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The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K+-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure.
Murphy, D, Ster, IC, Kaski, JC, Anderson, L, Banerjee, D
BMC nephrology. 2021;(1):254
Abstract
BACKGROUND CKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy. METHODS We propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants' RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George's Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline. DISCUSSION This trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded. TRIAL REGISTRATION EudraCT number 2020-002946-18. Registered on 08 June 2020. Online record pending.
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Comparison of in vitro biocompatibility and antibacterial activity of two calcium silicate-based materials.
Liu, M, He, L, Wang, H, Su, W, Li, H
Journal of materials science. Materials in medicine. 2021;(5):52
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Abstract
This study is aimed at comparing and evaluating the biocompatibility and antibacterial activities of mineral trioxide aggregate (MTA) and iRoot BP Plus as novel retro-filling materials. Discs of both materials were prepared and incubated for 72 h to obtain material extracts in medium. Flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used to assess the rate of apoptosis and proliferation of human periodontal ligament stem cells (hPDLSCs) when exposed to eluates of both materials. The expression levels of alkaline phosphatase, collagen type I, osteocalcin, Runt-related transcription factor-2, and Osterix were tested for evaluating the osteogenic differentiation of hPDLSCs. The antibacterial activities of both materials were compared by the direct contact test. The hPDLSCs stimulated by MTA or iRoot BP Plus eluates showed significantly higher cell viability than that of the control group with no eluates. No significant differences were observed among the percentages of necrotic and apoptotic cells stimulated by MTA and iRoot BP Plus eluates and the control group. The expression of all osteogenic differentiation markers of hPDLSCs in both experimental groups were significantly higher than those of the control group, while the increment values in MTA group were significantly higher than those of the iRoot BP Plus group. The antibacterial activity against Enterococcus faecalis showed no significant difference between MTA and iRoot BP Plus. Therefore, both materials may be suitable for retro-filling applications.
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An evaluation of sodium zirconium cyclosilicate as a treatment option for hyperkalemia.
Takkar, C, Nassar, T, Qunibi, W
Expert opinion on pharmacotherapy. 2021;(1):19-28
Abstract
INTRODUCTION Hyperkalemia, defined as serum potassium level > 5.0 mEq/l, is associated with serious cardiac dysrhythmias, sudden death and increased mortality risk. It is common in patients with chronic kidney disease (CKD), diabetes (DM) and heart failure (HF), particularly in those treated with the renin-angiotensin-aldosterone system (RAAS) inhibitors or potassium-sparing diuretics. Although these drugs have documented renal and cardiac protective benefits, frequent hyperkalemia associated with their use often dictates administration of suboptimal doses or their discontinuation altogether. Treatment for chronic hyperkalemia in these settings has been challenging; however, the recent introduction of two new potassium-binding resins has revolutionized our approach to treating hyperkalemia. AREAS COVERED We review key clinical data relating to the pharmacokinetics, efficacy and safety of sodium zirconium cyclosilicate (SZC) as a treatment option for hyperkalemia. EXPERT OPINION SZC and Patiromer are promising new agents for lowering serum potassium in hyperkalemic patients, including those with CKD, with and without DM or HF, facilitating the use of the RAAS inhibitors for renal and cardiac protection. Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. Clinical trials showed that SZC lowers serum potassium within 1 h, although it is not approved for treating acute hyperkalemia. SZC was well tolerated and associated with minimal adverse effects.
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Investigation of characteristics as endodontic sealer of novel experimental elastin-like polypeptide-based mineral trioxide aggregate.
Kim, HJ, Jang, JH, Kim, SY
Scientific reports. 2021;(1):10537
Abstract
Although mineral trioxide aggregates (MTA) have been adopted as an endodontic sealer because of excellent sealing effect and bioactive property and been modified with improvement of its characteristics, the developed MTA sealers have not yet satisfied all the ideal requirements of endodontic sealers. The aim of this study was to assess the characteristics of elastin-like polypeptide (ELP)-incorporated MTA for use as an endodontic sealer and compare them with those of commercial MTA sealers. Two commercial MTA sealers and three experimental ELP-incorporated MTA sealers with 0.3, 0.4, and 0.5 liquid/powder (L/P) ratio for 10 wt% ELP liquid were evaluated. The push-out bond strength, flow rate, sealer penetrability and wash-out resistance were tested and the sealer-dentin interface was observed using a scanning electron microscope (SEM). Our study revealed the ELP-incorporated MTA sealer, especially in 0.4 L/P ratio, exhibited the higher push-out bond strength and flow rate (P < 0.05), and equal or superior sealer penetration and remarkable wash-out resistance compared to commercial MTA sealers. The groups of ELP-based experimental sealers also exhibited more intimate contact with dentin compared to the commercial MTA sealers. Our research will suggest the possible adoption of the ELP-incorporated MTA as endodontic sealer for clinical use.
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Acute Inositol-Stabilized Arginine Silicate Improves Cognitive Outcomes in Healthy Adults.
Gills, JL, Campitelli, A, Jones, M, Paulson, S, Myers, JR, Madero, EN, Glenn, JM, Komorowski, J, Gray, M
Nutrients. 2021;(12)
Abstract
Inositol-stabilized arginine silicate (ASI) is an ergogenic aid that upregulates nitric oxide. Acute ASI supplementation improves working memory and processing speed in young adults but there is a lack of data examining other cognitive tasks. Therefore, the purpose of this study was to examine acute ASI effects on young healthy adults by assessing multiple cognitive domains. Nineteen young adults (20.9 ± 3.2 years) completed this randomized, double-blind, crossover study consuming ASI (1.5 g ASI + 12 g dextrose) and placebo (12 g dextrose). The participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and two digital cognitive assessments before consuming the supplement and then completed the same battery of tests 60 min post-supplementation. Repeated measures ANOVA demonstrated that ASI consumption significantly improved total RBANS and immediate memory scores compared to the placebo (p < 0.05). However, no significant differences were displayed between trials for other cognitive domains (p > 0.05). Acute ASI ingestion increased overall RBANS scores and immediate memory scores in young adults. More research is needed to examine the acute effects of ASI on other domains of cognition, in older populations, and its long-term effects on cognition.
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Effects of Inositol-Enhanced Bonded Arginine Silicate Ingestion on Cognitive and Executive Function in Gamers.
Sowinski, R, Gonzalez, D, Xing, D, Yoo, C, Jenkins, V, Nottingham, K, Dickerson, B, Humphries, M, Leonard, M, Ko, J, et al
Nutrients. 2021;(11)
Abstract
Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7-14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.
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Autologous Bone Graft Versus Silicate-Substituted Calcium Phosphate in the Treatment of Tunnel Defects in 2-Stage Revision Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized Controlled Study With a Minimum Follow-up of 2 Years.
von Recum, J, Gehm, J, Guehring, T, Vetter, SY, von der Linden, P, Grützner, PA, Schnetzke, M
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2020;(1):178-185
Abstract
PURPOSE To compare and evaluate knee laxity and functional outcomes between autologous bone graft and silicate-substituted calcium phosphate (Si-CaP) in the treatment of tunnel defects in 2-stage revision anterior cruciate ligament reconstruction (ACLR). METHODS This prospective, randomized controlled trial was conducted between 2012 and 2015 with a total of 40 patients who underwent 2-stage revision ACLR. The tunnels were filled with autologous iliac crest cancellous bone graft in 20 patients (control group) and with Si-CaP in the other 20 patients (intervention group). After a minimum follow-up period of 2 years, functional outcomes were assessed by KT-1000 arthrometry (side-to-side [STS] difference), the Tegner score, the Lysholm score, and the International Knee Documentation Committee score. RESULTS A total of 37 patients (follow-up rate, 92.5%) with an average age of 31 years were followed up for 3.4 years (range, 2.2-5.5 years). The KT-1000 measurement did not show any STS difference between the bone graft group (0.9 ± 1.5 mm) and the Si-CaP group (0.7 ± 2.0 mm) (P = .731). One patient in the intervention group (5%) had an STS difference greater than 5 mm. Both groups showed significant improvements in the Tegner score, Lysholm score, and International Knee Documentation Committee score from preoperative assessment to final follow-up (P ≤ .002), without any difference between the 2 groups (P ≥ .396). Complications requiring revision occurred in 4 control patients (22%) and in 2 patients in the intervention group (11%) (P = .660). No complications in relation to Si-CaP were observed. CONCLUSIONS Equivalent knee laxity and clinical function outcomes were noted 3 years after surgery in both groups of patients. Si-CaP bone substitute is therefore a safe alternative to autologous bone graft for 2-stage ACLR. LEVEL OF EVIDENCE Level I, prospective, randomized controlled clinical trial.
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Fracture resistance of simulated immature roots using Biodentine and fiber post compared with different canal-filling materials under aging conditions.
Elnaghy, A, Elsaka, S
Clinical oral investigations. 2020;(3):1333-1338
Abstract
OBJECTIVE The aim of this study was to evaluate the fracture resistance of simulated immature roots using Biodentine (BD) and fiber post (FP) compared with different root canal-filling materials under aging conditions. MATERIALS AND METHODS One hundred and forty maxillary central anterior teeth were randomly divided into seven groups (n = 20/group). Negative control received no treatment. In the other groups, the root canals were prepared to simulate immature teeth. The root canals were filled with a 4-mm apical plug of BD and restored intraradicular with BD, BD + FP, composite resin (CR), CR + FP, and gutta-percha (GP). Positive controls were instrumented but without restoration. Teeth were subjected to thermocycling and received cyclic loading before fracture resistance test. Fracture resistance was conducted using a universal testing machine with a crosshead speed of 0.5 mm/min until fracture. Load to fracture was recorded in newtons (N). Data were statistically analyzed using one-way analysis of variance and Tukey's test at P < 0.05. RESULTS Root canals restored intraradicular with BD + FP and CR + FP showed the highest fracture resistance compared with the other experimental groups (P < 0.001). There was no significant difference in the fracture resistance between CR and BD groups (P = 0.998). GP and positive control groups were significantly lower resistance to fracture than the other groups (P < 0.001). CONCLUSIONS Intraradicular reinforcement with BD + FP and CR + FP enhanced the fracture resistance of simulated immature teeth than the other experimental groups. CLINICAL RELEVANCE Biodentine or composite resin combined with fiber post could be used to reinforce immature teeth with an apical Biodentine plug.
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Let Them Eat Healthy: Can Emerging Potassium Binders Help Overcome Dietary Potassium Restrictions in Chronic Kidney Disease?
Sussman, EJ, Singh, B, Clegg, D, Palmer, BF, Kalantar-Zadeh, K
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(6):475-483
Abstract
Potassium-rich foods might provide many health benefits even to people who have declining renal function. The barrier to obtaining these health benefits has long been the concern over hyperkalemia. There are new and novel treatment options available which may enable patients with chronic kidney disease to obtain the health benefits of eating a diet that contains foods such as fruits and vegetables which are high in potassium while reducing the risk of hyperkalemia. We conclude by emphasizing the need for clinical trials with patients on hemodialysis to directly compare the current standard of care, including a potassium-restricted diet, to a potassium-liberalized diet with a potassium binder. The outcome measures would be serum potassium (<5.3 mmol/L), assessments of acidosis, blood pressure, constipation, glycemic control, overhydration, and azotemia, all of which might change in a favorable direction with vegetarian diets as well as quality of life and satisfaction.
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Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE).
Peacock, WF, Rafique, Z, Vishnevskiy, K, Michelson, E, Vishneva, E, Zvereva, T, Nahra, R, Li, D, Miller, J
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2020;(6):475-486
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OBJECTIVES Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED). METHODS This exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+ ) from baseline until 4 hours after start of dosing. RESULTS Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was -0.41 (±0.11) mmol/L and -0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = -0.13 mmol/L, 95% confidence interval [CI] = -0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: -0.72 (±0.12) versus -0.36 (±0.11) mmol/L (LSM difference = -0.35 mmol/L, 95% CI = -0.68 to -0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours. CONCLUSIONS This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.