Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the Time to Onset and Outcome of Lenalidomide-induced Thrombosis and Embolism Using Spontaneous Reporting Database.

BACKGROUND/AIM: Lenalidomide (LND) is an oral antineoplastic agent used in the treatment of various malignant hematologic diseases, including multiple myeloma. Major adverse events of LND include myelosuppression, pneumonia, and thromboembolism. Thromboembolism is an adverse drug reaction (ADR) associated with poor outcomes, therefore anticoagulants are administered prophylactically. However, LND-induced thromboembolism has not been clearly characterized from clinical trials. The purpose of this study was to evaluate the incidence, timing, and outcome details of thromboembolism caused by LND using the JADER (Japanese Adverse Drug Event Report) database. PATIENTS AND METHODS: ADRs due to LND reported from April 2004 to March 2021 were selected. Data on thromboembolic adverse events were analyzed and relative risks were estimated using reported odds ratios (RORs) and 95% confidence intervals (CIs). In addition, the time of onset and outcome of thromboembolism were analyzed. RESULTS: There were 11,681 adverse events attributed to LND. Of these, 306 were thromboembolisms. The most frequently reported thrombosis with the highest ROR was deep vein thrombosis (DVT) (165 cases, ROR=7.12, 95%CI=6.09-8.33). The median onset of DVT (quartiles, 25-75%) was 80 (28-155) days. The parameter value (ß) was 0.87 (0.76-0.99), suggesting the onset of DVT early in treatment. The prognosis of DVT due to LND was recovery and remission in 34% and 43% of patients, respectively, but 7.9% did not recover. CONCLUSION: DVT is the most frequent thromboembolism in LND, and early treatment is important.

Cerebral venous thrombosis associated with hyperhomocysteinemia and iron-deficiency anemia induced by autoimmune gastritis: A case report and literature review.

Cerebral venous thrombosis (CVT) is a rare disease, occurring in 0.5%-1% of all patients with strokes. Systemic and hereditary diseases and traumas are potential causes of CVT. We report a case of CVT and systemic thromboembolism complicated with hyperhomocysteinemia and iron-deficiency anemia caused by autoimmune gastritis. A 47-year-old female patient was admitted to the emergency department due to difficulty in movement, impaired consciousness, and urinary incontinence. Brain computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral thalamic edema associated with venous sinus thrombosis and embolic cerebral infarction in the deep white matter of the bilateral cerebral hemispheres. In addition, contrast enhanced whole-trunk CT scan showed deep femoral thrombosis and pulmonary artery embolism. She had no medical history of diseases or drug use that may cause thrombosis. Blood test results revealed iron-deficiency anemia and hyperhomocysteinemia, which were determined to be the cause of systemic thromboembolism. The patient tested positive for intrinsic factor antibodies. Moreover, the patient was diagnosed with autoimmune gastritis by gastrointestinal endoscopy. Therapies including anticoagulant and replacement with iron and vitamin B12 were administered. The patient was discharged from the hospital without neurological deficits. A favorable clinical course was achieved with anticoagulant administration and replacement therapy with iron and vitamin B12 for cerebral arteriovenous embolism that developed due to autoimmune gastritis.

Evidence-Based Nursing Model in Interventional Thrombolysis for Acute Lower Extremity Arterial Embolism.

Acute lower extremity arterial embolism (AE) is a serious clinical emergency, and, if not treated in time, it can easily lead to limb ischemia and necrosis and eventually facing amputation, which seriously damages patients' physical and mental health. In the past, the conventional drug thrombolytic therapy had slow and limited efficacy, and the best time for treatment is easily delayed, while arterial dissection and thrombectomy treatment, although fast, is traumatic and has many complications, which is not easily accepted by patients. The aim of this study was to investigate the value of evidence-based care model in the application of interventional thrombolysis for acute lower limb arterial embolism. Seventy-two patients with acute lower limb arterial embolism who underwent interventional thrombolysis treatment received by the Department of Vascular Surgery of our hospital from July 2016 to December 2021 were randomly divided into a control group (given conventional nursing services) and a quality group (given full quality nursing services) to compare the effect of nursing services in the two groups. The results showed that the postoperative psychological status of patients in the quality group was significantly better than that of patients in the control group (P < 0.05). The total incidence of postoperative adverse events and the total treatment efficiency of the quality group were better than those of the control group (P < 0.05). The efficacy of quality nursing care in patients with acute lower extremity arterial embolism is more desirable than conventional nursing care and is recommended. The site of vascular occlusion after bypass surgery can be clarified when angiography is performed after thrombolytic therapy, which can help secondary surgical intervention to prolong the time to patency. The efficacy of quality nursing care in patients with acute lower extremity arterial embolism is more desirable than that of conventional nursing care and is recommended.

Effectiveness and Safety of Rivaroxaban versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Polypharmacy.

BACKGROUND: Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications. METHODS: This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m2 and the presence of polypharmacy (1-4, 5-9, or ≥ 10 concurrent medications). Outcomes of stroke, systemic embolism, and major bleeding were compared between the rivaroxaban and warfarin cohorts after propensity score matching (PSM). RESULTS: A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups. CONCLUSIONS: In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Efficacy of Percutaneous Intraarterial Facial/Supratrochlear Arterial Hyaluronidase Injection for Treatment of Vascular Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.

BACKGROUND: Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. OBJECTIVES: The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. METHODS: We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. CONCLUSIONS: It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.

Hyaluronic Acid Embolism Treated with Subcutaneous High and Low Hyaluronidase Doses: Efficacy and Surrounding Tissue Effect.

BACKGROUND: The use of hyaluronidase in hyaluronic acid vascular occlusion has been evaluated; however, the models used do not accurately assimilate the facial morphologic characteristics or study the effects on adjacent tissues. The purpose of this study was to determine an effective concentration of subcutaneous hyaluronidase to dissolve a hyaluronic acid embolism and its effect on surrounding tissue. METHODS: Fifteen rabbits were divided into six groups. An inguinal incision was performed on the femoral artery to create a hyaluronic acid embolism in the control and treatment groups (low-, medium-, and high-hyaluronidase groups). Hyaluronidase was injected subcutaneously. Photographic follow-up, histologic analysis, and quantification of hyaluronic acid were performed. Kruskal-Wallis test and post hoc with Bonferroni correction (p < 0.05) was used to compare the presence of hyaluronic acid in the arterial lumen between groups. RESULTS: Despite the persistence of intravascular hyaluronic acid, macroscopic and microscopic differences were found between the embolism control group and embolism hyaluronidase high-dose group. Histologic analysis demonstrated thrombosis throughout groups. Skeletal muscle was least affected in the embolism hyaluronidase 500 IU group with less lysis and inflammatory infiltrate. CONCLUSIONS: A 500 IU hyaluronidase dose partially prevents the damage caused by the embolism, and does not affect the surrounding tissue. The use of thrombolytic therapy combined with higher doses of hyaluronidase subcutaneously in this model is proposed.

Protective effect of glycyrrhizin on coronary microembolization-induced myocardial dysfunction in rats.

Coronary microembolization (CME)-induced inflammation and cardiomyocyte apoptosis are two key factors contributing to CME-induced myocardial dysfunction. High-mobility group box-1 (HMGB1) plays essential role in progression of CME-induced injury and inhibition of HMGB1 has been shown to be protective. In present study, the potential effects of glycyrrhizin, a HMGB1 inhibitor, on CME-induced myocardial dysfunction are evaluated. Using a rat model of CME, we administrated glycyrrhizin in rats prior to CME induction. The level of HMGB1, TNF-α, iNOS, IL-6, IL-1ß, cleaved caspase-3, Bax, and Bcl-2 were measured. The serum level of cardiac troponin I, creatine kinase, was detected. The cardiac function and cardiomyocyte apoptosis were evaluated. The activation of TLR4/NF-κB signaling pathway was analyzed. Glycyrrhizin prevented CME-induced production of HMGB1, TNF-α, iNOS, IL-6, and IL-1ß. Glycyrrhizin inhibited CME-induced cardiomyocyte apoptosis and the expression of cleaved caspase-3 and Bax, while enhanced the expression of Bcl-2. Glycyrrhizin decreased cardiac troponin I and creatine kinase levels and improved cardiac function. Glycyrrhizin prevented the activation of HMGB1/TLR4/NF-κB signaling pathway. Glycyrrhizin ameliorated myocardial dysfunction in CME rats by preventing inflammation and apoptosis of cardiomyocytes.

Cryptotanshinone ameliorates cardiac injury and cardiomyocyte apoptosis in rats with coronary microembolization.

Coronary microembolization (CME) is a prevalent cardiovascular disease, especially nowadays when percutaneous coronary intervention is widely applied. However, neither cardio-protective agents nor devices for distal protection could effectively prevent the occurrence of CME. Therefore, we aimed to develop a new drug for CME. Rats were orally administrated with different doses of Cryptotanshinone (CTS, 5, 15, 45 mg/kg) daily for 2 weeks, respectively, following CME surgery. Then cardiac function and cardiac injury were evaluated in CME rats as well as measuring oxidative stress and apoptosis in cardiomyocytes. Compared to sham group, CME operation induced cardiac dysfunction, cardiac injury, the activation of platelet and endothelium, cardiomyocyte apoptosis and oxidative stress, all of which could be dose-dependently restored by CTS pretreatment. Moreover, NF-κB signaling pathway participated in the development of CME and also in the preventive process of CTS against CME. CTS might serve as a potential and promising candidate drug to prevent the occurrence of CME.

Transvascular Hydrolysis of Hyaluronic Acid Filler With Hyaluronidase: An Ex Vivo Study.

BACKGROUND: Despite the favorable safety profile of hyaluronic acid (HA) dermal fillers, side effects can occur. Skin necrosis is one of the most severe early-occurring complications resulting from accidental vascular impairment. Hyaluronidase (HYAL) is commonly used to degrade HA chains, allowing the degraded product to pass through vessels, and thus relieving the vascular obstruction. OBJECTIVE: The purpose of this study is to evaluate, in an ex vivo setting, the capability of HYAL to degrade crosslinked HA that was injected into human vessels. MATERIALS AND METHODS: During a neck dissection, a portion of the anterior jugular vein and facial artery was harvested. The vein and artery specimens were filled with 25 mg/mL of crosslinked HA filler. Each specimen was soaked in 0.5 mL of HYAL (300 IU/mL), in its own test tube, for 4 hours, after which the remaining HA was quantified. RESULTS: The remaining HA volume was found to be 0.02 mL in the vein segment and 0.002 mL in the artery segment. CONCLUSION: A single administration of HYAL may not be adequate to restore blood flow in the event of embolism, and relatively high doses of this enzyme must be injected hourly into the affected tissue until resolution is complete.

Preventing venous thrombo-embolism after nonmajor orthopedic surgery.

The venous thromboembolism risk is low to moderate in nonmajor orthopedic surgery. The literature is unconclusive. New emerging data are now available. The global patient risk has to be taken into account to determine the need for any prophylaxis.

Diffuse Cutaneous Manifestations after Drug-Coated Balloon Angioplasty.

We present here a case of an uncommon cutaneous manifestation after paclitaxel-coated balloon angioplasty. In this case, the patient underwent drug-coated balloon angioplasty for stenosis of a prior vein bypass graft. The patient subsequently developed extensive cutaneous lesions not confined to a single arterial distribution. This case represents a rare complication related to paclitaxel-eluting balloons and provides a cautionary tale as well as clinical acumen for providers in using such devices in their practice.

Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy.

Recombinant tissue plasminogen activator (rtPA) is the only thrombolytic agent that has been approved by the FDA for treatment of ischemic stroke. However, a high dose intravenous infusion is required to maintain effective drug concentration, owing to the short half-life of the thrombolytic drug, whereas a momentous limitation is the risk of bleeding. We envision a dual targeted strategy for rtPA delivery will be feasible to minimize the required dose of rtPA for treatment. For this purpose, rtPA and fibrin-avid peptide were co-immobilized to poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (PMNP) to prepare peptide/rtPA conjugated PMNPs (pPMNP-rtPA). During preparation, PMNP was first surface modified with avidin, which could interact with biotin. This is followed by binding PMNP-avidin with biotin-PEG-rtPA (or biotin-PEG-peptide), which was prepared beforehand by binding rtPA (or peptide) to biotin-PEG-maleimide while using click chemistry between maleimide and the single -SH group in rtPA (or peptide). The physicochemical property characterization indicated the successful preparation of the magnetic nanoparticles with full retention of rtPA fibrinolysis activity, while biological response studies underlined the high biocompatibility of all magnetic nanoparticles from cytotoxicity and hemolysis assays in vitro. The magnetic guidance and fibrin binding effects were also confirmed, which led to a higher thrombolysis rate in vitro using PMNP-rtPA or pPMNP-rtPA when compared to free rtPA after static or dynamic incubation with blood clots. Using pressure-dependent clot lysis model in a flow system, dual targeted pPMNP-rtPA could reduce the clot lysis time for reperfusion by 40% when compared to free rtPA at the same drug dosage. From in vivo targeted thrombolysis in a rat embolic model, pPMNP-rtPA was used at 20% of free rtPA dosage to restore the iliac blood flow in vascular thrombus that was created by injecting a blood clot to the hind limb area.

Left Ventricular Thrombi and Embolic Events in Takotsubo Syndrome despite Therapeutic Anticoagulation.

INTRODUCTION: Takotsubo syndrome (TTS) may be complicated by left-ventricular (LV) thrombus formation in 1.3-5.3% of patients. Risk factors for thrombi comprise apical TTS, elevated levels of C-reactive protein and troponine, thrombocytosis, persisting ST segment elevation and right-ventricular involvement. Embolic risk appears high, and anticoagulation is recommended. CASE PRESENTATION: We present 3 females, aged 60-82 years, with TTS-associated LV thrombi and cerebral embolism despite therapeutic anticoagulation. Two patients showed apical and 1 patient midventricular ballooning. In 2 patients LV thrombi had not been present at the first echocardiographic examination. LV thrombi were multiple and highly mobile in 2 patients; 1 patient had a single immobile thrombus associated with spontaneous echocardiographic contrast (SEC). In each case, 3 of the described risk factors for LV thrombus formation were identified. The embolic stroke occurred 41-120 h after TTS symptom onset and 21-93 h after the initiation of therapeutic anticoagulation. Two patients were discharged with a neurological deficit, and 1 of them eventually died as a consequence of the stroke. LV thrombectomy to prevent embolism, which has been reported in a small number of cases, had not been considered in our patients. CONCLUSION: At present, the management of patients with TTS-related thrombi is still unclear, and further studies are urgently needed to assess the best methods for imaging and anticoagulation and to determine the role of thrombolysis and cardiac surgery. Until these studies are available, we suggest the following approach: patients with a TTS-related thrombus should be monitored by echocardiography while receiving anticoagulation. In case of highly mobile LV thrombi, the heart team may consider cardiac surgery to prevent systemic embolism. The role of SEC in TTS remains to be determined.

Evaluation of Intraarterial Thrombolysis in Treatment of Cosmetic Facial Filler-Related Ophthalmic Artery Occlusion.

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy. METHODS: This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSIONS: The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Antiplatelets, anticoagulants, and colonoscopic polypectomy.

The management of antiplatelet and anticoagulant (ie, antithrombotic) agents is challenging in the periendoscopic setting. In this state-of-the-art update, we review current best practice recommendations focusing on the risk of immediate and delayed postpolypectomy bleeding in the context of drug discontinuation (ie, temporary interruption) and drug continuation. The data regarding polypectomy technique (cold snare vs conventional thermal-based) and prophylactic placement of hemostatic clips are evaluated to assess whether these endoscopic techniques are beneficial in reducing postpolypectomy bleeding. Finally, clinical takeaways are provided to facilitate safer polypectomy among patients on antiplatelet and anticoagulant agents.

Blindness After Facial Filler Injections: The Role of Extravascular Hyaluronidase on Intravascular Hyaluronic Acid Embolism in the Rabbit Experimental Model.

BACKGROUND: Blindness caused by ophthalmic artery embolism is the most catastrophic complication of facial hyaluronic acid (HA) injections. Extravascular (retrobulbar) injection of hyaluronidase has been suggested as a salvage in this calamitous situation. However, the effectiveness of this treatment still lacks consensus. OBJECTIVES: The aim of this study was to investigate the role of extravascular hyaluronidase in dissolving intravascular HA occlusion. METHODS: Two different animal experiments were performed: (1) isolated rabbit abdominal aorta segments filled with HA were treated with extravascular immersion of highly concentrated hyaluronidase for 90 minutes, followed by gross observation, microscopic examination, particle size analysis, and immunohistochemical staining; and (2) live rabbit auricular arteries were first occluded with HA and then immediately treated with extravascular injection of hyaluronidase. The ears were then evaluated by gross observation, microscopic examination, and perfusion studies after 60 minutes and again after 90 minutes. RESULTS: The HA within the aorta segments showed no gross or microscopic changes after treatment with extravascular hyaluronidase. Hyaluronidase could only be detected in adventitia of the aortae, instead of in vascular smooth muscle, tunica intima, or vascular lumen. The occluded auricular arteries showed no reperfusion after extravascular injection of hyaluronidase. CONCLUSIONS: In this rabbit model, extravascular hyaluronidase was unable to penetrate into the arterial lumen of the isolated abdominal aorta or the live auricular artery of the rabbit to dissolve intravascular HA within a 90-minute time limit, thus casting doubt on whether extravascular (retrobulbar) hyaluronidase injection has a role in treating ophthalmic artery embolism caused by HA injections.

Efficacy and Safety of Nonvitamin K Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer: A Study-Level Meta-Analysis.

OBJECTIVES: In this study-level meta-analysis, we evaluated the clinical outcome with nonvitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with cancer. BACKGROUND: Anticoagulation in AF patients with cancer is challenging given the coexistence of elevated thrombotic and bleeding risk. The efficacy and safety of NOACs in this setting remain unclear. METHODS: We included three randomized trials in our primary analysis (N = 2,661 patients) and three observational studies in our secondary, confirmatory analysis (N = 21,112 patients). Outcome measures were: the composite of any stroke or systemic embolism, ischemic stroke, venous thromboembolism, major bleeding, intracranial bleeding; and all-cause death. Mean follow-up duration was 2.2 years. RESULTS: In the primary analysis, the use of NOACs was associated with similar incidence of stroke/systemic embolism (odds ratio [OR] 0.70, 95% confidence interval 0.45-1.09; p = 0.11), ischemic stroke (OR 0.71, 0.31-1.64; p = 0.42), venous thromboembolism (OR 0.91, 0.33-2.53; p = 0.86), all-cause death (OR 1.02, 0.72-1.42; p = 0.93), and major bleeding (OR 0.81, 0.61-1.06; p = 0.13) compared with VKAs. The occurrence of intracranial bleeding was significantly lower in the NOACs versus VKAs group (OR 0.11, 0.02-0.63; p = 0.01). These results were overall confirmed in the secondary analysis, where there was additionally a significant reduction of stroke/systemic embolism, ischemic stroke, and venous thromboembolism with NOACs. CONCLUSION: In AF patients with malignancy, NOACs appear at least as effective as VKAs in preventing thrombotic events and reduce intracranial bleeding. NOACs may represent a valid and more practical alternative to VKAs in this setting of high-risk patients.

Experimentally Induced Arterial Embolism by Hyaluronic Acid Injection: Clinicopathologic Observations and Treatment.

BACKGROUND: Although major complications of hyaluronic acid injection rarely occur, with the rapidly growing number of procedures performed and their expanding applications, such complications warrant greater attention. Our study was designed to explore optimal treatment methods for hyaluronic acid-related vascular occlusion. METHODS: In the first part of the study, 60 rats were given intraarterial hyaluronic acid injected into the bilateral inferior epigastric arteries to establish an animal model, and were euthanized at different postinjection time points. The inferior epigastric artery was retrieved for pathologic examination. In the second part of the study, bilateral abdominal flaps supplied by the inferior epigastric artery were elevated in six groups of rats, and hyaluronic acid was injected into the right side, with each group receiving a different intervention. The flap survival rate was calculated and analyzed. RESULTS: In the first part of the study, pathologic examination revealed that the composition of the emboli caused by arterial hyaluronic acid-induced occlusion changed from pure hyaluronic acid to a hyaluronic acid-thrombus mixture. In the second part of the study, flap survival rates (mean percentages) were as follows: group A, 43.29 ± 9.28 percent; group B, 54.17 ± 10.86 percent; group C, 59.27 ± 13.40 percent; group D, 64.37 ± 8.61 percent; group E, 71.92 ± 19.06 percent; and group F, 57.47 ± 13.64 percent. Group A differed significantly from groups B, C, D, and E (p < 0.001). No significant difference was observed between groups A and F (p > 0.05). CONCLUSIONS: The combined use of intravenous or subcutaneous hyaluronidase and urokinase was most effective in treating hyaluronic acid injection-related arterial embolism after 45 minutes and 24 hours. This treatment may be ineffective after 48 hours.