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Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury.
Zhao, M, Sun, S, Huang, Z, Wang, T, Tang, H
Clinical journal of the American Society of Nephrology : CJASN. 2020;(1):70-78
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Abstract
BACKGROUND AND OBJECTIVES Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials. RESULTS In the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis. CONCLUSIONS Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.
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Twelve weeks of low volume sprint interval training improves cardio-metabolic health outcomes in overweight females.
Sun, S, Zhang, H, Kong, Z, Shi, Q, Tong, TK, Nie, J
Journal of sports sciences. 2019;(11):1257-1264
Abstract
This study compared the effects of 12-week sprint interval training (SIT), high-intensity interval training (HIIT), and moderate-intensity continuous training (MICT) on cardiorespiratory fitness (V̇O2peak), body mass and insulin sensitivity in overweight females. Forty-two overweight women (age 21.2 ± 1.4 years, BMI 26.3 ± 2.5 kg·m-2) were randomized to the groups of SIT (80 × 6-s sprints + 9-s rest), and isoenergetic (300KJ) HIIT (~9 × 4-min cycling at 90% V̇O2peak + 3-min rest) and MICT (cycling at 60% V̇O2peak for ~ 61-min). Training intervention was performed 3 d·week-1 for 12 weeks. After intervention, all three groups induced the same improvement in V̇O2peak (~ +25%, p < 0.001) and a similar reduction in body mass (~ - 5%, p < 0.001). Insulin sensitivity and fasting insulin levels were improved significantly on post-training measures in SIT and HIIT by ~26% and ~39% (p < 0.01), respectively, but remain unchanged in MICT. In contrast, fasting glucose levels were only reduced with MICT (p < 0.01). The three training strategies are equally effective in improving V̇O2peak and reducing body mass, however, the SIT is time-efficient. High-intensity training (i.e. SIT and HIIT) seems to be more beneficial than MICT in improving insulin sensitivity. Abbreviations: BMI: body mass index; CVD: cardiovascular disease; HIEG hyperinsulinaemic euglycaemic glucose; HIIT high-intensity interval training; HOMA-IR: homeostasis model assessment of insulin resistance; HR: heart rate; MICT moderate-intensity continuous training; RPE: ratings of perceived exertion; SIT: sprint interval training; T2D: type 2 diabetes; V̇O2peak: peak oxygen consumption.
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Comparison of High-Intensity Interval Training and Moderate-to-Vigorous Continuous Training for Cardiometabolic Health and Exercise Enjoyment in Obese Young Women: A Randomized Controlled Trial.
Kong, Z, Fan, X, Sun, S, Song, L, Shi, Q, Nie, J
PloS one. 2016;(7):e0158589
Abstract
OBJECTIVE The aim of this study was to compare the effects of 5-week high-intensity interval training (HIIT) and moderate-to-vigorous intensity continuous training (MVCT) on cardiometabolic health outcomes and enjoyment of exercise in obese young women. METHODS A randomized controlled experiment was conducted that involved thirty-one obese females (age range of 18-30) randomly assigned to either HIIT or MVCT five-week training programs. Participants in HIIT condition performed 20 min of repeated 8 s cycling interspersed with 12 s rest intervals, and those in MVCT condition cycled continuously for 40 min at 60-80% of peak oxygen consumption ([Formula: see text]O2peak), both for four days in a week. Outcomes such as [Formula: see text]O2peak, body composition estimated by bioimpedance analysis, blood lipids, and serum sexual hormones were measured at pre-and post-training. The scores of Physical Activity Enjoyment Scale (PAES) were collected during the intervention. RESULTS After training, [Formula: see text]O2peak increased significantly for both training programs (9.1% in HIIT and 10.3% in MVCT) (p = 0.010, η2 = 0.41). Although MVCT group had a significant reduction in total body weight (TBW, -1.8%, p = 0.034), fat mass (FM, - 4.7%, p = 0.002) and percentage body fat (PBF, -2.9%, p = 0.016), there were no significant between-group differences in the change of the pre- and post-measures of these variables. The HIIT group had a higher score on PAES than the MVCT group during the intervention. For both conditions, exercise training led to a decline in resting testosterone and estradiol levels, but had no significant effect on blood lipids. CONCLUSION Both HIIT and MVCT are effective in improving cardiorespiratory fitness and in reducing sexual hormones in obese young women; however, HIIT is a more enjoyable and time-efficient strategy. The mild-HIIT protocol seems to be useful for at least maintaining the body weight among sedentary individuals.
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[Comparison of the efficacy and safety of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin chemotherapy regimens in the treatment of advanced gastric cancer].
Wan, Y, Hui, H, Wang, X, Wu, J, Sun, S
Zhonghua zhong liu za zhi [Chinese journal of oncology]. 2016;(1):28-34
Abstract
OBJECTIVE To observe the efficacy and safety of chemotherapy regimens oxaliplatin combined with capecitabine (CAPOX) or oxaliplatin combined with tegafur, gimeracil and oteracil potassium capsules (S-1)(SOX), and to investigate the value of expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) proteins in tumor tissue for predicting the efficacy of CAPOX and SOX regimens in advanced gastric cancer patients. METHODS A total of 107 newly-diagnosed, stage Ⅲc/Ⅳ gastric cancer patients (no surgical indication, ECOG performance scores 0-2 and expected survival time ≥3 months) were recruited with 101 patients evaluated. The patients were randomly divided into two groups. One was study group in which the patients received CAPOX regimen. The other was control group received SOX regimen. Each patient received four cycles, at least two cycles chemotherapy every three weeks and followed up until death or lost. Tumor biopsies were obtained by gastroscopy for immunohistochemical examination of the expression of TP and DPD proteins before chemotherapy. Response rate (ORR), overall survival (OS) and time to tumor progression (TTP) of the patients were assessed. RESULTS The objective response rate (ORR) of the study and control groups was 49.0% (5/51) vs. 46.0% (23/50), respectively (P>0.05). The overall survival (OS) was 357.36±24.69 days in the study group and 349.87±22.63 days in the control group, and the time-to-progression (TTP) was 216.75±19.32 days in the study group and 220.54±18.47 days in the control group (P>0.05 for both). Stratified analysis showed that the ORR of TP-positive patients in the study group was significantly higher than that in the control group (72.0 % vs. 41.7 %, P=0.032). There was no significant difference in ORR between the TP-negative patients in the study and control groups (26.9% vs. 50.0%, P=0.087), while the ORR of DPD-positive patients in the control group was significantly higher than that of the study group (51.9% vs. 34.6%, P=0.046). There was no significant difference in the ORR between DPD-negative patients in the study and control groups (64.0% vs. 39.1%, P=0.084). The follow-up showed that the OS (378.42±22.56 days) and TTP (271.77±24.92 days) in the TP-positive patients of the study group were significantly longer than those of the control group (OS: 326.57±19.84 days, and TTP: 229.13±22.68 days)( P<0.05). The OS was 371.25±23.97 days and TTP was 264.66±21.36 days in the DPD-positive patients of control group, significantly longer than those of the study group (OS: 334.73±21.47days, and TTP: 208.58±20.70 days) (P<0.05). But there was no significant difference in the OS and TTP between the TP- and DPD-negative patients in the two groups (P>0.05). In respect of adverse events, both the rates of hematological and non-hematological toxicities were low and similar between the two groups (P>0.05), and well-tolerated by the patients. CONCLUSIONS Both CAPOX and SOX regimens are effective chemotherapeutic protocols in treatment of patients with advanced gastric cancer. The expression levels of TP and DPD in tumor tissue can be used as a predictive factor for the efficacy of capecitabine or tegafur, gimeracil and oteracil potassium capsules combined with oxaliplatin regimens. CAPOX chemotherapy regimen is more suitable for the TP-positive gastric cancer patients, and SOX regimen is more suitable for the DPS-positive gastric cancer patients.
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Collagen Type III and VI Turnover in Response to Long-Term Immobilization.
Sun, S, Henriksen, K, Karsdal, MA, Byrjalsen, I, Rittweger, J, Armbrecht, G, Belavy, DL, Felsenberg, D, Nedergaard, AF
PloS one. 2015;(12):e0144525
Abstract
BACKGROUND Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization. METHODS In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. RESULTS Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization. CONCLUSION The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.
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Salt loading and potassium supplementation: effects on ambulatory arterial stiffness index and endothelin-1 levels in normotensive and mild hypertensive patients.
Liu, Z, Peng, J, Lu, F, Zhao, Y, Wang, S, Sun, S, Zhang, H, Diao, Y
Journal of clinical hypertension (Greenwich, Conn.). 2013;(7):485-96
Abstract
The authors investigated effects of excessive salt intake and potassium supplementation on ambulatory arterial stiffness index (AASI) and endothelin-1 (ET-1) in salt-sensitive and non-salt-sensitive individuals. AASI and symmetric AASI (s-AASI) were used as indicators of arterial stiffness. Plasma ET-1 levels were used as an index of endothelial function. Chronic salt-loading and potassium supplementation were studied in 155 normotensive to mild hypertensive patients from rural northern China. After 3 days of baseline investigation, participants were maintained sequentially for 7 days each on diets of low salt (51.3 mmol/d), high salt (307.7 mmol/d), and high salt+potassium (60 mmol/d). Ambulatory 24-hour blood pressure (BP) and plasma ET-1 were measured at baseline and on the last 2 days of each intervention. High-salt intervention significantly increased BP, AASI, s-AASI (all P<.001); potassium supplementation reversed increased plasma ET-1 levels. High-salt-induced changes in BP, s-AASI, and plasma ET-1 were greater in salt-sensitive individuals. Potassium supplementation decreased systolic BP and ET-1 to a significantly greater extent in salt-sensitive vs non-salt-sensitive individuals (P<.001). Significant correlations were identified between s-AASI and ET-1 change ratios in response to both high-salt intervention and potassium supplementation (P<.001). Reducing dietary salt and increasing daily potassium improves arterial compliance and ameliorates endothelial dysfunction.
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Absorption and plasma disposition of genistin differ from those of genistein in healthy women.
Yuan, B, Zhen, H, Jin, Y, Xu, L, Jiang, X, Sun, S, Li, C, Xu, H
Journal of agricultural and food chemistry. 2012;(6):1428-36
Abstract
The chemical forms in which isoflavones appear in food or supplements seem to play an important role in their absorption efficiency. However, the influence of the chemical form of isoflavones on their plasma disposition has never been reported, although the metabolites of isoflavones circulating in the blood may have biological activity themselves. The purpose of the study was to investigate the pharmacokinetic profiles of genistein (GEN) and its phase II metabolites in the plasma and urine of healthy young women after multiple doses of pure aglycone and glucoside forms of GEN. Genistein-7-glucuronide (G-7-G), 4'-glucuronide (G-4'-G), 7-sulfate (G-7-S), 4'-sulfate (G-4'-S), 4',7-diglucuronide (G-4',7-diG), and 7-glucuronide-4'-sulfate (G-7-G-4'-S) besides unconjugated GEN were observed in human plasma after ingestion of GEN and its glucoside. Among these metabolites, G-4',7-diG and G-7-G-4'-S were the major ones, comprising both about 30% of the total amount of GEN in plasma. Compared with the aglycone, the amount of total GEN in vivo and those of G-4',7-diG and G-7-G-4'-S were increased after the glucoside intake. No difference was observed in urinary excretion between the aglycone and the glucoside. Overall, the absorption and plasma disposition of GEN were affected by the glucoside form.
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A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance hemodialysis patients.
Moran, J, Sun, S, Khababa, I, Pedan, A, Doss, S, Schiller, B
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2012;(1):102-7
Abstract
BACKGROUND Central venous catheters (CVCs) are used for vascular access in hemodialysis patients who have no alternative access or are awaiting placement or maturation of a permanent access. The major complications of CVCs are catheter-related bloodstream infection and clotting in the catheter lumen. STUDY DESIGN Parallel-group, randomized, multicenter clinical trial, with patients blinded to study intervention. SETTING & PARTICIPANTS 16 free-standing dialysis facilities in Northern California belonging to a single provider. 303 adult maintenance hemodialysis patients who were using a tunneled cuffed CVC for vascular access. INTERVENTION The treatment group received an antibiotic lock containing gentamicin 320 μg/mL in 4% sodium citrate, whereas the control group received the standard catheter lock containing heparin 1,000 U/mL. Both groups received triple-antibiotic ointment on the catheter exit site during dressing changes at each dialysis treatment. OUTCOMES Catheter-related bloodstream infection and catheter clotting. MEASUREMENTS Catheter-related bloodstream infection was defined as the occurrence of symptoms consistent with bacteremia together with positive blood culture results in the absence of another obvious source of infection. Catheter clotting was measured as the rate of thrombolytic agent use required to maintain adequate blood flow. A single patient could contribute more than one infection or clotting episode. RESULTS The rate of catheter-related bloodstream infection was 0.91 episodes/1,000 catheter-days in the control group and 0.28 episodes/1,000 catheter-days in the treatment group (P = 0.003). The time to the first episode of bacteremia was significantly delayed (P = 0.005). The rates of tissue plasminogen activator use were similar in the treatment and control groups: 2.36 versus 3.42 events/1,000 catheter-days, respectively (P = 0.2). LIMITATIONS The requirement for dialysis facility staff to prepare the treatment intervention prevented a completely blinded study. CONCLUSION Gentamicin 320 μg/mL in 4% sodium citrate used as a routine catheter lock in CVCs in patients on maintenance hemodialysis therapy markedly decreases the incidence of catheter-related bloodstream infection and is as effective as heparin 1,000 U/mL in preventing catheter clotting.
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A randomized controlled study comparing once-weekly to every-2-week and every-4-week dosing of epoetin alfa in CKD patients with anemia.
Pergola, PE, Gartenberg, G, Fu, M, Sun, S, Wolfson, M, Bowers, P
Clinical journal of the American Society of Nephrology : CJASN. 2010;(4):598-606
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Abstract
BACKGROUND AND OBJECTIVES Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment. RESULTS Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was -0.03 g/dl; and between Q4W and QW was -0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects. CONCLUSIONS Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.
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Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment.
Fleisher, AS, Sun, S, Taylor, C, Ward, CP, Gamst, AC, Petersen, RC, Jack, CR, Aisen, PS, Thal, LJ
Neurology. 2008;(3):191-9
Abstract
OBJECTIVE To compare volumetric MRI of whole brain and medial temporal lobe structures to clinical measures for predicting progression from amnestic mild cognitive impairment (MCI) to Alzheimer disease (AD). METHODS Baseline MRI scans from 129 subjects with amnestic MCI were obtained from participants in the Alzheimer's Disease Cooperative Study group's randomized, placebo-controlled clinical drug trial of donepezil, vitamin E, or placebo. Measures of whole brain, ventricular, hippocampal, and entorhinal cortex volumes were acquired. Participants were followed with clinical and cognitive evaluations until formal criteria for AD were met, or completion of 36 months of follow-up. Logistic regression modeling was done to assess the predictive value of all MRI measures, risk factors such as APOE genotype, age, family history of AD, education, sex, and cognitive test scores for progression to AD. Least angle regression modeling was used to determine which variables would produce an optimal predictive model, and whether adding MRI measures to a model with only clinical measures would improve predictive accuracy. RESULTS Of the four MRI measures evaluated, only ventricular volumes and hippocampal volumes were predictive of progression to AD. Maximal predictive accuracy using only MRI measures was obtained by hippocampal volumes by themselves (60.4%). When clinical variables were added to the model, the predictive accuracy increased to 78.8%. Use of MRI measures did not improve predictive accuracy beyond that obtained by cognitive measures alone. APOE status, MRI, or demographic variables were not necessary for the optimal predictive model. This optimal model included the Delayed 10-word list recall, New York University Delayed Paragraph Recall, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. CONCLUSION In moderate stages of amnestic mild cognitive impairment, common cognitive tests provide better predictive accuracy than measures of whole brain, ventricular, entorhinal cortex, or hippocampal volumes for assessing progression to Alzheimer disease.