-
1.
REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.
Bishop, CW, Ashfaq, A, Melnick, JZ, Vazquez-Escarpanter, E, Fialkow, JA, Strugnell, SA, Choe, J, Kalantar-Zadeh, K, Federman, NC, Ng, D, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2023;107:111899
-
-
-
Free full text
-
Plain language summary
Literature shows that vitamin D repletion may reduce the risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigate severity of coronavirus disease (COVID-19), and accelerate recovery. Sufficient serum level of 25-hydroxyvitamin D (25D) is postulated to potentiate COVID-19 vaccine effectiveness, boost innate and control adaptive immunity, and reduce post-infection cytokine storm and lung injury. The aim of this study was to evaluate the safety and efficacy of extended-release calcifediol capsules to treat symptomatic patients infected with SARS-CoV-2. This study is a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial titled REsCue. One hundred seventy-one symptomatic COVID-19 outpatients participants were enrolled. Patients were randomised (1:1) to 4 weeks of treatment with extended-release calcifediol (30 mcg/capsule) or matching placebo and a 2-week follow-up. Results show that extended-release calcifediol treatment was effective in increasing serum 25D levels to ≥50 ng/mL, which may have yielded significantly shorter resolution times for three aggregated respiratory symptoms (trouble breathing, chest congestion, and dry or hacking cough) commonly observed in patients with mild to moderate COVID-19. Authors conclude that the positive findings from this study warrant confirmation in additional larger studies.
Abstract
OBJECTIVES This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.
-
2.
PCSK9 inhibitors safely and effectively lower LDL after heart transplantation: a systematic review and meta-analysis.
Jennings, DL, Sultan, L, Mingov, J, Choe, J, Latif, F, Restaino, S, Clerkin, K, Habal, MV, Colombo, PC, Yuzefpulskaya, M, et al
Heart failure reviews. 2023;(1):149-156
Abstract
Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT; however, data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. A total of six studies including 97 patients were included. Over a mean follow-up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI - 119.15 to - 46.07; I2 = 82%) from baseline. Serious adverse drug reactions were rarely reported, and none was attributable to the PCSK9i therapy. Four studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. One study reported on immunologic safety, showing no DSA development within 1 month of therapy. Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.
-
3.
The Efficacy of Traditional Medicinal Plants in Modulating the Main Protease of SARS-CoV-2 and Cytokine Storm.
Choe, J, Har Yong, P, Xiang Ng, Z
Chemistry & biodiversity. 2022;(11):e202200655
-
-
Free full text
-
Abstract
Selected traditional medicinal plants exhibit therapeutic effects in coronavirus disease (Covid-19) patients. This review aims to identify the phytochemicals from five traditional medicinal plants (Glycyrrhiza glabra, Nigella sativa, Curcuma longa, Tinospora cordifolia and Withania somnifera) with high potential in modulating the main protease (Mpro) activity and cytokine storm in Covid-19 infection. The Mpro binding affinity of 13 plant phytochemicals were in the following order: Withanoside II>withanoside IV>withaferin A>α-hederin>withanoside V>sitoindoside IX>glabridin>liquiritigenin, nigellidine>curcumin>glycyrrhizin>tinocordiside>berberine. Among these phytochemicals, glycyrrhizin, withaferin A, curcumin, nigellidine and cordifolioside A suppressed SARS-CoV-2 replication and showed stronger anti-inflammatory activities than standard Covid-19 drugs. Both preclinical and clinical evidences supported the development of plant bioactive compounds as Mpro inhibitors.
-
4.
Safety, efficacy, and tolerability of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma.
Brown, ZJ, Gregory, S, Hewitt, DB, Iacono, S, Choe, J, Labiner, HE, Pawlik, TM
Surgical oncology. 2022;:101748
Abstract
Hepatocellular carcinoma (HCC) is a major cause of mortality worldwide with an increasing incidence due to escalating rates of obesity and non-alcoholic fatty liver disease. Unfortunately, a majority of patients with HCC present with advanced disease. The immune checkpoint inhibitor atezolizumab, a PD-L1 inhibitor, in combination with bevacizumab, anti-VEGF, has become the new standard of care for patients with advanced HCC after demonstrating improved overall and progression free survival over sorafenib. In this review, we discuss the evolving role of immune checkpoint inhibitors in the treatment of HCC and their safety, efficacy, and tolerability.
-
5.
High-density lipoprotein cholesterol and the risk of obstructive coronary artery disease beyond low-density lipoprotein cholesterol in non-diabetic individuals.
Kim, YG, Cho, YR, Park, GM, Won, KB, Ann, SH, Yang, DH, Kang, JW, Lim, TH, Kim, HK, Choe, J, et al
European journal of preventive cardiology. 2020;(7):706-714
Abstract
AIMS: The relationship between high-density lipoprotein cholesterol and the severity of coronary artery disease beyond low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy, remains uncertain. We evaluated the association between high-density lipoprotein cholesterol and obstructive coronary artery disease using parameters of any obstructive plaque, obstructive plaque in the left main coronary artery or proximal left anterior descending artery, and obstructive plaque in multi-vessels, according to low-density lipoprotein cholesterol levels. METHODS AND RESULTS We analyzed 5130 asymptomatic non-diabetics who underwent coronary computed tomography angiography for general health examination. Obstructive plaque was defined as a plaque with ≥50% luminal diameter stenosis. The participants were divided into three groups based on low-density lipoprotein cholesterol levels of ≤129, 130-159, and ≥160 mg/dl. The prevalence of any obstructive plaque (5.9% vs 6.4% vs 10.6%) and obstructive plaque in the left main coronary artery or proximal left anterior descending artery (2.1% vs 2.1% vs 4.3%) significantly increased with low-density lipoprotein cholesterol category (all p < 0.05). Compared with subjects with high-density lipoprotein cholesterol level ≥40 mg/dl, those with high-density lipoprotein cholesterol level <40 mg/dl had a significantly higher prevalence of any obstructive plaque (10.4% vs 5.1%), obstructive plaque in the left main coronary artery or proximal left anterior descending artery (3.6% vs 1.8%), and obstructive plaque in multi-vessels (4.3% vs 1.1%), only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Multiple regression analysis showed that increased high-density lipoprotein cholesterol levels were associated with a reduced risk of all obstructive coronary artery disease parameters only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). CONCLUSION Increased high-density lipoprotein cholesterol levels were independently associated with a lower risk of obstructive coronary artery disease in asymptomatic non-diabetics with low low-density lipoprotein cholesterol levels.
-
6.
Longitudinal Changes in Insulin Resistance, Beta-Cell Function and Glucose Regulation Status in Prediabetes.
Kim, CH, Kim, HK, Kim, EH, Bae, SJ, Choe, J, Park, JY
The American journal of the medical sciences. 2018;(1):54-60
Abstract
BACKGROUND The changes in insulin resistance and insulin secretion and their association with changes in glucose regulation status in Asians with prediabetes remain uncertain. MATERIALS AND METHODS We included Korean adults (aged 20-79 years) with prediabetes who underwent routine medical check-ups at a mean interval of 5 years. Prediabetes was defined as fasting plasma glucose (FPG) 5.6-6.9mmol/l or HbA1c 5.7-6.4% (39-46mmol/mol). Insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B) indices were assessed by homeostasis model assessment. Incident diabetes was defined as FPG ≥ 7.0mmol/l, HbA1c ≥ 6.5% (48mmol/mol), or initiation of antidiabetic medications. RESULTS Among the 7,208 participants with prediabetes, 4,410 (61.2%) remained as prediabetes (control group), 2,123 (29.5%) reverted to normal glucose regulation (regressors), and 675 (9.4%) progressed to type 2 diabetes (progressors) after 5 years. Compared with the control group, the progressors had higher baseline HOMA-IR (2.48 ± 1.45 versus 2.06 ± 1.20, P < 0.001), but similar baseline HOMA-%B (74.6 ± 47.6 versus 73.1 ± 41.4, P=0.68). By contrast, the regressors had lower baseline HOMA-IR (1.98 ± 1.14 versus 2.06 ± 1.20, P = 0.035) but higher baseline HOMA-%B (77.4 ± 43.1 versus 73.1 ± 41.4, P = 0.001). After 5 years, the progressors showed a 31% increase in HOMA-IR (2.48 ± 1.45 versus 3.24 ± 2.10, P < 0.001) and 15% decrease in HOMA-%B (74.6 ± 47.6 versus 63.8 ± 40.4, P < 0.001), whereas the regressors showed 29% decrease in HOMA-IR (1.98 ± 1.14 versus 1.41 ± 0.78, P < 0.001) and 4% increase in HOMA-%B (77.4 ± 43.1 versus 80.2 ± 47.9, P = 0.010). CONCLUSIONS Although increase in insulin resistance and decrease in beta-cell function both contributed to the progression to type 2 diabetes from prediabetes, longitudinal change in insulin resistance was the predominant factor in Koreans.
-
7.
Model for assessing cardiovascular risk in a Korean population.
Park, GM, Han, S, Kim, SH, Jo, MW, Her, SH, Lee, JB, Lee, MS, Kim, HC, Ahn, JM, Lee, SW, et al
Circulation. Cardiovascular quality and outcomes. 2014;(6):944-51
Abstract
BACKGROUND A model for predicting cardiovascular disease in Asian populations is limited. METHODS AND RESULTS In total, 57 393 consecutive asymptomatic Korean individuals aged 30 to 80 years without a prior history of cardiovascular disease who underwent a general health examination were enrolled. Subjects were randomly classified into the train (n=45 914) and validation (n=11 479) cohorts. Thirty-one possible risk factors were assessed. The cardiovascular event was a composite of cardiovascular death, myocardial infarction, and stroke. In the train cohort, the C-index (95% confidence interval) and Akaike Information Criterion were used to develop the best-fitting prediction model. In the validation cohort, the predicted versus the observed cardiovascular event rates were compared by the C-index and Nam and D'Agostino χ(2) statistics. During a median follow-up period of 3.1 (interquartile range, 1.9-4.3) years, 458 subjects had 474 cardiovascular events. In the train cohort, the best-fitting model consisted of age, diabetes mellitus, hypertension, current smoking, family history of coronary heart disease, white blood cell, creatinine, glycohemoglobin, atrial fibrillation, blood pressure, and cholesterol (C-index =0.757 [0.726-0.788] and Akaike Information Criterion =7207). When this model was tested in the validation cohort, it performed well in terms of discrimination and calibration abilities (C-index=0.760 [0.693-0.828] and Nam and D'Agostino χ(2) statistic =0.001 for 3 years; C-index=0.782 [0.719-0.846] and Nam and D'Agostino χ(2) statistic=1.037 for 5 years). CONCLUSIONS A risk model based on traditional clinical and biomarkers has a feasible model performance in predicting cardiovascular events in an asymptomatic Korean population.
-
8.
Beraprost enhances the APC function of B cells by upregulating CD86 expression levels.
Kim, J, Park, CS, Park, CH, Jeoung, DI, Kim, YM, Choe, J
Journal of immunology (Baltimore, Md. : 1950). 2011;(7):3866-73
Abstract
Lipid mediators are emerging as important regulators of the immune system. Based on our previous result that shows strong expression of prostacyclin synthase in the germinal center, we investigated whether prostacyclin would regulate the APC function of B cells. Owing to the very short half-life of prostacyclin in experimental conditions, we used a more stable analog, beraprost. Beraprost increased the amounts of the costimulatory molecule CD86 but not CD80 on the surface of activated B cells in time- and dose-dependent manners. However, the enhancing effect of beraprost was not observed on memory B cells, centroblasts, and centrocytes. Beraprost required BCR and CD40 signals to upregulate CD86 expression levels. Other prostanoids such as PGE(2), 6-keto-PGF(1α), and PGF(2α) failed to alter CD86 expression levels, whereas other prostacyclin analogs were as potent as beraprost. Results carried out with receptor antagonists revealed that beraprost enhanced CD86 levels by binding to prostacyclin receptor IP and by increasing intracellular cAMP concentrations. Beraprost-treated B cells potently stimulated allogeneic T cells, which was significantly abolished by CD86 neutralization. Our data imply an unrecognized cellular and molecular mechanism about the germinal center reactions.
