Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis.

Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-ß is a superfamily of cytokines with an important dual effect on the immune system. TGF-ß inhibits the Th1 response while facilitating the preservation of regulatory T cells (FOXP3+) in an immunoregulatory capacity. However, when IL-6 is present, it stimulates the Th17 response. Our aim was to analyze the regulatory effect of vitamin D on the in vivo TGF-ß signaling pathway in patients with relapsing-remitting multiple sclerosis (RRMS). A total of 21 patients with vitamin D levels < 30 ng/mL were recruited and supplemented with oral vitamin D. All patients were receiving disease-modifying therapy, with the majority being on natalizumab. Expression of SMAD7, ERK1, ZMIZ1, BMP2, BMPRII, BMP4, and BMP5 was measured in CD4+ lymphocytes isolated from peripheral blood at baseline and one and six months after supplementation. SMAD7 was overexpressed at six months with respect to baseline and month one. ERK1 was overexpressed at six months with respect to month one of treatment. No significant differences in expression were observed for the remaining genes. No direct correlation was found with serum vitamin D levels. BMPRII expression changed differentially in non-natalizumab- versus natalizumab-treated patients. Changes were observed in the expression of ERK1, BMP2, and BMP5 based on disease activity measured using the Rio-Score, BMP2 in patients who had relapses, and BMP5 in those whose EDSS worsened. Our results suggest indirect regulation of vitamin D in TGF-ß pathway genes in patients with RRMS.

Visceral extra-abdominal panniculitis after COVID19.

"Retractile mesenteritis" was the first name given to a rare, benign, inflammatory disease that affects the adipose tissue of the intestinal mesentery and less frequently other locations. Now labeled as mesenteric panniculitis, the pathogenic mechanism remains unclear. Several stimuli could be involved, and it is sometimes associated with other conditions such as malignancy or autoimmune diseases. We present a case of mesenteric panniculitis with extensive abdominal and extra-abdominal involvement that developed a few months after SARS-COV2 infection, raising the hypothesis of this virus as a potential trigger for autoinflammatory and autoimmune diseases.

Undertreatment or Overtreatment With Statins: Where Are We?

Statins, in addition to healthy lifestyle interventions, are the cornerstone of lipid-lowering therapy. Other low-density lipoprotein (LDL)-lowering drugs include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. As new evidence emerges from new clinical trials, therapeutic goals change, leading to renewed clinical guidelines. Nowadays, LDL goals are getting lower, leading to the "lower is better" paradigm in LDL-cholesterol (LDL-C) management. Several observational studies have shown that LDL-C control in real life is suboptimal in both primary and secondary preventions. It is critical to enhance the adherence to guideline recommendations through shared decision-making between clinicians and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities. This narrative review summarizes the evidence regarding the benefits of lipid-lowering drugs in reducing cardiovascular events, the pleiotropic effect of statins, real-world data on overtreatment and undertreatment of lipid-lowering therapies, and the changing LDL-C in targets in the clinical guidelines of dyslipidemias over the years.

Is there sufficient evidence to justify changes in dietary habits in heart failure patients? A systematic review.

The incidence and prevalence of heart failure (HF) is increasing worldwide, leading to high morbidity and mortality. The global management of HF involves lifestyle changes in addition to pharmacological treatments. Changes include exercise and dietary recommendations, mainly salt and fluid restriction, but without any clear evidence. We conducted a systematic review to analyse the degree of evidence for these dietary recommendations in HF. Only randomized controlled trials (RCT), and observational studies in humans were selected. Studies were considered eligible if they included participants with HF and sodium and/or fluid restriction. Publications in languages other than English or Spanish were excluded. We included 15 studies related to sodium or fluid restriction. Nine RCT and six observational studies showed some improvements in symptoms and quality of life and a degree of reduction in new hospitalizations, but the results are based on limited population groups, applying different methodologies, and with different restriction goals. We found a lack of clear evidence of the benefits of sodium/fluid restriction in chronic HF. The evidence is limited to few studies with conflicting results. Randomized clinical trials are needed to fill this gap in our knowledge.

Long-term follow-up of patients with venous thromboembolism and COVID-19: Analysis of risk factors for death and major bleeding.

INTRODUCTION: COVID-19 predisposes patients to a higher risk of venous thromboembolism (VTE), although the extent of these implications is unclear and the risk of bleeding has been poorly evaluated. To date, no studies have reported long-term outcomes of patients with COVID-19 and VTE. METHOD: Prospective observational study to evaluate long-term (90 days or more) outcomes of patients diagnosed with VTE (PE, DVT of the extremities, or both) in the setting of COVID-19. The main outcome of the study was a compound of major bleeding and death. RESULTS: The study comprised 100 patients (mean age 65 ± 13.9 years). At the time of VTE diagnosis, 66% patients were hospitalized, 34.8% of them in the ICU. Mean follow-up was 97.9 ± 23.3 days. During the study period, 24% patients died and median time to death was 12 (IQR: 2.25-20.75) days, 11% patients had major bleeding and median time to event was 12 (IQR: 5-16) days. The cause of death was PE in 5% and bleeding in 2% of patients. There were no VTE recurrences. The main study outcome occurred in 29% patients. Risk of death or major bleeding was independently associated with ICU admission (HR 12.2; 95% CI 3.0-48.3), thrombocytopenia (HR 4.5; 95% CI 1.2-16.5), and cancer (HR 21.6; 95% CI 1.8-259). CONCLUSION: In patients with COVID-19 and VTE, mortality and major bleeding were high and almost a third of deaths were VTE-related. The majority of complications occurred in the first 30 days. ICU admission, thrombocytopenia, and cancer are risk factors for poor prognosis.

The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil.

A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.

Relationship between tobacco consumption and health-related quality of life in adults living in a large metropolitan area.

The aim of this study was to analyze the relationship between health-related quality of life (HRQOL) and tobacco consumption in adult individuals (over the age of 15). The study was based on individual data from the City of Madrid Health Survey (ESCM05). Subjects were divided into three groups according to tobacco consumption: smokers, nonsmokers, and ex-smokers. HRQOL was measured using the COOP/WONCA quality-of-life vignettes. A multivariate adjustment with multinomial logistic regression was made, including the following as covariables: sociodemographic characteristics, comorbidities, drug use, and lifestyles. A total of 7341 individuals were interviewed (53.7% women), with an average age of 46.7 (SD = 19.02) years. The percentage of smokers was 27%, that of ex-smokers was 16.5%, and that of nonsmokers was 56.5%. There were no significant differences between smokers, ex-smokers, and nonsmokers in the raw scores obtained as totals from the COOP/WONCA questionnaire. Multivariate analysis revealed that smokers consume more antidepressant drugs (OR = 1.54, 95% CI = 1.09-2.16) and tranquilizers (OR = 1.91, 95% CI = 1.45-2.51), drink more alcohol (OR = 2.55, 95% CI = 2.11-3.08), get less physical exercise (OR = 1.33, 95% CI = 1.11-1.60), and have a lower quality of life (OR = 1.02, 95% CI = 1.00-1.04) than nonsmokers. Following adjustment for a significant number of covariables, sociodemographic as well as health-related, smokers consume more antidepressant drugs and tranquilizers, drink more alcohol, get less physical exercise, and demonstrate a lower HRQOL than nonsmokers.