Vessel Thrombosis Research Articles

Plasma Fibrinogen Change as a Predictor of Major Bleeding During Catheter-Directed Thrombolysis

Our primary objective was to determine the relationship between plasma fibrinogen levels (PFLs) and major bleeding complications during catheter-directed thrombolysis, including final, nadir, and change over time. Furthermore, we sought to evaluate additional predictors of bleeding outcomes, including duration of lysis and total dose of tissue plasminogen activator received. In this multicenter retrospective cohort study, we reviewed all patients undergoing catheter-directed thrombolysis between January 2016 and August 2021. Patients undergoing thrombolysis for management of peripheral arterial or venous thromboses, as well as for submassive pulmonary embolism, were included. We examined the relationships between PFLs during catheter-directed lysis and the incidence of major bleeding-that is significant hemorrhage requiring transfusion, intracranial hemorrhage, or hemorrhage requiring adjunctive procedures. We also examined the duration of lysis and total lytic agent dose received to assess for association with major bleeding. A total of 438 patients underwent catheter-directed lysis from January 1, 2016 through August 21, 2021, with a major bleeding rate of 16%. Patients who experienced major bleeding were more likely to be older (P=0.022), experience in-stent thrombosis (P=0.041), or have thrombosis in a lower extremity vessel (P=0.011). There was no association between the incidence of major bleeding and a nadir PFL of <150mg/dL (P=0.194). Those who experienced major bleeding complications had a significantly greater decrease in PFL from baseline to nadir. This was true for both absolute (P=0.029) and relative (P=0.034) PFL decrease. Only percent decrease remained a significant predictor when adjusting for age, thrombosis type, and thrombosis location (P=0.041). The PFL changes that were the best predictors of major bleeding complications were an absolute decrease of 146mg/dL, or a relative decrease of 47%, giving a sensitivity and specificity of 71% and 48%, respectively. If neither were true, the negative predictive value for major bleeding was 89% regardless of absolute PFL. In this large, multicenter cohort, there does not appear to be an association between absolute PFL and major bleeding during catheter-directed lysis. Specifically, the typical absolute threshold of < 150mg/dL was not an independent predictor of major bleeding. There was an association between percent-change in plasma fibrinogen and major bleeding, which aligns with the underlying physiologic mechanism of fibrinogen degradation coagulopathy. Applying a so-called "50-150 Rule" to catheter-directed lysis may decrease bleeding complications. That is, continued lysis should be re-evaluated if PFL drops by≥150mg/dL or by≥50% from baseline regardless of absolute PFL.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis.

Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Quantitative and Qualitative Characteristics of Atherosclerotic Plaques on Carotid Arteries in Patients with Antiphospholipid Syndrome: The Role of MDCT Angiography.

Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterious and venous thrombosis, miscarriage, and the presence of antiphospholipid antibodies (aPL) in the blood. As we know, APS is also characterised by accelerated atherosclerotic degeneration with an increased risk of thrombosis in all blood vessels, including the carotid arteries. Carotid artery stenosis can manifest in many different ways. The aim of this study is to present the results of our multidetector computerised tomography angiography (MDCTA) analysis of the carotid arteries in patients with primary and secondary APS compared with a control group. This study examined 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with secondary antiphospholipid syndrome (SAPS). The results were compared with a control group also comprising 50 patients. The groups were analysed with respect to age, sex and the presence of well-established risk factors for vascular disease. The study was conducted using MDCTA, where we analysed the quantitative and qualitative (morphologic) characteristics of carotid artery lesions. Patients from the control group had significantly elevated levels of cholesterol and triglycerides in comparison with patients with PAPS and SAPS (p < 0.001 and p < 0.05). The results show that carotid artery lesions were significantly more common in patients with APS (PAPS, n = 40, CI95: 0.50-0.75, p = 0.0322 and SAFS, n = 54, CI95: 0.59-0.80, p = 0.0004) than within the control group (n = 23). There was a statistically significant difference between patients with APS and the control group with respect to lesions in the distal segments (n = 27, CI95: 0.67-0.95, p = 0.0001), bulbi and proximal segments (n = 21, CI95: 0.84-1.00, p = 0.000005). The number of patients with one lesion (L) (n = 27) was significantly greater than the number of those with three (n = 10, CI95: 0.56-0.86, p = 0.0051) or four (n = 3, CI95: 0.73-0.98, p = 0.00001) lesions. There were also more patients with two lesions (n = 24) than those with four (n = 3) (CI95: 0.71-0.97, p = 0.00005). Carotid artery stenosis was shown as a percentage of the carotid artery lumen diameter (%DS). Stenosis of up to 30%, was more common in patients in the PAPS group (n = 12) than in the control group (n = 3) (CI95: 0.52-0.96, p = 0.0201), while the SAPS group (n = 17) had an even larger disparity (CI95: 0.62-0.97, p = 0.0017). We observed a highly significant difference in the frequency of stenoses between 30% and 50% DS between the PAPS group (n = 24) and the control group (n = 7) (CI95: 0.59-0.90, p = 0.0023), as well as the SAPS group (n = 30) (CI95: 0.65-0.92, p = 0.0002). A qualitative analysis of plaque morphology revealed that patients with PAPS had significantly more soft tissue lesions (n = 23) compared with calcified lesions (n = 2) (CI95: 0.74-0.99, p = 0.00003), as well as more mixed plaques (n = 9) and calcified plaques (n = 2) (CI95: 0.48-0.98, p = 0.0348). Patients within the SAPS group had significantly more soft tissue (n = 35) than calcified lesions (n = 3) (CI95: 0.79-0.98, p = 0.00000021), as well as more mixed lesions (n = 21) compared with calcified (n = 3) (CI95: 0.68-0.97, p = 0.0002). Our study shows that subclinical manifestations of carotid artery lesions were more common in patients with APS. We came to the conclusion that MDCTA is an accurate diagnostic method because it is a safe method that provides us with a great quantity of accurate information about the characteristics of atheromatous plaques, which aids us in the further planning of treatment for patients with APS.

The problem of inpatient thrombosis of coronary arteries in patients with COVID-19 on the background of intensive antithrombotic therapy

Myocardial infarction claims million lives on the planet each year. Pharmacotherapy in combination with percutaneous coronary interventions have significantly reduced morbidity and mortality in this cohort. Despite optimal therapy and prophylaxis, there is a group of patients with recurrent, often fatal, coronary thromboses. During the COVID-19 pandemic, some patients developed episodes of thrombosis in blood vessels of various organs, including brain, heart or lungs, even on therapeutic anticoagulation. The patient was admitted to the department of cardiology and reperfusion therapy, with a confirmed diagnosis of COVID-19 resulted in acute ST-segment elevation myocardial infarction. Patient underwent urgent coronary angiography with thromboaspiration and stenting of the infarct-dependent right coronary artery followed by optimal medical treatment with the use of triple antithrombotic therapy. His condition became stable with the resolution of ST-segment elevation on electrocardiogram. A few days later, the condition of the patient deteriorated again with recurrent of chest pain and a new ST segment elevation. Repeated coronary angiography revealed recurrent thrombosis in the right coronary artery. The mechanisms of thrombosis in COVID-19 are not fully understood. Among possible, the direct effect of the virus on tissues, activation of pro-inflammatory system and coagulation system, impaired vasodilation, and decreased fibrinolytic activity are discussed. These mechanisms may lead to vascular thrombosis in different organs, particularly heart, lungs, and brain.

An analytical method informed by clinical imaging data for estimating outlet boundary conditions in computational fluid dynamics analysis of carotid artery blood flow

Stroke occur mainly due to arterial thrombosis and rupture of cerebral blood vessels. Previous studies showed that blood flow-induced wall shear stress is an essential bio marker for estimating atherogenesis. It is a common practice to use computational fluid dynamics (CFD) simulations to calculate wall shear stress and to quantify blood flow. Reliability of predicted CFD results greatly depends on the accuracy of applied boundary conditions. Previously, the boundary conditions were estimated by varying values so that they matched the clinical data. It is applicable upon the availability of clinical data. Meanwhile, in most cases all that can be accessed are arterial geometry and inflow rate. Consequently, there is a need to devise a tool to estimate boundary values such as resistance and compliance of arteries. This study proposes an analytical framework to estimate the boundary conditions for a carotid artery based on the geometries of the downstream arteries available from clinical images.

Intratumoral thrombosis as a histological biomarker for predicting epidermal growth factor receptor alteration and poor prognosis in patients with glioblastomas.

Intratumoral thrombosis is a specific finding in glioblastomas and considered the origin of palisading necrosis. Its distribution and contribution to the glioblastoma pathophysiology and systemic thrombosis are obscure, although deep vein thrombosis is a common complication in glioblastoma cases. Clinicopathological and genetic analyses were performed on 97 glioblastoma tissue specimens to elucidate the role of thrombotic events and associated molecular abnormalities. Morphologically, intratumoral thrombosis was observed more frequently in vessels composed of single-layered CD34-positive endothelium and/or αSMA-positive pericytes in the tumor periphery, compared to microvascular proliferation with multi-channeled and pericyte-proliferating vessels in the tumor center. Intratumoral thrombosis was significantly correlated with the female sex, high preoperative D-dimer levels, and epidermal growth factor receptor (EGFR) amplification. The presence of one or more thrombi in 20 high-power fields was a predictive marker of EGFR amplification, with a sensitivity of 81.5% and specificity of 52.6%. RNA sequencing demonstrated that the group with many thrombi had higher EGFR gene expression levels than the group with few thrombi. The tumor cells invading along the vessels in the tumor periphery were positive for wild-type EGFR but negative for EGFRvIII, whereas the cells around the microvascular proliferation (MVP) in the tumor center were positive for both wild-type EGFR and EGFRvIII. Intratumoral thrombosis is an independent poor prognostic factor. Aberrant but exquisitely regulated EGFR can induce thrombosis in non-MVP vessels in the tumor invasion area and then promote palisading necrosis, followed by hypoxia, abnormal angiogenesis, and further tumor cell invasion.

Necrotizing Raynaud's phenomenon after recurrent COVID-19 infection

Raynaud's phenomenon (RP), which can be primary or secondary, is a common vascular clinical syndrome due to abnormal arteriolar vasospasm. Its treatment is most often conservative depending on the etiology. In recent years, there have been reports of RP as a syndrome after a previous SARS-CoV-2 infection, in patients of different genders and ages. As an etiological factor for the development of vascular pathology in these cases, two main mechanisms are assumed: an autoimmune process or the thrombosis of arterial vessels, leading to tissue ischemia, and the so-called necrotizing Raynaud's phenomenon. In the pathogenesis of Raynaud's phenomenon, the influence of local, neuronal and hormonal mediators is emphasized. Some studies prove the role of estrogens, which explains the higher incidence of RP among women. At present, there is no convincing evidence for "candidate genes" to be associated with Raynaud's phenomenon, despite studies by some authors (Susol et al., 2000; Pistorius et al., 2006). Vasospasm in digital ischemia may be further complicated by COVID-19 infection. Another potential component is hypercoagulation (further complicated by the presence of antiphospholipid antibodies in certain patients) and elevated levels of D-dimer. A state of hypercoagulation is caused by the so-called cytokine storm. This inflammatory state, as a result of endovascular damage, increased platelet activity and coagulation cascade, causes the so-called phenomenon of immunothrombosis. Overactivation of the coagulation pathway during cytokine storm results from increased activity of thrombin, which has an additional role in the inflammatory process through proteinase-activated receptors (PARs). Acrocyanosis due to excessive coagulation status has been described in critically ill patients with COVID-19. In these patients, gangrene may arise from impaired blood flow and insufficient healing of digital wounds, which is associated with elevated levels of C-reactive protein (CRP). Ischemic limb lesions, usually seen in older patients with severe clinical course of the disease, represent a dangerous, although rare, complication associated with COVID-19 and are due to arterial occlusions. They are extremely difficult to treat and often lead to amputations. In patients with antiphospholipid syndrome, arterial and venous thrombi are primarily caused by the formation of neutrophil extracellular traps (NET), which in turn activate platelets, and their excessive formation can lead to local thrombosis. In addition to platelet activation, neutrophils release tissue factor, which initiates the coagulation cascade. NETs bind coagulation factor XII and activate it, and also induce an inflammatory reaction in the vessel wall. According to the available knowledge to date, the hypothesis that digital necrosis in patients with COVID-19 is primarily related to the formation of NETs has been developed.&#x0D; Necrotizing Raynaud's phenomenon (NRP) is a vascular clinical syndrome characterized by vasoconstriction of distal resistance vessels following low temperatures or states of anxiety and stress. The first symptom is pain, due to lack of oxygen, which leads to tissue ischemia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause endotheliopathy with microvascular and macrovascular thrombotic events. COVID-19 induces hypercoagulation, thrombosis, endothelial damage, and inflammation leading to vasculitis. The coagulopathy, inflammation, and thrombosis seen in COVID-19 are potentiated by increased activity of clotting factors, loss of protective glycocalyx function, and decreased nitric oxide levels. The effects of COVID-19 in patients with RP are still being elucidated.&#x0D; This review presents a series of selected clinical cases associated with Raynaud's phenomenon (necrotic, new-onset, exacerbated, or as part of another systemic connective tissue disease) secondary to past COVID-19 infection or vaccination.&#x0D;

The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor

AbstractCardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown to limit platelet reactivity by activating the prostacyclin receptor. Here, we demonstrated the synthesis of a novel analog of 12-HETrE, known as CS585. Human blood and mouse models of hemostasis and thrombosis were assessed for the ability of CS585 to attenuate platelet activation and thrombosis without increasing the risk of bleeding. Human platelet activation was assessed using aggregometry, flow cytometry, western blot analysis, total thrombus formation analysis system, microfluidic perfusion chamber, and thromboelastography. Hemostasis, thrombosis, and bleeding assays were performed in mice. CS585 was shown to potently target the prostacyclin receptor on the human platelet, resulting in a highly selective and effective mechanism for the prevention of platelet activation. Furthermore, CS585 was shown to inhibit platelet function in human whole blood ex vivo, prevent thrombosis in both small and large vessels in mouse models, and exhibit long-lasting prevention of clot formation. Finally, CS585 was not observed to perturb coagulation or increase the risk of bleeding in the mouse model. Hence, CS585 represents a new validated target for the treatment of thrombotic diseases without the risk of bleeding or off-target activation observed with other prostaglandin receptor agonists.

A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies.

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services.

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.

Antiphospholipid Syndrome: State of the Art of Clinical Management.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder clinically characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. Currently, treatment is mainly focused on anticoagulation, but therapies targeting mechanisms involved in APS autoimmune pathogenesis could play an important role in specific settings. An evidence-based therapeutic approach is limited by the broad clinical spectrum of the syndrome and the nature of a "rare disease" that makes it difficult to carry out well-designed prospective studies. Vitamin K antagonists (AVK), notably warfarin, are the standard treatment for preventing recurrent venous thrombosis and perhaps also arterial thrombosis. Direct oral anticoagulants (DOACs) are not recommended at least in patients with triple positivity APS. Treatment options for the prevention of pregnancy complications in obstetric APS, as combined use of aspirin and heparin, low-dose prednisolone, hydroxychloroquine, intravenous immunoglobulin (IVIG), may improve pregnancy outcome. The catastrophic antiphospholipid syndrome (CAPS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. Glucocorticoids, heparin, plasma exchange or IVIG, rituximab, or eculizumab must be added to concurrent treatment of precipitating factors (e.g. infections) as rescue therapies. Finally, it has been observed that SARS COV2 infection may produce vascular complications mimicking the clinical and pathophysiological features of APS and particularly of CAPS. From this point of view, attention has been focused on the "protective" role of anticoagulant therapy in preventing thrombotic complication when these clinical conditions coexist.

Incidence, mechanisms, treatment, and outcomes of donor vessel injury during percutaneous coronary interventions for chronic total occlusion.

Donor vessel injury is a potentially life-threatening complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Our goal was to examine the incidence, mechanisms, treatment, and outcomes of patients with donor vessel injury in a large multicenter CTO PCI registry. We analyzed the baseline clinical and angiographic characteristics, and procedural outcomes of 12,349 CTO PCIs performed between 2012 and 2022 at 44 centers. The incidence of donor vessel injury was 0.35% (n = 43). The baseline clinical characteristics of patients with and without donor vessel injury were similar. Cases complicated by donor vessel injury were more complex with higher Japanese CTO score (2.9 ± 1.1 vs. 2.4 ± 1.3; p = 0.004) and lower procedural success rate (69.8% vs. 85.2%; p = 0.004). The retrograde approach was used more commonly in donor vessel injury cases (68.9% vs. 30.9%; p < 0.001). Most (53.5%) donor vessel injuries were guide catheter-induced, whereas 20.9% were due to donor vessel thrombosis. Of the 43 patients with donor vessel injury, 36 (83.7%) were treated with stenting and seven (16.3%) received a left ventricular assist device. The incidence of major adverse cardiovascular events (MACEs) was significantly higher in cases with donor vessel injury (23.3% vs. 2.0%; p < 0.001). Of the 43 patients with donor vessel injury, five patients (11.6%) experienced acute myocardial infarction and four patients (9.3%) died. Donor vessel injury, occurred in 0.35% of CTO PCIs performed by experienced operators, was mainly due to guide catheter-induced dissection or thrombosis and was associated with lower procedural success and higher MACE.

Abstract P2082: Thrombosis In The Coronary Microvasculature May Be Responsible For Impaired Cardiac Relaxation And Diastolic Dysfunction

Introduction: Heart Failure with Preserved Ejection Fraction (HFpEF) is proposed to be caused by endothelial dysfunction in cardiac small vessels. We previously identified Hhipl1,as a gene upregulated in the coronary vasculature of Leptin receptor deficient mice (Leprdb/db) a well-established mouse model of HFpEF. Importantly, Hhipl1 encodes for a decoy receptor of Desert Hedgehog (DHH) which is known to be critical for endothelial integrity. Objective: Our objective is to investigate the functional consequences of impaired Hedgehog (HH) signaling in the adult heart in order to identify novel mechanisms underlying the development of diastolic dysfunction. Method: Cdh5-Cre/ERT2, DhhFlox/Flox (DhhECKO) mice and their control littermates were administered with tamoxifen at 8 weeks of age to induce Dhh KO. Their cardiac function, exercise tolerance, and the phenotype of their coronary vasculature were assessed one month later. Results: DhhECKO mice presented significantly reduced exercise tolerance, increased end diastolic pressure (EDP) and Tau, with no change in their ejection fraction consistent with diastolic dysfunction. At molecular and cellular level, impaired cardiac relaxation in DhhECKO mice was associated with a significantly decreased phospholamban phosphorylation on Thr17 and an alteration of sarcomeric shortening in ex-vivo. Besides, as expected, DhhECKO mice exhibited phenotypic changes in their coronary vasculature including a prominent pro-thrombotic phenotype leading to an impaired capillary perfusion and local hypoxia. Notably, antiaggregant therapies (aspirin and clopidogrel) prevented the occurrence of both diastolic dysfunction and exercise intolerance in DhhECKO mice demonstrating for the first time that thrombosis may promote diastolic dysfunction. Importantly, we confirmed the critical role of thrombosis in Leprdb/db mice which also displayed increased cardiac small vessel thrombosis in comparison to control mice. Alike DhhECKO mice, we found that antiaggregants decreased EDP and improved exercise tolerance in Leprdb/db mice. Conclusion: Altogether, these results demonstrate that small vessel thrombosis may participate in the pathophysiology of heart failure with preserved ejection fraction.

Exponential Rise of Fungal Infection Reported in Rajkot Civil Hospital in Covid Pandemic Era: A Retrospective Study.

Mucormycosis is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes. Mucormycosis is an aggressive, life-threatening infection requiring prompt diagnosis and early treatment. Wide spread use of steroid and higher antibiotics may cause immune irregulation in post covid patients. A hallmark of mucormycosis infection is the presence of extensive angioinvasion with resultant vessel thrombosis and tissue necrosis. We reported exponential rising cases of fungal infection in covid pandemic era. Here we published epidemiological data of 773 fungal infected cases operated in ENT department of PDU Medical college, Rajkot in 2021. We have documented patients demographic data with comorbidity, paranasal sinuses with orbital, palatal and cerebral involvement, evaluation method, surgical and post surgical management protocol which we followed in our institute to treat all cases. We got promising result in terms of survival and less morbidity. Early presentation, less comorbidity, proper evaluation and immediate debridement with systemic antifungal coverage for adequate duration proved to be mainstay treatment of fungal infection in covid pandemic era.

AN INFLUENCE OF ACUTE CORONAVIRUS DISEASE ON HEPATIC TISSUE (LITERATURE REVIEW)

Nowadays we have a great number of patients who have suffered from acute coronavirus disease. More than 687 million people at least once had the positive COVID-test. Moreover, more than 27 thousand people are suffering from this disease in Ukraine now. SARS-CoV-2 virus can damage various organs and systems, primarily the respiratory system that will manifest in a dry cough, shortness of breath, general weakness, up to the development of acute respiratory distress syndrome, shock and acute heart failure. The damage of lover by SARS-CoV-2 virus can be both direct and indirect. The presence of liver damage often leads to a more severe course of acute coronavirus disease. In order to treat new cases more effectively and deal with complications of old ones it is necessary to study better the mechanisms of the viral effect on various organs, in particular the liver. The best way to find out this mechanism is to examine main laboratory and instrumental indicators, learn about the changes in histological sections.&#x0D; Aim. The aim of the research was to investigate the results of up-to-date researches of the main changes in laboratory and instrumental indicators because of acute coronavirus disease, as well as possible mechanisms of liver damage.&#x0D; Materials and methods. Analysis of open publications of Scopus, Web of Science, PubMed for the last 10 years.&#x0D; The results. In patients with acute coronavirus disease an increase in the levels of transaminases (in most cases due to alanine aminotransferase), lactate dehydrogenase, bilirubin, prolongation of prothrombin time, an increase in the level of D-dimer, and a decrease in the number of platelets and albumins were often observed. Histological examination of biopsies revealed diffuse lung damage, significant desquamation of pneumocytes and hyaline membranes, extensive interstitial fibrosis with areas of fibrinous exudation and inflammation in the alveolar space. Hepatocyte apoptosis, moderate microvascular and minor macrovascular steatosis were observed in the hepatic tissue. Thus, we can suppose that the possible mechanisms of liver damage are direct virus damage, immunomodulated inflammation, hypercoagulative processes, hepatic hypoxia, drug-induced damage. Virus SARS-CoV-2 can get into the cell using angiotensin-converting enzyme 2 receptors. Direct virus influence can be possible because of high quantity of ACE2 receptors in bile-ducts and hepatocytes. Great amount of them is also present in vascular endothelium. As a result of apoptosis of COVID- infected cells a great amount of cytokines is released. This can lead to immunomodulated damage of different organs including liver. Moreover, inflammation leads to hypercoagulable state that in future can cause hypoxia of hepatic tissue because of thrombosis of liver vessels. Cytokine storm that developed in patients with severe COVID-19 pneumonia can lead to the destruction of tissues in the center of inflammation. The large number of cytokines that are released can increase vascular permeability that leads to dyspnea and respiratory failure because of blood and fluid migration. Researches showed us that some of the drugs that are uses as a treatment for COVID-19 may cause drug-induced damage of liver. Remdesivir is known to increase hepatic enzymes, reducing the level of albumin and increasing the level of bilirubin. LPV/r caused side effects more often than other drugs.&#x0D; Conclusions. As a result of the research the main symptoms, clinical and instrumental changes typical for acute coronavirus infection, possible mechanisms of liver damage because of this disease were revealed. However, we don’t have enough information to prescribe a pathogenetically justified treatment so the further investigation is needed.

Median artery persistence in coexistence with a bifid median nerve and interconnections of the median with the ulnar nerve and vice versa

PurposeThis report describes a bilateral persistent median artery (PMA) originating from the ulnar artery and terminating at different levels of the upper limb. The PMA coexisted with a bilateral bifid median nerve (MN) and two bilateral interconnections (ICs characterized with the symbol -) of the MN with the ulnar nerve (UN) (MN-UN) and a unilateral reverse IC (UN-MN). Emphasis was given to the artery’s developmental background.MethodsThe PMA was identified in an 80-year-old formalin-embalmed donated male cadaver.ResultsThe right-sided PMA terminated at the wrist, posterior to the palmar aponeurosis. Two neural ICs were identified: the UN joined the MN deep branch (UN-MN), at the forearm’s upper third, and the MN deep stem joined the UN palmar branch (MN-UN), at the lower third (9.7 cm distally to the 1st IC). The left-sided PMA ended in the palm giving off the 3rd and 4th proper palmar digital arteries. An incomplete superficial palmar arch was identified by the contribution of the PMA, radial, and ulnar arteries. After the MN bifurcation into superficial and deep branches, the deep branches formed a loop, that was penetrated by the PMA. The MN deep branch communicated with the UN palmar branch (MN-UN).ConclusionsThe PMA should be evaluated as a causative factor of carpal tunnel syndrome. The modified Allen's test and the Doppler ultrasound may detect the arterial flow and the angiography may depict the vessel thrombosis in complex cases. PMA could also be a "salvage" vessel for the hand supply, in radial and ulnar artery trauma.

Attenuating Chronic Fibrosis: Decreasing Foreign Body Response with Acellular Dermal Matrix.

Surgical implants are increasingly used across multiple medical disciplines, with applications ranging from tissue reconstruction to improving compromised organ and limb function. Despite their significant potential for improving health and quality of life, biomaterial implant function is severely limited by the body's immune response to its presence: this is known as the foreign body response (FBR) and is characterized by chronic inflammation and fibrotic capsule formation. This response can result in life-threatening sequelae such as implant malfunction, superimposed infection, and associated vessel thrombosis, in addition to soft tissue disfigurement. Patients may require frequent medical visits, as well as repeated invasive procedures, increasing the burden on an already strained health care system. Currently, the FBR and the cells and molecular mechanisms that mediate it are poorly understood. With applications across a wide array of surgical specialties, acellular dermal matrix (ADM) has emerged as a potential solution to the fibrotic reaction seen with FBR. Although the mechanisms by which ADM decreases chronic fibrosis remain to be clearly characterized, animal studies across diverse surgical models point to its biomimetic properties that facilitate decreased periprosthetic inflammation and improved host cell incorporation. Impact Statement Foreign body response (FBR) is a significant limitation to the use of implantable biomaterials. Acellular dermal matrix (ADM) has been observed to decrease the fibrotic reaction seen with FBR, although its mechanistic details are poorly understood. This review is dedicated to summarizing the primary literature on the biology of FBR in the context of ADM use, using surgical models in breast reconstruction, abdominal and chest wall repair, and pelvic reconstruction. This article will provide readers with an overarching review of shared mechanisms for ADM across multiple surgical models and diverse anatomical applications.

Possible Kidney Complications after Application of Cell Technologies for the Repair of the Resected Liver.

The state of rat kidneys after injection of bone marrow multipotent stromal cells (MSC) labeled with Vybrant CM-Dil into intact or resected liver was studied by fluorescence microscopy. The main structural changes in the kidneys after MSC injection into intact and partially resected liver manifested as granular dystrophy and necrobiotic/necrotic changes in single epithelial cells of the distal tubules and collecting ducts, thrombosis of some vessels, progression of an ascending urinary tract infection (detection of dust-like fluorescent objects), which can be due to the immunomodulating or even immunosuppressive influence of MSC and their detritus. MSC injected into the intact or resected liver, as well as the products of their degradation were not detected in the kidneys at all terms of observation. After injection of MSC into partially resected liver, manifestations of bacterial contamination of the renal medulla appeared later. The injection of MSC into the liver can be complicated by thrombosis of the renal vessels, which should be taken into account when using this administration route in the cell therapy.

Thrombosis in the coronary microvasculature may be responsible for impaired cardiac relaxation and diastolic dysfunction

Heart failure with preserved ejection fraction (HFpEF) is proposed to be caused by endothelial dysfunction in cardiac small vessels. We previously identified Hhipl1, as a gene upregulated in the coronary vasculature of Leptin receptor deficient mice (Leprdb/db) a well-established mouse model of HFpEF. Importantly, Hhipl1 encodes for a decoy receptor of Desert Hedgehog (DHH) which is known to be critical for endothelial integrity. Our objective is to investigate the functional consequences of impaired Hedgehog (HH) signaling in the adult heart in order to identify novel mechanisms underlying the development of diastolic dysfunction. To do so, Cdh5-Cre/ERT2, DhhFlox/Flox (DhhECKO) mice and their control littermates were administered with tamoxifen at 8 weeks of age to induce Dhh KO. Their cardiac function, exercise tolerance, and the phenotype of their coronary vasculature were assessed one month later. DhhECKO mice presented significantly reduced exercise tolerance, increased end-diastolic pressure (EDP) and Tau, with no change in their ejection fraction consistent with diastolic dysfunction. At molecular and cellular level, impaired cardiac relaxation in DhhECKO mice was associated with a significantly decreased phospholamban phosphorylation on Thr17 and an alteration of sarcomeric shortening in ex-vivo. Besides, as expected, DhhECKO mice exhibited phenotypic changes in their coronary vasculature including a prominent pro-thrombotic phenotype (63 ± 6.2 vs. 25 ± 5.2 thrombi/mm2; P < 0.001) leading to an impaired capillary perfusion and local hypoxia. Notably, antiaggregant therapies (aspirin and clopidogrel) prevented the occurrence of both diastolic dysfunction and exercise intolerance in DhhECKO mice demonstrating for the first time that thrombosis may promote diastolic dysfunction. Importantly, we confirmed the critical role of thrombosis in Leprdb/db mice which also displayed increased cardiac small vessel thrombosis in comparison to control mice. Alike DhhECKO mice, we found that antiaggregants decreased EDP (6.3 ± 0.4 mmHg in aspirin-treated vs. 11.3 ± 0.79 in control mice; P = 0.001) and improved exercise tolerance in Leprdb/db mice (34 ± 2.52 min in aspirin-treated vs. 24 ± 3.55 in control mice; P = 0.004). Altogether, these results demonstrate that small vessel thrombosis may participate in the pathophysiology of heart failure with preserved ejection fraction.

Head and neck venous thrombosis secondary to pediatric otolaryngologic infection.

Head and neck venous thrombosis is a rare but potentially devastating complication of childhood otolaryngologic infections. This study examines the presentation and management of this condition. A retrospective chart review was performed on all pediatric patients with otolaryngologic infections complicated by cranial and cervical venous thrombosis at a tertiary children's hospital from 2007 to 2018. Patient demographics, presentation, site of infection, thrombosis location, implicated pathogen, length of hospital stay, need for surgery, and anticoagulant regimen were assessed. This study included 33 patients (mean age, 7.5 years; age range, 0.8-17 years; 19 [58%] male). The most common infection source was otologic (n=20), followed by ophthalmic and sinonasal pathology (n=9), and neck infections (n=4). The most common site of thrombosis secondary to ear pathology was the sigmoid sinus. The ophthalmic veins were the most common site of thrombosis for ophthalmic/sinonasal infections. Nine CN VI palsies, one CN VII palsy, and one CN III palsy were observed. Twenty-six subjects (79%) required surgical intervention. All those who experienced a nerve palsy required surgery. Length of hospitalization significantly differed with the stay for a neck infection complicated by thrombosis longer compared to otologic and sinonasal infections (F[2,30]=7.08, p=0.003). Length of hospital stay was significantly correlated with admission temperature (r=0.506, p=0.003) and CRP (r=0.400, p=0.03) but not WBC (r=0.181, p=0.31). Culture growth predominantly isolated a single causative organism rather than polymicrobial involvement. Forty-eight species were identified, most (n=41/48, 85%) being Gram-positive bacteria. Alpha-hemolytic Streptococcus was the most common isolate from children with vessel thrombosis secondary to ear infections, with Streptococcus pyogenes predominant in sinonasal infections and Staphylococcus aureus the most common in neck abscesses. There was significant variability in anticoagulation management within the patient population, but no bleeding complications were documented. Most patients had no evidence of underlying thrombophilia (n=15); for those with positive hypercoagulability screens, the most common positive marker was the presence of lupus inhibitor (n=6). Venous thrombosis resulting from adjacent otolaryngologic infection is a serious complication requiring proper recognition and management. The involved vasculature and cranial nerve findings are dependent on the anatomic location of the underlying infection. Cranial neuropathies in the presence of these infections should prompt evaluation for possible thrombosis.