Effect of orthodontic force on dental pulp histomorphology and tissue factor expression:

ABSTRACT Objectives To evaluate the effects of orthodontic force on histomorphology and tissue factor expression in the dental pulp. Materials and Methods Two reviewers comprehensively and systematically searched the literature in the following databases: Latin American and Caribbean Health Sciences, Embase, Cochrane, PubMed, Scopus, Web of Science, and Grey literature (Google Scholar, OpenGrey, and ProQuest) up to September 2020. According to the Population, Intervention, Comparison, Outcomes, Studies criteria, randomized clinical trials (RCTs) and observational studies that evaluated the effects of orthodontic force on dental pulp were included. Case series/reports, laboratory-based or animal studies, reviews, and studies that did not investigate the association between orthodontic force and pulpal changes were excluded. Newcastle-Ottawa Scale and Cochrane risk-of-bias tool were used to assess the risk of bias. The overall certainty level was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. Results 26 observational studies and five RCTs were included. A detailed qualitative analysis of articles showed a wide range of samples and applied methodologies concerning impact of orthodontic force on the dental pulp. The application of orthodontic force seems to promote several pulpal histomorphological changes, including tissue architecture, cell pattern, angiogenesis, hard tissue deposition, inflammation, and alteration of the expression levels of 14 tissue factors. Conclusions Although the included articles suggest that orthodontic forces may promote histomorphological changes in the dental pulp, due to the very low-level of evidence obtained, there could be no well-supported conclusion that these effects are actually due to orthodontic movement. Further studies with larger samples and improved methods are needed to support more robust conclusions.

Complement mediates binding and procoagulant effects of ultra-large HIT immune complexes

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by ultra-large immune complexes (ULICs) containing IgG antibodies to a multivalent antigen composed of platelet factor 4 (PF4) and heparin. The limitations of current anti-thrombotic therapy in HIT supports the need to identify additional pathways that may be targets for therapy. Activation of FcgRIIA by HIT ULICs initiates diverse procoagulant cellular effector functions. HIT ULICs are also known to activate complement, but the contribution of this pathway to the pathogenesis of HIT has not been studied in detail. We observed that HIT ULICs physically interact with C1q in buffer and plasma, activate complement via the classical pathway, promote co-deposition of IgG and activated C3 complement fragments (C3c) on neutrophil and monocyte cell surfaces. Complement activation by ULICs, in turn, facilitates Fcg receptor(R)-independent monocyte tissue factor expression, enhances IgG binding to the cell surface FcgRs and promotes platelet adhesion to injured endothelium. Inhibition of the proximal, but not terminal, steps in the complement pathway, abrogates monocyte tissue factor expression by HIT ULICs. Together, these studies suggest a major role for complement activation in regulating Fc-dependent effector functions of HIT ULICs, identify potential non-anticoagulant targets for therapy, and provide insights into the broader roles of complement in immune complex-mediated thrombotic disorders.

Monitoring of COVID-19-Associated Coagulopathy and Anticoagulation with Thromboelastometry

Introduction: Thrombosis occurs frequently in COVID-19. While the exact mechanism is unclear, 3 processes seem to play important roles in sepsis-related thrombosis and mortality: tissue factor expression on circulating monocytes and microparticles, hypercoagulability (increased clot firmness), and hypofibrinolysis. Rotational thromboelastometry is a point-of-care viscoelastic technique that uses the viscoelastic properties of blood to monitor coagulation. Using various assays, viscoelastometry could monitor this triad of changes in severely ill, COVID-19-positive patients. Similarly, with the increased incidence of coagulopathy, many patients are placed on anticoagulants, making management more difficult depending on the agents utilized. Viscoelastometry might also be used in these settings to monitor anticoagulation status and guide therapy, as it has in other areas. Case Presentation: We present a case series of 6 patients with different stages of disease and different management plans. These cases occurred at the height of the pandemic in New York City, which limited testing abilities. We first discuss the idea of using the NaHEPTEM test as a marker of tissue factor expression in COVID-19. We then present cases where patients are on different anticoagulants and review how viscoelastometry might be used in a patient on anticoagulation with COVID-19. Conclusion: In a disease such as COVID-19, which has profound effects on hemostasis and coagulation, viscoelastometry may aid in patient triage, disease course monitoring, and anticoagulation management.