic kidney disease for the primary prevention of ASCVD.

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In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells' (HSPCs') aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had lower-risk MDS, 84% had intermediate-1 risk MDS according to the International Prognostic Scoring System score, and 80% failed hypomethylating agent therapy.

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