Is Marginal Donor an Efficient Solution for Expanding the Donor Pool for Liver Transplant?

Once the techniques of hepatobiliopancreatic surgery improved, liver transplantation widely extended in different hospitals; therefore, the need of grafts and automatically of liver donors reported a significant increase in the last decade. In this respect, attention was focused on increasing the liver donor pool. The aim of this review is to study the benefits of using marginal grafts in liver transplantation. With the advent of multiple methods of liver preservation, the use of grafts previously considered unsuitable has become possible. Thus, extended allocation criteria have emerged. However, the allocation of these grafts must be carefully considered and analyzed in the context of both recipient and donor factors.

Resection of a Large Celiac Trunk Aneurysm Followed by Cadaveric Graft Reconstruction - A Case Report.

BACKGROUND/AIM: Celiac artery aneurysms represent rare eventualities which remain symptomatic for a long period of time; however, once diagnosed, it should be carefully monitored due to the high risk of developing life-threatening complications. When it comes to the types of therapeutic strategies, both endovascular and surgical therapies can be taken in consideration. CASE REPORT: Depending on the patency of the collateral network, simple ligation or graft placement should be performed. The aim of the current paper is to report the case of a patient diagnosed with a celiac trunk aneurysm who was successfully submitted to resection in association with iliac graft placement between the abdominal aorta and the common hepatic artery. CONCLUSION: Whenever celiac artery aneurysm is diagnosed, it should be closely monitored and treated, resection and reconstruction being a feasible method in order to avoid the development of a life-threatening complication.

Residual risk for coronary heart disease events and mortality despite intensive medical management after myocardial infarction.

BACKGROUND: High-intensity statins, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and antiplatelet agents (ie, intensive medical management) reduce coronary heart disease (CHD) risk after myocardial infarction (MI). OBJECTIVE: The objective of the study was to determine the risk of CHD events or death despite receiving intensive medical management after MI. METHODS: We studied 16,853 United States adults with health insurance in the MarketScan and Medicare databases who underwent percutaneous coronary intervention while hospitalized for MI between January 1, 2014 and June 30, 2015 and received intensive medical management within 30 days after hospital discharge. MI, CHD, and all-cause mortality rates from 30 days after hospital discharge through December 31, 2015 were compared with 67,412 individuals in each of three groups: (1) the general MarketScan and Medicare populations, (2) with diabetes, and (3) with a CHD history. RESULTS: Among beneficiaries intensively medically managed after their MI, recurrent MI, CHD events, and all-cause mortality rates were 47.1, 72.0, and 57.5 per 1000 person-years, respectively. The multivariable-adjusted hazard ratio (95% CI) comparing intensively medically managed beneficiaries after MI to the general population, those with diabetes, and those with a history of CHD were 8.54 (7.52-9.70), 7.40 (6.61-8.28), and 5.45 (4.92-6.05), respectively, for recurrent MI; 7.82 (7.07-8.64), 6.27 (5.74-6.86), and 4.45 (4.10-4.82), respectively, for CHD events; and 1.15 (1.05-1.25), 1.05 (0.97-1.14), and 1.06 (0.97-1.15), respectively, for all-cause mortality. CONCLUSION: Substantial residual risk for MI and CHD events remains despite intensive medical management after MI.

Curcumin Therapeutic Modulation of the Wnt Signaling Pathway.

Curcumin, isolated from the rhizome of Curcuma longa, is one of the most extensively studied phytochemicals. This natural compound has a variety of pharmacological effects including antioxidant, anti-inflammatory, anti-tumor, cardio-protective, hepato-protective and anti-diabetic. Wnt signaling pathway, one of the potential targets of curcumin through upregulation and/or downregulation, plays a significant role in many diseases, even in embryogenesis and development of various organs and systems. In order to exert an anti-tumor activity in the organism, curcumin seems to inhibit the Wnt pathway. The downstream mediators of Wnt signaling pathway such as c-Myc and cyclin D1 are also modified by curcumin. This review demonstrates how curcumin influences the Wnt signaling pathway and is beneficial for the treatment of neurological disorders (Alzheimer's and Parkinson's diseases), cancers (melanoma, lung cancer, breast cancer, colon cancer, endothelial carcinoma, gastric carcinoma and hepatocellular carcinoma) and other diseases, such as diabetes mellitus or bone disorders.

Exploring modularity in biological networks.

Network theoretical approaches have shaped our understanding of many different kinds of biological modularity. This essay makes the case that to capture these contributions, it is useful to think about the role of network models in exploratory research. The overall point is that it is possible to provide a systematic analysis of the exploratory functions of network models in bioscientific research. Using two examples from molecular and developmental biology, I argue that often the same modelling approach can perform one or more exploratory functions, such as introducing new directions of research, offering a complementary set of concepts, methods and algorithms for individuating important features of natural phenomena, generating proofs of principle demonstrations and potential explanations for phenomena of interest and enlarging the scope of certain research agendas. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'.

Statin therapy in athletes and patients performing regular intense exercise - Position paper from the International Lipid Expert Panel (ILEP).

Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as well as other previous attempts on this issue, including the ones from the International Lipid Expert Panel (ILEP), give only general recommendations on how to manage patients requiring statin therapy on regular exercises. Therefore, these guidelines in the form of the Position Paper are the first such an attempt to summary existing, often scarce knowledge, and to present this important issue in the form of step-by-step practical recommendations. It is critically important as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk.

Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: The aim of this meta-analysis of randomized placebo-controlled trials was to examine whether ursodeoxycholic acid treatment is an effective lipid-lowering agent. METHODS: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched in order to find randomized controlled trials evaluating the effect of ursodeoxycholic acid on lipid profile. A random-effect model and the generic inverse variance weighting method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A random-effects meta-regression model was performed to explore the association between potential confounders and the estimated effect size on plasma lipid concentrations. RESULTS: Meta-analysis of 20 treatment arms revealed a significant reduction of total cholesterol following ursodeoxycholic acid treatment (WMD: - 13.85 mg/dL, 95% CI: -21.45, - 6.25, p < 0.001). Nonetheless, LDL-C (WMD: -6.66 mg/dL, 95% CI: -13.99, 0.67, p = 0.075), triglycerides (WMD: - 1.42 mg/dL, 95% CI: -7.51, 4.67, p = 0.648) and HDL-C (WMD: -0.18 mg/dL, 95% CI: -5.23, 4.87, p = 0.944) were not found to be significantly altered by ursodeoxycholic acid administration. In the subgroup of patients with primary biliary cirrhosis, ursodeoxycholic acid reduced total cholesterol (WMD: - 29.86 mg/dL, 95% CI: -47.39, - 12.33, p = 0.001) and LDL-C (WMD: -37.27 mg/dL, 95% CI: -54.16, - 20.38, p < 0.001) concentrations without affecting TG and HDL-C. CONCLUSION: This meta-analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis.

A systematic review and meta-analysis of clinical trials investigating the effects of flaxseed supplementation on plasma C-reactive protein concentrations.

INTRODUCTION: Many experimental and clinical trials have suggested that flaxseed might be a potent antihypertensive, but the evidence concerning the effects of flaxseed supplements on plasma C-reactive protein (CRP) concentrations has not been fully conclusive. We assessed the impact of the effects of flaxseed supplementation on plasma CRP concentrations through a systematic review of literature and meta-analysis of available randomised controlled trials (RCTs). MATERIAL AND METHODS: The literature search included EMBASE, ProQuest, CINAHL, and PUBMED databases up to 1st February 2016 to identify RCTs investigating the effect of flaxseed supplements on plasma CRP concentrations. Meta-analysis was performed using a random-effects model, and effect size was expressed as weighed mean difference (WMD) and 95% confidence interval (CI). RESULTS: Meta-analysis of 17 selected RCTs with 1256 individuals did not suggest a significant change in plasma CRP concentrations following supplementation with flaxseed-containing products (WMD: -0.25 mg/l, 95% CI: -0.53, 0.02, p = 0.074). The effect size was robust in the leave-one-out sensitivity analysis. Subgroup analysis did not suggest any significant difference in terms of changing plasma CRP concentrations among different types of flaxseed supplements used in the included studies, i.e. flaxseed oil (WMD: -0.67 mg/l, 95% CI: -2.00, 0.65, p = 0.320), lignan extract (WMD: -0.32 mg/l, 95% CI: -0.71, 0.06, p = 0.103) and ground powder (WMD: -0.18 mg/l, 95% CI: -0.42, 0.06, p = 0.142). CONCLUSIONS: The meta-analysis of RCTs did not show a significant change in plasma CRP concentrations following supplementation with various flaxseed products. Large, well-designed studies should be still performed to validate the current results.

PCSK9 and neurocognitive function: Should it be still an issue after FOURIER and EBBINGHAUS results?

The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates the levels of low-density lipoprotein cholesterol and cardiovascular risk. Potential risks of adverse neurological effects of intensive lipid-lowering treatment have been hypothesized, as cholesterol is a component of the central nervous system. Moreover, several observations suggest that PCSK9 might play a role in neurogenesis, neuronal migration and apoptosis. In rodents, increased expression of PCSK9 has been detected in specific areas of the central nervous system during embryonic development; also, PCSK9 modulates low-density lipoprotein receptor levels in the ischemic brain areas. Despite a putative participation of PCSK9 in nervous system physiology, the absence of PCSK9 in knockout mice or in humans with loss-of-function mutations of PCSK9 gene has not been linked to neurological alterations. In recent years, some concerns have been raised about the potential neurological side effects of cholesterol-lowering treatments and, more specifically of PCSK9 inhibitors. In this review, the evidence regarding the function of PCSK9 in neuron differentiation, apoptosis, and migration and in nervous system development and latest clinical trials evaluating the effects of PCSK9 inhibitors on neurocognitive function will be described.

The Role of Nutraceuticals in Statin Intolerant Patients.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.

The impact of argan oil on plasma lipids in humans: Systematic review and meta-analysis of randomized controlled trials.

The study aims to investigate the effect of argan oil on plasma lipid concentrations through a systematic review of the literature and a meta-analysis of available randomized controlled trials. Randomized controlled trials that investigated the impact of at least 2 weeks of supplementation with argan oil on plasma/serum concentrations of at least 1 of the main lipid parameters were eligible for inclusion. Effect size was expressed as the weighted mean difference (WMD) and 95% confidence interval (95% CI). Meta-analysis of data from 5 eligible trials with 292 participants showed a significant reduction in plasma concentrations of total cholesterol (WMD: -16.85 mg/dl, 95% CI [-25.10, -8.60], p < .001), low-density lipoprotein cholesterol (WMD: -11.67 mg/dl, 95% CI [-17.32, -6.01], p < .001), and triglycerides (WMD: -13.69 mg/dl, 95% CI [-25.80, -1.58], p = .027) after supplementation with argan oil compared with control treatment, and plasma concentrations of high-density lipoprotein cholesterol (WMD: 4.14 mg/dl, 95% CI [0.86, 7.41], p = .013) were found to be increased. Argan oil supplementation reduces total cholesterol, low-density lipoprotein cholesterol, and triglycerides and increases high-density lipoprotein cholesterol levels. Additionally, larger clinical trials are needed to assess the impact of argan oil supplementation on other indices of cardiometabolic risk and on the risk of cardiovascular outcomes.

Does coffee consumption alter plasma lipoprotein(a) concentrations? A systematic review.

Coffee consumption alters plasma lipid and cholesterol concentrations, however, its effects on lipoprotein(a) (Lp(a)) have received little study. The aim of this PRISMA compliant systematic review was to examine the role of coffee on serum Lp(a). This study was prospectively registered (PROSPERO 2015:CRD42015032335). PubMed, Scopus, Web of Science and Cochrane Central were searched from inception until 9th January 2016 to detect trials and epidemiological studies investigating the impact of coffee on serum Lp(a) concentrations in humans. We identified six relevant publications describing nine experimental trials of various designs. There were a total of 640 participants across all studies and experimental groups. In short-term controlled studies, consumption of coffee, or coffee diterpenes was associated with either a reduction in serum Lp(a) of ≤11 mg/dL (6 trials, 275 participants), or no effect (2 trials, 56 participants). Conversely, one cross-sectional study with 309 participants showed serum Lp(a) was elevated in chronic consumers of boiled coffee who had a median Lp(a) of 13.0 mg/dL (range 0-130) compared with consumers of filtered coffee who had median Lp(a) 7.9 mg/dL (range 0-144). The effect of coffee on Lp(a) is complex and may follow a biphasic time-course. The type of coffee and the method of preparation appear to be important to determining the effect on Lp(a).

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

The effects of cinnamon supplementation on blood lipid concentrations: A systematic review and meta-analysis.

BACKGROUND: Cinnamon is a rich botanical source of polyphenols, whose positive effects on blood lipid concentrations have been hypothesized, but have not been conclusively studied. OBJECTIVE: The objective of the study was to systematically review and evaluate the effect of administration of cinnamon on blood lipid concentrations. METHODS: We assessed 13 randomized controlled trials with 750 participants investigating the effect of cinnamon supplementation on blood lipid concentrations. A meta-analysis was performed using random effect models, with weighted mean differences (WMDs; with 95% confidence interval [CI]) for endpoints calculated using a random effects model. RESULTS: No statistically significant effect of cinnamon was observed on blood low-density lipoprotein cholesterol (LDL-C; WMD: -0.16 mmol/L [-6.19 mg/dL], 95% CI: -0.35, 0.03 [-13.53, 1.16], P = .10) and high-density lipoprotein cholesterol (HDL-C; WMD: 0.05 mmol/L [1.92 mg/dL], 95% CI: -0.03, 0.12 [-0.03, 4.64], P = .21) concentrations. However, a statistically significant reduction in blood triglycerides (WMD: -0.27 mmol/L [-23.91 mg/dL], 95% CI: -0.39, -0.14 [-34.54, -12.40], P < .01) and total cholesterol concentrations (WMD: -0.36 mmol/L [-13.92 mg/dL], 95% CI: -0.63, -0.09 [-24.36, -3.48], P < .01) was observed. HDL-C was significantly elevated after the omission of 1 study (WMD: 0.04 mmol/L [1.54 mg/dL], 95% CI: 0.03, 0.06 [1.16, 2.32], P < .01) during our sensitivity analysis. A meta-regression analysis was conducted, and no significant association was found between changes in lipid parameters and cinnamon dose. In contrast, changes in blood levels of total cholesterol (slope: 0.09; 95% CI: 0.02, 0.16; P < .01), LDL-C (slope: 0.05; 95% CI: 0.001, 0.10; P = .05) and triglycerides (slope: 0.06; 95% CI: 0.04, 0.09; P < .01) were significantly and positively associated with the duration of supplementation. No statistically significant association was found between blood HDL-C changes and duration of supplementation. CONCLUSION: Cinnamon supplementation significantly reduced blood triglycerides and total cholesterol concentrations without any significant effect on LDL-C and HDL-C.

Effects of tibolone on fibrinogen and antithrombin III: A systematic review and meta-analysis of controlled trials.

Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either <12months (WMD: -7.64%, 95% CI: -16.58, +1.29, p=0.094) or ≥12months (WMD: -0.62%, 95% CI: -8.40, +7.17, p=0.876). With regard to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95% CI: -1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either <12months (WMD: +2.26%, 95% CI: -3.14, +7.66, p=0.411) or≥12months (WMD: +0.06%, 95% CI: -1.16, +1.28, p=0.926) duration. Consistent with the results of subgroup analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone.

Learning from large-scale neural simulations.

Large-scale neural simulations have the marks of a distinct methodology which can be fruitfully deployed in neuroscience. I distinguish between two types of applications of the simulation methodology in neuroscientific research. Model-oriented applications aim to use the simulation outputs to derive new hypotheses about brain organization and functioning and thus to extend current theoretical knowledge and understanding in the field. Data-oriented applications of the simulation methodology target the collection and analysis of data relevant for neuroscientific research that is inaccessible via more traditional experimental methods. I argue for a two-stage evaluation schema which helps clarify the differences and similarities between three current large-scale simulation projects pursued in neuroscience.

Effects of morning vs evening statin administration on lipid profile: A systematic review and meta-analysis.

BACKGROUND: Evidence about the optimal time of day at which to administer statins is lacking. OBJECTIVE: The objective of this study is to synthesize evidence about effects of morning vs evening statin administration on lipid profile. METHODS: We searched PubMed, SCOPUS, Web of Science, and Embase databases (from inception up to July 24, 2016) to identify the relevant studies. Mean differences (MDs) between the change scores in lipid parameters were pooled using a fixed-effect model. RESULTS: Eleven articles with 1034 participants were eligible for the analysis. The pooled analysis comparing effects of morning vs evening administration of statins on plasma total cholesterol (TC; P = .10), high-density lipoprotein cholesterol (P = .90), and triglycerides (P = .45) was not statistically significant. Low-density lipoprotein cholesterol (LDL-C) lowering was statistically greater in the evening-dose group (MD: 3.24 mg/dL, 95% CI: 1.23-5.25, P = .002). Subgroup analysis according to statin half-lives showed that evening dose of statins was significantly superior to morning dose for lowering LDL-C in case of both short and long half-life statins (MD: 9.68 mg/dL, 95% CI: 3.32-16.03, P = .003 and MD: 2.53 mg/dL, 95% CI: 0.41-4.64, P = .02, respectively) and also for TC reduction in case of short half-life statins only (P = .0005). CONCLUSIONS: LDL-C and TC lowering was significantly greater in the evening dose than in the morning dose in case of short-acting statins. Besides slight but significant effect on LDL-C, the efficacy of long-acting statins was equivalent for both regimens. Therefore, long-acting statins should be given at a time that will best aid compliance. Short-acting statins should be given in the evening.