Improved endovascular embolization of vascular conditions can generate better patient outcomes and minimize the need for repeat procedures. However, many embolic materials, such as metallic coils or liquid embolic agents, are associated with limitations and complications such as breakthrough bleeding, coil migration, coil compaction, recanalization, adhesion of the catheter to the embolic agent, or toxicity. Here, we engineered a shear-thinning biomaterial (STB), a nanocomposite hydrogel containing gelatin and silicate nanoplatelets, to function as an embolic agent for endovascular embolization procedures. STBs are injectable through clinical catheters and needles and have hemostatic activity comparable to metallic coils, the current gold standard. In addition, STBs withstand physiological pressures without fragmentation or displacement in elastomeric channels in vitro and in explant vessels ex vivo. In vitro experiments also indicated that STB embolization did not rely on intrinsic thrombosis as coils did for occlusion, suggesting that the biomaterial may be suitable for use in patients on anticoagulation therapy or those with coagulopathy. Using computed tomography imaging, the biomaterial was shown to fully occlude murine and porcine vasculature in vivo and remain at the site of injection without fragmentation or nontarget embolization. Given the advantages of rapid delivery, in vivo stability, and independent occlusion that does not rely on intrinsic thrombosis, STBs offer an alternative gel-based embolic agent with translational potential for endovascular embolization.
Thrombosis and its complications are among the most prevalent medical problems. Despite advancements in medical therapies, there is often incomplete resolution of these issues. The residual thrombus can undergo fibrotic changes over time through invaded fibroblasts from the surrounding tissues and eventually lead to the formation of a permanent clot. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we have further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembles the in vivo scenario. Our study suggests that in vitro 3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrosis models.
Deep vein thrombosis (DVT) is a major preventable cause of morbidity and mortality worldwide. Venous thromboembolism (VTE), which includes DVT and pulmonary embolism (PE), affects an estimated 1 per 1,000 people and contributes to 60,000-100,000 deaths annually. Normal blood physiology hinges on a delicate balance between pro- and anti-coagulant factors. Virchow's Triad distills the multitude of risk factors for DVT into three basic elements favoring thrombus formation: venous stasis, vascular injury, and hypercoagulability. Clinical, biochemical, and radiological tests are used to increase the sensitivity and specificity for diagnosing DVT. Anticoagulation therapy is essential for the treatment of DVT. With few exceptions, the standard therapy for DVT has been vitamin K-antagonists (VKAs) such as warfarin with heparin or fractionated heparin bridging. More recently, a number of large-scale clinical trials have validated the use of direct oral anticoagulants (DOACs) in place of warfarin in select cases. In this review, we summarize the pathogenesis, diagnosis, and medical management of DVT, with particular emphasis on anticoagulation therapy and the role of DOACs in the current treatment algorithm.
Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shapememory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel pre-clinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.
Social media enables the public sharing of information. With the recent emphasis on transparency and the open sharing of information between doctors and patients, the intersection of social media and healthcare is of particular interest. Twitter is currently the most popular form of social media used for healthcare communication; here, we examine the use of Twitter in medicine and specifically explore in what capacity using Twitter to share information on treatments and research has the potential to improve care. The sharing of information on Twitter can create a communicative and collaborative atmosphere for patients, physicians, and researchers and even improve quality of care. However, risks involved with using Twitter for healthcare discourse include high rates of misinformation, difficulties in verifying the credibility of sources, overwhelmingly high volumes of information available on Twitter, concerns about professionalism, and the opportunity cost of using physician time. Ultimately, the use of Twitter in healthcare can allow patients, healthcare professionals, and researchers to be more informed, but specific guidelines for appropriate use are necessary.
Deep vein thrombosis (DVT) is a major health problem worldwide. The risk of pulmonary embolism following DVT is well established, but the long-term vascular sequelae of DVT are often underappreciated, costly to manage, and can have extremely detrimental effects on quality of life. Treatment of DVT classically involves oral anticoagulation, which reduces the risk of pulmonary embolism but does not remove the clot. Anticoagulation therefore does little to prevent the venous damage and scarring that occurs following DVT, leaving the patient at risk for permanent venous insufficiency and development of post-thrombotic syndrome (PTS). Catheter-directed thrombolysis (CDT) is a minimally invasive endovascular treatment that is used as an adjunct to anticoagulation. CDT lowers the risk of PTS by reducing clot burden and protecting against valvular damage. A catheter is advanced directly to the site of thrombosis under fluoroscopy followed by a slow, prolonged infusion of a relatively low dose of thrombolytic agent. CDT restores venous patency faster than anticoagulation, which hastens the relief of acute symptoms. Adjunctive CDT modalities have become increasingly popular among interventional radiologists, allowing for additional mechanical thrombectomy or ultrasound-enhanced thrombolysis at the time of catheter placement. These pharmacomechanical CDT (PCDT) techniques have the potential to reduce treatment time and associated healthcare costs. Numerous observational and retrospective studies have consistently shown a benefit of CDT plus anticoagulation over anticoagulation alone for prevention of PTS. Patients with long life expectancy and acute thrombosis involving the iliac and proximal femoral veins (iliofemoral DVT) have the greatest benefit from CDT, which may decrease the risk of PTS and/or decrease the severity of PTS symptoms if they do occur. Randomized controlled trials remain limited but generally support the observational data. CDT also plays an important role in those with acute limb-threatening venous occlusion or severe symptoms from DVT. Although adverse outcomes are rare, a potential devastating outcome is intracranial bleeding. While the available literature suggests the risk of serious morbidity from bleeding is quite rare, the absolute risk of bleeding is not clear and will require outcomes data from randomized trials. Future studies should also examine the cost-effectiveness of CDT for PTS prevention, particularly with respect to quality-adjusted life years, and compare the effectiveness of available PCDT devices.
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