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Objective A ranula is a mucus-filled salivary pseudocyst that forms in the floor of the mouth, commonly arising from the sublingual or submandibular salivary glands following obstruction or trauma. Complete excision of the injured gland and removal of the cyst content is the first-choice therapy, but has the potential for complications related to injury to nearby structures. As such, minimally invasive approaches such as percutaneous sclerotherapy have been investigated. We aim to contribute to the literature by assessing the efficacy and safety of our technique through our experience with 18 patients over the last decade. Methods This retrospective study evaluated 18 patients with intraoral and plunging ranulas treated by percutaneous bleomycin ablation. The primary endpoint was the treatment result. Secondary endpoints included bleomycin dosage and complications. Results The study evaluated 12 males and six females with a median age of 23.5 years (range 13–39 years). At a final follow-up of at least 2 months (6.5±5.5 months), four patients demonstrated complete response (22%) and 14 patients demonstrated residual presence, recurrence, or regrowth of the lesion (78%). There were no statistically significant associations between outcomes and history of prior treatment, number of treatments, and size or type of ranula. No complications were noted. Conclusions Our findings indicate that bleomycin, while safe for use in various head and neck malformations, is of limited utility in ranula therapy when the offending gland is not addressed primarily.

The present work is dedicated to analysis and comparison of national and international practice standards for treatment of periprosthetic infection within a context of treatment center and speciality of physicians. The authors made a partial review of medical and legal issues related to the studied topic by the example of Russian Federation, Germany, USA, England. 118 orthopaedic surgeons were surveyed via internet aiming to evaluate the current medical practice in treatment of patients with periprosthetic infection. Survey demonstrated that there are clinical and organizational complexities in the medical care system for patients with PJI. Most often the responders reported difficulties in the medical succession and see the potential solution through creation of a network of large specialized centers. Resulting was the conclusion that physicians of all specialities should be involved in treatment of patients with periprosthetic infection. Treatment scope depends on professionalism of a physician and technical equipment of the clinic and should correspond to the best clinical practices (treatment protocols). Thus, a rapid routing of patient into more specialized hospitals. Implementation of such approach is possible with careful balancing between the quality of medical care and its proximity to the patient.

Background Since staged trans-arterial endovascular embolization (TAE) became the main strategy to treat vein of Galen aneurysmal malformation (VGAM), this otherwise lethal disease has become manageable. The antenatally diagnosed cases need proper planning for delivery and neonatal management. Symptomatic neonates with congestive heart failure (CHF) benefit from trans-umbilical TAE with closure of fistulas in order to reduce CHF and improve survival. In infants, symptomatic hydrocephalus or venous hypertension requires urgent TAE to facilitate normal brain development. Even in asymptomatic cases, staged TAE in a safe manner can be beneficial before development delay. Staged TAE of the choroidal feeding arteries has been reported to result in cure. However, some VGAMs remain technically challenging to obtain complete obliteration solely with this technique. If the choroidal feeders are not accessible after prior TAE, other options need to be sought. We reviewed the final few procedures in consecutively cured VGAM patients and assessed the techniques utilized to obtain total obliteration. Materials and Methods This is a retrospective chart and radiographic investigation of a consecutive series of 124 VGAM cases treated between 2004 and 2021 in our institution. Obvious arteriovenous malformation with aneurysmal dilatation of vein of Galen was not included. The strategy in this period was to repeat TAE of the choroidal feeders until the VGAM was totally occluded or until choroidal feeder access was no longer safe. In 81 out of 124 patients, the VGAM was totally or near totally (>95%) obliterated. There were 7 death because of the SHF instead of aggressive TAE or because of the hemorrhagic complication. 36 patients are currently undergoing staged embolization and total obliteration hasn’t been achieved and are therefore excluded from this study. Results Among the 81 cases, 66 cases (81%) achieved total to near total obliteration of the VGAM solely with staged TAE through choroidal artery or thalamoperforating artery feeders. Most of them were found to have total occlusion in the 3 to 6 month follow up angiogram after a final TAE, even when the malformation had been present at the final angiogram in the last TAE. In 4 cases (5%), the dural supply of the malformation was embolized with ONYX from the external carotid artery as the final procedure; and total obliteration was achieved. Transvenous embolization at the last procedure led to complete occlusion of the VGAM in 9 patients (11%). Two cases were referred to stereotactic radiosurgery (SRS) after the age of 10 and total obliteration of the residual malformation was confirmed in the 2 year follow up cerebral angiogram post SRS. There was one hemorrhagic complication occurring in a case after final TVE. Conclusions Staged transarterial n-BCA embolization of the choroidal arteries effected cure of VGAM with a good outcome in more than 80% of the 124 cases. If the access is challenging, multimodal approach with transdural ONYX embolization, transvenous embolization or even SRS can be considered. Further assessment of natural history of patients with near occlusion is warranted. Disclosures T. Shigematsu: None. J. Fifi: None. A. Berenstein: None.

Background Middle meningeal artery (MMA) embolization has emerged as a promising treatment modality for patients with chronic subdural hematoma (SDH). Onyx, particles, or coils are the most used embolic materials. Therefore, the safety and efficacy of n-butyl cyanoacrylate (n-BCA) embolization in these patients are not fully understood. We present the technical feasibility and efficacy of n-BCA embolization in the largest consecutive cohort to date. Methods This study is a retrospective analysis of a prospectively maintained database of consecutive patients with chronic or recurrent SDH treated with MMA embolization using diluted n-BCA with the ‘Sugar- Rush’ technique. Briefly, a 2.1 Fr microcatheter was used to selectively catheterize the distal frontal and posterior branches of the MMA. A 5-Fr intermediate catheter was advanced proximal to the origin of the MMA in the internal maxillary artery and used for Dextrose 5% (Sugar- Rush) injection via a 60 ml syringe while the primary operator was injecting n-BCA through the microcatheter. Complete obliteration of frontal and posterior branch of the MMA and lack of SDH recurrence in 3-6 months follow up CT scan were defined as efficacy outcomes. Cranial nerve palsy, vision loss, transient neurologic deficit and stroke were defined as safety outcomes. Results A total of 61 patients were identified with a mean (±SD) age of 62.5± 9. Seventy eight percent of the patients were male. Median (IQR) NIHSS score was 1 (3), 67% of the patients had midline shift and 36% had bilateral SDH. Forty nine percent of the patients had craniotomy, burr hole or Subdural Evacuating Port System (SEPS) placement prior to embolization. The embolization was performed under MAC anesthesia in 39 (64%) patients and radial access in 29 (48%) patients. In 6 patients (10%), coil embolization of the origin of the frontal or posterior branch was performed as super-selective catheterization of the branch was unsuccessful due to tortuous anatomy. Complete obliteration of frontal and posterior branches was achieved in 100% of the cases. In 25% of the patients, n-BCA penetrated the contralateral side. Follow up CT scan at 3-months and 6- months were available in 91% of the patients. Recurrent SDH was seen in only 1 patient on the side contralateral to treatment. No incidence of cranial nerve palsy, vision loss, or stroke occurred. One patient suffered a transient neurological deficit. Conclusion MMA embolization using diluted n-BCA with concomitant Dextrose 5% injection (Sugar-Rush) is associated with a high degree of distal penetration and complete branch occlusion and minimal risk of cranial nerve palsy or other thrombo-embolic complications. Clinical trials are warranted to compare long-term efficacy of this procedure with standard of care management. Disclosures S. Majidi: None. S. Matsoukas: None. R. De Leacy: None. P. Morgenstern: None. R. Soni: None. H. Shoirah: None. T. Shigematsu: None. J. Bederson: None. A. Berenstein: None. J. Mocco: None. J. Fifi: None. C. Kellner: None.

Background: Intra-articular treatment of knee osteoarthrosis (OA) with hyaluronic acid (IA-HA) is frequently used in Argentina, with different dosing forms and injection regimens. Our main objective was to provide real world data on the use and effectiveness of IA-HAMethods: In this observational retrospective cohort study we studied 1227 patients with knee osteoarthrosis treated with IA-HA 20mg/2ml weekly (76%-20mg group) and 40mg/2ml (24%-40mg group) according to usual practice intervals. Follow up was at 6 months and efficacy assessed by 5 point Likert scale and 50% or more response rate.Results: Median number of applications was 5 (20mg) and 3 (40mg). Both groups had a significant improvement in the Likert scale from baseline to 6 month. Median score improved from 4 (mean 3.77 ±0.69) at baseline to median of 2 (mean 1.99 ±0.76) at 6 months (20mg group, p

While infantile hemangiomas are very common, congenital hemangiomas are rare and less understood. Congenital hemangiomas are present at birth. They fall into 2 major categories: rapidly involuting congenital hemangioma and noninvoluting congenital hemangioma. Noninvoluting congenital hemangioma is the rarer of the 2 entities. If not recognized and treated appropriately, noninvoluting congenital hemangioma can lead to considerable morbidity. There is a paucity of literature regarding noninvoluting congenital hemangiomas. In this article, we will outline our experience with this condition, focusing on clinical and angiographic features. There is a distinct angiographic appearance of noninvoluting congenital hemangiomas involving an arterial-capillary web, a dense tumor blush with identifiable feeding arteries, no arteriovenous shunting, and variably present draining veins. Our experience with endovascular embolization and direct percutaneous treatment is the largest for this entity to date. Endovascular embolization and/or direct percutaneous sclerotherapy of this lesion may obviate subsequent surgical resection.

Background Management of vascular malformations requires microcatheter manipulation through distal tortuous arterial feeders Methods The use of the ACM in conjunction with flow-directed and over-the-wire microcatheters was evaluated in 25 neuroendovascular cases performed by a single operator for endovascular microcatheter embolization of intracranial vascular malformations over a 1-year period. The study evaluated angiographic evidence of distal microcatheter positioning, subsequent obliteration of the fistula at the location, and any complications. Results The microguidewire was used in microcatheter embolization of 10 vein of Galen malformations, 11 brain and head and neck arteriovenous malformations, 2 spinal dural arteriovenous fistulas, and 2 cranial dural arteriovenous fistulas. Good flow-directed and over-the-wire microcatheter placement using the ACM was possible across the spectrum of cases achieving optimal catheterization and safe embolization in all. There were no microguidewire- or microcatheter-related vessel spasms, dissections, or perforations during combined or individual manipulation and no contrast or embolic extravasation on fluoroscopy or postembolization angiography. Conclusions The ACM is a safe, sturdy microguidewire that provides good torque in distal arterial anatomy, while providing microcatheter support and maintaining tip configuration on repeated use.

Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, data on NF safety are scarce, and many physicians defer or refuse NF treatment because of concerns about drug tolerance. In a retrospective study of adverse drug reactions (ADRs) associated with NF treatment of ChD, children received NF doses of 10 to 15 mg/kg/day for 60 to 90 days, and adults received 8 to 10 mg/kg/day for 30 days. A total of 215 children (median age, 2.6 years; range, 0 to 17 years) and 105 adults (median age, 34 years; range, 18 to 57 years) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 adults and 63/215 children (odds ratio [OR] = 3.7; 95% confidence interval [CI], 2.2 to 6.3). We observed 215 ADRs, 131 in adults (median, 2 events/patient; interquartile range for the 25th to 75th percentiles [IQR25-75], 1 to 3) and 84 in children (median, 1 event/patient; IQR25-75 = 1 to 1.5) (Padjusted, 0.001). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous, and digestive systems were the most frequently affected, without differences between groups. Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95% CI = 1.5 to 24). Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence. (This study has been registered in ClinicalTrials.gov under identifier NCT04274101). Fil: Berenstein, Ariel José. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Falk, Nicolás Ariel. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Moscatelli, Guillermo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: González, Nicolas. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Garcia Bournissen, Facundo. Western University; Canadá Fil: Ballering, Griselda Edith. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Freilij, Hector León. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina

Background and importance Evidence suggests middle meningeal artery (MMA) embolization benefits adult patients with chronic subdural hematoma (CSDH) at high risk for recurrence or hemorrhagic complications. Yet, there has not been any report discussing MMA embolization in the pediatric population. Thus, we present a case of an infant with CSDH successfully managed with MMA embolization without surgical management. Clinical presentation A 5-mo-old girl with idiopathic dilated cardiomyopathy underwent surgical implantation of a left ventricular assist device for a bridge to heart transplantation. This was complicated by left ventricular thrombus causing stroke. She was placed on dual antiplatelet antithrombotic therapy on top of bivalirudin infusion. She sustained a left middle cerebral artery infarction, but did not have neurological deficits. Subsequent computed tomography scans of the head showed a progressively enlarging asymptomatic CSDH, and the heart transplant was repeatedly postponed. The decision was made to proceed with MMA embolization at the age of 7 mo. Bilateral modified MMA embolization, using warmed, low-concentration n-butyl-cyanoacrylate (n-BCA) from distal microcatheter positioning, allowed the embolic material to close the distal MMA and subdural membranous vasculature. The patient underwent successful heart transplant and the CSDH improved significantly. She remained neurologically asymptomatic and had normal neurological development after the MMA embolization. Conclusion MMA embolization may represent a safe and effective minimally invasive option for pediatric CSDH, especially for patients at high risk for surgery or hematoma recurrence.

Ever since screening for early breast cancer (BC) diagnosis was shown to decrease mortality from the disease, screening programs have been widely implemented throughout the world. Targeted age groups and schedules vary between countries but the majority use a population-based approach, regardless of personal BC risk. The purpose of this review was to describe current population-based screening practices, point out some of the shortcomings of these practices, describe BC risk factors and risk assessment models, and present ongoing clinical trials of personalized risk-adapted BC screening. Three ongoing, large-scale, randomized controlled clinical trials (WISDOM in the US, MyPEBS in Europe, and TBST in Italy) were identified through a search of the MEDLINE and US National Library of Medicine (ClinicalTrials.gov) databases. In these trials, women either undergo standard or personalized screening. The trials vary in methods of risk stratification and screening modalities, but all aim to examine whether personalized risk-adapted screening can safely replace the current population-based approach and lead to rates of advanced-stage BC at diagnosis comparable with those of current screening regimens. The results of these trials may change current population-based screening practices.

Salivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis., Graphical Abstract, Permanent salivary hypofunction is a major complication due to irradiation therapy in head and neck cancer patients. Lombaert et al. present a key translational advance where retro-ductal infusion of an adeno-associated virus serotype 2 (AAV2) vector expressing neurotrophic factor neurturin (CERE-120) into mouse and porcine salivary glands before irradiation reduces fibrosis, restores immune homeostasis, and prevents loss of saliva.

Duchenne muscular dystrophy (DMD) is a degenerative lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Cell therapy using different cell types, including mesenchymal stromal cells (MSCs), has been considered as a potential approach for the treatment of DMD. MSCs can be obtained from autologous sources such as bone marrow and adipose tissues or from allogeneic placenta and umbilical cord. The safety and therapeutic impact of these cells has been demonstrated in pre-clinical and clinical studies and their functions are attributed to paracrine effects that are mediated by secreted cytokines and extracellular vesicles. Here, we studied the therapeutic effects of placenta-derived MSCs (PL-MSCs) and their secreted exosomes using mouse and human myoblasts from healthy controls, Duchenne patients and mdx mice. Treatment of myoblasts with conditioned medium or exosomes secreted by PL-MSCs increased the differentiation of these cells and decreased the expression of fibrogenic genes in DMD patient myoblasts. In addition, these treatments also increased the expression of utrophin in these cells. Using a quantitative miR-29c reporter, we demonstrated that the PL-MSC effects were partly mediated by the transfer of exosomal miR-29c. Intramuscular transplantation of PL-MSCs in mdx mice resulted in decreased creatine kinase levels. PL-MSCs significantly decreased the expression of TGF-β and the level of fibrosis in the diaphragm and cardiac muscles, inhibited inflammation and increased utrophin expression. In vivo imaging analyses using MSCs labeled with gold nanoparticles or fluorescent dyes demonstrated localization of the cells in the muscle tissues up to 3 weeks post treatment. Altogether, these results demonstrate that PL-MSCs and their secreted exosomes have important clinical applications in cell therapy of DMD partly via the targeted delivery of exosomal miR-29c.

An unusual case of parasitism by Lagochilascaris minor infection is reported in a 38-year-old woman from Paraupebas, Para, Brazil. The article summarizes the main characteristics of the disease and its etiological agent, including prevalence, life cycle, clinical course and treatment.

Vein of Galen malformations (VOGMs) are rare developmental cerebrovascular lesions characterized by fistulas between the choroidal circulation and the median prosencephalic vein. Although the treatment of VOGMs has greatly benefited from advances in endovascular therapy, including technical innovation in interventional neuroradiology, many patients are recalcitrant to procedural intervention or lack accessibility to specialized care centers, highlighting the need for improved screening, diagnostics, and therapeutics. A fundamental obstacle to identifying novel targets is the limited understanding of VOGM molecular pathophysiology, including its human genetics, and the lack of an adequate VOGM animal model. Herein, the known human mutations associated with VOGMs are reviewed to provide a framework for future gene discovery. Gene mutations have been identified in 2 Mendelian syndromes of which VOGM is an infrequent but associated phenotype: capillary malformation–arteriovenous malformation syndrome (RASA1) and hereditary hemorrhagic telangiectasia (ENG and ACVRL1). However, these mutations probably represent only a small fraction of all VOGM cases. Traditional genetic approaches have been limited in their ability to identify additional causative genes for VOGM because kindreds are rare, limited in patient number, and/or seem to have sporadic inheritance patterns, attributable in part to incomplete penetrance and phenotypic variability. The authors hypothesize that the apparent sporadic occurrence of VOGM may frequently be attributable to de novo mutation or incomplete penetrance of rare transmitted variants. Collaboration among treating physicians, patients’ families, and investigators using next-generation sequencing could lead to the discovery of novel genes for VOGM. This could improve the understanding of normal vascular biology, elucidate the pathogenesis of VOGM and possibly other more common arteriovenous malformation subtypes, and pave the way for advances in the diagnosis and treatment of patients with VOGM.

Purpose Dilated superior ophthalmic vein (SOV) is an uncommon radiographic finding. The authors review the presentation, etiology, radiography, and visual implications of 113 patients with dilated SOV. Methods An observational case series and multicenter retrospective chart review were conducted. There were 113 patients with a dilated SOV. Outcome measures included patient demographics, clinical features, radiographic findings, diagnosis, and treatment, and treatment outcomes were assessed. Results Cases included 75 women (66%) and 38 men (34%) with a mean age of 49 ± 24 years (range, 0.4-90 years). Diagnoses fell under 6 categories: vascular malformation (n = 92, 81%), venous thrombosis (n = 11, 10%), inflammatory (n = 6, 5%), traumatic hemorrhage (n = 2, 2%), lymphoproliferative (n = 1, 1%), and infectious (n = 1, 1%). Imaging modalities utilized included MRI (n = 98, 87%), digital subtraction angiography (n = 77, 68%), CT (n = 29, 26%), and ultrasonography (n = 4, 4%). Disease status at last follow up included no evidence of disease (n = 57, 50%), alive with persistent disease (n = 53, 47%), and expired from disease (n = 3, 3%). Treatment and management was tailored to the underlying disease process with a mean follow up of 18 months (range, 1 day to 180 months). Visual impairment observed at presentation and last follow up across all cases was 26% and 22%, respectively. Conclusion Dilated SOV is a rare radiographic finding resulting from a wide spectrum of etiologies with clinical implications ranging from benign to sight- and life-threatening. Dilated SOV is most often found with dural-cavernous fistula or carotid-cavernous fistula, orbital or facial arteriovenous malformation, and venous thrombosis. Recognition of this finding and management of the underlying condition is critical.

Literature describing neodymium:yttrium-aluminum-garnet (Nd:YAG) photocoagulation and sclerotherapy for laryngeal venous malformations (VMs) is sparse. Here we present a case in which an extensive laryngeal VM in a 28-year-old female was managed through a combination of four serial Nd:YAG laser photocoagulation sessions and four bleomycin injections over the course of 2 years. The treatment plan resulted in resulted in noticeable lesion ablation, mucosalization, and significant improvement in symptoms. To our knowledge, this case is the first instance of bleomycin injection specifically into a laryngeal VM reported in the English medical literature. Laryngoscope, 130:2199-2201, 2020.

The treatment of congenital clubfoot has been changing rapidly since the mid-1990s with the worldwide use of the Ponseti method for serial casting and limited operative interventions. This method was first applied for isolated clubfeet and later on for other types of clubfoot (teratologic, residual, and neurogenic). Premature babies sustaining clubfoot commonly suffer from additional congenital and acquired medical problems. These may postpone clubfoot management until urgent issues are resolved. The current study describes early initiation of treatment of clubfoot in premature babies at the neonatal intensive care unit (NICU) and their outcomes. The study group included all babies diagnosed with clubfoot and managed in the NICU (for any etiology) between 2006 and 2012. Management was based on the Ponseti protocol for serial casting. We also report on neonates who died in the NICU before or during treatment. We specifically describe adverse events of early casting and situations necessitating removal of casts or termination of treatment. We diagnosed and treated 20 neonates with clubfoot (four females and 16 males, 10 bilateral cases). Gestational age ranged from 27 weeks to term. Eight were identified with clubfoot by prenatal sonographic survey and 10 were diagnosed with a defined syndrome. Seven had respiratory support, including one with a chest drain (50%). Length of stay in the NICU ranged from 3 to 90 days. Four neonates died while in the NICU (all syndromatic). In the remaining 16 cases, treatment began as early as medically possible. The first cast was applied within the first week of life in 14 cases. A total of 75 casts were applied during the study period. Three casts (4%) were removed because of leg edema or a need for venous access. Casts were routinely replaced every 4-7 days. Achilles tenotomies were performed in the NICU for babies achieving satisfactory correction. At last follow-up, 10 children were independent walkers and six were nonambulatory; all showed successful correction of clubfeet. The results of this study show that in most cases, clubfoot treatment is feasible and effective within the first week of life. Instances necessitating immediate cast removal are highlighted. Although while facing acute life-threatening medical problems, the treatment of clubfoot may not be considered a priority, most neonates will grow up into independent individuals; thus, every effort should be made to initiate the best clubfoot management with minimal delay.

BackgroundAnimal experimental studies are crucial for the development of endovascular devices and embolization techniques for intracranial aneurysms. The aim of the study was to describe the surgical creation technique for an aneurysm with a dilated shape and no definable aneurysm neck. The model should be reproducible in size and shape and stay patent over a long period of time. It should constitute a challenge to endovascular therapy and provide a valuable testing environment for new endovascular devices and techniques.MethodsSurgical creation of 30 no-neck aneurysms was attempted in 15 New Zealand White rabbits using a segment of jugular vein, which was transected, longitudinally opened and sutured to the anterior aspect of the common carotid artery. The first 14 aneurysms were used to develop the technique. Once the technique was mastered and the procedure was standardized, 16 consecutive aneurysms were created. For these aneurysms, digital subtraction angiography was employed after a mean of 120 days to confirm size and patency. All aneurysms were evaluated for patency.ResultsOverall aneurysm patency was 93%. Three complications occurred, two of which were related to the vascular anastomosis. Angiographic follow-up showed a median (SD) aneurysm base and height of 6.7 (0.76) mm and 3.2 (0.85) mm), respectively.ConclusionsThis technique allows creation of aneurysms without a neck which are reproducible in size and shape, and which remain patent. The model contributes to the list of aneurysm models fit for evaluation of embolization devices and techniques. It is particularly useful in exploring treatment options for wide-neck aneurysms and aneurysms which presently do not qualify for conventional coiling.

Duchenne muscular dystrophy (DMD) is a progressive, lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Loss of dystrophin leads to muscle fiber damage and impairment of satellite cell asymmetric division, which are essential for muscle regeneration. These processes ultimately result in muscle wasting and the replacement of the degenerating muscles by fibrogenic cells, a process that leads to the generation of fibrotic tissues. Preimplantation factor (PIF) is an evolutionary conserved 15-amino acid peptide secreted by viable mammalian embryos. Synthetic PIF (sPIF) reproduces the protective/regenerative effects of the endogenous peptide in immune disorders and transplantation models. In this study, we demonstrated that sPIF treatment promoted mouse and human myoblast differentiation and inhibited the expression of collagen 1A1, collagen 1A2, and TGF-β in DMD patient-derived myoblasts. Additionally, sPIF increased the expression of utrophin, a homolog of dystrophin protein. sPIF effects were mediated via the upregulation of lncRNA H19 and miR-675 and downregulation of let-7. sPIF also inhibited the expression of miR-21, a major fibrosis regulator. The administration of sPIF in mdx mice significantly decreased serum creatine kinase and collagen I and collagen IV expression in the diaphragm, whereas it increased utrophin expression in the diaphragm, heart and quadriceps muscles. In conclusion, sPIF promoted the differentiation of DMD myoblasts, increased utrophin expression via the H19/miRNA-675/let-7 pathway, and reduced muscle fibrosis possibly via the upregulation of miR-675 and inhibition of miR-21 expression. These findings strongly support pursuing sPIF as a potential therapeutic agent for DMD. Moreover, the completion of an sPIF phase I safety trial will further promote the use of sPIF for the treatment of muscular dystrophies.

An understanding of the vascular architecture of paragangliomas can aid in both diagnosis and treatment. There is a growing role for vascular evaluation and intervention of these highly vascular tumors. This article addresses the specifics of the vasculature of paragangliomas, with focus on preoperative imaging, preoperative balloon test occlusion and endovascular embolization. The authors present both common and improvised techniques.

RASA1-related disorders are vascular malformation syndromes characterized by hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. The number of cases reported is relatively small; and while the main clinical features are CMs and AVMs/AVFs, the broader phenotypic spectrum caused by variants in the RASA1 gene is still being defined. Here, we report the clinical and molecular findings in 69 unrelated cases with a RASA1 variant identified at ARUP Laboratories. Sanger sequencing and multiplex ligation-dependent probe amplification were primarily used to evaluate RASA1. Several atypical cases were evaluated using next-generation sequencing (NGS) and array-comparative genomic hybridization (aCGH). Sixty individuals had a deleterious RASA1 variant of which 29 were novel. Nine individuals had a variant of uncertain significance. Five large RASA1 deletions were detected, giving an overall deletion/duplication rate of 8.3% (5/60) among positive cases. Most (75.4%) individuals with a RASA1 variant had CMs, and 44.9% had an AVM/AVF. Clinical findings in several cases expand the RASA1 phenotype. Our data suggest that screening for large RASA1 deletions and duplications in this disorder is important and suggest that NGS multi-gene panel testing is beneficial for the molecular diagnosis of cases with complex vascular phenotypes.

PurposeTo evaluate the clinical outcome of patients with venous malformation (VM) involving the eyelid treated with bleomycin sclerotherapy.MethodsA retrospective review was performed of 18 consecutive patients with VM involving the eyelid who underwent bleomycin sclerotherapy. Patients’ clinical presentation, details of sclerotherapy, and post-sclerotherapy resolution of the lesion as well as any procedure-related complications were evaluated.ResultsTwelve women and six men of mean age 34.3±20.4 years underwent sclerotherapy with bleomycin. Chief complaints were cosmetic disfigurations with or without hemifacial deformity (n=2), pain in engorgement area (n=2), pain and swelling from venous thrombosis (n=2), swelling or engorgement obstructing their eyesight (n=2), or eyelid dysfunction (n=1). The lesions were only in the eyelid in three patients; otherwise they were extended out of the eyelid either superiorly (n=3), laterally (n=8), inferiorly (n=8), and/or posteriorly to the orbit (n=8) to various extents. Conjunctival involvement was present in 13 patients. 14 patients had received prior treatments including surgery, laser therapy, or non-bleomycin sclerotherapy. With an average three sessions of bleomycin sclerotherapy (average total dose 34.5 mg), more than 80% shrinkage was observed in seven patients (38.9%), 50–80% shrinkage in eight patients (44.4%), and 30–50% shrinkage in two patients (11.1%). One patient had recurrence, which was successfully treated again with bleomycin. No procedure-related complications were noted.ConclusionsThe use of bleomycin appears to be a simple, safe, and effective treatment for venous malformations involving the eyelid, avoiding more elaborate and challenging surgical or laser interventions, and is even effective in full thickness lesions.

BACKGROUND AND PURPOSE: Spinal cord AVMs represent rare and insufficiently studied pathologic entities. Embolization is thought to play an important role in the management of spinal cord AVMs. Factors for recurrent hemorrhage and the impact of endovascular treatment on prevention of recurrent hemorrhage remain to be confirmed. We aimed to assess recurrent hemorrhagic incidence of spinal cord AVMs and its prevention by endovascular treatment. MATERIALS AND METHODS: We reviewed 80 patients with spinal cord AVMs by spinal cord angiography who had hemorrhage before the first endovascular treatment at New York University Medical Center, Beth Israel Medical Center, or Roosevelt Hospital in New York. We compared the baseline and radiologic characteristics of patients with and without recurrent hemorrhage by the log-rank test and the Cox proportional hazards model. RESULTS: We observed recurrent hemorrhage in 35 (44%) patients (1/41 patients with endovascular treatment and 34/39 patients without endovascular treatment). The median length of total follow-up was 659 days (interquartile range, 129–2640 days), and the median length from first-to-recurrent hemorrhage was 369 days (interquartile range, 30–1596 days). The log-rank test revealed that endovascular treatment and venous thrombosis reduced recurrent hemorrhage, and associated aneurysm was related to recurrent hemorrhage. Even in multivariate analysis, the endovascular treatment reduced (hazard ratio, 0.027; P < .0001) and associated aneurysm increased (hazard ratio, 3.4; P = .044) the risk of recurrent hemorrhage. CONCLUSIONS: Endovascular embolization is the first choice of treatment for spinal cord AVMs and is effective in preventing recurrent hemorrhage.

Objectives/Hypothesis To describe a multidisciplinary approach to the treatment of airway vascular malformations (venous or lymphatic) with direct suspension rigid laryngoscopy and direct puncture transmucosal bleomycin sclerotherapy injected under road-mapping fluoroscopic monitoring, supplemented by Dyna-computed tomography utilization. Study Design Case series. Methods We performed a retrospective medical record and imaging review of four patients with venous malformations or lymphatic malformations located in the airway. Patients were treated with a combination of direct suspension laryngoscopy or rigid nasopharyngoscopy and image-guided direct puncture bleomycin sclerotherapy. Results Two patients presented to our institution with extensive lymphatic malformation of the neck, parapharyngeal, and retropharyngeal spaces, and two presented with venous malformation of the nasopharynx and oropharynx. All patients were treated with multiple sclerotherapy and debulking procedures before undergoing combined direct transmucosal puncture bleomycin sclerotherapy guided by direct laryngoscopy or nasopharyngoscopy. All patients had complete resolution of disease while maintaining a safe airway. Conclusions A multidisciplinary approach to airway vascular malformations with a combination of endoscopy and direct puncture bleomycin sclerotherapy was demonstrated to be a safe and effective treatment in our patient cohort. Direct laryngoscopy and nasopharyngoscopy provide easy access to the nasopharynx, oropharynx, retro- and/or parapharyngeal spaces and larynx. Unlike traditional agents, bleomycin induces minimal edema and therefore is an ideal substance to treat airway lesions. Level of Evidence 4. Laryngoscope, 126:205–211, 2016

While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention. Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Serra, M. Elina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Marzec, Jacqui. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Gibbons, Luz. Institute For Clinical Effectiveness And Health Policy, Ciudad Autonoma de Buenos Aires; Argentina Fil: Salim, Maximiliano. Hospital Evita Pueblo; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Rodriguez, Andrea. Hospital Mi Pueblo; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Reynaldi, Andrea. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Garcia, Alejandro. Fundación para la Investigación en Infectología Infantil; Argentina. Unidad Asistencial "Dr. César Milstein"; Argentina Fil: Bado, Daniela. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Buchholz, Ursula J.. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Hijano, Diego Raúl. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Newcomb, Dawn. Vanderbilt University; Estados Unidos Fil: Bellabarba, Miguel. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Ferolla, Fausto Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Vanderbilt University; Estados Unidos Fil: Berenstein, Ada. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Siniawaski, Susana. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Blumetti, Valeria. Swiss Medical Center; Argentina Fil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Medica E Invest.clinicas; Argentina Fil: Pinto, Leonardo. Fundación para la Investigación en Infectología Infantil; Argentina. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Lawrence, Andrea. Vanderbilt University; Estados Unidos Fil: Ossorio, Maria Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Grosman, Arnoldo. Hospital Espanol; Argentina Fil: Mateu, Cecilia Gabriela. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bayle, Carola. Hospital Nacional Professor Dr. Alejandro Posadas; Argentina Fil: Dericco, Alejandra. Hospital Nacional Professor Dr. Alejandro Posadas; Argentina Fil: Pellegrini, Mariana. Hospital Nacional Professor Dr. Alejandro Posadas; Argentina Fil: Igarza, Ignacio. Hospital Nacional Professor Dr. Alejandro Posadas; Argentina Fil: Repetto, Horacio A.. Hospital Nacional Professor Dr. Alejandro Posadas; Argentina Fil: Grimaldi, Luciano Alva. Hospital Zonal General de Agudos Lucio Meléndez; Argentina Fil: Gudapati, Prathyusha. Vanderbilt University; Estados Unidos Fil: Polack, Norberto R.. Unidad Asistencial "Dr. César Milstein"; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Shi, Min. National Institute of Environmental Health Sciences ; Estados Unidos Fil: Ferrero, Fernando Claudio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Stein, Renato T.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Peebles, R. Stokes. Vanderbilt University; Estados Unidos Fil: Boothby, Mark. Vanderbilt University; Estados Unidos Fil: Kleeberger, Steven R.. National Institute Of Environmental Health Sciences; Estados Unidos Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos

Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.

Background Percutaneous radiofrequency ablation (RFA) has been shown to be an effective treatment for soft tissue lesions and also benign bone tumors, especially osteoid osteoma. There are limited data regarding this technique in other bone tumors, specifically larger and more aggressive ones. Purposes To describe the use of RFA as a definitive treatment and an alternative to traditional open surgery for the treatment of chondromyxoid fibroma (CMF), a benign but locally aggressive bone tumor. Case presentation An 11.5-year-old girl was diagnosed with a 4-cm lytic bone lesion of the distal fibula. Evaluation, including biopsy, revealed CMF. It was managed by fluoroscopy-guided RFA only. Six-year follow-up demonstrated complete healing without damage to the adjacent distal fibular growth plate. Discussion and conclusions RFA induces local heat in the ablation field and causes tissue necrosis. The depth of heat penetration and the size of heated sphere are accurately controlled by modern types of ablation probes and accurate positioning. The current report demonstrates the ability to use this percutaneous technique for larger and more aggressive bone tumors than has been indicated previously.

BACKGROUND Vein of Galen aneurysmal malformation (VGAM) is a rare congenital vascular malformation representing

Previously we have reported that metastatic melanoma cell lines and tumor specimens have reduced expression of ADAR1 and consequently are impaired in their ability to perform A-to-I microRNA (miRNA) editing. The effects of A-to-I miRNAs editing on melanoma growth and metastasis are yet to be determined. Here we report that miR-378a–3p is undergoing A-to-I editing only in the non-metastatic but not in metastatic melanoma cells. The function of the edited form is different from its wild-type counterpart. The edited form of miR-378a-3p preferentially binds to the 3′-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotype. Indeed, edited miR-378a-3p but not its WT form inhibits melanoma metastasis in vivo. These results further emphasize the role of RNA editing in melanoma progression., In melanoma, reduced ADAR1 impairs A-to-I microRNA editing. Here, the authors show that miR-378a-3p undergoes this editing in non-metastatic cells and the edited form of miR-378a-3p binds to the PARVA oncogene, inhibiting its expression and preventing melanoma progression and metastasis.

Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options. O cisto do ducto tireoglosso (TDC) é uma expansão cística de um remanescente do trato do ducto tireoglosso. Carcinomas no TDC são extremamente raros e geralmente são achados incidentais após o procedimento de Sistrunk. Neste relato, é apresentado um caso incomum de uma mulher de 36 anos com carcinoma papilífero de tireoide concomitante surgindo no TDC e na glândula tireoide, seguido de uma discussão sobre as controvérsias em torno das possíveis origens de um carcinoma papilífero no TDC . , bem como as opções de gerenciamento atuais.

This article reports a case of primary cardiac angiosarcoma and a brief review is provided. A 44-year-old male patient was suspected of having myxoma in the right atrium. The tumor, on pathology examination, was shown to be a cardiac angiosarcoma. In the postoperative period, the patient developed a cardiac tamponade, requiring reoperation and evolving to death. Angiosarcomas are malignant tumors characterized by a devastating clinical course. They have a predilection for the right atrium, occurring between the third and fifth decades of life, with a male preponderance. Because of its rarity, the ideal treatment has not been identified yet.

Introduction Endovascular embolization of intracranial vascular malformations with N-butyl cyanoacrylate (nBCA) using a detachable tip microcatheter allows prolonged injection and decreases the risk of catheter retention. Methods Between March and December 2013, the Apollo 1.5 cm detachable tip microcatheter was used in five patients after being approved by both the Food and Drug Administration and the institutional review board as a compassionate use device. Nine pedicles were embolized and the follow-up ranged from 1 to 3 months. Results Five of the nine catheter tips detached. The length of reflux was not directly associated with the detachment of the distal tip. There were no cases of premature microcatheter detachment during navigation, manipulation with multiple microguidewire reintroduction and guidance. There was no leak of embolic agent at the detachment zone. Follow-up showed the detached tip to be stable without migration. Conclusions A detachable tip microcatheter offers an advance in the safety and effectiveness of nBCA embolization. Catheter retrieval becomes more controlled and less traumatic. Our initial experience is encouraging, and more experience is needed to categorically ascertain its safety and efficacy.

Objective To develop a more reliable methodology for monitoring the facial nerve in surgeries of vascular malformations where the extracranial segment of the nerve is at risk. Methods Our methodology comprises: (1) preoperative mapping to identify the anatomical location of the nerve branches, (2) continuous intraoperative monitoring of the compound muscle action potential (CMAP) by stimulating the facial nerve extracranially, in close proximity to where the trunk of the facial nerve exits the skull at the stylomastoid foramen, (3) intraoperative mapping to identify the nerve branches during surgical dissection and quantify the innervating contribution of each branch to the target muscle. Results Only three out of 201 surgeries (1.5%) had complete facial nerve trunk injury as a consequence of facial vascular malformation surgery. Conclusions We developed a new method to continuously stimulate the facial nerve extracranially eliciting an objective parameter—the CMAP amplitude—to constantly measure changes in the muscle responses throughout surgery, alerting the surgeon before the facial nerve is severely injured. Our methodology notably reduces the complete facial nerve injury during extracranial surgery of facial vascular malformations. Significance This comprehensive methodology may also be a valuable tool to prevent facial nerve injury during other types of extracranial surgeries where radical excisions are required.

Summary Introduction Onyx as an embolization agent for the management of vascular malformation is well established. We report our initial experience with dimethyl-sulphoxide (DMSO) compatible double lumen balloon catheters used for Onyx embolization. Methods and technique Between December 2011 and March 2013, we treated 22 patients aged between 1.5 to 70 years with two types of DMSO compatible dual-lumen balloon catheters (Scepter C and Ascent) to treat dural arteriovenous fistulas, brain arteriovenous malformation (AVM) with dural feeders, mandibular, facial, lingual, vertebral and paravertebral AVMs. The catheter has good navigability, compliant balloon on inflation formed a “plug” that has more resistance than Onyx plug enhancing better penetration. During injection, the balloon remained stable without spontaneous deflation or rupture and withstood the pressure build-up well. The retrieval of the catheter in most cases took less than a minute (19/28) while in five, it was less than five minutes and in the remaining four, it was longer that includes a trapped catheter on prolonged attempted retrieval resulted in an epidural hematoma, requiring emergent surgical evacuation. The fluoroscopy time is reduced, as we do not form a proximal onyx plug, the injection time is shorter along with easy and instantaneous removal of the catheter after balloon deflation in most cases. Conclusion Dual-lumen balloon catheter Onyx embolization is a safe and effective technique. Currently, an important tool to circumvent some of the shortcomings associated with Onyx embolization. The catheter has good navigability, the balloon has stability, tolerance, enhances penetrability. It is easy to retrieve the microcatheter. With the experience gained, and with more compliant balloon catheters available, this technique can be applied to cerebral vessels in near future.

In 1976 an infant boy initially presented with a choroidal vein of Galen malformation (cVOGM). Craniotomy and clipping of the anterior cerebral artery and posterior choroidal arteries was performed, which was reported in the literature 40 years ago. The patient remained asymptomatic until age 42 when he re-presented with an isolated intraventricular hemorrhage. Angiography demonstrated cVOGM with venous sinus occlusive disease leading to venous hypertension and subsequent intraventricular hemorrhage. The angiogram also demonstrated a ‘pseudo-nidus’ composed of multiple arterial-to-arterial anastomoses that had developed as a result of the original surgical treatment. We embolized a portion of the lesion to reduce the venous hypertension. The patient has been asymptomatic for more than 2 years. To our knowledge, this is the first reported case of a symptomatic neonatal VOGM treated with open surgery that required embolization as an adult for a delayed hemorrhagic presentation.

Key differences exist in the epidemiology, pathophysiology, and clinical presentation of vascular lesions of the cerebellum in children versus adults. An understanding of these differences and an appreciation of the distinct imaging features of these lesions aid in distinguishing normal vascular variations from pathology, in predicting lesion etiology, and in directing effective treatment strategies. This paper reviews the embryogenesis of the normal vascular system of the cerebellum and brainstem and then discusses the clinical and imaging features of the common vascular lesions affecting these structures in the pediatric population.

BackgroundIntracranial vascular malformations in children are being addressed through a variety of treatment modalities including open surgery, external beam radiation, and image-guided neuroendovascular procedures. These patients often receive multiple treatments and incur serial exposures to ionizing radiation which has been linked to tumor development in population-based data.ObjectiveThis study quantifies the effect of collimation on exposures from single procedures and over patient lifetimes to estimate excess risk of lifetime tumor development.Methods215 patients aged 0–21 years from a single center took part in the study. Radiation exposure from neuroendovascular procedures was tabulated and converted to brain doses using modeled data and extrapolated to risk ratios using results of population-based estimates found in the literature.ResultsLifetime and per procedure risk was highest in patients with brain arteriovenous malformations, brain arteriovenous fistulas, and vein of Galen malformations, a reflection of our institutional referral patterns. Across all pathologies the per procedure excess relative risk decreased from 13.4 to 2.3 when full collimation was employed. Lifetime excess relative risk decreased from 49.0 to 7.7 for full collimation.ConclusionsThis is the first study to quantify the effect of collimation on lifetime and per procedure risk of tumor development in a pediatric population. In addition to collimation, technical and operator-based aspects of the neurointerventional suite are discussed to further reduce patient exposure without sacrificing image quality.

OBJECTIVE: To demonstrate the relationship between the size, degree of retraction and topography of rotator cuff injuries and the degree of rise of the humeral head, and to evaluate the influence of gravity, using magnetic resonance imaging (MRI). METHODS: We evaluated 181 shoulder MRIs from 160 patients aged over 45 years, between November 2013 and July 2014. The patients were divided into two groups: one control (no lesion or partial damage to the rotator cuff); and the other with complete tears of the rotator cuff. We measured the acromiohumeral distance in the sagittal plane, and established the shortest distance between the apex of the head and the acromion. RESULTS: In this study, 96 examinations on female patients (53.04%) and 58 on male patients (46.96%) were evaluated. The mean age was 63.27 years: in the control group, 61.46; and in the group with injuries, 65.19. From analysis on the measurements of the subacromial space, we observed significantly higher values in the control group (7.71 mm) than in the group with injuries (6.99). In comparing the control group with some specific subgroup, i.e. posterosuperior (6.77), anteroposterior-superior (4.16) and retraction Patte III (5.01), we confirmed the importance of topography and degree of retraction in relation to the rise of the humeral head. CONCLUSION: The rise of the humeral head was directly related to the size, degree of retraction and topography of the rotator cuff injuries, with greater degrees of rise in cases of superior and posterior lesions and anteroposterior-superior (massive) lesions. The assessment using MRI was not influenced by the force of gravity. OBJETIVO: Demonstrar a relação entre o tamanho, grau de retração e topografia das lesões do manguito rotador com o grau de ascensão da cabeça umeral e avaliar a influência da força da gravidade na ressonância magnética. MÉTODOS: Avaliamos 181 ressonâncias magnéticas de ombro de 160 pacientes com mais de 45 anos, entre novembro de 2013 e julho de 2014. Os pacientes eram divididos em dois grupos, um de controle (sem lesão ou com lesão parcial do MR) e outro com lesão completa do MR. Fizemos a mensuração da distância acrômio-umeral nos cortes sagitais e foi estabelecida a menor distância entre o ápice da cabeça e o acrômio. RESULTADOS: Foram avaliados neste estudo 96 (53,04%) exames de pacientes do sexo feminino e 58 de pacientes do sexo masculino (46,96%). A idade média foi 63,27 anos, a do grupo controle 61,46 e a do grupo com lesão 65,19. Ao analisar as medidas do espaço subacromial, observamos valores significativamente maiores no grupo controle (7,71 mm) do que no grupo com lesão (6,99). Quando comparamos o grupo controle com alguns subgrupos específicos, posterossuperior (6,77), anteroposterossuperior (4,16) e retração Patte III (5,01), confirmamos a importância da topografia e grau de retração para ascensão da cabeça umeral. CONCLUSÃO: A ascensão da cabeça umeral tem relação direta com o tamanho, grau de retração e a topografia das lesões do manguito rotador, com graus maiores de ascensão nas lesões posterossuperiores e anteroposterossuperiores (extensas). A avaliação feita pela ressonância magnética não sofre influência da força da gravidade.

Mutation of the FMS-like tyrosine kinase-3 (FLT3) gene occurs with a frequency of 20-25% in acute myeloid leukemia (AML). Different studies have reported conflicting results, stating the importance of the length, position and number of internal tandem duplications (ITDs) for prognostic significance. In the present study, FLT3-ITD mutations were found in 51 (23%) of 218 patients with AML. Using sequence analysis we categorized ITD integration sites according to functional regions of the FLT3 receptor. Median ITD size was 61 bp. The insertion site was strongly correlated with ITD size: more C-terminal located inserted fragments were significantly bigger. Our data confirm that FLT3-ITD mutations identify a subset of young patients with AML with normal cytogenetics but with inferior outcome. Patients with AML with mutation localization outside the juxtamembrane domain showed no correlation with worse prognosis. A high mutant/wild-type ratio appears to have a major impact on the prognostic relevance.

The aim of this study was to show the different origins and courses of the extracranial VA on CTA with special emphasis on embryological considerations. The duplicated VA is an anomaly that has been assumed to predispose for dissection and to be associated with aneurysms. We report its frequency and clinical significance. We retrospectively reviewed CTA of 539 patients by using a contrast-enhanced CTA protocol of the VA on CT. Ninety-four-point-two percent of left VA originated from left subclavian artery and entered the transverse foramen at C6 in nearly all cases. Six-point-three-percent of left VA (m = 4 %, f = 10 %) originated from the aortic arch and entered the transverse foramen either at C4, C5 or C7 but never at C6. One case of an aberrant retroesophageal right VA originated from the aortic arch distal to the left subclavian artery and entered at C7 (0.19 %). All other right VA originated from the right subclavian artery (99.8 %) and entered between C4 and C6. We diagnosed four cases of duplicated VA (0.74 %) with a female predominance (1.9 %) without any signs of dissection on CTA. Two cases with VA duplication had intracranial arterial aneurysms. The VA is a longitudinal anastomosis of segmental metameric arteries. The level of entrance into the transverse foramen indicates which metameric artery or arteries persist. Duplication corresponds to persistence of two segmental arteries and is a rare phenomenon. VA duplication might be associated with vascular lesions.

The authors present a rare case of arteriovenous fistula (AVF) of the basal vein of Rosenthal draining into a dilated vein of Galen managed by transarterial endovascular embolization. A male infant born at full term following a normal pregnancy and delivery with congestive heart failure, on investigation with MR imaging and MR angiography was found to have a basal vein of Rosenthal fistula with a dilated vein of Galen. His congestive heart failure was treated medically, and the AVF was managed electively at 10 months of age with successful transarterial endovascular embolization. The authors discuss the embryological aspects related to the pathological entity and the various clinical presentations, investigations, and management options. Management is primarily endovascular embolization; microsurgery is performed for a few selected cases, and radiosurgery has a limited role in older patients. Endovascular embolization is a safe and effective way to manage this malformation, with an excellent outcome if the AVF is eliminated by proper embolization at the fistulous point.

●Abstract● Objectives: The HydroSoft and HydroFrame coils are a new generation of coils designed to further improve the safety and durability of aneurysm coiling using hydrogel technology. The authors report their experience using the HydroSoft and HydroFrame coils for the treatment of intracranial aneurysms. Methods: Immediate and follow-up angiographic results procedure-related complications and retreatments were retrospectively analyzed for 106 intracranial saccular aneurysms in 103 patients treated with the HydroSoft and HydroFrame coils during a 50-month period. Results: The incidence of thromboembolic complications was 5.7%. Procedure-related morbidity and mortality rates were each 0.9%. None of the patients with unruptured aneurysms developed hydrocephalus. Immediate post-procedure angiograms showed complete aneurysm occlusion in 34.9% of cases neck remnant in 36.8% and incomplete occlusion in 28.3%. Angiographic follow-up was obtained in 51.9% (55 of 106 aneurysms; average 16 months; range 6-45 months). In these 55 aneurysms the rate of immediate complete occlusion was 27.3% after treatment which increased to 50.9% on follow-up and the overall recanalization rate was 14.5%. No recanalization was observed in the 8 aneurysms treated with stent-assisted coiling in combination with HydroSoft and HydroFrame coil placement. Conclusions: The overall safety profile of the HydroSoft and HydroFrame coils appears to be acceptable. Preliminary midterm observation suggests that these new-generation hydrogel coils will improve the durability of angiographic occlusion when compared with immediate post-embolization results and can reduce the rate of aneurysm recanalization.

Animal models are necessary to develop and test innovations in aneurysm therapy before clinical introduction. This review aims at identifying the most likely candidates for standardizing preclinical testing of aneurysm devices. We systematically searched electronic databases for publications on animal aneurysm models from 1961–2008 to assess the methodologic quality of the studies and collect data on the patency and angiographic and pathologic outcomes of treatments. There has been a steady increase in the annual number of publications with time. Species that were most frequently used were dogs, rabbits, and rodents, followed by swine. Most publications are single-laboratory studies with variables and poorly validated outcome measures, a small number of subjects, and limited standardization of techniques. The most appropriate models to test for recurrences after endovascular occlusion were the surgical bifurcation model in dogs, and the elastase-induced aneurysm model in rabbits. A standardized multicenter study is needed to improve the preclinical evaluation of endovascular devices in aneurysm therapy.

OBJECTIVE To assess the feasibility and analyze angiographic and histological results of experimental aneurysms treated with an embolic-containing device (ECD) and to test a liquid embolic agent (LEA), N-butyl cyanoacrylate. METHODS Four experimental large bifurcation aneurysms and 1 large sidewall aneurysm were created in 5 dogs. These venous pouch aneurysms were occluded endosaccularly with an ECD and N-butyl cyanoacrylate. Angiographic and/or histopathological data were analyzed at 1 day (bifurcation), 1 week (bifurcation), 4 months (sidewall), 6 months (bifurcation), and 12 months (bifurcation). RESULTS Aneurysm dimensions were 16 to 18 mm in length, 6 to 8 mm in width, and a neck measuring 6 to 8 mm. Immediately after the procedure, 2 of 4 bifurcation aneurysms were 100% occluded. In one case, glue had spilled into the parent artery. One occluded aneurysm recanalized at 6 months. One occluded aneurysm remained closed at 12 months. Histopathological analysis of the 6- and 12-month specimens showed adherence of glue to the aneurysm wall, no appreciable inflammatory response to the ECD, and aneurysm wall fibrosis with adventitial chronic inflammation. The aneurysm necks were covered by neointima with the presence of endothelialization. CONCLUSION Within the limitations of this experimental study, treatment of large, wide-necked aneurysms with the ECD and LEA may be feasible. Suboptimal technique and ECD geometry can cause leakage of LEA into the parent vessel or incomplete apposition of the ECD/glue to the aneurysm wall. However, the ECD and glue injection technique did achieve complete occlusion in 1 aneurysm that persisted 1 year later. The histopathological findings in this instance are moderately encouraging. Further investigations of an ECD with N-butyl cyanoacrylate or another LEA are warranted.

●Abstract● Objective: To report efficacy of transarterial Onyx embolization of dural arteriovenous fistulas (DAVFs) previously treated with N-butyl cyanoacrylate (NBCA). Two cases are presented with special considerations given to the technical and anatomical aspects based on operative findings. Case Presentation: Superior petrosal and tentorial DAVFs presented with tinnitus and cortical venous reflux, headache with decreased cognitive function respectively. The DAVFs were initially treated with multiple injections of NBCA ending in persistently remaining fistula, subsequently leading to recurrence. Transarterial Onyx embolization was performed, resulting in penetration of Onyx into the complex vascular network and draining veins, with retrograde filling of multiple feeding arterie s. The affected sinus was preserved. Conclusion: With the potential of better penetration of Onyx, transarterial Onyx embolization may be capable of treating recurrent NBCAtreated DAVFs. Larger number of cases and longer follow-up are required to determine the efficacy and safety of transarterial Onyx embolization of DAVFs.

OBJECTIVE: To study the incidence and clinical outcomes of intraoperative aneurysm rupture (IOR) during endovascular coil embolization at a single large volume center and to review the literature on this subject to determine whether IOR rupture rate and mortality correlate with volume of aneurysms treated at a given center and years since the institution of Guglielmi detachable coils as a treatment modality. METHODS: We reviewed the aneurysm database at the Center for Endovascular Surgery since its inception (1997–2003) and reviewed 600 consecutively treated intracranial aneurysms in which coiling was attempted. All patients who sustained an IOR were studied. Procedural and follow-up angiograms as well as clinical outcomes were retrospectively reviewed. A literature review was conducted. RESULTS: Six patients (1.0%) experienced IOR (1.4% in acutely ruptured lesions, 0% in unruptured). All six had presented with diffuse subarachnoid hemorrhage (Fisher Grade 3) and in good clinical grade (Hunt & Hess Grades 1–3). One patient was rendered permanently disabled secondary to delay in controlling the IOR. All others were neurologically unchanged. A review of the literature revealed a trend in correlation between volume of aneurysms treated and IOR rate; no statistically significant correlation was found between volume of aneurysms treated or years since the introduction of GDC technology and IOR rates or mortality. CONCLUSION: IOR remains a serious risk of endosaccular coiling of intracranial aneurysms, with aneurysms presenting with subarachnoid hemorrhage at greater risk for this complication. This risk can be minimized with very low associated morbidity and mortality (incidence 1%, 17% morbidity, 0% mortality at our institution).

BACKGROUND: Nonalcoholic fatty liver disease comprises a spectrum of lesions ranging from steatosis to cirrhosis, with nonalcoholic steatohepatitis being the progressive form of the disease. Alcohol intake, viral hepatitis and other liver diseases must be excluded. Liver biopsy is the gold standard for diagnosis of the disease and is the only method able to differentiate nonalcoholic steatohepatitis from simple steatosis, to grade inflammation and to stage fibrosis. AIMS: To analyze the histopathological findings and evaluate interobserver agreement in biopsies previously diagnosed as steatosis or steatohepatitis. METHODS: Seventy needle biopsies were analyzed according to Brunt et al.(4), with modifications in the grading and staging components. Clinical data of patients were collected. Interobserver agreement was calculated based on histopathological findings. RESULTS: Mild nonalcoholic steatohepatitis (grade 1) was the most common form. If fibrosis was detected, stage 1 was the most frequent. Interobserver agreement was very good for macrovesicular steatosis (K W = 0,82) and good for lobular inflammation (K W = 0,68) and fibrosis (K W = 0,73). CONCLUSIONS: The classification of Brunt et al., with modifications, can be applied to diagnosis not only of nonalcoholic steatohepatitis but also of nonalcoholic fatty liver disease, representing a reliable method for use in the daily practice of pathologists.