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Safety of bempedoic acid in patients at high cardiovascular risk and with statin intolerance.
Bays, HE, Bloedon, LT, Lin, G, Powell, HA, Louie, MJ, Nicholls, SJ, Lincoff, AM, Nissen, SE
Journal of clinical lipidology. 2024;(1):e59-e69
Abstract
BACKGROUND Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins. OBJECTIVE To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies. METHODS CLEAR Outcomes was a double-blind trial conducted in 13,970 patients randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years. RESULTS In patients who received at least one dose (7,001 bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, hemoglobin, aminotransaminases, and uric acid were consistent with the known safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, including tendon rupture, occurred in 2 % of patients in both treatment groups. Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; AE related to gallbladder disease were similar between treatment groups. CONCLUSIONS Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid.
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Short-Term Nutritional Support Improves The Preoperative Nutritional Status of Infants With Non-Restrictive Ventricular Septal Defect: A Prospective Controlled Study.
Xu, LP, Lin, SH, Zhang, QL, Zheng, Y, Lin, G
The heart surgery forum. 2022;(5):E745-E749
Abstract
OBJECTIVE To investigate the effect of short-term nutritional support on improving preoperative nutritional status of infants with non-restrictive ventricular septal defect. METHODS A prospective randomized controlled study was conducted from June 2021 to December 2021 at a provincial children's hospital in China. The difference of nutritional status between the intervention group and the control group after short-term nutritional support was compared. RESULTS After one month of nutritional support, the weight, STRONGkids score, albumin, prealbumin, and hemoglobin in the intervention group significantly were higher than those in the control group (P < 0.05). The postoperative intensive care time and discharge time of the two groups significantly were lower in the intervention group than those in the control group (P < 0.05). CONCLUSION The preoperative nutritional support of 1 month for infants with non-restrictive ventricular septal defect can effectively improve their preoperative nutritional status and promote postoperative recovery.
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The effect of periodic ketogenic diet on newly diagnosed overweight or obese patients with type 2 diabetes.
Li, S, Lin, G, Chen, J, Chen, Z, Xu, F, Zhu, F, Zhang, J, Yuan, S
BMC endocrine disorders. 2022;22(1):34
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Currently, the ketogenic diet is gaining popularity in managing Type 2 diabetes (T2D). Ketogenic diets replace carbohydrates with fat and include limited carbohydrates and adequate protein. This randomised controlled trial evaluated the effects of the 12-week ketogenic diet on sixty overweight or obese T2D patients. Both the ketogenic and control diabetes diet groups achieved significant reductions in weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting blood glucose, fasting insulin, and HbA1c. However, the ketogenic group showed significantly greater reductions in body mass, blood lipids, and blood glucose than the control group. In the ketogenic diet group, serum uric acid levels were higher than those in the control diet group. It was found that the control diet group adhered to the diet for a longer period than the ketogenic diet group, whose willingness to adhere to the diet long-term was weaker. More robust long-term studies are needed to evaluate the long-term effects of a ketogenic diet. In this study, more patients who followed the ketogenic diet experienced hypoglycaemic events during the first four weeks. Healthcare providers should exercise caution when recommending a short term therapeutic ketogenic diet.
Abstract
BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.
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Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial.
Orkin, C, Squires, KE, Molina, JM, Sax, PE, Sussmann, O, Lin, G, Kumar, S, Hanna, GJ, Hwang, C, Martin, E, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021;(1):33-42
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BACKGROUND Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96. METHODS DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96. RESULTS Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar. CLINICAL TRIALS REGISTRATION NCT02403674.
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Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease.
Chen, J, Huang, Y, Xie, H, Bai, H, Lin, G, Dong, Y, Shi, D, Wang, J, Zhang, Q, Zhang, Y, et al
Asia Pacific journal of clinical nutrition. 2020;(3):483-490
Abstract
BACKGROUND AND OBJECTIVES To study the effects of a low-carbohydrate and high-fiber diet and education on patients with nonalcoholic fatty liver disease. METHODS AND STUDY DESIGN We randomly divided 44 patients with nonalcoholic fatty liver disease into two groups: low-carbohydrate and high-fiber diet and education (intervention group), and education alone (control group). Liver and kidney function, fasting plasma glucose, insulin resistance index, body composition, and controlled attenuation parameter were detected before and after the intervention. RESULTS After 2 months, the body fat, body weight, abdominal circumference, and visceral fat area, fasting plasma glucose, insulin resistance index, and levels of serum alanine aminotransferase, aspartate transaminase, uric acid, and insulin of the intervention group were significantly lower than before (p<0.05). In the female intervention group, the insulin resistance index and levels of serum alanine aminotransferase, uric acid, triglyceride, fasting plasma glucose, and C-peptide were lower and the level of serum high-density lipoprotein cholesterol was higher than in the female control group (p<0.05). In the male intervention group, the levels of serum alanine aminotransferase, triglyceride, and fasting plasma glucose were lower and the level of serum high-density lipoprotein cholesterol was higher compared with the male control group (p<0.05). CONCLUSIONS A low-carbohydrate and high-fiber diet and education can effectively reduce the body weight and body fat of patients with nonalcoholic fatty liver disease and improve metabolic indicators such as liver enzymes, blood glucose, blood lipid, and uric acid. Our female patients showed significantly better improvement in the indicators than our male patients.
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Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial.
Orkin, C, Squires, KE, Molina, JM, Sax, PE, Wong, WW, Sussmann, O, Kaplan, R, Lupinacci, L, Rodgers, A, Xu, X, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019;(4):535-544
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BACKGROUND Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. METHODS DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment-naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). RESULTS Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (-1.6 vs +8.7 mg/dL and -3.8 vs +13.3 mg/dL, respectively). CONCLUSIONS In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF. CLINICAL TRIALS REGISTRATION NCT02403674.
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Sorafenib in Hepatopulmonary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Kawut, SM, Ellenberg, SS, Krowka, MJ, Goldberg, D, Vargas, H, Koch, D, Sharkoski, T, Al-Naamani, N, Fox, A, Brown, R, et al
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2019;(8):1155-1164
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The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2 ) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, -3.8 to 7.0 mm Hg) and those allocated to placebo (-2.4 mm Hg; IQR, -4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.
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Weight loss achieved using an energy restriction diet with normal or higher dietary protein decreased the number of CD14++CD16+ proinflammatory monocytes and plasma lipids and lipoproteins in middle-aged, overweight, and obese adults.
Kim, JE, Lin, G, Zhou, J, Mund, JA, Case, J, Campbell, WW
Nutrition research (New York, N.Y.). 2017;:75-84
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Monocytes are involved in immune responses, and specific monocyte subpopulations (MS) that express intermediate to high levels of CD16 are associated with obesity and cardiovascular events. Consuming high protein (HP) when dieting improves body composition and cardiometabolic health outcomes, but whether HP affects MS during weight loss remains unknown. We assessed the effect of HP on energy restriction (ER)-induced changes in MS in overweight and obese adults. The relations between MS and plasma lipids and lipoproteins were also examined. We hypothesized that, independent of protein intake, ER-induced weight loss would decrease the numbers of MS and that MS and plasma lipids and lipoproteins would be related. Thirty-two adults (age 52 ± 1 years, body mass index 31.3 ± 0.5 kg/m2, means ± S.E.) consumed either a normal protein (n=18) or HP (n=14) (0.8 vs 1.5 g•kg-1•d-1 protein) ER diet (750-kcal/d [3138-kJ/d] deficit) for 16 weeks. The HP diet included 0.7 g•kg-1•d-1 of milk protein isolate. Fasting plasma lipids, lipoproteins, and the numbers of MS were analyzed. Over time, independent of protein intake, CD14++CD16+ cell number decreased, whereas CD14dimCD16++, CD14+CD16+, and CD14+CD16- cell numbers remained unchanged. CD14dimCD16++ cell number was negatively associated with total cholesterol (TC) and triglyceride, while CD14++CD16+ cell number was positively associated with TC, low-density lipoprotein cholesterol (LDL), TC to high-density lipoprotein cholesterol (HDL) ratio, and LDL to HDL ratio. Weight loss achieved while consuming an ER diet with either normal or high protein may improve immunity by partially decreasing proinflammatory monocytes. Associations between MS and plasma lipids and lipoproteins are confirmed in overweight and obese adults.
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Effect of 40 mg versus 10 mg of atorvastatin on oxidized low-density lipoprotein, high-sensitivity C-reactive protein, circulating endothelial-derived microparticles, and endothelial progenitor cells in patients with ischemic cardiomyopathy.
Huang, B, Cheng, Y, Xie, Q, Lin, G, Wu, Y, Feng, Y, Gao, J, Xu, D
Clinical cardiology. 2012;(2):125-30
Abstract
BACKGROUND There are few recent data to delineate the beyond lipids-decreased effect of statins and the effect of different doses of statins on endothelial-derived microparticles (EMPs) and circulating endothelial progenitor cells (EPCs) in patients with ischemic cardiomyopathy (ICM). HYPOTHESIS Statins might have the beyond lipids-decreased effect and there were different effects between different doses of statins on EMPs and circulating EPCs in patients with ICM. METHODS One hundred patients with ICM and 100 healthy examined people, who served as the normal control group, were recruited to this study. Patients were randomly divided into 2 groups: 10-mg atorvastatin group (n = 50) and 40-mg atorvastatin group (n = 50). All subjects were followed for 1 year. The levels of serum lipids, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein (hsCRP), circulating EPCs, and EMPs were examined in all subjects. The incidences of adverse reactions in the 2 study groups were determined. RESULTS At the beginning of this study, there were no significant differences in baseline characteristics between the 2 study groups. At the end of this study, the levels of total cholesterol, low-density lipoprotein, serum hsCRP, oxLDL, and circulating EMPs were significantly decreased; circulating EPCs were significantly increased in the 40-mg atorvastatin group compared to the 10-mg atorvastatin group, P < 0.05. The multivariate linear regression analysis indicated that receiving only 40 mg of atorvastatin had a significant effect on the levels of circulating EPCs (β = 0.252,P = 0.014). There were no significant differences in the adverse reactions between the 2 groups. CONCLUSIONS Use of 40 mg of atorvastatin might decrease the levels of circulating EMPs and increase the number of circulating EPCs in patients with ICM in comparison with 10 mg of atorvastatin, and the effect might be independent of the decrease of lipids, oxLDL, and hsCRP.
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[Protective effect of aminophylline on cerebral injury during cardiopulmonary bypass in infants].
Pan, S, Lin, G, Jiang, H, Huang, R
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2009;(11):1126-31
Abstract
OBJECTIVE To investigate the protective effect of aminophylline on cerebral injury induced by cardiopulmonary bypass (CPB) in infants. METHODS Forty patients who underwent ventricular septal defect within 3 years old were randomly divided into 2 groups(20 cases in each group).Aminophylline group:aminophylline (5 mg/kg) was injected slowly via the vein after anesthesia and maintained at a dose of 0.5 mg/(kg.h) until the end of CPB. CONTROL GROUP aminophylline was replaced by Ringer's lactated solution. Samples were obtained at the beginning of CPB (T(1)),the end of CPB (T(2)),6 h (T(3)) and 24 h (T(4)) after the operation to measure S-100 beta protein, NSE, tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and interleukin-10 (IL-10) concentration by ELISA in the 2 groups. RESULTS Compared with the time point immediately before CPB, the S-100beta protein,NSE, TNF-alpha, and IL-8 concentration in the 2 groups began to increase with the start of CPB, reached a climax at the end of CPB (T(2)),decreased gradually 6 h after the termination of CPB(T(3)) and could not restore to the level before CPB at T(4)(24 h after the termination of CPB).IL-10 in the 2 groups both increased after the CPB. At T(2) and T(3), S-100beta protein,NSE, TNF-alpha, and IL-8 concentrations were significantly lower than those in the aminophylline group (P<0.05 or P<0.01), while IL-10 was just the opposite. CONCLUSION There is cerebral damage induced by CPB. Aminophylline may play a protective role in cerebral injury by modulating the balance between the pro-inflammatory factor and anti-inflammatory factor to reduce the level of S-100beta protein and NSE during CPB and open cardiac surgeries.