Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network.

BACKGROUND: Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells. METHODS: EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide. RESULTS: GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88. CONCLUSION: Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment.

Edoxaban treatment in a post-infarction experimental model.

BACKGROUND: The sequelae of myocardial infarction (MI) require specific pharmacological therapy to minimise the post-MI remodelling, which in many cases evolves into cardiovascular complications. The aim of this study was to analyse the effect of edoxaban, an oral anticoagulant, on cardiac recovery in a rat model of permanent coronary artery ligation. METHODS: An experimental method to assess the post-MI remodelling in rats for 4 weeks, based on cardiac magnetic resonance imaging (MRI) and final histological analysis of the hearts was performed. The influence of daily oral treatment with edoxaban (20 mg/kg/day) for 28 days post-MI was analysed in comparison to vehicle. RESULTS: In our model, edoxaban was shown to be safe and bleeding was observed in 1 of 10 animals. General physical recovery of the treated animals was shown by higher body weight recovery compared with non-treated animals (38.6 ± 2.9 vs. 29.9 ± 3.1 g, respectively, after 28 days). There was not a pronounced effect of edoxaban in post-MI cardiac remodelling, but mitigated fibrosis was observed by the reduced expression of vascular endothelial growth factor and tumour growth factor ß1 in the peri-infarct zone. CONCLUSIONS: Our analysis provided the experimental basis to support the feasibility of MRI to study cardiac function and characterise myocardial scarring in a rat model. Overall data suggested the safety of edoxaban in the model, and compared to placebo, it showed a better post-MI recovery, probably by reducing fibrosis of the heart. Further research on mid-term cardiac recovery with edoxaban after MI is justified.

Outcomes of rapid deployment aortic valve replacement with concomitant cardiac procedures.

Background: Rapid deployment aortic valve replacement (RD-AVR) has been recently introduced with encouraging results. Outcomes of isolated RD-AVR include good hemodynamic profile, facilitation of minimally invasive techniques, and reduction of surgical times. However, role of this prosthesis in concomitant surgery is not well known. Methods: In 2016, we formed a registry to monitor the introduction of this prosthesis, RApid Deployment Aortic Replacement (RADAR). We aim to report mid-term outcomes focusing on patients who had RD-AVR combined with other surgical procedures. Results: Between July 2012 and February 2021, 370 patients were included in this registry (mean age, 75.8±8.0 years; 64.32% male; mean EuroSCORE II, 3.5±2.8). Of these, 128 (34.59%) had concomitant procedures including myocardial revascularization surgery in 69 patients (53.91%), surgery on the ascending aorta in 34 (26.56%), and procedures on other valves in 10 patients (7.81%). There were no significant differences between the isolated AVR and concomitant AVR groups in postoperative complications, in-hospital mortality (4.72% vs. 3.32%, P=0.524), or hemodynamic behavior of these prostheses. Three-year survival was 83.73% and 89.89% in the isolated and concomitant AVR group respectively. There was no difference in survival between the two groups (log-rank test, P=0.4124). Conclusions: Our results support the safety and efficacy of the Edwards INTUITY valve system even in complex aortic valve disease with additional cardiac procedures. RD-AVR could become a useful tool for concomitant surgeries where surgical times are expected to be prolonged.

Left Ventricular Papillary Fibroelastoma.

INTRODUCTION: Cardiac papillary fibroelastoma is a rare benign primary cardiac tumor typically found on the valvular structures of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. We report the case of a 66-year-old male who presented with cerebellar infarctions and was found to have a mobile mass attached to the endocardial surface of the anteroseptal wall of the left ventricle. Cardiac magnetic resonance imaging demonstrated late gadolinium enhancement. Surgical excision of the cardiac mass was performed via the transaortic approach without intra-operative complications. Histopathologic examination confirmed the diagnosis of a papillary fibroelastoma. Some aspects related to the etiology, diagnosis and management of this entity are discussed.

Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1ß (IL-1ß); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 ß, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.

Biomechanical characteristics of different methods of neo-chordal fixation to the papillary muscles.

BACKGROUND AND AIM OF THE STUDY: Several techniques have been described for neo-chordal fixation to the papillary muscles without any reported clinical differences. The objective of this study is to compare in vitro the biomechanical properties of four of these common techniques. METHODS: We studied the biomechanical properties of expanded polytetrafluoroethylene neo-chordal fixation using four techniques: nonknotted simple stitch, nonknotted figure-of-eight stitch, knotted pledgeted mattress stitch, and knotted pledgeted stitch using commercially available prefabricated loops. Neo-chordae were submitted to a total of 20 traction-relaxation cycles with incremental loads of 1, 2, and 4 N. We calculated the elongation, the force-strain curve, elasticity, and the maximum tolerated load before neo-chordal failure. RESULTS: The elongation of the neo-chordae was lowest in the simple stitch followed by the figure-of-eight, the pledgeted mattress, and he commercially prefabricated loops (p < .001). Conversely, the elastic modulus was highest in the simple stitch followed by the figure-of-eight, the pledgeted mattress, and the prefabricated loops (p < .001). The maximum tolerated load was similar with the simple stitch (28.87 N) and with the figure-of-eight stitch (31.39 N) but was significantly lower with the pledgeted mattress stitch (20.51 N) and with the prefabricated loops (7.78 N). CONCLUSION: In vitro, neo-chordal fixation by nonknotted simple or nonknotted figure-of-eight stitches resulted in less compliance as opposed to the use of knotted pledgeted stitches. Fixation technique seemed to influence neo-chordal biomechanical properties, however, it did not seem to affect the strength of the suture when subjected to loads within physiological ranges.

Does Pacemaker Implantation After Surgical Aortic Valve Replacement Impact Long-Term Morbidity and Mortality? A Focused Review.

Permanent pacing remains a serious complication that can occur in the postoperative period of surgical aortic valve replacement. The reported incidence is variable, and there are many perioperative factors that have been linked with a greater need for permanent pacing. Permanent pacing can also be associated with late lead-related and cardiac complications that can affect late outcome. However, the degree of late dependence on pacemakers is varied, and some studies have shown that a substantial proportion of patients do not need long-term pacing. Some groups have found that permanent pacing was associated with a negative impact on long-term survival in these patients. A common finding among these studies is that the groups of patients with pacemakers had higher preoperative surgical risk and comorbidity status. This makes it difficult to establish whether permanent pacing on its own represents a risk factor for late mortality or whether it is simply a marker that reflects the higher complexity and comorbidities in this group of patients.

Wildlife susceptibility to infectious diseases at global scales.

Disease transmission prediction across wildlife is crucial for risk assessment of emerging infectious diseases. Susceptibility of host species to pathogens is influenced by the geographic, environmental, and phylogenetic context of the specific system under study. We used machine learning to analyze how such variables influence pathogen incidence for multihost pathogen assemblages, including one of direct transmission (coronaviruses and bats) and two vector-borne systems (West Nile Virus [WNV] and birds, and malaria and birds). Here we show that this methodology is able to provide reliable global spatial susceptibility predictions for the studied host-pathogen systems, even when using a small amount of incidence information (i.e., [Formula: see text] of information in a database). We found that avian malaria was mostly affected by environmental factors and by an interaction between phylogeny and geography, and WNV susceptibility was mostly influenced by phylogeny and by the interaction between geographic and environmental distances, whereas coronavirus susceptibility was mostly affected by geography. This approach will help to direct surveillance and field efforts providing cost-effective decisions on where to invest limited resources.

Ischemic ventricular septal rupture with patent coronary bypass grafts due to occluded septal branch, a case report.

BACKGROUND: Ischemic ventricular septal rupture (VSR) is a lethal complication that occurs either after spontaneous or iatrogenic occlusion of one of the major epicardial coronary vessels. To the best of our knowledge, this is the first reported case of a VSD after a septal branch occlusion in a patient with patent coronary artery grafts to both the left anterior descending and posterior descending arteries. METHODS: We present a rare case of anterior ischemic VSR due to the occlusion of a major septal branch. The patient had previous coronary artery bypass grafts and his left internal mammary artery conduit to the anterior descending artery was patent. The culprit lesion that resulted in the development of the VSR was the occlusion of a major septal branch. DISCUSSION: The presence of collateral circulation in chronic coronary occlusive disease may provide a protective effect against the development of transmural myocardial necrosis which may reduce the risk of septal rupture. This case highlights the fact that patent coronary artery grafts may not protect from future ischemic VSR. CONCLUSION: Major septal branches with significant disease should be assessed for percutaneous options if technically feasible as dictated by the Heart Team.

Synergism between obesity and HFpEF on neutrophils phenotype and its regulation by adipose tissue-molecules and SGLT2i dapagliflozin.

The adiposity invokes innate immune activity, coronary microvascular dysfunction and consequently heart failure preserved ejection fraction (HFpEF). Our aim was to study the neutrophils profile on obesity and cardiovascular disease and its regulation by adipose tissue-secretome and dapagliflozin. We have isolated neutrophils from patients undergoing open heart surgery (19 women and 51 men). Its migration activity was performed with culture-transwell, transcriptional studies of proteolytic enzymes, adhesion molecules or receptors were analysed by real-time PCR and proteomics (from 20 patients) analysis by TripleTOF mass spectrometer. Differentiated HL-60 (dHL-60) was used as a preclinical model on microfluidic for endothelial cells attaching assays and genes regulation with epicardial and subcutaneous fat secretomes from patients (3 women and 9 men) or dapagliflozin 1-10 µM treatments. The transcriptional and proteomics studies have determined higher levels of adhesion molecules in neutrophils from patients with obesity. The adhesion molecule CD11b levels were higher in those patients with the combined obesity and HFpEF factors (1.70 ± 0.06 a.u. without obesity, 1.72 ± 0.04 a.u. obesity or HFpEF without obesity and 1.79 ± 0.08 a.u. obesity and HFpEF; p < .01). While fat-secretome induces its upregulation, dapagliflozin can modulated it. Because CD11b upregulation is associated with higher neutrophils migration and adhesion into endothelial cells, dapagliflozin might modulate this mechanism on patients with obesity and HFpEF.

American Mammals Susceptibility to Dengue According to Geographical, Environmental, and Phylogenetic Distances.

Many human emergent and re-emergent diseases have a sylvatic cycle. Yet, little effort has been put into discovering and modeling the wild mammal reservoirs of dengue (DENV), particularly in the Americas. Here, we show a species-level susceptibility prediction to dengue of wild mammals in the Americas as a function of the three most important biodiversity dimensions (ecological, geographical, and phylogenetic spaces), using machine learning protocols. Model predictions showed that different species of bats would be highly susceptible to DENV infections, where susceptibility mostly depended on phylogenetic relationships among hosts and their environmental requirement. Mammal species predicted as highly susceptible coincide with sets of species that have been reported infected in field studies, but it also suggests other species that have not been previously considered or that have been captured in low numbers. Also, the environment (i.e., the distance between the species' optima in bioclimatic dimensions) in combination with geographic and phylogenetic distance is highly relevant in predicting susceptibility to DENV in wild mammals. Our results agree with previous modeling efforts indicating that temperature is an important factor determining DENV transmission, and provide novel insights regarding other relevant factors and the importance of considering wild reservoirs. This modeling framework will aid in the identification of potential DENV reservoirs for future surveillance efforts.

Surgicel-Related Uptake on Positron Emission Tomography Scan Mimicking Prosthetic Valve Endocarditis.

A 78-year-old patient who underwent an aortic valve replacement presented 6 months later with clinical symptoms suspicious for prosthetic valve endocarditis. Echocardiography showed no features suggestive of endocarditis, but a positron emission tomography/computed tomography with fluorine-18-fluorodeoxyglucose (18F-FDG PET/CT) scan showed an area of hyper-uptake around the ascending aorta. We realized that the sheet of Surgicel (Ethicon, Bridgewater, NJ) hemostat had been placed over the aortotomy suture line at the time of surgery. Another follow-up PET/CT scan performed 22 months later showed that the hyper-uptake focus remained persistent. False-positive hyper-uptake on an 18F-FDG PET/CT scan owing to local hemostatics should be considered when interpreting the findings of this technique.

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open-heart surgery.

The modulation of acetylcholine (ACh) release by botulinum toxin injection into epicardial fat diminishes atrial fibrillation (AF) recurrence. These results suggest an interaction between autonomic imbalance and epicardial fat as risk factors of AF. Our aim was to study the inflammatory, lipidic and fibroblastic profile of epicardial stroma from patients who underwent open-heart surgery, their regulation by cholinergic activity and its association with AF. We performed in vitro and ex vivo assays from paired subcutaneous and epicardial stromal cells or explants from 33 patients. Acute ACh effects in inflammation and lipid-related genes were analysed by qPCR, in intracellular calcium mobilization were performed by Fluo-4 AM staining and in neutrophil migration by trans-well assays. Chronic ACh effects on lipid accumulation were visualized by AdipoRed. Plasma protein regulation by parasympathetic denervation was studied in vagotomized rats. Our results showed a higher pro-inflammatory profile in epicardial regarding subcutaneous stromal cells. Acute ACh treatment up-regulated monocyte chemoattractant protein 1 levels. Chronic ACh treatment improved lipid accumulation within epicardial stromal cells (60.50% [22.82-85.13] vs 13.85% [6.17-23.16], P < .001). Additionally, patients with AF had higher levels of fatty acid-binding protein 4 (1.54 ± 0.01 vs 1.47 ± 0.01, P = .005). Its plasma levels were pronouncedly declined in vagotomized rats (2.02 ± 0.21 ng/mL vs 0.65 ± 0.23 ng/mL, P < .001). Our findings support the characterization of acute or chronic cholinergic activity on epicardial stroma and its association with AF.

CD5L, Macrophage Apoptosis Inhibitor, Was Identified in Epicardial Fat-Secretome and Regulated by Isoproterenol From Patients With Heart Failure.

OBJECTIVES: Neurohormonal dysfunction, which can regulate epicardial fat activity, is one of the main promoters of atrial fibrillation (AF) in patients with heart failure (HF). Our aim was to study the epicardial fat mediators for AF in patients with HF and its catecholaminergic regulation. METHODS: We have included 29 patients with HF who underwent cardiac surgery and were followed up for 5 years. Released proteins by epicardial adipose tissue (EAT) after isoproterenol treatment were identified by nano-high-performance liquid chromatography (HPLC) and triple time-of-flight (TOF) analysis. Common and differential identified proteins in groups of patients with AF before and after surgery were determined by the FunRich tool. Plasma and epicardial fat biopsy proteins were quantified by western blot. RESULTS: Our results identified 17 common released proteins by EAT, after isoproterenol treatment, from HF patients who suffered AF or developed new-onset AF during follow-up. Mostly, they were involved on inflammatory response and extracellular matrix. One of them was CD5L, a macrophage apoptosis inhibitor. Its secretion by isoproterenol treatment was validated on western blot. The CD5L levels on epicardial fat were also higher in the group of male patients who present or develop AF (0.44 ± 0.05 vs. 0.18 ± 0.15; p < 0.016). However, there were no differences regarding plasma levels. CONCLUSION: Our results suggest the role of epicardial fat CD5L as a mediator of AF and its possible paracrine effect by catecholaminergic activity.

Aortic Valve Replacement In Alkaptonuric Ochronosis.

Alkaptonuria is an autosomal recessive inborn error of metabolism of the aromatic amino acids. Deficiency of the homogentisate1,2-dioxygenase leads to an increased blood and urinary concentration of homogentisc acid resulting in a slow accumulation of its oxidation products in the connective tissues (ochronosis). The most common clinical manifestation of ochronosis is arthropathy whereas cardiac involvement is very infrequent. We report the case of a patient with ochronotic involvement of the aortic valve who underwent a valve replacement. Some aspects of pathogenesis, and treatment are discussed.

Clinical study of an outbreak of postoperative mediastinitis caused by Serratia marcescens in adult cardiac surgery.

OBJECTIVES: Nosocomial infection caused by Serratia marcescens after cardiac surgery is rare but causes high rates of morbidity and mortality. Knowledge about postoperative mediastinitis due to S. marcescens is limited. The purpose of this work was to study the clinical presentation, management and outcome of an outbreak of postoperative sternal infection due to S. marcescens. METHODS: During a 7-week period, a total of 54 patients underwent open heart procedures in our hospital. A postoperative wound infection caused by S. marcescens was diagnosed in 10 patients. We performed a clinical study to investigate patient characteristics and outcomes as well as the possible source of the infection. RESULTS: The mean age of the infected patients was 74.5 ± 10 years. Mediastinitis was present in 6 cases, superficial wound infection in 3 and isolated bacteraemia in 1. Purulent exudate through the sternal incision was observed in all infected cases except in 1 patient, who presented only with bacteraemia. Serratia marcescens was isolated from the samples taken from all infected wounds. The mean time elapsed between the operation and the isolation S. marcescens was 5.9 ± 2.4 days. Response to treatment was favourable in all cases except 1, who died. Contamination of the aqueous chlorhexidine solution used to prepare the patients' skin with S. marcescens was reported. Microbiological studies demonstrated that S. marcescens strains isolated from patients and from the aqueous chlorhexidine solution belonged to the same clone. CONCLUSIONS: The use of an aqueous chlorhexidine solution contaminated with S. marcescens caused an outbreak of postoperative sternal wound infections. The time elapsed between wound contamination and signs of infection was brief, but the systemic inflammatory response and tissue necrosis were limited. Alcohol-based solutions are recommended for the prevention of surgical site infections.

Preliminary Aquatic Physical Therapy Core Sets for Children and Youth With Neurological Disorders: A Consensus Process.

PURPOSE: To report on the preliminary aquatic physical therapy core sets for children and youth with neurological disorders using the International Classification of Functioning, Disability and Health-children and youth version. METHODS: A formal and structured consensus process was developed, integrating the findings of preparatory studies: a systematic literature review, expert survey with 69 participants, and a qualitative study with 43 participants. RESULTS: Five preliminary aquatic physical therapy core sets were described: a Comprehensive Core Set (64 categories); a Common Brief (13 categories); and 3 age-specific Core Sets: infant (below 6 years, 18 categories), school-age (from 6 to <14 years, 22 categories), and youth (from 14 to 18 years, 19 categories). CONCLUSIONS: Consensus among aquatic physical therapists' expert opinions identified the relevant intervention categories available when treating children and youth with neurological disorders. This list of intervention categories can be used in practice, research, education, and health administration.

Postoperative hyperbilirubinemia and Gilbert's syndrome in patients undergoing cardiac surgery.

We report a series of seven patients with Gilbert's syndrome undergoing cardiac surgery. Early and transient increase of total, direct, and indirect bilirubin without other complications was observed. Although this is a benign process, we believe that this disease should be routinely included in the differential diagnosis of postoperative jaundice after cardiopulmonary bypass.

Asistencia combinada con oxigenador extracorpóreo de membrana venoarterial e Impella para el espasmo coronario difuso después de revascularización miocárdica / Combined venoarterial extracorporeal membrane oxygenation and impella for diffuse coronary spasm after surgical myocardial revascularization

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