scholarly journals The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications

2020 ◽  
Vol 127 (4) ◽  
pp. 571-587 ◽  
Author(s):  
James D. McFadyen ◽  
Hannah Stevens ◽  
Karlheinz Peter
Keyword(s):  
Multiorgan Failure ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Antithrombotic Drugs ◽  
Therapeutic Implications ◽  
Endothelial Cell Surface ◽  
Vein Thrombosis ◽  
Recent Emergence ◽  
Venous Thromboembolic ◽  
Thrombotic Complications

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude. Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke. Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality. The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface. However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke. Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19. Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance. Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects. The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications. The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

scholarly journals Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1548
Author(s):  
Mustafa N. Mithaiwala ◽  
Danielle Santana-Coelho ◽  
Grace A. Porter ◽  
Jason C. O’Connor
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Kynurenine Pathway ◽  
Economic Problem ◽  
Cns Disease ◽  
Therapeutic Implications ◽  
Efficacious Treatment ◽  
The Central Nervous System ◽  
Significant Health

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.

scholarly journals Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (9) ◽  
pp. 1926
Author(s):  
Hiroto Inaba ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Detailed Analysis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Therapeutic Implications

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.

scholarly journals Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 607
Author(s):  
Alice Indini ◽  
Francesco Grossi ◽  
Mario Mandalà ◽  
Daniela Taverna ◽  
Valentina Audrito
Keyword(s):  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Biological Behavior ◽  
Therapeutic Implications ◽  
Systemic Treatments

Malignant melanoma represents the most fatal skin cancer due to its aggressive biological behavior and high metastatic potential. Treatment strategies for advanced disease have dramatically changed over the last years due to the introduction of BRAF/MEK inhibitors and immunotherapy. However, many patients either display primary (i.e., innate) or eventually develop secondary (i.e., acquired) resistance to systemic treatments. Treatment resistance depends on multiple mechanisms driven by a set of rewiring processes, which involve cancer metabolism, epigenetic, gene expression, and interactions within the tumor microenvironment. Prognostic and predictive biomarkers are needed to guide patients’ selection and treatment decisions. Indeed, there are no recognized clinical or biological characteristics that identify which patients will benefit more from available treatments, but several biomarkers have been studied with promising preliminary results. In this review, we will summarize novel tumor metabolic pathways and tumor-host metabolic crosstalk mechanisms leading to melanoma progression and drug resistance, with an overview on their translational potential as novel therapeutic targets.

scholarly journals Recurrence of Upper Extremity Deep Vein Thrombosis Secondary to COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 878
Author(s):  
Yesha H. Parekh ◽  
Nicole J. Altomare ◽  
Erin P. McDonnell ◽  
Martin J. Blaser ◽  
Payal D. Parikh
Keyword(s):  
Deep Vein Thrombosis ◽  
Lower Extremity ◽  
Upper Extremity ◽  
Thromboembolic Events ◽  
Vein Thrombosis ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Deep Vein

Infection with SARS-CoV-2 leading to COVID-19 induces hyperinflammatory and hypercoagulable states, resulting in arterial and venous thromboembolic events. Deep vein thrombosis (DVT) has been well reported in COVID-19 patients. While most DVTs occur in a lower extremity, involvement of the upper extremity is uncommon. In this report, we describe the first reported patient with an upper extremity DVT recurrence secondary to COVID-19 infection.

scholarly journals Higher anticoagulation targets and risk of thrombotic events in severe COVID-19 patients: bi-center cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julie Helms ◽  
◽  
François Severac ◽  
Hamid Merdji ◽  
Maleka Schenck ◽  
...  
Keyword(s):  
Cohort Study ◽  
Mortality Rate ◽  
Bleeding Risk ◽  
Tertiary Hospital ◽  
Biological Data ◽  
Bleeding Complications ◽  
Therapeutic Group ◽  
Vein Thrombosis ◽  
Icu Stay ◽  
Thrombotic Complications

Abstract Background Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected. Results One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14–0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03–0.81]; DVT: 0.13 [0.01–0.89], stroke: 0.06 [0–0.68], all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05). Conclusion Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.

scholarly journals Screening for Cancer in Patients with Acute Venous Thromboembolic Disease

2021 ◽  
Vol 41 (01) ◽  
pp. 042-047
Author(s):  
Marc Blondon
Keyword(s):  
Cancer Screening ◽  
Whole Body ◽  
Care Providers ◽  
Vein Thrombosis ◽  
Risk Assessment Models ◽  
Occult Cancer ◽  
Pet Ct ◽  
Venous Thromboembolic ◽  
Deep Vein ◽  
Active Cancer

AbstractActive cancer causes approximately 25% of all acute events of venous thromboembolism (VTE). While most of the cancer diagnoses are known or clinically apparent at the time of VTE, care providers and patients may be worried about the 3 to 8% risk of occult cancer occurring in the year after VTE. Several studies have compared limited to extensive cancer screening after acute VTE, especially with the addition of abdominal computed tomography (CT) or whole-body PET-CT, with the hope to shorten the time to cancer diagnosis and lead to less advanced cancer stages. These studies have not shown improved clinical outcomes with an extensive screening, and have led to current recommendations of limited screening for cancer in patients with acute VTE, including unprovoked cases. Several risk assessment models have been developed to identify patients at greatest risk of occult cancer, however, with low discriminative performances and no current clinical usefulness. Some clinical situations may empirically deserve a more thorough cancer screening, such as unprovoked upper extremity deep vein thrombosis (DVT), bilateral leg DVT, descending leg DVT, or recurrent VTE during anticoagulation.

scholarly journals Diagnosis, Prevention, Treatment and Surveillance of Anthracycline-Induced Cardiovascular Toxicity in Pediatric Cancer Survivors

Hearts ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 45-60
Author(s):  
Valerie Curren ◽  
Niti Dham ◽  
Christopher Spurney
Keyword(s):  
Pediatric Cancer ◽  
Systolic Function ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Imaging Biomarkers ◽  
Cancer Therapies ◽  
Cardiovascular Toxicity ◽  
Treatment Protocols ◽  
Mechanisms Of Toxicity ◽  
Pediatric Cancer Survivors

Advances in pediatric cancer therapies have dramatically improved the likelihood of survival. As survivors are aging, however, we are now understanding that treatment carries a significant risk of cardiovascular toxicity, which can develop immediately, or even many years after completing therapy. Anthracycline derivates are some of the most commonly used agents in pediatric oncology treatment protocols, which have a dose-dependent correlation with the development of cardiac toxicity. As we learn more about the mechanisms of toxicity, we are developing prevention strategies, including improvements in surveillance, to improve early diagnosis of heart disease. Current survivorship surveillance protocols often include screening echocardiograms to evaluate systolic function by measuring the ejection fraction or fractional shortening. However, these measurements alone are not enough to capture early myocardial changes. The use of additional imaging biomarkers, serum biomarkers, electrocardiograms, as well as cholesterol and blood pressure screening, are key to the early detection of cardiomyopathy and cardiovascular disease. Medical treatment strategies are the same as those used for heart failure from other causes, but earlier recognition and implementation can lead to improved long term outcomes.

scholarly journals Factors predictive of venous thrombotic complications in patients with isolated superficial vein thrombosis

2003 ◽  
Vol 38 (5) ◽  
pp. 944-949 ◽  
Author(s):  
Sara Quenet ◽  
Silvy Laporte ◽  
Hervé Décousus ◽  
Alain Leizorovicz ◽  
Magali Epinat ◽  
...  
Keyword(s):  
Superficial Vein ◽  
Vein Thrombosis ◽  
Superficial Vein Thrombosis ◽  
Thrombotic Complications

Dextran and postoperative thromboembolism

1975 ◽  
Vol 13 (11) ◽  
pp. 41-43
Keyword(s):  
Platelet Aggregation ◽  
Coagulation Factors ◽  
Venous Thromboembolic Disease ◽  
Vein Thrombosis ◽  
Dextran 70 ◽  
Lower Blood ◽  
Venous Thromboembolic ◽  
Reduce Platelet Aggregation ◽  
Increase Platelet Aggregation ◽  
Deep Vein

Two preparations of dextran have been tried for prevention of venous thromboembolic disease, dextran-40 (average m. w. 40,000) and dextran-70 (average m.w. 70,000). Dextrans reduce platelet aggregation and lower blood viscosity.1 Dextran may also reduce the peri-operative rise in the coagulation factors V and VIII.2 However, in some tests dextrans increase platelet aggregation3 and accelerate fibrin formation,4 so that only clinical trial can show whether dextran reduces the incidence of either deep-vein thrombosis or of pulmonary embolism.

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