Thrombotic Changes Research Articles

Preserved prenatal lung growth assessed by fetal MRI in the omicron-dominated phase of the SARS-CoV-2 pandemic.

With SARS-CoV-2 evolving, disease severity and presentation have changed due to changes in mechanisms of entry and effector site as well as due to effects of vaccination- and/or infection-acquired immunity. We re-assessed fetal lung pathology in pregnancies with uncomplicated SARS-CoV-2 infections during the late, omicron-dominated pandemic phase to inform disease understanding and pregnancy consultation. In this case-control study, fetal lung volumes were assessed by fetal MRI in 24 pregnancies affected by mild maternal SARS-CoV-2 infection during the omicron-dominated pandemic phase with prevailing immunity through vaccination and/or prior SARS-CoV-2 infection. Fetal lung volumes (normalized to estimated fetal weight) in 24 pregnancies (GA 33.3 ± 3.8, 12 female fetuses) following mild, uncomplicated SARS-CoV-2 infection did not differ significantly from both, published reference values (96.3% ± 22.5% of 50th percentile reference values, p = 0.43), or fetal lung volumes of a site-specific, non-COVID control group (n = 15, 94.2% ± 18.5%, p = 0.76). Placental assessment revealed no group differences in thrombotic changes or placental heterogeneity (p > 0.05, respectively), and fetal lung volume did not correlate with placental heterogeneity when adjusting for gestational age at scan (p > 0.05). Assessment of fetal lung volume by MRI revealed unaffected lung growth in pregnancies affected by uncomplicated SARS-CoV-2 infection in the omicron-dominated pandemic phase in the presence of prevailing hybrid immunity. This finding contrasts sharply with the observed reduction in fetal lung volume following maternal alpha-variant infection in the pre-vaccination era and might reflect tropism- as well as immunity-related effects. Question: Is fetal lung development affected by mild maternal SARS-CoV-2 infection during the omicron-dominated phase of the pandemic? Fetal lung volume in 24 affected pregnancies did not differ significantly from published reference values or fetal lung volumes in 15 site-specific, non-COVID-affected control pregnancies. Preserved fetal lung volume following mild maternal SARS-CoV-2 infection during the omicron-dominated phase contrasts with previous findings of reduced volume in unvaccinated pregnancies during the alpha-dominated pandemic phase. These observations might reflect tropism- as well as immunity-related effects.

Case report: Woven-like coronary arteries in a patient with polycythemia vera

BackgroundWoven coronary artery (WCA) is a rare and underdiagnosed congenital anomaly that involves multiple thin and tortuous epicardial arterial conduits reassembling distally into a single lumen. Recanalized thrombus may present as woven-like coronary arteries, appearing similar to WCA on angiographic images.Case presentationA 58-year-old female patient with intermittent chest pain for 5 years and polycythaemia vera (PV) for 8 years. The left anterior descending artery was presented like WCA on coronary angiography and finally confirmed as recanalized thrombus by optical coherence tomography(OCT), which might have been caused by PV. Given the patient’s high thrombotic risk of PV and thrombotic changes in the left circumflex artery (LCX), we ultimately chose a conservative treatment without stenting.ConclusionsOCT would be needed for the diagnosis and differential diagnosis of woven-like coronary arteries. And physicians should take an appropriate treatment in a personalized way in patients with PV.

Otogenic brain abscess as a complication of acute otitis media in an adult female patient – a case report and literature review

<b>Introduction:</b>Ear abscess of the brain occurs in 0.3–1.3/100,000 of the population per year, and about 30% of abscesses are accompanied by other intracranial complications. Such complications can occur in the course of both chronic and acute otitis media, but the latter is extremely rare.<b>Aim:</b> To present a case of temporal lobe abscess in the course of acute otitis media (AOM) in an adult.<b>Case study: </b> The patient was admitted to the Hospital Emergency Department (ED) with symptoms of AOM with purulentleakage from the right ear and disturbance of consciousness. In addition to inflammatory changes in the middle ear, a CTscan showed zones of swelling in the right temporal lobe with suspicion of a forming temporal lobe abscess on the rightside. The treatment administered included urgent anthromastoidectomy and right-sided tympanostomy, as well as empiricalantibiotic therapy. Six days after admission, a follow-up magnetic resonance imaging (MRI) scan of the brain showedprogression of the lesions, complete formation of the abscess, and thrombotic changes in the cerebral venous sinuses werealso described. Further treatment included drainage of the temporal lobe abscess. A significant improvement in generaland neurological condition was achieved. Conservative treatment was continued and regression of the right temporal lobeabscess was achieved, and a follow-up RM study confirmed stable thrombotic lesions in the right transverse sinus.<b>Conclusions:</b> The occurrence of intracranial complications in the course of AOM in adults is extremely rare. Deterioration of the general condition and the appearance of consciousness disturbances in the course of AOM may indicate developing intracranial complications. Implementation of multidisciplinary diagnostic and therapeutic management makes it possible to achieve good therapeutic results.

Vasculopathy Leading to Stroke in Adult Onset Still’s Disorder

Abstract Background Rheumatological disorders may predispose patients to hypercoagulability and/or vasculopathy increasing stroke risk. Adult-Onset Still’s Disease (AOSD) is not usually associated with either, with only two reported cases in the literature to have had strokes. We present a case of AOSD with acute stroke manifesting as lateral medullary syndrome. We hypothesize that vasculopathy and thrombocytosis may have contributed to stroke occurrence. We further explore the possible underlying pathomechanism in this patient population. Case Presentation A 35-year-old woman with AOSD on methotrexate, tocilizumab and daily prednisone presented with vertigo and numbness involving her right face and left arm. She was found to have an ischemic stroke in the lateral medulla with vertebral artery thrombotic changes. No recent trauma. Investigation of other underlying stroke etiologies was unyielding with negative lupus anticoagulants, ANCAs and normal ESR and CRP. Discussion & Conclusion Our case marks the third report of stroke occurrence in AOSD in the literature. While our patient had no elevated inflammatory markers, she still developed stroke due to ongoing endothelial inflammation and thrombotic changes in the vertebral artery. The presence of vascular involvement leading to stroke may provide initial insight into the nature of this event. Further research should thus be done to investigate the exact mechanism of stroke and vasculopathy in AOSD patients.

LPL rs264, PROCR rs867186 and PDGF rs974819 Gene Polymorphisms in Patients with Unstable Angina.

Coronary artery disease is caused by changes in the coronary arteries due to the atherosclerotic process and thrombotic changes. A very important role in the development of the atherosclerotic process in the coronary vessels is played by the inflammatory process and the immune response. Due to the important role of lipids and the coagulation process in the atherosclerotic process, research has also focused on genes affecting lipid metabolism and the coagulation system. Lipoprotein lipase (LPL) is an enzyme that metabolises lipids, hydrolysing triglycerides to produce free fatty acids and glycerol. Protein C (PC) is an essential component of coagulation and fibrinolysis. It is activated on the endothelial surface by the membrane-bound thrombin-thrombomodulin complex. Platelet-derived growth factor (PDGF) has a number of important functions in processes related to fibroblast and smooth muscle cell function. Due to their influence on lipid metabolism and coagulation processes, LPL, PROCR (endothelial cell protein C receptor) and PDGF may affect the atherosclerotic process and, thus, the risk of coronary heart disease. The aim of the study was to examine the associations between the LPL rs264, PROCR rs867186 and PDGF rs974819 gene polymorphisms and the risk of unstable angina and selected clinical parameters. The study included 232 patients with unstable angina and 144 healthy subjects as the control group. Genotyping was performed using real-time PCR. There were no statistically significant differences in the distribution of the polymorphisms tested between the patients with unstable angina and the control subjects. The results showed associations between the PROCR rs867186 and PDGF rs974819 polymorphisms and some clinical parameters in patients with unstable angina. In patients with the PDGF rs974819 CC genotype, there were increased values for cholesterol and LDL serum levels in comparison with patients with the PDGF rs974819 CT and TT genotypes. In patients with the PROCR rs867186 AA genotype, HDL serum levels were lower than in patients with the GA genotype. The results of our study did not show that the LPL rs264, PROCR rs867186 and PDGF rs974819 gene polymorphisms were significant risk factors for unstable angina in our population. The results of the study suggest that PDGF rs974819 and PROCR rs867186 may be associated with some parameters of lipid metabolism.

Hydroxychloroquine in obstetrics: potential implications of the prophylactic use of hydroxychloroquine for placental insufficiency during pregnancy.

Proper placentation during early pregnancy is a key factor for maintaining a healthy pregnancy. Placental insufficiency leads to critical complications such as preeclampsia, fetal growth restriction, and fetal demise. These complications are often associated with pathological findings of restricted remodeling and obstructive lesions of the myometrial spiral arteries, which have high recurrence rates during subsequent pregnancies. Currently, there are no pharmacological interventions other than aspirin for the prevention of preeclampsia. Hydroxychloroquine (HCQ), a well-known antimalarial drug, reduces inflammatory and thrombotic changes in vessels. For decades, the use of HCQ for autoimmune diseases has resulted in the successful prevention of both arterial and venous thrombotic events and has been extended to the treatment of lupus and antiphospholipid antibody syndrome during pregnancy. HCQ reduces the risk of preeclampsia with lupus by up to 90%. Several recent studies have investigated whether HCQ improves pregnancy outcomes in women with a history of poor outcomes. In addition, in vitro and animal studies have demonstrated the beneficial effects of HCQ in improving endothelial dysfunction and alleviating hypertension and proteinuria. Therefore, we hypothesized that HCQ has the potential to attenuate the vascular inflammatory and thrombogenic pathways associated with placental insufficiency and conducted a multicenter clinical trial on the efficacy of combining aspirin with HCQ for pregnancies at high risk for preeclampsia in Korea. This study summarizes the potential effects of HCQ on pregnancies with placental insufficiency and the implications of HCQ treatment in the field of obstetrics.

COMORBIDITY AND CAUSE OF DEATH IN THE DIFFERENT VARIANTS OF SARS-COV-2 VIRUS, WITH CONTRIBUTION OF 20 AUTOPSY CASES

Analyzing the clinical and epidemiological data of COVID-19 suggests that specific comorbidities increase the risk of infection leading to worse lung injury and an even higher risk of death. The most common comorbidities reported up till now are hypertension, cardiovascular diseases, and diabetes. Aim to study: The design of the study includes comorbidity of patients and cause of death in alfa, delta, and omicron variants of SARS-CoV-2 virus, histological changes in the lungs, thrombotic complications of coronavirus infection and laboratory tests concerning thrombotic changes. Materials and Methods: We systematically evaluated 20 autopsies of patients deceased by COVID-19 infection. Collecting data was from February 28th, 2020, until June 2022. The cases were diagnosed with a PCR (Polymerase Chain Reaction) test and a rapid antigen test. 10 of the deceased patients were from the first, second, third, and fourth wave (I group) infected predominantly with the alfa and delta variants of coronavirus (from March 2020 until October 2021), and 10 patients infected after that date with predominantly the omicron variant (II group). Results: Most patients were over 50 years of age with multiple co-morbidities (28-88, average 63.9). Post-mortem case studies have shown Arterial hypertension in 80% (I/II gr), 60%/90% of patients with chronic ischemic heart disease, chronic and acute ischemic brain disease in 30%/10%, atherosclerosis, 60%/90%, diabetes mellitus 30%/40%, obesity stage III, 100%/95%). Clinical laboratory studies, in connection with thrombotic complications, revealed the increased value of creatine kinase, fibrinogen, D-dimers, and CRP. Lymphopenia was observed in 60%.All of the cases with COVID-19 viral desquamative pneumonia, at different stages, developed vascular thrombosis in medium-sized pulmonary vessels. Two patients developed pulmonary thromboembolism. We established 5 patients with generalized thrombosis. Three patients were complicated by infarcts in the brain, kidney, and spleen. Conclusion: The autopsies revealed a consistent pattern of pulmonary alveolar damage and generalized vascular/thrombotic disease in patients with frequent co-morbidities. The high frequency of generalized thrombotic complications was observed in predominant alfa and delta variants of the infection, while in the group with the omicron prevailing variant, the lung lesions were dominant, without extrapulmonary thrombotic complications, which we explain by the effective antithrombotic therapy. Major complications in these patients were secondary bacterial infection, sepsis, and respiratory distress syndrome.

The main causes of death in patients with COVID-19.

By March 21, 2022, 6.1 million deaths from COVID-19 were reported, most of them in the United States, Brazil, and India. Between January 1, 2020, and December 31, 2021, the global estimated mortality due to the COVID-19 pandemic was 120.3 deaths (113.1-129.3) per 100,000 of the population for all ages. So far, many of the potentially fatal mechanisms of COVID-19 have been reported. In this manuscript, we analyzed the available data on the causes of deaths from COVID-19. This analysis suggests that the primary attributable cause of death from COVID-19 is multiple organ failure resulting from numerous pathological mechanisms, including genetic predisposition to the severe inflammatory response. Increased inflammatory response affects the lungs locally as well as systemic thrombotic microangiopathy. It seems that many comorbidities associated with an increased mortality rate among patients with COVID-19 per se predispose them to an increased risk of thrombotic changes. Furthermore, the role of inflammation in the lungs and the changes that lead to hypoxia cannot be overlooked. However, the thrombotic changes in microcirculation seem to be the most dominant.

Язвенный колит, наследственная тромбофилия и коронавирусная инфекция как звенья одной цепи: клинический случай коморбидности у девочки 12 лет

We present the clinical case of a 12-year-old girl with acute ulcerative colitis (UC), which was clinically manifested by blood in the stool, and genetic thrombophilia, which in turn was manifested by thrombotic changes in the veins of the left lower limb and clinically we faced with the swelling of the left leg. At the colonoscopy and histological examination of biopsies we established the pathological changes in the mucous membrane of the large intestine, on CT of the abdominal organs with contrast enhancement and ultrasound of the lower extremities found the venous thrombosis. The complexity of this clinical case is due to the difficulty of differential diagnosis of thrombotic complications of UC and hereditary thrombophilia.The main therapy for thrombosis causes a high risk of aggravation of hematological manifestations of UC, which required a long-term selection of suitable therapy that allowed the thrombotic masses to dissolve without gastrointestinal bleeding. The condition of patient was improved significantly against the background of therapy with sulfasalazine and heparin. Key words: genetic thrombophilia, heparin, colonoscopy, sulfasalazine, thrombosis, ulcerative colitis

Abstract 9801: Late Onset Phrenic Nerve Injury Post PPM Placement

Background: Transient phrenic nerve paralysis is a known immediate complication of cardiac implantable electronic device implants. Proposed mechanisms include direct nerve injury during venipuncture, nerve compression from a mediastinal hematoma, or local anesthetic instillation. However, the authors present a rare case of phrenic nerve injury as a late complication of permanent pacemaker (PPM) placement after excluding other etiologies. Case Summary: A 39 year-old female with a history of hypertension and diabetes underwent dual-chamber permanent pacemaker (PPM) placement due to sinus node dysfunction. She presented a year later with a subacute onset of progressive dyspnea on exertion that worsened over the four days prior to admission. Dyspnea was associated with right neck and shoulder pain. Chest radiography at presentation showed elevated right hemidiaphragm. A fluoroscopic sniff test confirmed right hemidiaphragm paralysis. Chest computed tomography revealed no anatomic abnormalities. Magnetic resonance imaging of the cervical spine showed no spinal cord or nerve root lesions. Electromyography confirmed right phrenic nerve injury as the etiology of elevated right hemidiaphragm. She continued to experience exertional dyspnea and orthopnea. Thoracic surgery scheduled the patient for insertion of a diaphragmatic pacemaker. She was discharged pending her surgery. Discussion: Late onset diaphragmatic paralysis due to phrenic nerve injury is a rare complication of PPM insertion. The mechanism of phrenic nerve injury from PPM insertion is unclear. It may result from direct or indirect phrenic nerve micro-injury by the relatively stiff pacemaker leads or peel-away introducers, resulting in slow Wallerian degeneration of the phrenic nerve fibers. In addition, microhematomas, undetected by chest computed tomography, inflammatory or thrombotic changes of the subclavian vein or the superior vena cava may influence the adjacent phrenic nerve.

Pulmonary Vascular Thrombosis in COVID-19: Clinical and Morphological Parallels

Aim. We aimed to study the histological and thrombotic changes in lung vessels in patients who died with COVID-19, to access the correlation between anticoagulation therapy (ACT) and thrombotic events (TE), treatment results, clinical and laboratory patients' characteristics.Material and Methods. We retrospectively analyzed treatment results of patients hospitalized with COVID-19 and lung vessel samples of the deceased patients. Dynamic changes and highest levels of D-dimer and fibrinogen were studied in its correlation with the disease severity according to SOFA score, computer tomographic (CT) results, lung, renal and hepatic dysfunction. The association between different doses of ACT and treatment results, laboratory indicators and thrombotic events was accessed. The histological lung vessels examination was performed using Martius Scarlet Blue (MSB)staining.Results. 313 patients were included in the study (61 patients died). The median age of hospitalized patients was 60 years (IQR 51-66 years). The frequency of the intravitallyconfirmed TE was 4,8%. The strong statistical association was revealed between D-dimer level and 3-4 points SOFA score, patients' mortality, oxygen support requirement, CT3-CT4 pneumonia, glomerular filtration rate and TE. There was no mortality in patients with D-dimer normal references, but in cases with three times elevation reached 13%, 48,5% - in cases with 3-6 times elevation and 64,6% - in cases with more than 6 times elevation. The strong statistical association was registered between fibrinogen and SOFA score, CT 3-4 pneumonia, patients' mortality. D-dimer and fibrinogen levels demonstrated weak correlation. There was no statistical correlation between prophylactic, intermediate and therapeutic ACT and D-dimer and fibrinogen levels, CT results, patients' mortality. MSBstaining was used in 36 deceased patients tissue samples. 1394 lung vessels were analyzed. Lung vessels thrombi persisted in samples of all 36 patients (100%). Vessels with the diameter 3,5-30 mm were thrombosed in 7%, with the diameter 0,034-0,84 mm - in 48%, with the diameter 0,85-3,4 mm - in 45%. The frequency of thrombi persisted 06 hours, 6-12 hours, 12-18hours, 18-24 hours and more than 24 hours was12%, 14%, 62%, 5% and 7% respectively.Conclusion. Thrombi of different ages from fresh to organized were observed in one third of lung vessels in all deceased patients. Lung vessels thrombosis plays an important role in pathogenesis and thanatogenesis of COVID-19. The D-dimer level correlates with lung, renal dysfunction, patients' mortality and doesn't show any correlation with ACT and can be accepted as a criterion of lung vessel thrombotic progression.

Venous injection of a triphasic calcium-based implant in a sheep model of pulmonary embolism demonstrates minimal acute systemic effects

PurposeImplant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage.MethodsSix skeletally mature female sheep were randomly assigned (n = 3) to either the PMMA or the triphasic implant (AGN1, composition: calcium sulfate, β-tricalcium phosphate, brushite) treatment group. Femoral veins of each sheep were directly injected with 0.5 mL of implant material to mimic leakage volumes reported during PMMA vertebroplasty. To compare acute systemic effects of the materials, cardiovascular parameters, laboratory coagulation markers, and calcium and sulfate serum levels were monitored for 60 min after implant injection. Thrombotic and embolic events were evaluated by radiologic imaging, necropsy, and histopathology.ResultsHeart rate, systemic arterial blood pressure, arterial oxygenation, arterial carbon dioxide content, and coagulation markers remained within physiological range after either AGN1 or PMMA injection. No blood flow interruption in the larger pulmonary vessels was observed in either group. Lung histopathology revealed that the severity of thrombotic changes after AGN1 injection was minimal to slight, while changes after PMMA injection were minimal to massive.ConclusionAcute systemic effects of intravascular AGN1 appeared to be comparable to or less than that of intravascular PMMA. Furthermore, in this preliminary study, the severity and incidence of pulmonary histological changes were lower for AGN1 compared to PMMA.

P96 ACUTE CORONARY SYNDROME AND CORONARY ARTERY KINK

Abstract Coronary artery kink is a variant of anomalous coronary artery, not related to vessel disease. Often it is associated with coronary artery tortuosity (CAT) and fibromuscular dysplasia. The pathogenesis and clinical implications are not fully understood. Kinks are hypothesized to cause coronary blood flow alterations that can results in ischemia and even in acute coronary syndrome. It is speculated that coronary artery kinks are most often caused by guide wire straightening and seen after wiring the artery, but that is not always the case. We describe the case of a 55 years old woman, with familiar history of CAD. In 2019 she had percutaneous Patent Foramen Ovale closure intervention. She presented to the Emergency Department complaining chest pain radiating into the neck. The ECG was normal, but Troponin I levels were mildly elevated (2,1 ng/ml) and ipokinesia of basal and mid segment of the anterior intraventricular spetum was found at the ecoscopy. The patient was admitted to Cardiology department with diagnosis of unstable angina and urgent coronary angiography was performed. At a first glance the coronary arteries did not exhibit significant arteriosclerotic or thrombotic changes. However, upon a closer review, a focal kink of the mid left descending coronary artery was found. This coronary kink folded the LAD during systole causing a transient stenosis that resolved during diastole. Management of coronary kinks is controversial. In the past, literature suggested treatment with coronary stenting as one of the management options. However there are reported cases of adverse outcomes, such as shifting of kink proximally, requiring an additional stenting. We decided to treat patient with medical approach: beta–blockers at the tolerated doses was initiated, in addition to ACE–Inibithor, Aspirin and statin. Stenting of the coronary artery was not a choice, due to the possibility of shifting (as described in literature) and stent fracture. At a one month follow up the patient presented asymptomatic for angina, palpitation or dyspnea. Even if rarely coronary artery kink is a potential cause of myocardial ischemia and its treatment is often challenging to improve patient quality of life and to prevent adverse cardiac event.

Non-Traditional Pathways for Platelet Pathophysiology in Diabetes: Implications for Future Therapeutic Targets.

Cardiovascular complications remain the leading cause of morbidity and mortality in individuals with diabetes, driven by interlinked metabolic, inflammatory, and thrombotic changes. Hyperglycaemia, insulin resistance/deficiency, dyslipidaemia, and associated oxidative stress have been linked to abnormal platelet function leading to hyperactivity, and thus increasing vascular thrombotic risk. However, emerging evidence suggests platelets also contribute to low-grade inflammation and additionally possess the ability to interact with circulating immune cells, further driving vascular thrombo-inflammatory pathways. This narrative review highlights the role of platelets in inflammatory and immune processes beyond typical thrombotic effects and the impact these mechanisms have on cardiovascular disease in diabetes. We discuss pathways for platelet-induced inflammation and how platelet reprogramming in diabetes contributes to the high cardiovascular risk that characterises this population. Fully understanding the mechanistic pathways for platelet-induced vascular pathology will allow for the development of more effective management strategies that deal with the causes rather than the consequences of platelet function abnormalities in diabetes.

Utility and diagnostic test properties of pulmonary and cardiovascular point of care ultra-sonography (POCUS) in COVID-19 patients admitted to critical care unit.

BackgroundWe conducted this study to assess the diagnostic test properties of point of care ultrasonography (POCUS) of lung and cardiovascular system in prediction of mortality in COVID-19 patients. MethodsThis is a cross-sectional study of 178 Covid-19 patients; POCUS was performed within one hour of admission to the ICU. We estimated sensitivity, specificity, positive predictive value, negative predictive value for prediction of mortality. ResultsThe mean (SD) age of these patients was 57.3 (12.8) years. The findings were on cardiac ultrasonography were: mild pericardial effusion (45%), chamber dilatation (15%), hypokinesia (11%), and low ejection fraction (8%). In our study, 30 patients (17%) had died. A cut-off score of > to 13 (for lung ultrasound score [LUS]) had high sensitivity for mortality (93.3%, 95% CI: 77.9–99.2%). However, low ejection fraction (92.3%, 95% CI: 86,6–96.1%), and thrombosis in either vein (96.5%, 95% CI: 92.0–98.9%) were specific for mortality. A combination of LUS > =13 or low ejection fraction or thrombosis or spontaneous echo contrast (slow flow) improved sensitivity for mortality to 96.7% (95% CI: 82.8–99.9%). The agreement between LUS of > =13 and CT score of moderate/severe was 85.7% (95% CI: 62.8–100%). The interrater agreement between these two parameters was 0.82 (95% CI: 0.68, 0.97). ConclusionsMulti-organ POCUS is effective in diagnosis, prognosis, and management of COVID-19 patients. Rather than just lung ultrasound, clinicians should use multiorgan POCUS for early identification of severe lung involvement and thrombotic changes; it may help reduce mortality in these patients.

Abstract P260: SARS-Cov-2 Spike Protein S1-Mediated Endothelial Injury And Pro-Inflammatory State Is Amplified By Dihydrotestosterone And Prevented By Mineralocorticoid Antagonism

Objectives: Men are disproportionately affected by the coronavirus disease-2019 (COVID-19) and experience higher mortality as compared to women. Endothelial dysfunction has been proposed as a major inciting factor of pro-inflammatory and thrombotic changes in COVID-19 infection. The vascular effects of androgen signaling and inflammatory cytokines in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated endothelial damage are not defined. Methods: Here, we determined the effects of SARS-CoV-2 spike protein-mediated endothelial damage under conditions of exposure to androgens and TNF-α. We tested the therapeutic effects of approved drugs: angiotensin receptor blockade by valsartan and mineralocorticoid receptor antagonism by spironolactone. Circulating endothelial injury markers VCAM-1 and E-selectin were measured in the plasma from men and women diagnosed with COVID-19. Results: Exposure of endothelial cells (ECs) in vitro to androgen dihydrotestosterone (DHT) exacerbated spike protein S1-mediated endothelial injury transcripts for cell adhesion molecules E-selectin, VCAM-1, and ICAM-1 and anti-fibrinolytic PAI-1 (P<0.05), as well as increased THP-1 monocyte adhesion to ECs (P=0.032). Spironolactone dramatically reduced DHT+S1-induced endothelial activation. Pre-treatment of ECs with valsartan did not increase endothelial activation by S1. TNF-α exacerbated S1-induced EC activation and spironolactone abrogated this effect. Analysis of plasma from patients hospitalized with COVID-19 showed concordant higher VCAM-1 in men as compared to women. Conclusions: Androgen exposure promoted spike protein-mediated endothelial injury by increasing markers of inflammation and thrombosis. A beneficial therapeutic effect of the FDA-approved drug spironolactone was observed, supporting a rationale for further evaluation as an adjunct treatment in COVID-19.

Investigation of the effects of St. John’s wort (Hypericum perforatum) oil on the methotrexate-induced gastrointestinal mucosa injury and hepatotoxicity in mice

St. John's wort oil is one of the herbal product which used for therapeutic purposes. To investigate the effects of St. John's Wort oil on irritated gastrointestinal mucosa and liver. The study is based on experimental animal trials. 21 healthy swiss albino mice were randomly divided into three groups: control group, group-2, group-3. The methotrexate (20 mg/kg) was given intraperitoneally as a single dose on the 1st day to the group-2 and group-3. St. John's Wort oil (4 ml/kg) was administered by gavages into the stomach daily for 7 days to the group-3. Following the necropsy, the gastrointestinal mucosa samples and the liver tissue samples were collected for histopathological evaluation. No pathology was found in the gastrointestinal mucosa and liver of control group. No pathology was found in the mice of group-3 in histopathological examination of the gastric mucosa. Significant hyperplasia and mononuclear cell infiltrations in lamina propria were observed in the mice of the group-2’s intestinal mucosa. The group-3 mice's intestinal mucosa was similar to control group's intestinal mucosa. In liver histopathology, mononuclear cell infiltrations and locally degenerative changes in the periportal area, vascular congestion and sinusoidal enlargement, thrombotic changes in the vessels, bile duct hyperplasia, megalocytosis in hepatocytes in some areas were observed in the livers of group-2 mice. Only a mild sinusoidal enlargement was noted in group-3's liver. According to the data we obtained in our study, St. John's Wort oil has protective and restorative effects especially on liver and intestinal mucosa if it is used consciously.

Evaluation of latest viscoelastic coagulation assays in the transcatheter aortic valve implantation setting

BackgroundPoint of care viscoelastic measures with thromboelastography (TEG; Haemonetics Corporation, Switzerland) and thromboelastometry (ROTEM, Tem Innovations GmbH, Germany) now supersede laboratory assays in the perioperative assessment and management of coagulation....

Assessment Of Factors Of Vascular Wall Damage In Depressive Disorders In Patients With Myocardial Infarction

The study of pathogenetic predictors of the development of anxiety-depressive disorders in myocardial infarction will make it possible to develop ways of their correction, thereby reducing the frequency of complications of the postinfarction period. Clinical studies were based on the examination of 58 patients with MI (mean age 59.2 ± 4.7 years) who were admitted to the cardiological hospital for treatment, and the observation data for them at the stage of rehabilitation. On the basis of the presence of anxiety-depressive symptoms, the patients were divided into 2 groups. The first control group consisted of 14 patients with MI without depressive disorders. The second group included 44 age-matched patients who underwent MI with symptoms of anxiety and depression without comorbid cardiovascular pathology. The diagnosis of myocardial infarction was based on the results of clinical examination, ECG changes, laboratory parameters, and echocardiographic data. In order to assess the mental status of the subjects, subjective methods were used: the hospital anxiety and depression scale (HADS) for patients in a somatic hospital and recommended for use in patients with post-infarction period. Markers of endothelial dysfunction in blood plasma were determined by enzyme immunoassay using appropriate test systems. Since fibrinogen is one of the key factors in the blood coagulation process, disorders of which with a tendency to thrombotic changes are one of the central links in the pathogenesis of MI, the level of oxidized fibrinogen with parameters of the functional state of endothelial cells was studied. In the early stages after myocardial infarction, the level of oxidized fibrinogen was 1.7 times higher in the study group compared to the control, although, in general, the level of fibrinogen in the study group was within normal values. In the subsequent periods of the study, the level of oxidized fibrinogen was in high values and, on average, exceeded the control values by 1.64 times. Since one of the key roles in the development of dysfunction and endothelial destruction is assigned to the factors of oxidative stress, a correlation analysis of the relationship between the oxidative modification of fibrinogen and the parameters of endothelial function was carried out. A direct correlation was shown between the level of oxidized fibrinogen and the level of Endothelin-1 (r = 0.78, p <0.01), and a direct correlation with the level of von Willebrand factor (r = 0.365, p <0.01). Linear regression analysis confirmed the associations of oxidized fibrinogen with the indicated parameters of endothelial dysfunction. Based on the results obtained, it can be emphasized that with MI, in patients with developed DS, along with increased oxidative changes in lipids and plasma proteins, there is also a significant oxidative modification of fibrinogen, which does not depend on the concentration of fibrinogen. Oxidized fibrinogen potentiates potentially prothrombogenic changes in the vascular-platelet link of hemostasis, in particular, the acceleration of leukocyte-platelet aggregation. The revealed signs of thrombotic and hypercoagulant hemostasis disorders in patients with MI with depressive disorders, such as signs of endothelial dysfunction, elevated von Willebrand factor levels, are associated with oxidative changes in plasma fibrinogen in patients with MI with the development of DS, have a high diagnostic value.

Neutrophil-mediated immune response as a possible mechanism of acute unilateral vestibulopathy.

This study aimed to investigate the underlying pathogenesis of acute unilateral vestibulopathy (AUV) using gene expression profiling combined with bioinformatics analysis. Total RNA was extracted from the peripheral blood mononuclear cells of ten AUV patients in the acute phase and from ten controls. The differentially expressed genes (DEGs) between these two groups were screened using microarray analysis with the cut-off criteria (|fold changes| > 1.5 and p-value < 0.05). Functional enrichment analysis of DEGs was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and the protein-protein interaction (PPI) network was constructed using the STRING (Search Tool for the Retrieval of Interacting Genes) database. There were 57 DEGs (50 up-regulated and 7 down-regulated) identified in the AUV group. Functional enrichment analysis showed that most of the up-regulated DEGs were significantly enriched in terms related to the neutrophil-mediated immune pathway. From the PPI network, the top ten hub genes were extracted by calculating four topological properties, and most of them were related to the innate immune system, inflammatory processes and vascular disorders. The complete blood count tests showed that the neutrophil-to-lymphocyte ratio was significantly higher in the 72 AUV patients than in the age-matched controls (2.93±2.25 vs 1.54±0.61, p < 0.001). This study showed that the neutrophil-mediated immune pathway may contribute to the development of AUV by mediating inflammatory and thrombotic changes in the vestibular organ.