scholarly journals The Potential Role of Coagulation Factor Xa in the Pathophysiology of COVID-19: A Role for Anticoagulants as Multimodal Therapeutic Agents

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e288-e299
Author(s):  
Galit H. Frydman ◽  
Michael B. Streiff ◽  
Jean M. Connors ◽  
Gregory Piazza
Keyword(s):  
Potential Role ◽  
Alveolar Epithelium ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Therapeutic Agents ◽  
Increased Risk ◽  
Potential Therapeutic Role ◽  
Risk Patients ◽  
Multiple Cells

AbstractSARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19.

scholarly journals The Rivaroxaban Program and the Management of Unmet Needs in Thromboembolic Disease

2018 ◽  
Vol 118 (S 01) ◽  
pp. S2-S11
Author(s):  
A. Camm
Keyword(s):  
Potential Role ◽  
Unmet Needs ◽  
Antiplatelet Agent ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Thromboembolic Disease ◽  
Coagulation Cascade ◽  
Vascular Protection ◽  
Randomized Controlled

AbstractRivaroxaban is a non-vitamin K antagonist oral anticoagulant that acts as a direct factor Xa inhibitor, and is widely used for the prevention and treatment of thromboembolic disorders. As further knowledge gaps are identified in thrombosis management, the rivaroxaban research program has expanded in an attempt to elucidate the wider benefits of rivaroxaban. An increased understanding of the interactions taking place within the coagulation cascade may support a broader role for rivaroxaban (2.5 mg twice daily [bid] or 5 mg bid) in the setting of vascular protection, either alone or in combination with an antiplatelet agent. The aim of this article is to describe the potential role of rivaroxaban in the context of vascular protection and provide an overview of recently completed and ongoing randomized controlled trials of rivaroxaban in the areas of stroke prevention, venous protection and vascular protection.

Role of Montgomery salivary stent placement during pharyngolaryngectomy, to prevent pharyngocutaneous fistula in high-risk patients

2012 ◽  
Vol 127 (1) ◽  
pp. 54-57 ◽  
Author(s):  
S Bondi ◽  
L Giordano ◽  
P Limardo ◽  
M Bussi
Keyword(s):  
Statistical Analysis ◽  
High Risk ◽  
Retrospective Analysis ◽  
Stent Placement ◽  
Pharyngocutaneous Fistula ◽  
Preventive Effect ◽  
Increased Risk ◽  
Risk Patients ◽  
Base Of The Tongue

AbstractObjective:To evaluate the incidence of pharyngocutaneous fistula after pharyngolaryngectomy with and without a Montgomery salivary stent.Design:Retrospective analysis of patients with factors that predispose to the development of pharyngocutaneous fistula (i.e. disease extending to the supraglottic region, base of the tongue or pyriform sinuses, and/or radiochemotherapy).Subjects:Between 2002 and 2008, 85 pharyngolaryngectomies were performed in our clinic. Of these patients, 31 were at increased risk of fistula development, of whom 45 per cent developed fistulas post-operatively. This subgroup of 31 patients was compared with a second subgroup of 22 patients at high risk of fistula development, treated between 2009 and 2011 with pharyngolaryngectomy and with a Montgomery salivary stent placed in advance during closure of the neopharynx.Results:Statistical analysis showed a significant reduction in the rate of fistula development, from 45 to 9 per cent (p < 0.01), with application of the salivary stent.Conclusion:These data confirm the preventive effect of a salivary stent placed during pharyngolaryngectomy, for patients at high risk of fistula development.

scholarly journals Comprehensive analysis of the effect of rs2295080 and rs2536 polymorphisms within the mTOR gene on cancer risk

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Guang-Hui Qi ◽  
Chun-Hui Wang ◽  
Hong-Ge Zhang ◽  
Jian-Guo Yu ◽  
Fei Ding ◽  
...  
Keyword(s):  
Sequential Analysis ◽  
Potential Role ◽  
Mammalian Target Of Rapamycin ◽  
Pooled Analysis ◽  
Chinese Patients ◽  
Trial Sequential Analysis ◽  
Urinary System ◽  
Increased Risk ◽  
Prostate Cancers

Abstract There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P&lt;0.05, OR (odds ratio) &lt;1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P&lt;0.05, OR&gt;1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of “population-based” control source via the allele, heterozygote, dominant, and carrier comparisons (P&lt;0.05, OR&gt;1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer.

scholarly journals The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2485
Author(s):  
Stephanie Sanders ◽  
Denise M. Herpai ◽  
Analiz Rodriguez ◽  
Yue Huang ◽  
Jeff Chou ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Potential Role ◽  
Therapeutic Agents ◽  
Brain Parenchyma ◽  
Low Grade ◽  
Effective Management ◽  
Diffuse Infiltration ◽  
Protein Levels ◽  
The Brain

Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.

Pregnancy exposure to perfluoroalkyl substances, prolactin concentrations and breastfeeding in the Odense Child Cohort

2021 ◽  
Author(s):  
Clara Amalie Gade Timmermann ◽  
Marianne Skovsager Andersen ◽  
Esben Budtz-Jørgensen ◽  
Henriette Boye ◽  
Flemming Nielsen ◽  
...  
Keyword(s):  
Cell Phone ◽  
Potential Role ◽  
Text Messages ◽  
Perfluoroalkyl Substances ◽  
Serum Prolactin ◽  
Public Health Importance ◽  
Increased Risk ◽  
Duration Of Breastfeeding

Abstract Context Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, though not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. Objective To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and elucidate the potential role of serum-prolactin concentrations in pregnancy. Materials and methods Pregnant women from the Odense Child Cohort provided blood samples for analysis of five major PFAS (n=1300) and prolactin concentrations (n=924). They subsequently provided information about the duration of breastfeeding in questionnaires at three and eighteen months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. Results Increased serum concentrations of PFOS, PFOA, PFNA and ∑PFAS were associated with a 16% (95% CI: 4-30%), 14% (95% CI: 2-26%), 14% (95% CI: 3-27%), and 20% (95% CI: 6-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. Conclusions These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences.

An Update on Carotid Stent Trials and Perspectives

2009 ◽  
Vol 4 (1) ◽  
pp. 92
Author(s):  
Stefan Bertog ◽  
Marius Hornung ◽  
Jennifer Franke ◽  
Nina Wunderlich ◽  
Horst Sievert ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Stenosis ◽  
The Elderly ◽  
Symptomatic Carotid ◽  
Stent Restenosis ◽  
Asymptomatic Patients ◽  
Symptomatic Carotid Stenosis ◽  
Increased Risk ◽  
Risk Patients

The presence of carotid artery stenosis is associated with an increased risk of stroke. Carotid endartectomy (CEA) has been demonstrated to reduce the stroke risk in standard-risk patients with symptomatic carotid stenosis as well as in asymptomatic patients, provided that the operative risk is low. The role of percutaneous carotid intervention is less clear. There are no trials that compare percutaneous carotid intervention with medical management. Although trial results comparing CEA with carotid artery stenting (CAS) are variable and/or controversial, some trials have demonstrated promising results and have fostered enthusiasm for the performance of ongoing trials comparing CAS with CEA. This article focuses on the results of completed trials and outlines ongoing and planned trials that aim to clarify the role of CAS in patients with carotid stenosis. In addition, potential unresolved problems associated with CAS, such as CAS in the elderly, in-stent restenosis and distal embolisation, are discussed.

scholarly journals The Role of Proteoglycans in Contributing to Placental Thrombosis and Fetal Growth Restriction

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Joanne M. Said
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Potential Role ◽  
Pregnancy Complication ◽  
Growth Restriction ◽  
Increased Risk ◽  
Fetus And Neonate

Fetal growth restriction is an important pregnancy complication that has major consequences for the fetus and neonate as well as an increased risk of long-term morbidity extending into adulthood. The precise aetiology of most cases of fetal growth restriction is unknown although placental thrombosis is a common feature in many of these cases. This paper will outline the potential role of proteoglycans in contributing to placental thrombosis and fetal growth restriction.

scholarly journals Is there a role for inherited TR βmutation in human carcinogenesis?

2012 ◽  
Vol 56 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Letícia Schwerz Weinert ◽  
Lucieli Ceolin ◽  
Mírian Romitti ◽  
Eduardo Guimarães Camargo ◽  
Ana Luiza Maia
Keyword(s):  
Thyroid Hormone ◽  
Potential Role ◽  
Thyroid Hormone Receptor ◽  
Close Association ◽  
Common Finding ◽  
Illustrative Case ◽  
Increased Risk ◽  
Exon 9

Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited disorder characterized by end-organ reduced sensitivity to thyroid hormone. This syndrome is caused by mutations of the thyroid hormone receptor (TR) β gene, and its clinical presentation is quite variable. Goiter is reported to be the most common finding. A close association of TRβ mutations with human cancers has become apparent, but the role of TRβ mutants in the carcinogenesis is still undefined. Moreover, higher TSH levels, described in RTH syndrome, are correlated with increased risk of thyroid malignancy, whereas TSH receptor stimulation is likely to be involved in tumor progression. We report here an illustrative case of a 29 year-old patient with RTH caused by a mutation in exon 9 (A317T) of TRβ gene, who presented multicentric papillary thyroid cancer. We review the literature on this uncommon feature, and discuss the potential role of this mutation on human tumorigenesis, as well as the challenges in patient follow-up.

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