Thoracic aortic pseudoaneurysm: Inside its pathophysiology.

OBJECTIVES: Our aim was to investigate pathophysiology of pseudoaneurysm of the thoracic aorta, an acute or chronic pathology, respectively, secondary to blunt thoracic trauma and aortitis, or complicating a deep penetrating aortic ulcer, intraparietal hematoma, aortic aneurysm, and even aortic graft, often with atherosclerosis as a common background. METHODS: Given the relative rarity of this disease, an "inductive" retrospective method made it possible to retrieve clinical, radiological, and histopathological elements, which were mutually compared and validated through a "deductive" process of reinterpretation. RESULTS: We have identified three main structural constituents of this disease: a cavity, a single blood entry port, communicating with the aortic lumen, and a pseudocapsule. It is often caused by a chronic degenerative pathology of the intima and medial layers of the aorta, typically involving elastic fibers and smooth muscle cells, with possible intermediate stages of deep aortic ulcer or intraparietal hematoma. Otherwise, the acute onset may be secondary to acute aortitis or aortic injury. CONCLUSIONS: Today, thanks to the current angiographic tools represented by 3-D high resolution multidetector CT and MRI angiography, the diagnosis of thoracic aortic pseudoaneurysm is easier, as well as its surgical indications.

Hypertriglyceridemia: Molecular and Genetic Landscapes.

Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.

Circadian and sex differences in post-ischemic vasodilation and reactive hyperemia in young individuals and elderly with and without type 2 diabetes.

OBJECTIVE: Cardiovascular events show morning preference and sex differences, and are related to aging and type 2 diabetes. We assessed circadian variations and sex differences in vascular conductance (VC) and blood flow (BF) regulations following a brief bout of forearm ischemia. METHODS: Young healthy individuals (H18-30) and elderly without (H50-80) and with type 2 diabetes (T2DM50-80) of both sexes were included. Forearm VC and BF, and mean arterial pressure (MAP) at baseline and following circulatory reperfusion were measured at 6 a.m. and 9 p.m. RESULTS: In the morning compared to evening, following reperfusion, the VC and BF increments were similar in H18-30 (p>.71), but lower in H50-80 (p<.001) and T2DM50-80 (p<.01). VC and BF following circulatory reperfusion were higher in men than women in H18-30 (p<.001), but similar between sexes in the older groups (p>.23). CONCLUSIONS: Forearm vasodilation following reperfusion is attenuated in the morning in the elderly, impairing BF towards an ischemic area. Diabetes does not affect the circadian regulation of VC and BF, but that of MAP. There are sex differences in VC and BF at baseline and after circulatory reperfusion at a young age, being greater in men, which disappear with aging without being affected by diabetes.

Mitochondrial DNA as inflammatory DAMP: a warning of an aging immune system?

Senescence of the immune system is characterized by a state of chronic, subclinical, low-grade inflammation termed 'inflammaging', with increased levels of proinflammatory cytokines, both at the tissue and systemic levels. Age-related inflammation can be mainly driven by self-molecules with immunostimulant properties, named Damage/death Associated Molecular Patterns (DAMPs), released by dead, dying, injured cells or aged cells. Mitochondria are an important source of DAMPs, including mitochondrial DNA - the small, circular, double-stranded DNA molecule found in multiple copies in the organelle. mtDNA can be sensed by at least three molecules: the Toll-like receptor 9, the NLRP3 inflammasomes, and the cyclic GMP-AMP synthase (cGAS). All these sensors can lead to the release of proinflammatory cytokines when engaged. The release of mtDNA by damaged or necrotic cells has been observed in several pathological conditions, often aggravating the course of the disease. Several lines of evidence indicate that the impairment of mtDNA quality control and of the organelle homeostasis associated with aging determines an increase in the leakage of mtDNA from the organelle to the cytosol, from the cell to the extracellular space, and into plasma. This phenomenon, mirrored by an increase in mtDNA circulating levels in elderly people, can lead to the activation of different innate immune cell types, sustaining the chronic inflammatory status that is characteristic of aging.

Labile plasma iron and echocardiographic parameters are associated with cardiac events in ß-thalassemic patients.

BACKGROUND AND AIM: Notwithstanding the improvement in therapies, patients affected by thalassemia major (TM) and intermedia (TI) are still at high risk of cardiac complications. This study aimed at evaluating the incidence and predictive factors for developing cardiac events in adult ß-TM and TI patients. POPULATION AND METHODS: Data on diagnosis and clinical history were collected retrospectively; prospective data on new-onset cardiac failure and arrhythmias, echocardiographic parameters, biochemical variables including non-transferrin-bound iron (NTBI) and labile plasma iron (LPI), magnetic resonance imaging (MRI) T2* measurement of hepatic and cardiac iron deposits, and iron chelation therapy were recorded during a 6-year follow-up. RESULTS: Thirty-seven patients, 29 TM and 8 TI, were included. At baseline, 8 TM patients and 1 TI patient had previously experienced a cardiac event (mainly heart failure). All patients were on chelation therapy and only 3 TM patients had mild-to-severe cardiac siderosis. During follow-up, 11 patients (29.7%) experienced a new cardiac event. The occurrence of cardiac events was correlated to high LPI levels (OR 12.0, 95% CI 1.56-92.3, p .017), low mean pre-transfusion haemoglobin (OR 0.21, 95% C.I. 0.051-0.761, p .21) and echocardiographic parameters suggestive of myocardial hypertrophy. Multivariate analysis disclosed high LPI and left ventricle mass index (LVMI) as independent variables significantly associated with cardiac events. Cardiac iron deposits measured by MRI T2* failed to predict cardiac events. CONCLUSION: LPI, Hb levels and echocardiographic parameters assessing cardiac remodelling are associated with cardiac events in adult TM and TI patients. LPI might represent both a prognostic marker and a potential target for novel treatment strategies. Further studies are warranted to confirm our findings on larger populations.

Early cardiovascular prevention: the crucial role of nurse-led intervention.

The present comment on Qiu's work intends to emphasize two points: (1) Cardiovascular prevention must start early due to the progressive nature of atherosclerosis. (2) growing evidence that coaching performed by nurses leads to effective results. Nurses can intercept the young population who must be sensitized and educated about prevention.

Energy drinks, substance use and arrhythmias in young subjects.

The present letter to editor discusses the manuscript "Energy drinks, substance use, and posttraumatic stress symptoms among Palestinian athletes: the mediating role of perceived self-efficacy and resilience" by Bdier D and Mahamid F.

To the Editor: Pathophysiology of Splenic Arteriovenous Fistula.

A splenic arteriovenous fistula causes a "prehepatic" hypertension in the portal venous system with the double mechanism of an increased blood amount and mainly its high pressure inflow. It aggravates for a secondary fibrosis of the portal vein branches and "capillarization" of the hepatic sinusoids, adding a further "intra-hepatic" component. The subsequent development of portosystemic collaterals induces the risk of gastrointestinal hemorrhages All this suggests to perform a close monitoring of every case of splanchnic aneurysm or pseudo-aneurysm, through the current cross-section imaging tools, for their possible evolution in an arteriovenous fistula, and to consider an early therapy, also endovascular, before any secondary damage of the liver parenchyma. In this case the treatment of the portal vein hypertension can be "ethiological" and resolutive.

Mitochondrial damage-associated molecular patterns stimulate reactive oxygen species production in human microglia.

Microglia are the resident innate immune cells of the central nervous system and exert functions of host defense and maintenance of normal tissue homeostasis, along with support of neuronal processes in the healthy brain. Chronic and dysregulated microglial cell activation has increasingly been linked to the status of neuroinflammation underlying many neurodegenerative diseases, including multiple sclerosis (MS). However, the stimulus (or stimuli) and mechanisms by which microglial activation is initiated and maintained MS are still debated. The purpose of our research was to investigate whether the endogenous mitochondrial (mt)-derived damage-associated molecular patterns (MTDs) mtDNA, N-formyl peptides and cardiolipin (CL) contribute to these phenomena. We characterized the effects of the abovementioned MTDs on microglia activation in vitro (i.e. using HMC3 cells) by evaluating the expression of gene coding for proteins involved in their binding and coupled to downstream signaling pathways, the up-regulation of markers of activation on the cell surface and the production of pro-inflammatory cytokines and reactive oxygen species. At the transcriptional level, significant variations in the mRNA relative expression of five of eleven selected genes were observed in response to stimulation. No changes in activation of antigenic profile or functional properties of HMC3 cells were observed; there was no up-regulation of HLA-DR expression or increased secretion of tumor necrosis factor-α and interleukin-6. However, after stimulation with mtDNA and CL, an increase in cellular oxidative stress, but not in the mt ROS O2-, compared to control cells, were observed. There were no effects on cell viability. Overall, our data suggest that MTDs could cause a failure in microglial activation toward a pro-inflammatory phenotype, possibly triggering an endogenous regulatory mechanism for the resolution of neuroinflammation. This could open a door for the development of drugs selectively targeting microglia and modulating its functionality to treat MS and/or other neurodegenerative conditions in which MTDs have a pathogenic relevance.

Energy drinks and medical students: Bad drinking during COVID-19 quarantine.

The present letter to editor comments the manuscript "Caffeine and high energy drink use and knowledge by nurses in three countries" presenting some data on energy drinks obtained from a questionnaire administered to undergraduate medical students.