Guideline-Optimised Treatment in Heart Failure-Do Higher Doses Reduce Systemic Inflammation More Significantly?

Background: Chronic inflammation is a constant phenomenon which accompanies the heart failure pathophysiology. In all phenotypes of heart failure, irrespective of the ejection fraction, there is a permanent low-grade activation and synthesis of proinflammatory cytokines. Many classes of anti-remodelling medication used in the treatment of chronic heart failure have been postulated to have an anti-inflammatory effect. Methods: This retrospective study enrolled 220 patients and focused on evaluating the effect of the most used active substances from these classes in reducing the level of inflammatory biomarkers (C reactive protein, erythrocyte sedimentation rate and fibrinogen) after initiation or up-titration. Our research is evaluating if this anti-inflammatory effect intensifies while raising the dose. The evaluation was performed at two visits with an interval between them of 6 months. Results: From the beta-blockers class, carvedilol showed a reduction in erythrocyte sedimentation rate (ESR), in low (6.25 mg, bi daily) and medium (12.5 mg, bi daily) doses. At the same time, sacubitril/valsartan showed a reduction in CRP levels. This effect was obtained only in the medium (49/51 mg, bi daily) and high (97/103 mg, bi daily) doses, with the maximum reduction being observed in the high dose. Conclusions: From the classes of medication evaluated, the study showed a significant reduction in ESR levels in the low and medium doses of carvedilol and a reduction in CRP values in the cases of medium and high doses of ARNI.

Inflammation in Heart Failure-Future Perspectives.

Chronic heart failure is a terminal point of a vast majority of cardiac or extracardiac causes affecting around 1-2% of the global population and more than 10% of the people above the age of 65. Inflammation is persistently associated with chronic diseases, contributing in many cases to the progression of disease. Even in a low inflammatory state, past studies raised the question of whether inflammation is a constant condition, or if it is, rather, triggered in different amounts, according to the phenotype of heart failure. By evaluating the results of clinical studies which focused on proinflammatory cytokines, this review aims to identify the ones that are independent risk factors for heart failure decompensation or cardiovascular death. This review assessed the current evidence concerning the inflammatory activation cascade, but also future possible targets for inflammatory response modulation, which can further impact the course of heart failure.

Revisiting the Intestinal Microbiome and Its Role in Diarrhea and Constipation.

The gut microbiota represents a community of microorganisms (bacteria, fungi, archaea, viruses, and protozoa) that colonize the gut and are responsible for gut mucosal structural integrity and immune and metabolic homeostasis. The relationship between the gut microbiome and human health has been intensively researched in the past years. It is now widely recognized that gut microbial composition is highly responsible for the general health of the host. Among the diseases that have been linked to an altered gut microbial population are diarrheal illnesses and functional constipation. The capacity of probiotics to modulate the gut microbiome population, strengthen the intestinal barrier, and modulate the immune system together with their antioxidant properties have encouraged the research of probiotic therapy in many gastrointestinal afflictions. Dietary and lifestyle changes and the use of probiotics seem to play an important role in easing constipation and effectively alleviating diarrhea by suppressing the germs involved. This review aims to describe how probiotic bacteria and the use of specific strains could interfere and bring benefits as an associated treatment for diarrhea and constipation.

Gut Microbiome Changes in Gestational Diabetes.

Gestational diabetes mellitus (GDM), one of the most common endocrine pathologies during pregnancy, is defined as any degree of glucose intolerance with onset or first discovery in the perinatal period. Physiological changes that occur in pregnant women can lead to inflammation, which promotes insulin resistance. In the general context of worldwide increasing obesity in young females of reproductive age, GDM follows the same ascending trend. Changes in the intestinal microbiome play a decisive role in obesity and the development of insulin resistance and chronic inflammation, especially in patients with type 2 diabetes mellitus (T2D). To date, various studies have also associated intestinal dysbiosis with metabolic changes in women with GDM. Although host metabolism in women with GDM has not been fully elucidated, it is of particular importance to analyze the available data and to discuss the actual knowledge regarding microbiome changes with potential impact on the health of pregnant women and newborns. We analyzed peer-reviewed journal articles available in online databases in order to summarize the most recent findings regarding how variations in diet and metabolic status of GDM patients can contribute to alteration of the gut microbiome, in the same way that changes of the gut microbiota can lead to GDM. The most frequently observed alteration in the microbiome of patients with GDM was either an increase of the Firmicutes phylum, respectively, or a decrease of the Bacteroidetes and Actinobacteria phyla. Gut dysbiosis was still present postpartum and can impact the development of the newborn, as shown in several studies. In the evolution of GDM, probiotic supplementation and regular physical activity have the strongest evidence of proper blood glucose control, favoring fetal development and a healthy outcome for the postpartum period. The current review aims to summarize and discuss the most recent findings regarding the correlation between GDM and dysbiosis, and current and future methods for prevention and treatment (lifestyle changes, pre- and probiotics administration). To conclude, by highlighting the role of the gut microbiota, one can change perspectives about the development and progression of GDM and open up new avenues for the development of innovative therapeutic targets in this disease.

The Interplay Between Gut Microbiota and miRNAs in Cardiovascular Diseases.

The human microbiota contains microorganisms found on the skin, mucosal surfaces and in other tissues. The major component, the gut microbiota, can be influenced by diet, genetics, and environmental factors. Any change in its composition results in pathophysiological changes that can further influence the evolution of different conditions, including cardiovascular diseases (CVDs). The microbiome is a complex ecosystem and can be considered the metagenome of the microbiota. MicroRNAs (miRNAs) are speculated to interact with the intestinal microbiota for modulating gene expressions of the host. miRNAs represent a category of small non-coding RNAs, consisting of approximately 22 nucleotides, which can regulate gene expression at post-transcriptional level, by influencing the degradation of mRNA and modifying protein amounts. miRNAs display a multitude of roles, being able to influence the pathogenesis and progression of various diseases. Circulating miRNAs are stable against degradation, due to their enclosure into extracellular vesicles (EVs). This review aims to assess the current knowledge of the possible interactions between gut microbiota, miRNAs, and CVDs. As more scientific research is conducted, it can be speculated that personalized patient care in the future may include the management of gut microbiota composition and the targeted treatment against certain expression of miRNAs.

Gut Microbiome, Functional Food, Atherosclerosis, and Vascular Calcifications-Is There a Missing Link?

The gut microbiome is represented by the genome of all microorganisms (symbiotic, potential pathogens, or pathogens) residing in the intestine. These ecological communities are involved in almost all metabolic diseases and cardiovascular diseases are not excluded. Atherosclerosis, with a continuously increasing incidence in recent years, is the leading cause of coronary heart disease and stroke by plaque rupture and intraplaque hemorrhage. Vascular calcification, a process very much alike with osteogenesis, is considered to be a marker of advanced atherosclerosis. New evidence, suggesting the role of dietary intake influence on the diversity of the gut microbiome in the development of vascular calcifications, is highly debated. Gut microbiota can metabolize choline, phosphatidylcholine, and L-carnitine and produce vasculotoxic metabolites, such as trimethylamine-N-oxide (TMAO), a proatherogenic metabolite. This review article aims to discuss the latest research about how probiotics and the correction of diet is impacting the gut microbiota and its metabolites in the atherosclerotic process and vascular calcification. Further studies could create the premises for interventions in the microbiome as future primary tools in the prevention of atherosclerotic plaque and vascular calcifications.

MicroRNAs as monitoring markers for right-sided heart failure and congestive hepatopathy.

The last decades showed a worrying increase in the evolution of cardiovascular diseases towards different stages of heart failure (HF), as a stigma of the western lifestyle. MicroRNAs (miRNAs), non-coding RNAs, which are approximately 22-nucleotide long, were shown to regulate gene expression at the post-transcriptional level and play a role in the pathogenesis and progression of HF. miRNAs research is of high interest nowadays, as these molecules display mechanisms of action that can influence the course of evolution of common chronic diseases, including HF. The potential of post-transcriptional regulation by miRNAs concerning the diagnosis, management, and therapy for HF represents a new promising approach in the accurate assessment of cardiovascular diseases. This review aims to assess the current knowledge of miRNAs in cardiovascular diseases, especially right-sided heart failure and hepatomegaly. Moreover, attention is focused on their role as potential molecular biomarkers and more promising aspects involving miRNAs as future therapeutic targets in the pathophysiology of HF.

The Management of Pancreatic Trauma - A Continuous Challenge.

Background: The aim of this analysis was to assess the factors that influence the severity of pancreatic trauma cases, also underlining the importance of early and accurate diagnosis and proper management of each case. Methods: This study is a retrospective analysis of patients that were presented to the Clinical Emergency Hospital of Bucharest, Romania, in several periods of time: 1985-1990 (50 patients); 1990-1999 (102 patients); 2000-2005 (56 patients); 2012-2019 (48 patients). Results: The mean age was around 40 years old, with predominance of male incidence in all the groups and traffic accidents (blunt trauma) as the main cause of injury. Most patients (almost 50% in each group) were operated on within the first 24 hours from hospital presentation. The general mortality rate varied: 42% (1985-1990), 23.5% (1990-1999), 12.7% (2000-2005) and 33% (2012-2015). Pancreatic mortality rate was 6% (1985-1990 and 1990-1999), 3.5% (2000-2005) and 8% (2012-2019). Conclusions: During the last 35 years, the preoperative diagnosis in patients with trauma of the pancreas remained a challenge and the treatment of the pancreatic trauma suffered a very interesting evolution- from the very frequent laparotomy to the nonoperative management and the damage control. These procedures produced a significant decreasing of the negative or nontherapeutic laparotomies. For the effectiveness of treatment, methods must be correlated with the lesion score.