0
selected
-
1.
Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events.
Khan, SS, Post, WS, Guo, X, Tan, J, Zhu, F, Bos, D, Sedaghati-Khayat, B, van Rooij, J, Aday, A, Allen, NB, et al
JAMA. 2023;(20):1768-1777
-
-
Free full text
-
Abstract
IMPORTANCE Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts. OBJECTIVE To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model. DESIGN, SETTING, AND PARTICIPANTS Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands. EXPOSURE Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score. MAIN OUTCOMES AND MEASURES Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed. RESULTS The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years). CONCLUSIONS AND RELEVANCE In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.
-
2.
Vitamin K2 as a potential therapeutic candidate for the prevention of muscle cramps in hemodialysis patients: A prospective multicenter, randomized, controlled, crossover pilot trial.
Xu, D, Yang, A, Ren, R, Shan, Z, Li, YM, Tan, J
Nutrition (Burbank, Los Angeles County, Calif.). 2022;:111608
Abstract
OBJECTIVES Muscle cramps occur in 33% to 78% of patients with dialysis. The etiology of muscle cramps is poorly understood, and no clear evidence-based prevention or treatment strategies exist. Improved interventions are urgently needed. The aim of this study was to investigate the effect of vitamin K2 in reducing the frequency and severity of muscle cramps in hemodialysis (HD) patients. METHODS This multicenter, randomized, placebo-controlled, crossover clinical trial was conducted from June 2019 to May 2020. Each participant received vitamin K2 (360 µg/d) or placebo for two 4-wk phases, and then crossed to the alternative arm for two 4-wk phases after a 2-wk washout. The primary endpoint was the frequency of muscle cramps during HD. The secondary endpoints were severity and duration of muscle cramps during HD. RESULTS A total of 523 patients with maintenance HD were screened for muscle cramps, including 41 patients with muscle cramps refractory to conventional interventions, were enrolled. Nineteen patients in the vitamin K2-initial group and 20 in the placebo-initial group completed the protocol, and were included in the final analysis. Vitamin K2 reduced the frequency, duration, and severity of muscle cramps in HD patients (all P < 0.05). The frequency, duration, and severity of muscle cramps in HD patients increased again after crossing over to the placebo. There were no serious adverse events. One patient experienced gastrointestinal discomfort when taking vitamin K2. CONCLUSIONS This pilot trial demonstrated that vitamin K2 supplementation could decrease the frequency, duration, and severity of muscle cramps in HD patients.
-
3.
A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer.
Zheng, X, Xu, Z, Ji, Q, Ge, M, Shi, F, Qin, J, Wang, F, Chen, G, Zhang, Y, Huang, R, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(20):5502-5509
-
-
Free full text
-
Abstract
PURPOSE Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase III SELECT study; however, it has not been tested in Chinese patients with RR-DTC. PATIENTS AND METHODS Chinese patients with confirmed RR-DTC (n = 151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for progression-free survival and objective response rate were conducted using Response Evaluation Criteria in Solid Tumors v1.1 and confirmed by independent imaging review. All adverse events were assessed and monitored. RESULTS Progression-free survival was significantly longer with lenvatinib treatment [n = 103; median 23.9 months; 95% confidence interval (CI), 12.9-not estimable] versus placebo (n = 48; median 3.7 months; 95% CI, 1.9-5.6; hazard ratio = 0.16; 95% CI, 0.10-0.26; P < 0.0001). The objective response rate was 69.9% (95% CI, 61.0-78.8) in the lenvatinib arm and 0% (95% CI, 0-0) in the placebo arm. At data cutoff, 60.2% of patients receiving lenvatinib remained on treatment; treatment-emergent adverse events led to lenvatinib discontinuation in 8.7% of patients. Overall, treatment-emergent adverse events of grade ≥3 occurred in 87.4% of patients in the lenvatinib arm, the most common being hypertension (62.1%) and proteinuria (23.3%). CONCLUSIONS Lenvatinib at a starting dose of 24 mg/day significantly improved progression-free survival and objective response rate in Chinese patients with RR-DTC versus placebo. There were no new or unexpected toxicities. Results are consistent with those from SELECT involving patients with RR-DTC.
-
4.
Standardized Uptake Value Using Thyroid Quantitative SPECT/CT for the Diagnosis and Evaluation of Graves' Disease: A Prospective Multicenter Study.
Dong, F, Li, L, Bian, Y, Li, G, Han, X, Li, M, Liu, J, Xue, Y, Li, Y, Hu, Y, et al
BioMed research international. 2019;:7589853
Abstract
The clinical applications of the quantitative single photon emission computed tomography (SPECT)/computed tomography (CT) are being expanded to a variety of fields of nuclear medicine. However, clinical application of quantitative SPECT/CT for the evaluation of Graves' disease (GD) still needs further investigation. Our aim was to investigate the feasibility of standard uptake value (SUV) of the thyroid for the clinical diagnosis and evaluation of GD. In this prospective multicenter study, 116 patients diagnosed with GD (Graves group) and 74 healthy volunteers (control group) were enrolled from 8 different hospitals. All patients underwent technetium pertechnetate (99mTcO4 -) SPECT/CT imaging with Q.Metrix quantitative software and 24-hour thyroid radioactive iodine uptake (24h-RAIU) test. The SUVmax and SUVmean in Graves group were significantly higher than those of control group (P<0.01). Cut-off values of SUVmax and SUVmean to predict GD were 231.425 and 116.66 by ROC curves, respectively. The SUVmax and SUVmean in Graves patients were significantly related to serum thyroxine level with correlation coefficient of 0.493 and 0.512 for FT3 and 0.449 and 0.464 for FT4, respectively (all P<0.01). Additionally, the SUVmax and SUVmean in GD positively correlated with 24h-RAIU with a coefficient of 0.832 and 0.830, respectively (P<0.01). The volumes determined by Q.Metrix (35.65 ± 20.56ml) of 72 subjects also positively correlated with that from ultrasound (36.67 ± 21.00ml) with a coefficient of 0.927 (P<0.01). SUV measurements derived from thyroid SPECT/CT may be useful for the clinical diagnosis and evaluation of GD.