A New Nomenclature for the Very Low-Calorie Ketogenic Diet (VLCKD): Very Low-Energy Ketogenic Therapy (VLEKT). Ketodiets and Nutraceuticals Expert Panels: "KetoNut", Italian Society of Nutraceuticals (SINut) and the Italian Association of Dietetics and Clinical Nutrition (ADI).

PURPOSE OF REVIEW: In an attempt to clarify the most appropriate nomenclature for the very low-calorie ketogenic diets (VLCKD), we propose to change the nomenclature and acronym of this medical nutrition therapy. The new definition and acronym proposed by the "KetoNut" panel of experts of the Italian Society of Nutraceuticals (SINut) and the Italian Association of Dietetics and Clinical Nutrition (ADI) is Very Low-Energy Ketogenic Therapy (VLEKT). RECENT FINDINGS: In the last few years, different authors have focused on the issue of confusion in the nomenclature of ketogenic diets. In detail, have been differentiated the VLCKD that provides < 800 kcal per day, which is intended for the weight loss in the medical treatment of obesity, and a eucaloric ketogenic diet, which contains more calories from fat (predominantly unsaturated) and with specific ketogenic ratios, for allow growth in children while helping, at the same time, to establish epileptic seizure control. In recent years, ketogenic diets have attracted great interest for their efficacy in the treatment of epilepsy and other neurological diseases but also in patients with overweight and obesity-related metabolic disorders. Nevertheless, although ketogenic diets are a dietary intervention designed to induce nutritional ketosis, different diets with different macronutrients' composition have been called with this name. The confusion in the nomenclature of ketogenic diets may result in significant bias and mistakes in the interpretation of the current scientific evidence.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Cholesterol-Lowering Bioactive Foods and Nutraceuticals in Pediatrics: Clinical Evidence of Efficacy and Safety.

Long-term exposure to even slightly elevated plasma cholesterol levels significantly increases the risk of developing cardiovascular disease. The latest evidence recommends an improvement in plasma lipid levels, even in children who are not affected by severe hypercholesterolemia. The risk-benefit profile of pharmacological treatments in pediatric patients with moderate dyslipidemia is uncertain, and several cholesterol-lowering nutraceuticals have been recently tested. In this context, the available randomized clinical trials are small, short-term and mainly tested different types of fibers, plant sterols/stanols, standardized extracts of red yeast rice, polyunsaturated fatty acids, soy derivatives, and some probiotics. In children with dyslipidemia, nutraceuticals can improve lipid profile in the context of an adequate, well-balanced diet combined with regular physical activity. Of course, they should not be considered an alternative to conventional lipid-lowering drugs when necessary.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.

The Possible Role of Probiotic Supplementation in Inflammation: A Narrative Review.

The fine balance between symbiotic and potentially opportunistic and/or pathogenic microorganisms can undergo quantitative alterations, which, when associated with low intestinal biodiversity, could be responsible for the development of gut inflammation and the so-called "intestinal dysbiosis". This condition is characterized by the disbalance of a fine synergistic mechanism involving the mucosal barrier, the intestinal neuroendocrine system, and the immune system that results in an acute inflammatory response induced by different causes, including viral or bacterial infections of the digestive tract. More frequently, however, dysbiosis is induced slowly and subtly by subliminal causal factors, resulting in a chronic condition related to different diseases affecting the digestive tract and other organs and apparatuses. Studies on animal models, together with studies on humans, highlight the significant role of the gut microbiota and microbiome in the occurrence of inflammatory conditions such as metabolic syndrome and cardiovascular diseases (CVDs); neurodegenerative, urologic, skin, liver, and kidney pathologies; and premature aging. The blood translocation of bacterial fragments has been found to be one of the processes linked to gut dysbiosis and responsible for the possible occurrence of "metabolic endotoxemia" and systemic inflammation, associated with an increased risk of oxidative stress and related diseases. In this context, supplementation with different probiotic strains has been shown to restore gut eubiosis, especially if administered in long-term treatments. The aim of this review is to describe the anti-inflammatory effects of specific probiotic strains observed in clinical trials and the respective indications, highlighting the differences in efficacy depending on strain, formulation, time and duration of treatment, and dosage used.

An Expert Opinion on the Role of the Rosuvastatin/Amlodipine Single Pill Fixed Dose Combination in Cardiovascular Prevention.

Current cardiovascular disease prevention strategies are based on the management of cardiovascular risk as a continuum, redefining the therapeutic goals for each individual based on the estimated global risk profile. Given the frequent clustering of the principal cardiovascular risk factors, such as hypertension, diabetes and dyslipidaemia, in the same individual, patients are required to take multiple drugs to achieve therapeutic targets. The adoption of single pill fixed dose combinations may contribute to achieve better control of blood pressure and cholesterol compared to the separate administration of the individual drugs, mostly due to better adherence related to therapeutic simplicities. This paper reports the outcomes of an Expert multidisciplinary Roundtable. In particular, the rational and potential clinical use of the single pill fixed dose combination "Rosuvastatin-Amlodipine" for the management of concomitant hypertension/hypercholesterolemia in different clinical fields are discussed. This Expert Opinion also illustrates the importance of an early and effective management of total cardiovascular risk, highlights the substantial benefits of combining blood pressure and lipid-lowering treatments in a single-pill fixed dose combination and attempts to identify and overcome the barriers to the implementation in clinical practice of the fixed dose combinations with dual targets. This Expert Panel identifies and proposes the categories of patients who may benefit the most from this fixed dose combination.

Natural Course of COVID-19 and Independent Predictors of Mortality.

BACKGROUND: During the SARS-CoV-2 pandemic, several biomarkers were shown to be helpful in determining the prognosis of COVID-19 patients. The aim of our study was to evaluate the prognostic value of N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) in a cohort of patients with COVID-19. METHODS: One-hundred and seven patients admitted to the Covid Hospital of Messina University between June 2022 and January 2023 were enrolled in our study. The demographic, clinical, biochemical, instrumental, and therapeutic parameters were recorded. The primary outcome was in-hospital mortality. A comparison between patients who recovered and were discharged and those who died during the hospitalization was performed. The independent parameters associated with in-hospital death were assessed by multivariable analysis and a stepwise regression logistic model. RESULTS: A total of 27 events with an in-hospital mortality rate of 25.2% occurred during our study. Those who died during hospitalization were older, with lower GCS and PaO2/FiO2 ratio, elevated D-dimer values, INR, creatinine values and shorter PT (prothrombin time). They had an increased frequency of diagnosis of heart failure (p < 0.0001) and higher NT-pro-BNP values. A multivariate logistic regression analysis showed that higher NT-pro-BNP values and lower PT and PaO2/FiO2 at admission were independent predictors of mortality during hospitalization. CONCLUSIONS: This study shows that NT-pro-BNP levels, PT, and PaO2/FiO2 ratio are independently associated with in-hospital mortality in subjects with COVID-19 pneumonia. Further longitudinal studies are warranted to confirm the results of this study.

Mushroom-Based Supplements in Italy: Let's Open Pandora's Box.

Mushrooms and derivates are well known to the scientific community for having different health benefits and exhibit a wide range of pharmacological activities, including lipid-lowering, antihypertensive, antidiabetic, antimicrobic, antiallergic, anti-inflammatory, anticancer, immunomodulating, neuroprotective and osteoprotective actions. In Europe, medical mushrooms are mainly marketed in the form of food supplements as single components or combined with other nutraceuticals. In this context, the first peculiarity that distinguishes it is the safety established through the "history of consumption" that characterizes that mushroom. However, the cultivation of medicinal mushrooms on a large scale is performed mainly in China, where most of the production facilities do not have internationally recognized good manufacturing practices, despite that many European companies that sell myotherapies are supplied by Chinese manufacturers. This is particularly evident in Italy, where an arsenal of mushroom products is marketed in the form of powders and extracts not always of ascertained origin and sometimes of doubtful taxonomic identification, and thus not meeting the quality criteria required. The growing interest in mycotherapy involves a strong commitment from the scientific community to propose supplements of safe origin and genetic purity as well as to promote clinical trials to evaluate its real effects on humans. The purpose of this research is to analyze different mushroom-based dietary supplements used in medicine as monotherapy on the Italian market and to evaluate their composition and quality. The molecular identification of the sequences with those deposited in GenBank allowed for identifying 6 out of 19 samples, matching with those deposited belonging to the species indicated in the label, i.e., Lentinula edodes (samples 1, 4, 12 and 18) and Ganoderma lucidum (samples 5 and 10). Samples containing Ganoderma, labeled in the commercial product as G. lucidum, showed sequences that showed homology of 100% and 99% with G. resinaceum and G. sichuanense. An additional investigation was carried out in order to determine the active fungal ingredients, such as ergosterol, aflatoxins, heavy metals, nicotine and total glucan. The results obtained and shown in the manuscript highlight how the data were not only in line with what is expected with respect to what is indicated in the labels.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Uric Acid and Hypertension: a Review of Evidence and Future Perspectives for the Management of Cardiovascular Risk.

Uric acid is the final product of purine metabolism, and its increased serum levels have been directly involved in the pathogenesis and natural history of hypertension. The relationship between elevated uric acid and hypertension has been proven in both animals and humans, and its relevance is already evident in childhood and adolescent population. The mechanism responsible for blood pressure increase in hyperuricemic subjects is implicating both oxidative stress and intracellular urate activity with a primary involvement of XOR (xanthine-oxidoreductase activity). An increase in the relative risk of hypertension has been confirmed by genetic data and by large meta-analyses of epidemiological data. The effects of urate-lowering treatment on blood pressure control in patients with elevated serum uric acid has been investigated in a small number of reliable studies with a large heterogeneity of patient populations and study designs. However, 2 large meta-analyses suggest a significant effect of urate-lowering treatment on blood pressure, thus confirming the significant relationship between high serum urate and blood pressure. The future research should be focused on a more appropriate identification of patients with cardiovascular hyperuricemia by considering the correct cardiovascular threshold of serum urate, the time-course of uricemia fluctuations, and the identification of reliable markers of urate overproduction that could significantly clarify the clinical and therapeutic implications of the interaction between serum uric acid and hypertension.

Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project.

BACKGROUND: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. METHODS: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. RESULTS: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. CONCLUSIONS: The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria.

Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia.

INTRODUCTION: Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. AREAS COVERED: This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. EXPERT OPINION: Data from the clinical trials in the ORION program demonstrated efficacy and safety of inclisiran in patients with dyslipidemia. Adverse events were similar in the inclisiran and placebo groups in the clinical trials, although injection-site reactions were more frequent with inclisiran than with placebo. Although the combination of efficacy and safety makes inclisiran a good option for the treatment of dyslipidemia compared to other PCSK9 targeting therapeutic strategies, however, further studies should exclude the possibility that inclisiran, through lower-affinity interactions, may influence other mRNAs in the physiological milieu.

Long-term consequences of previous preeclampsia and complicated pregnancy: analysis of echocardiographic aspects.

AIM: To evaluated echocardiographic aspects in women with history of preeclampsia or preeclampsia-related complications in their previous pregnancies. MATERIALS AND METHODS: Consecutive women receiving echocardiography during daily clinical echolab activity were studied using complete echocardiographic examination data and anamnestic data collection of hypertension, diabetes, dyslipidemia, and rheumatic diseases. Studied women should have at least one pregnancy in more than the 10 past years, and were subdivided into two groups according to the history of complicated or physiological pregnancy. Complicated pregnancies were defined by preeclampsia or preeclampsia-related complication, such as preterm delivery or small-for-gestational age newborn. Echocardiographic parameters and prevalence of hypertension, diabetes, dyslipidemia, and rheumatic disease were compared between the two groups of studied women. RESULTS: From March 2016 to May 2020, 545 women were studied, of whom 218 had a history of complicated pregnancy (mean age 60.81 ±â€Š11.109 years vs. 62.78 ±â€Š9.758 years of not complicated pregnancy; P = 0.03). Compared with physiological pregnancy women, complicated pregnancy ones were shorter (159.97 ±â€Š6.608 vs. 161.42 ±â€Š6.427 cm; P = 0.012) with lower body surface area (1.678 ±â€Š0.1937 vs. 1.715 ±â€Š0.1662 m2; P = 0.02), had higher prevalence of diabetes (6.9 vs. 3.1%; P = 0.04; odds ratio = 2.34; CI 1.0323--5.3148) and rheumatic diseases (33 vs. 22.3%; P = 0.006; odds ratio = 1.72; CI 1.1688--2.5191), and showed a slight, not significant higher prevalence of hypertension. As for echocardiographic parameters, they showed significantly higher values of end-diastolic left ventricular posterior wall (LPWd) (P = 0.034), a trend toward a more concentric geometry, and a worse longitudinal systolic left and right ventricle performance, represented by lower tissue Doppler systolic waves (septal: 7.41 ±â€Š1.255 vs. 7.69 ±â€Š1.376 cm/s; P = 0.018; and tricuspidalic: 12.64 ±â€Š2.377 vs. 13.32 ±â€Š2.548 cm/s; P = 0.003). CONCLUSION: Patients with previous preeclampsia present an increased risk of hypertension, diabetes, and rheumatic diseases, suggesting that these women could share a specific predisposition to a high-risk profile. Furthermore, they show a higher prevalence of classically considered echocardiographic hypertensive-derived cardiac damage, suggesting structural and functional left ventricular modifications as subclinical aspects of long-term worse cardiovascular prognosis for these women.

Laboratory and Instrumental Risk Factors Associated with a Sudden Cardiac Death Prone ECG Pattern in the General Population: Data from the Brisighella Heart Study.

Sudden cardiac death (SCD) remains a daunting problem and a major public health issue. We applied the validated Electrocardiogram (ECG) score to the Brisighella Heart Study (BHS) cohort, in order to verify if there were also other recognized laboratory and instrumental risk factors for cardiovascular disease associated with a sudden death risk-prone pattern. We examined the ECG traces of 1377 participants of the 2016 BHS survey and identified 33 subjects at high risk for SCD (while 1344 subjects had no cumulative ECG abnormalities). Serum uric acid (SUA) and carotid-femoral pulse wave velocity (cfPWV) values were significantly higher in the high-risk cohort (p < 0.05) and were both independently associated with the presence of ECG abnormalities [Odd ratio (OR) = 2.14, p < 0.05-OR = 1.23, p < 0.05, respectively]. A similar independent correlation was found with long-term non-steroid anti-inflammatory drugs (NSAIDs) use, more widespread among high-risk subjects (OR = 1.19, p < 0.05). Conversely, the analysis did not show any significant association with impaired renal function (p = 0.09). This study showed that long-term NSAID use and high SUA and cfPWV values are independent risk factors for ECG abnormalities predictive of SCD. These findings herald the need for further prospective research to identify the optimal combination of SCD risk markers in order to prevent fatal events.

Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.

OBJECTIVE: Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events. METHODS: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ±â€Š66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes. RESULTS: Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ±â€Š15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ±â€Š24.6 and 85.2 ±â€Š13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group. CONCLUSION: Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.

Clinical Applications of Astaxanthin in the Treatment of Ocular Diseases: Emerging Insights.

Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in microalgae and seafood such as salmonids, shrimps and lobsters. Due to its unique molecular structure, astaxanthin features some important biologic properties, mostly represented by strong antioxidant, anti-inflammatory and antiapoptotic activities. A growing body of evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases, ranging from the anterior to the posterior pole of the eye. Therefore, the present review aimed at providing a comprehensive evaluation of current clinical applications of astaxanthin in the management of ocular diseases. The efficacy of this carotenoid in the setting of retinal diseases, ocular surface disorders, uveitis, cataract and asthenopia is reported in numerous animal and human studies, which highlight its ability of modulating several metabolic pathways, subsequently restoring the cellular homeostatic balance. To maximize its multitarget therapeutic effects, further long-term clinical trials are warranted in order to define appropriate dosage, route of administration and exact composition of the final product.