Amino acids to prevent cardiac surgery-associated acute kidney injury: a randomized controlled trial.

BACKGROUND: This study aimed to examine the preventive effect of amino acids on postoperative acute kidney injury (AKI). METHODS: This was single-center, patient- and assessor-blinded, randomized controlled trial. Patients who underwent aortic surgery with cardiopulmonary bypass were included. The intervention group received 60 g/day of amino acids for up to 3 days. The control group received standard care. The primary outcome was the incidence of AKI. We assessed the effect of amino acids on AKI using a Cox proportional hazards regression model. RESULTS: Sixty-six patients were randomly assigned to the control or intervention group. One patient in the control group withdrew consent after randomization. The incidence of AKI was 10 patients (30.3%) in the intervention group versus 18 patients (56.2%) in the control group (adjusted hazard ratio, 0.44; 95% confidence interval, 0.20-0.95; P = 0.04). CONCLUSIONS: This trial demonstrated a significant reduction in AKI incidence with amino acid supplementation. TRIAL REGISTRATION: jRCT, jRCTs051210154. Registered 31 December 2021, https://jrct.niph.go.jp/re/reports/detail/69916.

Double-blinded randomized controlled trial to reveal the effects of Brazilian propolis intake on rheumatoid arthritis disease activity index; BeeDAI.

BACKGROUND AND AIMS: Brazilian propolis reportedly contributed to suppressing disease activity in a mouse model of rheumatoid arthritis (RA), suggesting new treatment options using Brazilian propolis. However, only results from animal experiments have been available, and the suppressive effects of Brazilian propolis on disease activity in humans with RA remain unknown. The purpose of this study was to clinically validate how Brazilian propolis intake changes disease activity in RA patients. METHODS: This study was conducted as a multicenter, double-blinded, randomized, placebo-controlled, parallel-group study of 80 women with RA (median age, 61.5 years; interquartile range, 56.0 to 67.3 years) showing moderate disease activity on Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). Test tablets containing Brazilian propolis were used in Group P (40 patients), and Brazilian propolis-free placebo tablets were used as control in Group C (40 patients). Group P received 5 tablets of propolis (508.5 mg of propolis) daily, and Group C received 5 tablets of placebo daily. The intervention lasted 24 weeks, with change in DAS28-ESR set as the primary endpoint. As secondary endpoints, other disease activity assessment (DAS28 using C-reactive protein, simplified disease activity index, clinical disease activity index), ultrasonographic evaluation of synovitis, activities of daily living, quality of life, changes in cytokine levels, and adverse events over the course of the study were also assessed. Data were statistically analyzed by analysis of covariance. RESULTS: No significant differences in the primary endpoint were identified between groups (Group P vs Group C, effect: 0.14, 95% confidence interval: -0.21 to 0.49, p = 0.427). Likewise, no significant differences were seen between groups for any secondary endpoints. The adverse event rate during the study period was 28% in Group P and 33% in Group C. CONCLUSIONS: Brazilian propolis exerted no effects on disease activity in patients with RA.

Effectiveness of music therapy for alleviating pain during haemodialysis access cannulation for patients undergoing haemodialysis: a multi-facility, single-blind, randomised controlled trial.

BACKGROUND: Repeated pain during haemodialysis access cannulations is a serious problem for haemodialysis patients even when prescribed oral or topical analgesics. Although some studies have observed the efficacy of music therapy for improving pain and anxiety, its effectiveness during haemodialysis access cannulations during dialysis is uncertain. The purpose of this study is to investigate the effects of music therapy for pain when cannulating haemodialysis access for haemodialysis patients. METHODS: A prospective, multi-facility, single-blind, crossover, randomised controlled trial will be implemented. The intervention includes listening to Mozart, along with a white noise control condition. One hundred twenty haemodialysis patients will be enrolled across five facilities. Patients will be randomly allocated to either an Early-sequence group or a Later-sequence group. The Early-sequence group will receive cannulation while listening to Mozart's Sonata for two pianos in D major (K.448) during the second week (Music period) and white noise during the fourth week (White noise period). The Later-sequence group will receive cannulation along with white noise first, followed by Mozart. All patients will also undergo cannulation during a no-sound period (wearing only headphones) during the first and third week (No-sound period). The music or no-music protocol will begin 8 min prior to the cannulating procedure, and participants will finish listening after starting haemodialysis during each period. The primary outcomes that will be assessed include the Visual Analogue Scale (VAS) score for pain during cannulation, and secondary outcomes are blood pressure, heart rate, VAS anxiety score, State-Trait Anxiety Inventory score, and salivary amylase activity. The operators who are in charge of haemodialysis access cannulation will be blind to the listening condition and VAS report. DISCUSSION: The proposed study has several methodological benefits. First, using white noise is a suitable control condition for addressing the role of sound in pain management. Additionally, using a crossover design with repeated measurements can help control individual differences between participants, which should better distinguish between- and within-participant variability. Overall, music therapy is a safe and inexpensive intervention that does not have the problematic side effects typically associated with pharmacological treatment. If effective, music therapy can be easily implemented for reducing pain and anxiety during cannulation. TRIAL REGISTRATION: This trial was prospectively registered to UMIN Clinical Trials Registry on 1 July 2018 (UMIN 000032850).

Crosstalk between tumor necrosis factor-alpha signaling and aryl hydrocarbon receptor signaling in nuclear factor -kappa B activation: A possible molecular mechanism underlying the reduced efficacy of TNF-inhibitors in rheumatoid arthritis by smoking.

OBJECTIVES: To examine the influence of smoking on biologics treatment against different therapeutic targets, such as TNFα, IL-6, and T cell, in rheumatoid arthritis (RA) and elucidate the underlying molecular mechanism. METHODS: The association between drug-discontinuation due to poor therapeutic response and smoking status was analyzed individually in biologics against different therapeutic targets by a multivariable logistic regression analysis using the "NinJa" Registry, one of the largest cohorts of Japanese RA patients. In vitro enhancement of TNFα-induced NF-κB activation and subsequent proinflammatory cytokine production by cigarette chemical components was examined by RT-PCR, qPCR, ELISA, and western blotting using an immortalized rheumatoid synovial cell line, MH7A. RESULTS: The rate of drug-discontinuation due to poor therapeutic response was higher in the current smoking group than in the never- or ever-smoking groups (the odds ratio of current/never smoking: 2.189, 95%CI; 1.305-3.672,P = 0.003; current/ever: 1.580, 95%CI; 0.879-2.839,P = 0.126) in the TNF inhibitor (TNFi) treatment group. However, this tendency was not observed in either the IL-6 or T cell inhibitor treatment groups. Cigarette smoke chemical components, such as benzo[α]pyrene, known as aryl hydrocarbon receptor (AhR) ligands, themselves activated NF-κB and induced proinflammatory cytokines, IL-1ß and IL-6. Furthermore, they also significantly enhanced TNFα-induced NF-κB activation and proinflammatory cytokine production. This enhancement was dominantly inhibited by Bay 11-7082, an NF-κB inhibitor. CONCLUSIONS: These results suggest a crosstalk between TNFα signaling and AhR signaling in NF-κB activation which may constitute one of the molecular mechanisms underlying the higher incidence of drug-discontinuation in RA patients undergoing TNFi treatment with smoking habits.

Effect of omega-three polyunsaturated fatty acids on inflammation, oxidative stress, and recurrence of atrial fibrillation.

The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin [IL]-6, IL-8, IL-10, tissue necrosis factor alpha, monocyte chemoattractant protein-1, and vascular endothelial growth factor), N-terminal-pro-brain-type natriuretic peptide, and oxidative stress (urinary F2-isoprostanes). AF recurred in 74 patients (58.7%) randomized to n-3 PUFAs and in 30 patients (46.9%) who received placebo; time to recurrence of AF did not differ significantly in the 2 groups (hazard ratio 1.20; 95% confidence interval 0.76 to 1.90, adjusted p = 0.438). Compared with placebo, n-3 PUFAs did not result in clinically meaningful changes in concentrations of inflammatory markers, N-terminal-pro-brain-type natriuretic peptide or F2-isoprostanes. In conclusion, in patients with paroxysmal or persistent AF, treatment with n-3 PUFAs 4 g/day did not reduce the recurrence of AF, nor was it associated with clinically important effects on concentrations of markers of inflammation and oxidative stress. (Clinical trial registration number, NCT 00552084.).

Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients.

BACKGROUND: Chronic systemic inflammation is common in patients with chronic kidney disease on dialysis (CKD5D) and has been considered a key mediator of the increased cardiovascular risk in this patient population. In this study, we tested the hypothesis that supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) will attenuate the systemic inflammatory process in CKD5D patients. METHODS: The design was a randomized, double-blinded, placebo controlled pilot trial (NCT00655525). Thirty-eight patients were randomly assigned in a 1 : 1 fashion to receive 2.9 g of eicosapentaenoic acid (C20:5, n-3) plus docosahexaenoic acid (C22:6, n-3) versus placebo for 12 weeks. The primary outcome was change in pro-inflammatory chemokines measured by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Secondary outcomes were changes in systemic inflammatory markers. Analysis of covariance was used to compare percent change from baseline to 12 weeks. RESULTS: Thirty-one patients completed 12 weeks and three patients completed 6 weeks of the study. Median age was 52 (interquartile range 45, 60) years, 74% were African-American and 79% were male. Supplementation of ω-3 PUFAs effectively decreased the LPS-induced PBMC expression of RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) and MCP-1 (Monocyte Chemotactic Protein-1; unadjusted P = 0.04 and 0.06; adjusted for demographics P = 0.02 and 0.05, respectively). There was no significant effect of the intervention on serum inflammatory markers (C-reactive protein, interleukin-6 and procalcitonin). CONCLUSIONS: The results of this pilot study suggest that supplementation of ω-3 PUFAs is beneficial in decreasing the levels of endothelial chemokines, RANTES and MCP-1. Studies of larger sample size and longer duration are required to further evaluate effects of ω-3 PUFAs on systemic markers of inflammation, other metabolic parameters and clinical outcomes, particularly cardiovascular outcomes in CKD5D patients.

Preliminary efficacy of group medical nutrition therapy and motivational interviewing among obese African American women with type 2 diabetes: a pilot study.

OBJECTIVE: To assess the efficacy and acceptability of a group medical nutritional therapy (MNT) intervention, using motivational interviewing (MI). RESEARCH DESIGN & METHOD: African American (AA) women with type 2 diabetes (T2D) participated in five, certified diabetes educator/dietitian-facilitated intervention sessions targeting carbohydrate, fat, and fruit/vegetable intake and management. Motivation-based activities centered on exploration of dietary ambivalence and the relationships between diet and personal strengths. Repeated pre- and post-intervention, psychosocial, dietary self-care, and clinical outcomes were collected and analyzed using generalized least squares regression. An acceptability assessment was administered after intervention. RESULTS: Participants (n = 24) were mostly of middle age (mean age 50.8 ± 6.3) with an average BMI of 39 ± 6.5. Compared to a gradual pre-intervention loss of HbA1c control and confidence in choosing restaurant foods, a significant post-intervention improvement in HbA1c (P = 0.03) and a near significant (P = 0.06) increase in confidence in choosing restaurant foods were observed with both returning to pre-intervention levels. 100% reported that they would recommend the study to other AA women with type 2 diabetes. CONCLUSION: The results support the potential efficacy of a group MNT/MI intervention in improving glycemic control and dietary self-care-related confidence in overweight/obese AA women with type 2 diabetes.

Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones.

Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case-control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002-December 2009). Each fluoroquinolone-resistant case (n=25) was matched to two fluoroquinolone-susceptible controls (n=50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal-Wallis, P=0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR=1.79, 95% CI 1.22-2.64), but duration of exposure to older fluoroquinolones was not (OR=0.94, 95% CI 0.50-1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors.

The effect of resistance exercise to augment long-term benefits of intradialytic oral nutritional supplementation in chronic hemodialysis patients.

BACKGROUND: Resistance exercise combined with intradialytic oral nutrition (IDON) supplementation improves net protein balance in the acute setting in chronic hemodialysis patients. We hypothesized that combination of long-term resistance exercise and IDON would improve markers of muscle mass and strength further compared with IDON alone. METHODS: Thirty-two participants (21 male; mean age, 43 ± 13 years) on chronic hemodialysis were randomly assigned to IDON plus resistance exercise (NS + EX), or IDON (NS) alone for 6 months. IDON consisted of a lactose-free formula consisting of protein, carbohydrate, and fat. Three sets of 12 repetitions of leg-press were completed before each dialysis session in the NS + EX arm. Primary outcome measurement was lean body mass. Muscle strength and other nutritional parameters were measured as secondary outcomes. RESULTS: Of 32 participants, 22 completed the 6-month intervention. There were no statistically significant differences between the study interventions with respect to changes in lean body mass and body weight, when comparing NS + EX to NS. There were also no statistically significant differences in any of the secondary outcomes measured in the study. Body weight (80.3 ± 16.6 kg, 81.1 ± 17.5 kg, and 80.9 ± 18.2 kg at baseline, month 3, and month 6, respectively; P = .02) and 1-repetition maximum (468 ± 148 lb, 535 ± 144 lb, and 552 ± 142 lb, respectively; P = .001) increased statistically significantly during the study for all patients combined. CONCLUSION: This study did not show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone. When both treatments groups were combined, body weight and muscle strength improved during the study.

Oral protein supplementation alone improves anabolism in a dose-dependent manner in chronic hemodialysis patients.

OBJECTIVE: We examined the protein anabolic effects of Pro-Stat 64, a high nitrogen-containing, enzyme-hydrolyzed, tryptophan-fortified, collagen protein supplement administrated during hemodialysis, at two different dosing regimens. DESIGN: This was a randomized, controlled, prospective study with 3 different groups: control, single dose of supplementation, and double dose of supplementation. SETTING: This study was performed at a clinical research center. PATIENTS: Six prevalent chronic hemodialysis (HD) patients were enrolled: 5 males, 1 female, 4 African Americans, and 2 Caucasians. Their mean age was 45 +/- 11 years (S.D.). Two patients were diabetic. METHODS: Protein turnover studies were performed using amino-acid (AA) balance and primed constant infusion of L-(1-(13)C) leucine. MAIN OUTCOME MEASURE: Whole-body protein balance was determined according to substrate kinetics. RESULTS: There were no statistically significant difference at any time point between protocols for blood chemistries and hormonal markers, except for minor variations in plasma glucose. All plasma AA groups displayed decreases during a control study, in which no supplementation was given. Compared with the control group, plasma nonessential AA and total AA concentrations were statistically significantly higher during HD after both single and double doses of supplementation. The forearm arteriovenous AA balance was statistically significantly better for essential, nonessential, and total AA uptake after both single-dose and double-dose supplementation compared with the control group, except for nonessential AA, which was significantly better only after a double dose. Whole-body protein breakdown and net protein balance were statistically significantly better during HD with a double-dose administration in a dose-dependent manner, compared with the control and single-dose groups. CONCLUSIONS: Oral AA supplementation alone improves whole-body and skeletal muscle protein anabolism in a dose-dependent manner in chronic HD patients. These data should be taken into account during clinical decision-making or when designing clinical trials of nutritional supplementation.