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1.
Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data.
Brockmeyer, M, Parco, C, Vargas, KG, Westenfeld, R, Jung, C, Kelm, M, Roden, M, Akbulut, C, Schlesinger, S, Wolff, G, et al
Journal of nephrology. 2024;(2):309-321
Abstract
BACKGROUND Absolute treatment benefits-expressed as numbers needed to treat-of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome. METHODS From Kaplan-Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI). RESULTS Twelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months. CONCLUSION The present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.
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2.
Effect of Olive Oil Hydrogel as a Fat Replacer in Beef Meatballs.
Palamutoğlu, R, Kasnak, C, Ünaldı, BÖ, Duman, S, Baydır, AT
Food technology and biotechnology. 2024;(1):110-118
Abstract
RESEARCH BACKGROUND Meat and meat products are essential sources of dietary saturated fatty acids. However, excessive consumption of meat and meat products may be harmful to human health. The study evaluates the effect of fat replacement with hydrogels (olive oil in water emulsions gelled by gelatine) in meatballs. EXPERIMENTAL APPROACH The effect of replacing fat with different ratios of hydrogel (control, 25 (F25), 50 (F50), 75 (F75) and 100 % (F100)) on the chemical (fatty acids and thiobarbituric acid reactive substances (TBARS)) and physical (cooking loss, diameter reduction, fat retention, water retention, colour and texture analysis) characteristics of the meatballs were analyzed. RESULTS AND CONCLUSIONS The fat content of raw meatball samples was reduced from (31.2±2.2) to (10.5±0.4) % in the sample with the highest fat substitution (F100). The energy levels of the F100 samples were almost 56 % lower than of the control group. Monounsaturated fatty acids (MUFAs) represented the dominant group in all substitution rates of the meatballs, followed by saturated fatty acids (SFAs) and finally polyunsaturated fatty acids (PUFAs). Among the raw meatball samples, the highest oxidation occurred in the F50 and F100 groups. However, it was determined that the difference between F25 and F75 and the difference between control and F75 were not statistically significant (p˃0.05). When the cooked samples were compared, the highest thiobarbituric acid (TBA) value was found in the F50 sample, followed by the F100 and F75 samples. The difference between the mean values of springiness and cohesiveness of the samples was not significant (p˃0.05). The hardness value of samples decreased significantly (p˂0.001) with >75 % fat replacement. NOVELTY AND SCIENTIFIC CONTRIBUTION It can be concluded that the oil replacement rate that may satisfy consumer demand without impairing the product technological and chemical quality should be <75 %. As the fat replacement ratio increases, the SFA content of cooked meatballs decreases, while the MUFA and PUFA contents increase. Considering the positive effects of reducing the intake of SFAs and increasing the intake of unsaturated fatty acids on non-communicable diseases such as cardiovascular diseases, fat replacement in meatballs is important for future developments.
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3.
Ketogenic diet for epilepsy and obesity: Is it the same?
Tagliabue, A, Armeno, M, Berk, KA, Guglielmetti, M, Ferraris, C, Olieman, J, van der Louw, E
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2024;(3):581-589
Abstract
The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.
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4.
Protein phosphorylation and kinases: Potential therapeutic targets in necroptosis.
Shi, Y, Wu, C, Shi, J, Gao, T, Ma, H, Li, L, Zhao, Y
European journal of pharmacology. 2024;:176508
Abstract
Necroptosis is a pivotal contributor to the pathogenesis of various human diseases, including those affecting the nervous system, cardiovascular system, pulmonary system, and kidneys. Extensive investigations have elucidated the mechanisms and physiological ramifications of necroptosis. Among these, protein phosphorylation emerges as a paramount regulatory process, facilitating the activation or inhibition of specific proteins through the addition of phosphate groups to their corresponding amino acid residues. Currently, the targeting of kinases has gained recognition as a firmly established and efficacious therapeutic approach for diverse diseases, notably cancer. In this comprehensive review, we elucidate the intricate role of phosphorylation in governing key molecular players in the necroptotic pathway. Moreover, we provide an in-depth analysis of recent advancements in the development of kinase inhibitors aimed at modulating necroptosis. Lastly, we deliberate on the prospects and challenges associated with the utilization of kinase inhibitors to modulate necroptotic processes.
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5.
Impact of fibre supplementation on microbiome and resilience in healthy participants: A randomized, placebo-controlled clinical trial.
Eveleens Maarse, BC, Eggink, HM, Warnke, I, Bijlsma, S, van den Broek, TJ, Oosterman, JE, Caspers, MPM, Sybesma, W, Gal, P, van Kraaij, SJW, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2024
Abstract
BACKGROUND AND AIMS The gut microbiome exerts important roles in health, e.g., functions in metabolism and immunology. These functions are often exerted via short-chain fatty acid (SCFA) production by gut bacteria. Studies demonstrating causal relationships between interventions targeting the microbiome and clinical outcomes are limited. This study aimed to show a causal relationship between microbiome modulation through fibre intervention and health. METHODS AND RESULTS This randomized, double-blind, cross-over study included 65 healthy subjects, aged 45-70 years, with increased metabolic risk (i.e., body mass index [BMI] 25-30 kg/m2, low to moderate daily dietary fibre intake, <30g/day). Subjects took daily a fibre mixture of Acacia gum and carrot powder or placebo for 12 weeks, with an 8-week wash-out period. Faecal samples for measurement of SCFAs and microbiome analysis were collected every 4 weeks. Before and after each intervention period subjects underwent the mixed-meal PhenFlex challenge Test (PFT). Health effects were expressed as resilience to the stressors of the PFT and as fasting metabolic and inflammatory state. The fibre mixture exerted microbiome modulation, with an increase in β-diversity (p < 0.001). α-diversity was lower during fibre mixture intake compared to placebo after 4, 8 and 12 weeks (p = 0.002; p = 0.012; p = 0.031). There was no effect observed on faecal SCFA concentrations, nor on any of the primary clinical outcomes (Inflammatory resilience: p = 0.605, Metabolic resilience: p = 0.485). CONCLUSION Although the intervention exerted effects on gut microbiome composition, no effects on SCFA production, on resilience or fasting metabolic and inflammatory state were observed in this cohort. REGISTRATION NUMBER CLINICALTRIALS.GOV: NCT04829396.
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6.
Early-life nutrition and adult-life outcomes.
Alves, JGB, Alves, LV
Jornal de pediatria. 2024;(Suppl 1):S4-S9
Abstract
OBJECTIVES To verify the association between early-life nutrition and chronic adult diseases. DATA SOURCES Medline, Embase, Cochrane Database, and Lilacs. SUMMARY OF FINDS The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that a mismatch between early-life circumstances and later-life situations may have an impact on chronic diseases. In this review, the authors emphasize the research supporting the impact of early nutrition on the origins of adult height, obesity and metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and reproductive outcomes. CONCLUSION Even though this is a new topic and there are still many research questions to be answered, there is strong evidence that both deficiency and excess nutrition in early life can cause epigenetic changes that have effects that last a lifetime and contribute to the development of chronic diseases. Public health efforts to protect adults from getting chronic diseases should focus on nutrition in the first 1000 days of life, from conception to the end of the second year of life.
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7.
O-GlcNAcylation: a pro-survival response to acute stress in the cardiovascular and central nervous systems.
Xue, Q, Ji, S, Xu, H, Yu, S
European journal of medical research. 2024;(1):174
Abstract
O-GlcNAcylation is a unique monosaccharide modification that is ubiquitously present in numerous nucleoplasmic and mitochondrial proteins. The hexosamine biosynthesis pathway (HBP), which is a key branch of glycolysis, provides the unique sugar donor UDP-GlcNAc for the O-GlcNAc modification. Thus, HBP/O-GlcNAcylation can act as a nutrient sensor to perceive changes in nutrient levels and trigger O-GlcNAc modifications of functional proteins in cellular (patho-)physiology, thereby regulating diverse metabolic processes. An imbalance in O-GlcNAcylation has been shown to be a pathogenic contributor to dysfunction in metabolic diseases, including type 2 diabetes, cancer, and neurodegeneration. However, under acute stress conditions, protein O-GlcNAc modification exhibits rapid and transient upregulation, which is strongly correlated with stress tolerance and cell survival. In this context, we discuss the metabolic, pharmacological and genetic modulation of HBP/O-GlcNAc modification in the biological system, the beneficial role of O-GlcNAcylation in regulating stress tolerance for cardioprotection, and neuroprotection, which is a novel and rapidly growing field. Current evidence suggests that transient activation of the O-GlcNAc modification represents a potent pro-survival signalling pathway and may provide a promising strategy for stress-related disorder therapy.
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8.
Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with chronic kidney disease: meta-analysis of phase 3 randomized controlled trials.
Minutolo, R, Liberti, ME, Simeon, V, Sasso, FC, Borrelli, S, De Nicola, L, Garofalo, C
Clinical kidney journal. 2024;(1):sfad143
Abstract
BACKGROUND Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are new therapeutic agents for anaemia in chronic kidney disease (CKD). We evaluated by meta-analysis and meta-regression the efficacy and safety of HIF-PHIs in patients with CKD-related anaemia. METHODS We selected phase 3 randomized clinical trials (RCTs) comparing HIF-PHIs and erythropoiesis-stimulating agents (ESAs) in dialysis and non-dialysis patients. Efficacy outcomes were the changes from baseline of haemoglobin, iron parameters (hepcidin, serum iron, TIBC, TSAT, ferritin) and intravenous iron dose; as safety outcomes we considered cancer, adjudicated major adverse cardiovascular events (MACE), MACE+ (MACE plus hospitalization for hearth failure or unstable angina or thromboembolic event), thrombotic events (deep vein thrombosis, pulmonary embolism), arterovenous fistula (AVF) thrombosis and death. RESULTS We included 26 RCTs with 24 387 patients. Random effect meta-analysis of the unstandardized mean difference between HIF-PHIs and ESAs showed a significant change in haemoglobin levels from baseline of 0.10 g/dL (95% CI 0.02 to 0.17). Meta-regression analysis showed a significantly higher haemoglobin change for HIF-PHIs in younger patients and versus short-acting ESA (0.21 g/dL, 95% CI 0.12 to 0.29 versus -0.01, 95% CI -0.09 to 0.07 in studies using long-acting ESA, P < .001). No significant effect on heterogeneity was found for type of HIF-PHIs. In comparison with ESAs, HIF-PHIs induced a significant decline in hepcidin and ferritin and a significant increase in serum iron and TIBC, while TSAT did not change; intravenous iron dose was lower with HIF-PHI (-3.1 mg/week, 95% CI -5.6 to -0.6, P = .020). Rate ratio of cancer (0.93, 95% CI 0.76 to 1.13), MACE (1.00, 95% CI 0.94 to 1.07), MACE+ (1.01, 95% CI 0.95 to 1.06), thrombotic events (1.08, 95% CI 0.84 to 1.38), AVF thrombosis (1.02, 95% CI 0.93 to 1.13) and death (1.02, 95% CI 0.95 to 1.13) did not differ between HIF-PHIs and ESAs. CONCLUSIONS HIF-PHIs at the doses selected for the comparisons are effective in correcting anaemia in comparison with ESA therapy with a significant impact on iron metabolism without notable difference among various agents. No safety signals emerge with use of HIF-PHIs.
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9.
Associations between Cardiometabolic Risk Factors and Increased Consumption of Diverse Legumes: A South African Food and Nutrition Security Programme Case Study.
Mkhize, X, Oldewage-Theron, W, Napier, C, Duffy, KJ
Nutrients. 2024;(3)
Abstract
The programme aimed to improve selected cardiometabolic risk (CMR) variables using a nutritional intervention among farmers who reported hypertensive disorders as hindrances during agricultural activities. The intervention had two case controls (n = 103) [experimental group-EG (n = 53) and control group-CG (n = 50)] which were tracked and whose blood pressure measurements, dietary intake, blood indices for cholesterol concentration and glucose levels from pre- and post-intervention surveys after the baseline survey (n = 112) were analysed. The interval for data collection was 12 weeks (±120 days) after five legume varieties were consumed between 3 and 5 times a day, and servings were not <125 g per at least three times per week. Sixty-five per cent of farmers were above 60 years old, with mean age ranges of 63.3 (SD ± 6.3) years for women and 67.2 (SD ± 6.7) for men. The post-intervention survey revealed that EG blood results indicated nutrient improvement with p <= 0.05 for blood glucose (p = 0.003) and cholesterol (p = 0.001) as opposed to the CG. A trend analysis revealed that cholesterol (p = 0.033) and systolic blood pressure (SBP); (p = 0.013) were statistically significant when comparing genders for all study phases. Interventions focusing on legumes can improve hypertension and cardiovascular disease and fast-track the achievement of SGDs 3 and 12 through community-based programmes.
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10.
Management of cancer-associated thromboembolism in vulnerable population.
Laporte, S, Benhamou, Y, Bertoletti, L, Frère, C, Hanon, O, Couturaud, F, Moustafa, F, Mismetti, P, Sanchez, O, Mahé, I, et al
Archives of cardiovascular diseases. 2024;(1):45-59
Abstract
Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data, on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with CAT on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR<30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (<50,000 platelets/μL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.
keywords:"Cardiovascular Diseases" OR (Cardiovascular AND Diseases) OR "Cardiovascular Diseases" OR (cardiovascular AND disease) OR "cardiovascular disease"