Portal Vein Thrombosis in Patients with Liver Cirrhosis: What Went Wrong?

Purpose: This study aimed to explore inflammatory biomarkers, stool's functional bacterial groups and their possible link to portal vein thrombosis (PVT) in patients with liver cirrhosis (LC). Materials and Methods: An observational study of 300 participants: 200 inhospital cirrhotic patients, who met inclusion criteria, equally assigned into two groups, based on the presence or absence of PVT and 100 healthy controls was carried out. Results: The PVT group displayed significant differences related to older age, cigarettes smoking history, emergency admission, higher Child-Pugh score, metabolic related disorders and nonalcoholic fatty liver disease, as well as non-obstructive aspects, with chronic thrombi. The PVT group exhibited significant differences related to biomarkers such as tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), D-dimers (D-D), as well as gut overall dysbiosis (DB) and alteration of different functional bacterial groups of the gut microbiota. Strong positive correlations were observed between PVT severity, and TNF-alpha, CRP, D-D as well as lipopolysaccharide (LPS) positive bacteria. Esophageal varices, age and abdominal pain were independent predictors for PVT severity as well as CRP, TNF-alpha and D-D. Conclusion: Patients with LC and PVT displayed elevation of TNF-alpha, CRP, D-D alterations of the functional gut microbiota, as well as several morphological and clinical particularities. Although the LPS positive gut microbiota was linked to inflammatory biomarkers and PVT severity, it was not proven to be an independent predictor of the PVT severity like CRP, TNF-alpha and D-D.

Metformin and empagliflozin modulate monoamine oxidase-related oxidative stress and improve vascular function in human mammary arteries.

Monoamine oxidases (MAOs), mitochondrial enzymes with two isoforms, A and B, have been recently recognized as significant contributors to oxidative stress in the cardiovascular system. The present study was purported to assess the effect of metformin and empagliflozin on MAO expression, oxidative stress and vascular reactivity in internal mammary arteries harvested from overweight patients with coronary heart disease subjected to bypass grafting. Vascular rings were prepared and acutely incubated (12 h) with high glucose (GLUC, 400 mg/dL) or angiotensin II (AII, 100 nM) and metformin (10 µM) and/or empagliflozin (10 µM) and used for the assessment of MAO expression (qRT-PCR and immune histochemistry), reactive oxygen species (ROS, confocal microscopy and spectrophotometry), and vasomotor function (myograph). Ex vivo stimulation with GLUC or AII increased both MAOs expression, ROS production and impaired relaxation to acetylcholine (ACh) of the vascular rings. All effects were alleviated by incubation with each antidiabetic drug; no cumulative effect was obtained when the drugs were applied together. In conclusion, MAO-A and B are upregulated in mammary arteries after acute stimulation with GLUC and AII. Endothelial dysfunction and oxidative stress were alleviated by either metformin or empagliflozin in both stimulated and non-stimulated vascular samples harvested from overweight cardiac patients.

Metformin Acutely Mitigates Oxidative Stress in Human Atrial Tissue: A Pilot Study in Overweight Non-Diabetic Cardiac Patients.

Metformin, the first-line drug in type 2 diabetes mellitus, elicits cardiovascular protection also in obese patients via pleiotropic effects, among which the anti-oxidant is one of the most investigated. The aim of the present study was to assess whether metformin can acutely mitigate oxidative stress in atrial tissue harvested from overweight non-diabetic patients. Right atrial appendage samples were harvested during open-heart surgery and used for the evaluation of reactive oxygen species (ROS) production by means of confocal microscopy (superoxide anion) and spectrophotometry (hydrogen peroxide). Experiments were performed after acute incubation with metformin (10 µM) in the presence vs. absence of angiotensin II (AII, 100 nM), lipopolysaccharide (LPS, 1 µg/mL), and high glucose (Gluc, 400 mg/dL). Stimulation with AII, LPS, and high Gluc increased ROS production. The magnitude of oxidative stress correlated with several echocardiographic parameters. Metformin applied in the lowest therapeutic concentration (10 µM) was able to decrease ROS generation in stimulated but also non-stimulated atrial samples. In conclusion, in a pilot group of overweight non-diabetic cardiac patients, acute incubation with metformin at a clinically relevant dose alleviated oxidative stress both in basal conditions and conditions that mimicked the activation of the renin-angiotensin-aldosterone system, acute inflammation, and uncontrolled hyperglycemia.

Monoamine Oxidase (MAO) Is Expressed at the Level of Mitral Valve with Severe Regurgitation in Hypertrophic Obstructive Cardiomyopathy: A Case Report.

Hypertrophic obstructive cardiomyopathy (HOCM) is one of the most common hereditary heart diseases. The severely hypertrophied interventricular septum combined with the systolic anterior movement (SAM) of the mitral valve (MV) frequently cause a significant pressure gradient in the left ventricular outflow tract associated with varying degrees of mitral regurgitation (MR). We present the case of a 64-year-old female patient who was diagnosed with HOCM two years ago and was admitted to the Institute of Cardiovascular Disease with exertion dyspnea and fatigue. Transthoracic echocardiography revealed concentric, asymmetrical left ventricular hypertrophy, an elongated anterior mitral leaflet (AML) and a significant SAM causing severe regurgitation, with indication for valvular replacement Monoamine oxidase (MAO), a mitochondrial enzyme, with 2 isoforms, MAO-A and B, has emerged as an important source of reactive oxygen species (ROS) in the cardiovascular system, but literature data on its expression in valvular tissue is scarce. Therefore, we assessed MAO-A and B gene (qPCR) and protein (immune fluorescence) expression as well as ROS production (spectrophotometry and confocal microscopy) and in the explanted MV harvested during replacement surgery. MAO expression and ROS production (assessed by both methods) were further augmented following ex vivo incubation with angiotensin II, an effect that was reversed in the presence of either MAO-A (clorgyline) or B (selegiline) inhibitor, respectively. In conclusion, MAO isoforms are expressed at the level of severely impaired mitral valve in the setting of HOCM and can be induced in conditions that mimic the activation of renin-angiotensin-aldosterone system. The observation that the enzyme can be modulated by MAO inhibitors warrants further investigation in a patient cohort.

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed.

Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

Molecular Monitoring of Allogeneic Stem Cell Transplantation in Fanconi Anemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice in patients with Fanconi anemia (FA). The aim of our study is to evaluate the impact and benefits of allogenic matched donor HSCT in a case of a 12 year-old girl with FA, who displayed good clinical evolution following 2 months post-transplantation. METHODS: In the pre-transplant phase, reference blood samples from the donor and recipient were collected on EDTA. The DNA from blood samples was extracted using an automated Maxwell® 48 RSC instrument (Promega, USA) with the Maxwell® RSC Whole blood DNA kit (Promega, USA). For DNA quantification, the PowerQuant System kit (Promega, USA) was used with the ABI 7500 Real-time PCR system (Applied Biosystems, USA). The amplification of the short tandem repeat markers was performed using the 24plex Investigator QS kit (Qiagen, Germany) on a ProFlex PCR System. Furthermore, the PCR products were separated and detected on an ABI 3500 Genetic Analyzer (Applied Biosytems, USA). RESULTS: Thirty days post transplantation, a complete chimerism (CC) was achieved with a full replacement by do-nor derived hematopoietic cells. Sixty days post transplantation, the CC status was maintained with improvement of hematological findings. CONCLUSIONS: In FA, chimerism monitoring after HSCT provides useful information regarding engraftment or possibility of post-transplantation complications such as graft versus host disease.

A Review of the Role of Transthoracic and Transesophageal Echocardiography, Computed Tomography, and Magnetic Resonance Imaging in Cardioembolic Stroke.

Stroke is a major source of morbidity and mortality worldwide, accounting for the second largest cause of mortality and the third greatest cause of disability. Stroke is frequently preceded by a transient ischemic attack (TIA). The etiologies of 20-30% of ischemic strokes are unknown, and thus are termed "cryptogenic strokes". About 25% of ischemic strokes are cardioembolic. Strokes occur at a rate of around 2% per year in individuals with heart failure with reduced ejection fraction (HFrEF), with a strong correlation between stroke risk and the degree of ventricular impairment. Furthermore, stroke risk is augmented in the absence of anticoagulation therapy. Cardioembolic strokes, when treated inadequately, have a greater predilection for recurrences than atherothrombotic strokes, both early and late in life. The role of a patent foramen ovale in strokes, specifically in "cryptogenic strokes", is a matter of concern that deserves due attention. The use of tissue-engineered heart valves and aspirin for minimizing the risk of stroke is recommended. Transthoracic echocardiography (TTE) is advantageous for assessing heart function in the acute phase of ischemic stroke. Transesophageal echocardiography (TEE) is considered the criterion standard procedure for detecting LAA thrombi. Computed tomography (CT) scans are good imaging modalities for identifying and excluding bleeding. Magnetic resonance imaging (MRI) images are by far the most effective imaging technique available for assessing the brain parenchymal state. We conducted a thorough review of the literature on the use of imaging modalities, highlighting the important contribution of TTE, TEE, CT, and MRI in the evaluation of cardioembolic stroke.

Gallstone Disease and Bacterial Metabolic Performance of Gut Microbiota in Middle-Aged and Older Patients.

Background: Gallstone disease (GSD) is more commonly presented in aged people. Purpose: The purpose of the study was to explore the insights of metabolic performance of bacterial species from gut microbiota as well as the clinical background in middle-aged and elderly patients with GSD. Patients and Methods: This is an observational study concerning 120 research participants. Of those, 90 patients with symptomatic GSD addressed for cholecystectomy, average age 59.83 ± 15.32 years: 45 with cholesterol rich gallstones (CGSs), 45 with pigment gallstones (PGSs) and 30 healthy controls joined this observational study. Clinical examination, lab work-ups, upper and lower digestive video-endoscopies, abdominal ultrasound/CT and gallbladder motility assessment by Dodd's method were performed. Overall stool dysbiosis (DB) was assessed as 1 = minor, 2 = mild, 3 = severe, species being identified by matrix-assisted laser desorption ionization method. Stool samples from dysbiotic patients were analyzed by a next generation sequencing method with operational taxonomic unit identification. Results: Patients with GSD presented with a significant high range of overall gut DB (p < 0.0001) when compared with controls. Those with CGSs compared with those having PGSs displayed significant clinical differences related to elderly age, lifestyle and diet particularities, obesity, dyslipidemia, nonalcoholic fatty liver disease, hypertension, type 2 diabetes mellitus or impaired glucose tolerance, as well as motility disturbances of gallbladder with a decrease of the ejection fraction. Significant increase of overall DB range and alterations of several functional bacterial species with a decrease of butyrate, lactate, acetate/propionate and methane producers, mucin degrading bacteria, biodiversity index of microbiota, as well as an increase of lipopolysaccharide positive bacteria were significantly present in patients with CGSs. Conclusion: Middle-aged and elderly patients with GSD and a clinical background characterized by particular lifestyle, metabolic and gallbladder motility issues displayed significant modifications of biodiversity, overall gut DB and alterations of several functional bacterial species, with a decrease of their metabolic performance.

Dyspepsia and Gut Microbiota in Female Patients with Postcholecystectomy Syndrome.

BACKGROUND: Gallstone disease (GSD) represents one of the most frequent digestive disorders, highly reported in female gender. The purpose of the study was to explore the clinical and gut microbiota particularities of female patients with postcholecystectomy syndrome (PCS) and the possible relationship between gut dysbiosis (DB) and abdominal complaints. PATIENTS AND METHODS: In total, 129 female participants: 104 outpatients divided into two equal groups, 52 PCS (+), 52 PCS (-) and 25 healthy controls were consecutively enrolled in this observational study. Patients underwent clinical examination with assessment of pain, bloating, transit disturbances, abdominal ultrasound/computer tomography/magnetic resonance imaging/endoscopic retrograde cholangiopancreatography, upper and lower digestive endoscopies. Laboratory work-ups and stool microbiology assessments were performed for all study participants (patients and controls). Stool microorganisms were identified by matrix-assisted laser desorption ionization - time-of-flight- mass spectrometry and in patients with DB also by next-generation sequencing. RESULTS: Older age, complicated gallstones disease, associated conditions like diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome were significantly present in PCS (+) group, as well as sedentary lifestyle and diets characterized by a low fiber intake (p<0.0001). PCS (+) patients displayed significant differences related to the incidence and severity of overall gut microbiota DB, decreased H index of biodiversity and the unbalanced Firmicutes/Bacteroidetes (F/B) ratios by comparison to the PCS (-) group (p<0.0001). Strong positive correlations of the severity of overall DB with bloating and the intestinal habit disorders, as well as of F/B ratios to all abdominal symptoms were noted. CONCLUSION: PCS in female patients was associated with older age, sedentary lifestyle, specific dietary habits, history of complicated gallstone disease, diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome, as well as gut microbiota particularities. Overall DB and unbalanced F/B ratios were strongly correlated to abdominal complaints.

Chameleonic appearance of caseous calcification of the mitral valve - still a problem for its appropriate management.

According to the research literature, the caseous calcification of the mitral annulus (CCMA) is a rare variant of the mitral annulus calcification (MAC) entity, described mostly in elderly women. The aim of this study was to present the case of a 53-year-old female patient with caseous calcification of the mitral valve annulus and posterior cusp, which was diagnosed as papillary fibroelastoma. An echo-dense and quasi-homogeneous tumoral mass, measuring 1.6∕1.4 cm, at the level of the posterior mitral ring was detected by echocardiographic examination, as well as by cardiac magnetic resonance imaging (MRI). Histopathological analysis revealed fibrous connective tissue with myxoid areas, hyaline degeneration with unstructured necrosis and dystrophic calcifications, which was consisting with the operative findings of a "toothpaste tumor", or caseous calcification of the mitral valve. Differential diagnosis with other cardiac tumors, abscesses, thrombi or fibroelastomas is emphasized.

[The electroacupuncture in patients recently operated for peripheral arterial disease. A comparative study of the two electrostimulation techniques]. / Electroacupunctura la bolnavii vasculari periferici recent operati. Studiu comparativ a doua tehnici de electrostimulare.

UNLABELLED: Possible hemodynamic effects of electro acupuncture (A), by two electro stimulation techniques, were studied at patients with femuro - popliteal bypass revascularization. MMATERIAL AND METHOD:In a prospective study, we evaluated two EA techniques, by calculating the ankle-brachial index (ABI) and by estimating the pain with Numeric Rating Scale (NRS: 0 - 10). The patients were grouped in lot A (30 patients) and B (50 patients) according with the EA technique used. In both lots were used the same acupuncture points (acupoint): Pc6, P9, St36 and Sp6. These acupoints are adjacent to peripheral nerves median, radial, peroneal and safenous nerve. Needles, after insertion, were kept in place for 30 minutes. The electro stimulation (2 Hz) was only for 2 minutes in the lot A and for 30 minutes in the lot B. RESULTS: The blood pressure data and ABI shows a significant increase of ABI (between 0.033 and 0.052) after EA at 5 minutes in the both lots (p < 0.05). At 30 minutes, ABI is increased in lot B, but in the lot A the ABI is elevated only at the non surgical leg (p < 0.05). The decrease of pain post EA is better in the lot B (NRS: initially 2.48--post EA pain decreased to 1.46 and remained 1.66 at 2 hours; p < 0.001), than lot A. CONCLUSIONS: The electro stimulation of certain acupoints, at the operated peripheral arterial disease patients, interfere with tissular perfusion and increase temporally ABI. The pain is diminished more significantly by the 30 minutes electro stimulating technique.