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 .

Relationship Between Direct Oral Anticoagulant Doses and Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- ANAFIE Registry Sub-Analysis.

BACKGROUND: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death. CONCLUSIONS: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

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.

Acute Myocardial Infarction Due to Coronary Artery Embolism during Chemotherapy with mFOLFOX-6 Plus Bevacizumab for Metastatic Colon Cancer.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, may be associated with arterial embolisms. We herein report a case of acute myocardial infarction caused by coronary embolism during combination chemotherapy with mFOLFOX-6 and bevacizumab in a patient with metastatic colon cancer. Thromboembolism occurred only in the distal right posterolateral branch without stenotic lesions or plaque rupture in the proximal branch of the right coronary artery. Sole thromboaspiration was successfully performed; the final angiogram demonstrated no stenosis in the right coronary artery. Bevacizumab may be associated with acute coronary syndrome in patients with coronary risk factors, despite no significant coronary narrowing.

Effect of Polypharmacy on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- A Sub-Analysis of the ANAFIE Registry.

BACKGROUND: This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged ≥75 years) Japanese population with non-valvular atrial fibrillation (NVAF).Methods and Results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anticoagulants [OACs]): 0-4 [38.8%], 5-8 [43.3%], and ≥9 [17.9%]). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events. CONCLUSIONS: Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.

Systemic embolism in amyloid transthyretin cardiomyopathy.

AIMS: Although systemic embolism is a potential complication in transthyretin amyloid cardiomyopathy (ATTR-CM), data about its incidence and prevalence are scarce. We studied the incidence, prevalence and factors associated with embolic events in ATTR-CM. Additionally, we evaluated embolic events according to the type of oral anticoagulation (OAC) and the performance of the CHA2 DS2 -VASc score in this setting. METHODS AND RESULTS: Clinical characteristics, history of atrial fibrillation (AF) and embolic events were retrospectively collected from ATTR-CM patients evaluated at four international amyloid centres. Overall, 1191 ATTR-CM patients (87% men, median age 77.1 years [interquartile range-IQR 71.4-82], 83% ATTRwt) were studied. A total of 162 (13.6%) have had an embolic event before initial evaluation. Over a median follow-up of 19.9 months (IQR 9.9-35.5), 41 additional patients (3.44%) had an embolic event. Incidence rate (per 100 patient-years) was 0 among patients in sinus rhythm with OAC, 1.3 in sinus rhythm without OAC, 1.7 in AF with OAC, and 4.8 in AF without OAC. CHA2 DS2 -VASc did not predict embolic events in patients in sinus rhythm whereas in patients with AF without OAC, only those with a score ≥4 had embolic events. There was no difference in the incidence rate of embolism between patients with AF treated with vitamin K antagonists (VKAs) (n = 322) and those treated with direct oral anticoagulants (DOACs) (n = 239) (p = 0.66). CONCLUSIONS: Embolic events were a frequent complication in ATTR-CM. OAC reduced the risk of systemic embolism. Embolic rates did not differ with VKAs and DOACs. The CHA2 DS2 -VASc score did not correlate well with clinical outcome in ATTR-CM and should not be used to assess thromboembolic risk in this population.

Cardiac Perforation Caused by Cement Embolism after Percutaneous Vertebroplasty: A Report of Two Cases.

BACKGROUND: Percutaneous vertebroplasty (PVP) is a minimally invasive surgical technique in which polymethyl methacrylate (PMMA) is injected into the weakened vertebral body to strengthen it. However, this procedure is associated with various complications, the most common being cement leakage. Cardiac perforation caused by cement escape into the venous system is another complication, which is rare but potentially life-threatening even if not treated promptly. CASE PRESENTATION: Here, we report two elderly patients who developed cardiac perforation caused by cement escape into veins following PVP. Both patients had a history of severe osteoporosis. On admission, they presented with lower back pain and limited movement. MRI revealed vertebral bodies compression fracture in both patients. Considering the advanced age of the patients, PVP was performed to avoid the risk of potential complications associated with nonoperative therapy. Unfortunately, the rare and fatal postoperative complication, cardiac perforation caused by cement escape into veins, occurred in both patients. Emergency open-heart surgery was performed to remove cement material and repair the heart, both patients recovered well and were discharged. CONCLUSIONS: Although PVP is a safe and minimally invasive surgical technique, it is associated with various serious complications as seen in the present cases. We therefore recommend that surgeons should be aware of such complications. Appropriate timing of surgical operation, meticulous surgical procedures, early intraoperative and postoperative monitoring of cement leakage may improve outcomes of patients with such complications.

Effect of Cancer on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- Substudy of the ANAFIE Registry.

BACKGROUND: Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed.Methods and Results:In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer. CONCLUSIONS: Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

Safety of oil-based contrast medium for hysterosalpingography: a systematic review.

Recent meta-analyses have shown that a hysterosalpingography (HSG) with oil-based contrast increases pregnancy rates in subfertile women. However, the frequency of complications during or after an HSG with oil-based contrast in subfertile women and/or their offspring is still unclear. This systematic review and meta-analysis, without restrictions on language, publication date or study design, was performed to fill this knowledge gap. The results show that the most frequently reported complication was intravasation of contrast, which occurred in 2.7% with the use of oil-based contrast (31 cohort studies and randomized controlled trials [RCT], 95% CI 1.7-3.8, absolute event rate 664/19,339), compared with 2.0% with the use of water-based contrast (8 cohort studies and RCT, 95% CI 1.2-3.0, absolute event rate 18/1006). In the cohort studies and RCT there were 18 women with an oil embolism (18/19,339 HSG), all without serious lasting consequences. Four cases with serious consequences of an oil embolism were described (retinal oil embolism [n = 1] and cerebral complaints [n = 3]); these reports did not describe the use of adequate fluoroscopy guidance during HSG. In conclusion, the most frequently reported complication after an HSG with oil-based contrast is intravasation occurring in 2.7%. In total four cases with serious consequences of oil embolisms in subfertile women were published.

Cutaneous Polymer-Coating Embolism After Endovascular Procedures: Report of Two Cases and a Literature Review.

ABSTRACT: Different hydrophilic and hydrophobic polymers are used as lubricious coatings to reduce vascular traumas in minimally invasive percutaneous procedures. Although they are usually very safe, there is still a risk of serious complications in patients undergoing such procedures, mostly derived from the devices' coating detachment and systemic embolization. The lungs are the most common organ involved, followed by the central nervous system. Yet, cutaneous embolization is unusual, and only 19 cases are available in the literature. Most commonly, they present as asymptomatic retiform purpura on the lower legs, which tends to involve spontaneously. Correct clinical diagnosis is not suspected in most cases, being cholesterol emboly or vasculitis the preferred options. Time interval since surgical procedure and appearance of lesions vary widely but they generally start in the first few days. Histopathological identification of the embolus as bluish, amorphous intraluminal material in dermal vessels is diagnostic, but vasculitic signs are not present. We report 2 cases of skin lesions as the main manifestation of polymer embolization after endovascular surgical procedures. In both cases, biopsy allowed identification of embolized foreign material and lesions resolved without specific treatment.

Facial palsy after embolization with Squid® 12.

Endovascular procedures with liquid embolic agents such as ethylene-vinyl alcohol (EVOH) copolymers are indicated before surgical treatment of cervical paraganglioma. Consequently, these agents are now available as low viscosity formulations, one of which is Squid 12, which are demonstrating superior vascular penetration. Cases of facial paralysis secondary to embolization of cervical vascular lesions with classic embolic agents have been reported in the English literature, however, this complication has not been described with new generation options such as Squid 12.We describe the case of a 43-year-old patient with a left neck carotid paraganglioma. Embolization was performed under general anaesthesia before surgical excision. In the immediate postoperative period, the patient developed total left facial palsy. Since the imaging tests (Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)) and neurological examination showed no involvement of additional cranial nerves (CN), we hypothesise that the main cause of this complication is ischemia of the vasa nervorum of CN VII secondary to embolization. Almost six months later, the patient continues to present total facial paralysis (Grade VI House-Brackmann facial paralysis scale), and palsy of the left CN X and XII as a complication secondary to surgical resection of the paraganglioma.This case is relevant since it is the first clinical case of permanent facial paralysis secondary to embolization with Squid 12.

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.

Pancreas lipiodol embolism induced acute necrotizing pancreatitis following transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report and literature review.

RATIONALE: Transcatheter arterial chemoembolization (TACE) is recognized as one of the most commonly used modalities for non-surgical treatment for advanced hepatocellular carcinoma (HCC). Ectopic lipiodol embolism is an extremely rare complication of TACE. PATIENT CONCERNS: A 61-year-old man who had a 10-year history of cirrhosis caused by hepatitis B infection was diagnosed with ascites and HCC. Subsequently, the patient underwent TACE. However, he experienced persistent left upper abdominal pain, poor appetite, nausea, moderate fever and accompanied by elevation of serum and urine amylase on the 2nd and 3nd day after treatment. DIAGNOSES: The patient was diagnosed as having acute hemorrhagic necrotizing pancreatitis based on biochemical and inflammatory markers and CT findings. We deduced that the acute necrotizing pancreatitis was caused by a small branch of the left hepatic artery feeding the pancreas tail and embolizing the drug and lipiodol shunting to the tail of the pancreas. INTERVENTIONS: The patient was treated for 5 days according to the comprehensive treatment of acute necrotizing pancreatitis, by the inhibition of the secretion of pancreatic juice, relieving pain, and total parenteral nutrition and forbidding diet. The symptoms of the patient were observed to improve, and SAMS and urinary amylase (UAMS) level decreased to 143 IU/L and 254 IU/L, respectively and oral diet was permitted. OUTCOME: After a period of 2 weeks, the contrast abdominal CT showed slightly decreased fluid collection of the peri-pancreatic space. Moreover, it also showed flocculous and linear high-density shadow in the pancreatic tail, suggesting lipiodol deposition in the pancreatic tail. Subsequently, the symptoms were observed to abate, and the patient left the hospital. On the 21st day after TACE, the patient had a follow up in our outpatient department; the biochemical characteristics and inflammatory markers were observed to be normal CONCLUSION:: AP is still a rare complication after TACE. Etiology is still attributed to the occurrence of shunting and embolization drug reflux. Strategies strengthening the catheter tip that is placed as close to the distal branches of the hepatic artery for the possible careful injection of embolic materials is still the key to avoid post-TACE AP.

The Role of Hyaluronidase for the Skin Necrosis Caused by Hyaluronic Acid Injection-Induced Embolism: A Rabbit Auricular Model Study.

BACKGROUND: Skin necrosis is considered the most serious complication of hyaluronic acid dermal filler injection procedures. To effectively treat skin necrosis, hyaluronidase injection is one of the essential preventative treatments, and yet optimal complication management remains an unmet need. Therefore, this paper investigates the effects of hyaluronidase injection timing on the treatment of skin necrosis. METHODS: In an in vitro experiment, the carbazole method was used to determine the degradation time of hyaluronic acid gels in a large volume of hyaluronidase. In vivo experimental rabbit ear models were developed to simulate the skin necrosis caused by hyaluronic acid and the test animals distributed into five groups. Except one control group, the other four groups were injected with a large volume of hyaluronidase as treatment at 2 h, 4 h, 8 h and 16 h, respectively, after models were built. The necrosis degree of models was analyzed with necrotic area and histologic examination on the postoperative 7th day. Besides, temperatures of rabbit ears were observed to demonstrate the healing process of flap models. RESULTS: The average necrotic area of flaps in the 2-h and 4-h injection groups showed a significant difference compared with that of the control group (p < 0.05; p < 0.05). The histologic examination showed that there were HA embolisms, vascular thrombolytic recanalization and arteriovenous thromboses in the survival area. In addition, the mean temperatures of the rabbit ear flaps fluctuated over time and showed clear differences between distal and proximal parts. CONCLUSIONS: The area of flap necrosis positively correlates with injection timing of the large volume of hyaluronidase. More importantly, when injection timing is within 4 h, treatment effectiveness will be significantly improved. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. 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 .

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.

Risk Comparison of Filler Embolism Between Polymethyl Methacrylate (PMMA) and Hyaluronic Acid (HA).

BACKGROUND: The incidence of vascular complications varies among different fillers. The main purpose of this study was to compare the risk of embolism between PMMA (Artecoll) and hyaluronic acid (HA, Restylane) after artery injection. METHODS: Rabbit ears were injected via the central artery with 0.1 ml PMMA (group A), 0.1 ml HA (group B), 0.2 ml PMMA (group C), or 0.2 mL HA (group D), respectively. The formation of transparent emboli was monitored right after injection. Tissue necrosis and histopathological changes were analyzed on day 7. RESULTS: With 0.1 ml injected volume, PMMA was dispersed within a few minutes and only 5% of the injected ears had mild necrosis on day 7, while HA tended to form obvious transparent emboli, an indication of blood vessel clotting, and 60% of injected ears showed necrosis on day 7. With 0.2 ml injected volume, PMMA had a risk of complete blood vessel clotting in between 0.1 ml PMMA group and 0.1 ml HA group, and 30% of injected ears had necrosis; in contrast, 100% of 0.2 ml HA-injected ears showed transparent emboli and necrosis. The necrosis areas were significantly increased in the HA groups compared with PMMA groups at the same injection volumes. HA injection also caused dilation of small blood vessels. CONCLUSION: At the same injection volume, PMMA had less risk of embolism compared with HA. With increased injection volume, there were increased risks of embolism and necrosis for both PMMA and HA. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. 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 .

Presentation and management of symptomatic central bone cement embolization.

BACKGROUND CONTEXT: With more cement augmentation procedures done, the occurrence of serious complications is also expected to rise. Symptomatic central cement embolization is a rare but very serious complication. Moreover, the pathophysiology and treatment of intrathoracic cement embolism remain controversial. PURPOSE: In this case series, we are trying to identify various presentations and suggest our emergent management scheme for symptomatic central cement embolization. PATIENT SAMPLE: Retrospective case series of nine patients with symptomatic central cement embolism identified after vertebroplasty with 24 months of follow-up. Level IV. OUTCOME MEASURES: The degree of dyspnea measured by the New York Heart Association (NYHA) score and/or death related to cement embolism induced cardio/respiratory failure at the final follow-up at 24 months. METHODS: The nine patients, eight females, and one male had a mean age of 70.25 years (range 65-78 years) and were operated between January 2004 and December 2014. They had percutaneous vertebroplasty for osteoporotic non-traumatic and malignant vertebral collapse of dorsal and lumbar vertebrae. Post-vertebroplasty dyspnea and stitching chest pain were striking in the nine patients. After exclusion of cardiac ischemia and medical pulmonary causes for dyspnea, we identified radiopaque lesions on the chest X-ray. Further echocardiography and high-resolution chest CT were performed for optimal localization. Emergent heart surgery was performed in two patients: interventional therapy was conducted in one patient, while the remaining six patients were conservatively treated by anticoagulation. The management decision was taken in the setting of an interdisciplinary meeting depending on localization, fragmentation, and clinical status. RESULTS: All patients of this series showed gradual improvement and an uneventful hospital stay. During our 24-month follow-up phase, eight patients showed no subsequent cardiological and/or respiratory symptoms (NYHA I). However, one mortality due to advanced malignancy occurred. Preoperative anemia was the only common intersecting preoperative parameter among these nine patients. CONCLUSIONS: After cement augmentation, close clinical monitoring is mandatory. A chest CT is pivotal in determining the interdisciplinary management approach in view of the availability of necessary expertise, facilities and the location of the cement emboli whether accessible by cardiac or vascular surgical means. The clinical presentation and its timing may vary and the patient may be seen subsequently by other health care providers obligating a wide-spread awareness for this serious entity among health care providers for this age group as spine surgeons, family and emergency room doctors, and institutional or home-care nurses. Most symptomatic central cement emboli may be treated conservatively.

Exploring the Possibility of a Retrograde Embolism Pathway from the Facial Artery to the Ophthalmic Artery System In Vivo.

BACKGROUND: Blindness caused by soft tissue fillers is an extremely low-probability event, but it results in great concern because of its devastating consequences. Currently, the mechanism of an embolism is usually considered to be an accidental injection of fillers into the blood vessels of the face, such as a facial artery, and then retrograding into the ophthalmic artery system, which causes retinal ischemic necrosis. In addition, previous studies have shown that there are anastomoses between facial arteries and branches of the ophthalmic artery in cadavers. An in vivo study, however, has not yet been reported. METHODS: This study was approved by the institutional review board of Xijing Hospital, Fourth Military Medical University. Under general anesthesia, we dissected the same side of the face and eyeball in rabbits to manifest the facial artery and retina separately. Later, a needle (27 g) connected to a syringe (10 ml) full of methylene blue was inserted into a rabbit facial artery. Then, after poking a tiny hole in the central retinal artery, methylene blue was injected into the facial artery as quickly as possible (0.5 ml per second). At the same time, we carefully observed whether the central retinal artery had dye spillover or staining in the sclera. If blue dye was observed in the eye ground and/or the sclera, then it was thought to have entered the ophthalmic artery system (a positive result). In contrast, if none of the blue dye was observed, it was considered a negative result. A Chi-square (χ 2) test with a fourfold table was used to compare the differences in the frequencies of blue dye observed between living and dead rabbits. A value of p < 0.05 was considered significant. RESULTS: One of the 20 rabbits showed the appearance of blue dye in the ophthalmic artery system in vivo, and the remaining 19 living rabbits had negative results. All 20 of the dead rabbits showed dye appearance in the eye ground. A statistically significant difference existed between the living and dead rabbits (p < 0.05). CONCLUSION: In vivo, fillers can retrogradely enter the ophthalmic artery if the fillers entered the facial artery. Although the possibility is much lower in vivo than it is in corpses, adequate attention should be paid because of the catastrophic complications. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. 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 .

Comparison of Intra-arterial and Subcutaneous Testicular Hyaluronidase Injection Treatments and the Vascular Complications of Hyaluronic Acid Filler.

BACKGROUND: Hyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied. OBJECTIVE: To evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections. MATERIALS AND METHODS: The authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2. RESULTS: Nearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups. CONCLUSION: A complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option.