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In some vein of galen aneurysmal malformation (VGAM) patients, transvenous embolization (TVE) is an attractive option, but its safety is unclear. Here we report the first two VGAM patients treated using the Chapot “pressure cooker” technique (ChPC). Methods Two patients, one 5-year-old and one 7-year-old, both presented with congestive heart failure in the newborn period and were subsequently treated in the newborn period with multiple, staged TAEs with n-BCA for choroidal VGAMs. Results We achieved progressive reduction in shunting and flow but were unable to accomplish complete closure of the malformation: in both patients, a small residual with numerous perforators persisted. The decision was made to perform TVE using the CHPC. In this technique, a guiding catheter is placed transjugular into the straight sinus (SS). One or two detachable tip microcatheters are advanced to the origin of the SS. Another microcatheter is advanced and the tip placed between the distal marker and the detachment zone of the former. Coils and n-BCA are used to prevent reflux of Onyx. Conclusions In this study, we recognized two important factors of traditional VGAM treatment that may cause interventionalists to consider the ChPC to treat VGAM: (1) without liquid embolic, deployed coils may not occlude the fistula entirely. (2) There is the concern of causing delayed bleeding should the arterial component of the fistula rupture. ChPC ameliorates these issues by offering complete closure of the fistula with liquid embolic material in TVE.

Multiple de novo brain arteriovenous malformations (bAVM) have been reported in the literature, raising questions about the contended purely congenital nature of these lesions. We present the 15-year course of a pediatric patient, who initially presented at age 5 with a thalamic cavernous malformation and was treated with radiosurgery, and then subsequently developed a thalamic de novo bAVM immediately adjacent to the initial lesion location, discovered 2 years later. Treatment of the bAVM entailed two transarterial embolizations and one radiosurgery session which ultimately led to complete angiographic resolution. Finally, this patient’s course was complicated by intraparenchymal hemorrhage and acute obstructive hydrocephalus, and further imaging revealed two newly formed cavernous malformations, also associated with the initial lesion’s location, that have remained stable since their formation. This case likely represents the second-hit model for the formation of vascular malformations, as sparsely supported by the current literature. According to this, genetically aberrant, yet quiescent, brain areas might promote the de novo formation of vascular malformations after brain injury, including radiation.

INTRODUCTION Appropriate treatment of scalp arteriovenous malformations (SAVMs) remains largely unclear given the rarity of reported cases. This single-institution case series presents consecutive patients with extracranial SAVMs and long-term follow up.The primary aim of this study was to review treatment decisions, evaluate clinical outcomes, and compare our experience to available literature in order to better understand SAVMs and improve future outcomes. MATERIALS AND METHODS A retrospective review of consecutive patients with extracranial SAVMs between January 2015 and December 2019 was performed. Treatment factors of interest included embolization method, embolic agents, and decision to proceed with surgical resection. Relevant clinical outcomes included recurrence rates, cure rates, and complications. RESULTS Seven patients were included in the present series. Satisfactory outcomes were ultimately achieved for all 7 patients using embolization with or without combined surgical resection. Embolizations performed in combination with resection were curative in 4 of 4 cases (100%). Embolizations performed without resection were curative in 0 of 4 cases (0%), satisfactory in 2 of 4 cases (50%), and unsatisfactory in 2 of 4 cases (50%). DISCUSSION All SAVM patients in this series were treated satisfactorily using embolization with or without operative resection. This study strongly suggests that embolization combined with surgical resection during the same admission yields the best treatment outcomes for SAVMs, specifically demonstrating lower rates of recurrence and embolization-related complications. Decisions on whether or not to proceed with resection should be made by the interventional radiologist, the plastic surgeon, and the patient together.

Background The WHO SAGE Working Group on Vaccine Hesitancy developed the Vaccine Hesitancy Scale (VHS) to identify and compare hesitancy in different global settings. The objectives of the study were to describe and analyze vaccine hesitancy and to validate the VHS in a group of parents in Buenos Aires city, Argentina. Methods A cross-sectional survey was conducted in parents of 1–3 and 12–15 year-old children at three health centres in Buenos Aires City, between June 2018 and May 2019. Sociodemographic data were collected together with history of refusal and/or delay in children’s vaccination (defined as hesitancy). The 10-item VHS using 5-point Likert-scale (higher scores indicating lower hesitancy) was administered and children’s immunization record cards were verified. Link between hesitancy and socio-demographic variables, and hesitancy and vaccination status was analyzed for five specific vaccines. Cronbach‘s α was used to determine internal consistency reliability and factor analysis to confirm survey subdomains. Simple and multiple regression analysis was used to examine associations between VHS scores and hesitancy, and VHS scores and vaccination status. Results Six hundred parents were surveyed and 469 immunization cards verified; 11.5% (n = 69) parents were hesitant. High maternal educational level showed significant association with hesitancy (OR 2.66 95% CI: 1.20–5.9) in the adjusted model. Hesitancy was significantly associated with incomplete MMR vaccination in children (OR 4.43 95% CI: 1.08–8.20) and HPV vaccination in adolescents (OR 3.75 95% CI: 1.54–9.12). Cronbach‘s α was 0.66 and factor analysis identified three underlying constructs: “Benefits”, “Harms” and “Confidence in healthcare system”. High scores in VHS were associated with lack of hesitancy (OR 1.2 95% CI: 1.13–1.27) and complete vaccination status (OR 1.07 95% CI: 1.02–1.12). Conclusions Hesitancy was associated with high maternal educational level, and incomplete MMR and HPV immunization status in children and adolescents. VHS was a reliable and valid tool in this population.

Vein of Galen aneurysmal malformation (VGAM) is a rare anomaly associated with poor outcomes from high output cardiac failure and neurologic complications. Studies addressing fetal cardiovascular status and outcomes in this population are limited. A single-center retrospective review was conducted on patients with a prenatal diagnosis of VGAM who underwent a fetal echocardiogram between January 2015 and July 2019. Fetal echocardiographic data, brain magnetic resonance imaging (MRI) findings and outcomes were collected. Nine fetuses [median gestational age at echocardiogram 34 (1.1) weeks] were included. All patients had superior vena cava dilation and reversal of diastolic flow in the transverse aortic arch. Median cardiothoracic (CT) ratio was 0.39 (0.09). Right ventricular (RV) and left ventricular (LV) dysfunction was present in 66% and 11% fetuses, respectively. Four out of five patients that underwent postnatal endovascular neurosurgical interventions at our center were alive at follow-up (mean 2.7 years). Of the non-survivors (n = 5), 3 received comfort care because of severe brain damage and died in the neonatal period. Non-survivors more commonly had > mild tricuspid regurgitation (TR) (40% vs. 25%) and > mild RV dilation (60% vs. 25%). Combined cardiac index (CCI) was higher in non-survivors when compared to survivors (672.7 vs. 530.2 ml/kg/min, p = 0.016). Fetuses with significant parenchymal damage on brain MRI tended to have a higher CCI than those without (979.8 vs. 605.0 ml/kg/min, p = 0.047). RV dysfunction, TR and elevated CCI are more commonly seen in non-survivors with VGAM. A higher CCI is seen in those deemed untreatable due to significant parenchymal volume loss. Future multicenter studies are needed to assess for prenatal prediction of outcomes in this high-risk population.

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.

Chagas disease (ChD), caused by Trypanosoma cruzi, has a global prevalence due to patient migration. However, despite its worldwide distribution, long-term follow-up efficacy studies with nifurtimox (NF) are scarce and have been conducted with only small numbers of patients. A retrospective study of a large cohort of ChD treated children and adults with NF. Treatment response was evaluated by clinical, parasitological, and serological after-treatment evaluation. A total of 289 patients were enrolled, of which 199 were children and 90 adults. At diagnosis, 89.6% of patients were asymptomatic. Overall, all symptomatic patients showed clinical improvement. At baseline, parasitemia was positive in 130 of 260 (50%) patients. All but one adult patient had cleared their parasitemia by the end of treatment. That patient was considered a treatment failure. Median follow-up time for children was 37.7 months, with an interquartile range of (IQR

Objective: to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive. Design: We describe a non-consanguineous pedigree composed by several individuals with short stature, including 2 pediatric patients with typical diagnosis of isolated growth hormone deficiency (IGHD) and 4 other siblings with severe short stature, low serum IGF-1 and IGFBP-3, but normal stimulated GH levels, suggesting growth hormone insensitivity (GHI) in the latter group. Results: Patients with classical IGHD phenotype carried a heterozygous variant in GH1: c.626G>A (p.R209H). Data from the extended pedigree suggested GH1 as the initial candidate gene, which showed the same pathogenic heterozygous GH1 variant in the four siblings with short stature and a biochemical pattern of GHI. Conclusions: We suggest considering GH1 sequencing in children with short stature associated to low IGF-1 and IGFBP-3 serum levels, even in the context of normal response to growth hormone provocative testing (GHPT). Fil: Sanguineti, Nora María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Braslavsky, Debora Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Scaglia, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Keselman, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Ballerini, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Ropelato, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Suco, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Vishnopolska, Sebastián Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina 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 Fil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Pérez Millán, Maria I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Camper, Sally. University Of Michigan. College Of Literature, Sciences And Arts. Molecular, Cellular And Developmental Biology; Estados Unidos Fil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina

Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less common in children than in adults, though they are similar in their aggressive clinical behavior. In adults, glioblastoma is the most lethal tumor of the central nervous system. Insulin-like growth factor 1 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that, in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors, worst clinical outcome, and increased risk of death. Herein we explore the role of IGF1R intracellular localization by comparing two glioblastoma cell lines that differ only in their IGF1R capacity to translocate to the nucleus.

BACKGROUND AND PURPOSE: Two-thirds of lymphatic malformations in children are found in the head and neck. Although conventionally managed through surgical resection, percutaneous sclerotherapy has gained popularity. No reproducible grading system has been designed to compare sclerotherapy outcomes on the basis of radiologic findings. We propose an MR imaging–based grading scale to assess the response to sclerotherapy and present an evaluation of its interrater reliability. MATERIALS AND METHODS: A grading system was developed to stratify treatment outcomes on the basis of interval changes observed on MR imaging. By means of this system, 56 consecutive cases from our institution with formally diagnosed head and neck lymphatic malformations treated by sclerotherapy were retrospectively graded. Each patient underwent pre- and posttreatment MR imaging. Each study was evaluated by 3 experienced neuroradiologists. Interrater reliability was assessed using the Krippendorff α statistic, intraclass coefficient, and 2-way Spearman ρ correlation. RESULTS: The overall Krippendorff α statistic was 0.93 (95% CI, 0.89–0.95), denoting excellent agreement among raters. Intraclass coefficients with respect to consistency and absolute agreements were both 0.97 (95% CI, 0.96–0.98), illustrating low variability. Every combination of individual rater pairs demonstrated statistically significant (P < .01) linear Spearman ρ correlations, with values ranging from 0.90 to 0.95. CONCLUSIONS: The proposed radiographic grading scale demonstrates excellent interrater reliability. Adoption of this new scale can standardize reported outcomes following sclerotherapy for head and neck lymphatic malformation and may aid in the investigation of future questions regarding optimal management of these lesions.

Endovascular embolization is the mainstay for treatment of infantile dural sinus malformations.1 2 Distal access and flow control are limiting factors in controlled embolization.3–6 The Scepter mini catheter (Microvention, Aliso Viejo, California, USA) is a low-profile, dual-lumen balloon microcatheter designed to provide navigability in small-caliber, tortuous intracranial vessels. In this technical video, we demonstrate the staged embolization of a dural sinus malformation with multiple arteriovenous fistulae using the Scepter mini catheter (video 1). In the newborn patient, embolizations were performed through the parietal branches of the left and right middle meningeal arteries. The catheter easily navigated into the small feeding arteries. No neurological complications occurred due to the procedures. Post-embolization injections demonstrated significant flow reduction into the malformation. Three-month follow-up angiography illustrated resolution of the previously dilated left transverse sinus. Complete obliteration of the dural sinus malformation was achieved in the newborn patient.Video 1Curative embolization in two stages with the Scepter mini balloon microcatheter. ΑP, anteroposterior; CCA, common carotid artery.

Study question: Does standardised treatments used in children and adolescents with haematologic malignancies, including acute lymphoblastic (ALL) or myeloid leukaemia (AML) and non-Hodgkin lymphoma (NHL), affect endocrine function of the developing testes? Summary answer: Therapy of haematologic malignancies do not provoke an overt damage of Sertoli and Leydig cell populations, as revealed by normal levels of anti-Müllerian hormone (AMH) and testosterone, but a mild primary testicular dysfunction may be observed, compensated by moderate gonadotropin elevation, during pubertal development. What is known already: Evidence exists on the deleterious effect that chemotherapy and radiotherapy have on germ cells, and some attention has been given to the effects on Leydig and Sertoli cells of the adult gonads, but information is virtually non-existent on the effects of oncologic treatment on testicular somatic cell components during childhood and adolescence. Study design, size, duration: A retrospective, analytical, observational study included 97 boys with haematological malignancies followed at two tertiary paediatric public hospitals in Buenos Aires, Argentina, between 2002 and 2015. Participants/materials, setting, methods: Clinical records of males aged 1-18 years, referred with the diagnoses of ALL, AML or NHL for the assessment of gonadal function, were eligible. We assessed serum levels of AMH and FSH as biomarkers of Sertoli cell endocrine function and testosterone and LH as biomarkers of Leydig cell function. Main results and the role of chance: All hormone levels were normal in the large majority of patients until early pubertal development. From Tanner stage G3 onwards, while serum AMH and testosterone kept within the normal ranges, gonadotropins reached mildly to moderately elevated values in up to 35.9% of the cases, indicating a compensated Sertoli and/or Leydig cell dysfunction, which generally did not require hormone replacement therapy. Limitations, reasons for caution: Serum inhibin B determination and semen analysis were not available for most patients; therefore, we could not conclude on potential fertility impairment or identify whether primary Sertoli cell dysfunction resulted in secondary depleted spermatogenesis or whether primary germ cell damage impacted Sertoli cell function. Wider implications of the findings: The regimens used in the treatment of boys and adolescents with ALL, AML or NHL in the past two decades seem relatively safe for endocrine testicular function; nonetheless, a mild primary testicular endocrine dysfunction may be observed, usually compensated by slightly elevated gonadotropin secretion by the pituitary in adolescents, and not requiring hormone replacement therapy. No clinically relevant risk factor, such as severity of the disease or treatment protocol, could be identified in association with the compensated endocrine dysfunction. Study funding/competing interest(s): This work was partially funded by grants PIP 11220130100687 of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and PICT 2016-0993 of Fondo para la Investigación Científica y Tecnológica (FONCYT), Argentina. R.A.R., R.P.G. and P.B. have received honoraria from CONICET (Argentina) for technology services using the AMH ELISA. L.A.A. is part-time employee of CSL Behring Argentina. The other authors have no conflicts of interest to disclose. Fil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Arozarena, María. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Prada, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Bargman, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Sanzone, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Morales Bazurto, Marjorie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Gutiérrez, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Bedecarras, Patricia Gladys. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Kannemann, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Elena, Graciela O.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Gottlieb, Silvia Elisa. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina 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 Fil: Ropelato, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Aversa, Luis A.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Rey, Rodolfo Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina

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.

The objective of this work was to evaluate thermal paper (TP) tickets used in Argentina as a potential source of bisphenol A (BPA) that could impact humans and the environment. BPA in TP was measured by HPLC ranging from 11.1 to 30.5 mg BPAg

Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery. The aim of this study was to identify risk factors for OASI in women with a previous vaginal delivery. We further attempted to detect specific risk factors for severe OASI in this subgroup.We conducted a retrospective cohort study between 2003 and 2019. The study group included women who had a singleton, live, vertex, vaginal delivery at term and who also had at least one previous vaginal delivery. The control group included women with at least one previous vaginal delivery without OASI. General medical history, obstetric history, and ante-, intra- and post-partum data were collected and compared between groups.Following implementation of the inclusion criteria, 79,176 women were included. Allocation to study groups was according to OASI occurrence: 135 patients (0.2%) had a third- or fourth-degree perineal tear, while 79,041 patients (99.8%) had no such injury. Multivariate analysis revealed that one previous vaginal delivery, birthweight ≥ 3900 g (90th percentile), vacuum-assisted vaginal delivery and episiotomy were associated with increased risk of OASI. Comparison of more severe OASI (3C and 4th-degree) cases to the control group showed similar results with the addition of prolonged second stage and younger age to risk factors associated with severe OASI while episiotomy was no longer significant.In women with a previous vaginal delivery, one vs. two or more previous vaginal deliveries, increased birthweight, vacuum-assisted vaginal delivery and episiotomy are risk factors for OASI.

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.

Background Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007. Objectives To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA. Search methods For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019. Selection criteria We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status. Data collection and analysis Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence. Main results This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GCS One study with 1317 participants compared the use of LMWH versus GCS. There was no clear difference in the risk of PE (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence). LMWH use did reduce the risk of DVT compared to people using GCS (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). No clear difference in effects was seen between the groups for asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence); major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence) or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). Levels of thromboembolic events were higher in the GCS group than in any other group. We downgraded the certainty of the evidence for imprecision resulting from overall small event numbers; risk of bias due to concerns about lack of blinding, and indirectness as we were uncertain about the direct clinical relevance of asymptomatic DVT detection. Authors' conclusions There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.

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.

BackgroundNavigable, large diameter aspiration catheters demonstrate markedly improved recanalization rates over smaller lumen devices in suction embolectomy. We evaluated the performance of a novel aspiration catheter system designed to maximize lumen size, and compare it to other commercially available aspiration catheters.MethodsThe 6F R4Q aspiration catheter system comprises a proximal pusher wire of 117 cm length connected to a distal catheter of 25 cm length. When placed through standard guide catheters and into the cerebral circulation, the proximal catheter makes a tight seal between its outer surface and the guide catheter’s inner surface. During aspiration, in vitro flow rates and tip suction force under gentle retraction were compared among 10 commercially available aspiration catheters and the R4Q system.ResultsThe R4Q 6F, 5F, 4F, and 3F catheters achieved flow rates at least 21.9%, 24.7%, 61.9%, and 244.7% greater than the other catheters tested respectively and the R4Q 6F produced a 140.2% higher tip force than a catheter of similar size. Fluid flow rate in the R4Q 6F increased on retraction into the guide catheter, delivering a 58.2% increase from fully extended to fully retracted.ConclusionThe R4Q design demonstrates a substantial increase in aspirated flow rate and suction force due to an increased effective diameter than standard tubular catheter designs tested. The prominent increase in the aspiration parameters measured in vitro supports the potential for improved clinical results during stroke thrombectomy procedures.

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.

The sequence variability of the Epstein–Barr virus has been extensively studied throughout previous years in isolates from various geographic regions and consequent variations at both genetic and genomic levels have been described. However, isolates from South America were underrepre-sented in these studies. Here, we sequenced 15 complete EBV genomes that we analyzed together with publicly available raw NGS data for 199 EBV isolates from other parts of the globe by means of a custom-built bioinformatic pipeline. The phylogenetic relations of the genomes, the geographic structure and variability of the data set, and the evolution rates for the whole genome and each gene were assessed. The present work contributes to overcoming the scarcity of complete EBV genomes from South America and is the most comprehensive geography-related variability study, which involved determining the actual contribution of each EBV gene to the geographic segregation of the entire genome. Moreover, to the best of our knowledge, we established for the first time the evolution rate for the entire EBV genome based on a host–virus codivergence-independent assumption and assessed their evolution rates on a gene-by-gene basis, which were related to the encoded protein function. Considering the evolution of dsDNA viruses with a codivergence-independent approach may lay the basis for future research on EBV evolution. The exhaustive bioinformatic analysis performed on this new dataset allowed us to draw a novel set of conclusions regarding the genome evolution of EBV. Fil: Blazquez, Ana Catalina. 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 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 Fil: Torres, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina Fil: Izquierdo, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Lezama, Carol. 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 Fil: de Matteo, Elena Noemí. 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 Fil: Lorenzetti, Mario Alejandro. 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 Fil: Preciado, María Victoria. 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

The objective of this study was to measure the impact of the mechanized chlorpyrifos, copper oxychloride and myclobutanil application in a small peach orchard, on humans (operators, bystanders and residents) and on the productive soil. The mean Potential Dermal Exposure (PDE) of the workers (tractor drivers) was 30.8 mL·h− 1 ± 16.4 mL·h− 1, with no specific pesticide distribution on the laborers body. Although the Margin of Safety (MOS) factor for the application stage were above 1 (safe condition) for myclobutanil and cooper oxycloride it was below 1 for chlorpyrifos. The mix and load stage remained as the riskier operation. Pesticide found on the orchard soil ranged from 5.5% to 14.8% of the total chlorpyrifos, copper oxychloride and myclobutanil applied. Pesticide drift was experimentally measured, finding values in the range of 2.4% to 11.2% of the total pesticide applied. Using experimental drift values, bystander (for one application), resident (for 20 applications) and earthworm (for one application) risk indicators (RIs) were calculated for the chlorpyrifos plus copper oxychloride and for myclobutanil treatments for different distances to the orchard border. Earthworm RI was correlated with experimental Eisenia andrei ecotoxicological assays (enzymatic activities: cholinesterases, carboxylesterases and glutathione S-transferases; behavioral: avoidance and bait-lamina tests) with good correlation. Fil: Berenstein, Giselle Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Nasello, Soledad. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Beiguel, Erica Patricia. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Flores, Pedro Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Di Schiena, Johanna. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Basack, Silvana Beatriz. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Hughes, Enrique Alejandro. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Zalts, Anita. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina Fil: Montserrat, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de General Sarmiento. Instituto de Ciencias. Área de Química; Argentina

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.

We have previously found that Drosophila melanogaster only has one deoxyribonucleoside kinase, Dm-dNK, however, capable to phosphorylate all four natural deoxyribonucleosides. Dm-dNK was originally isolated from an embryonic cell line. We wanted to study the expression of Dm-dNK during development from embryonic cells to adult flies and found declining Dm-dNK activity during development and no activity in adult flies. Surprisingly, the extract from adult flies exhibited a strong inhibitory effect on deoxyribonucloside kinase activity. The dNK-inhibitor was precipitable with ammonium sulfate, and was purified to a high degree by gel-filtration as indicated by LC-MS/MS analysis. Since the inhibitor eluted from G-200 gel-filtration with a size of 10-13 kDa, we named it P12. We tested the purified fraction for specificity towards various enzymes and found that both mammalian and bacterial dNKs were inhibited, whereas there was no effect on hexokinase and pyruvate kinases and acidic phosphatase. However, when tested against cyclin B-dependent kinase, we found a strong inhibitory effect. Both with human Cdk1/CycB and S. pombe Cdc2/B-type cyclin the purified fraction from Superdex 200 that inhibited Dm-dNK, also inhibited the two protein kinases to the same degree. Furthermore, testing P12 in a DNA polymerase based assay we found that the 3'-5'-exonuclease part of the DNA polymerase (Klenow polymerase) was activated.

The volume of biological, chemical and functional data deposited in the public domain is growing rapidly, thanks to next generation sequencing and highly-automated screening technologies. These datasets represent invaluable resources for drug discovery, particularly for less studied neglected disease pathogens. To leverage these datasets, smart and intensive data integration is required to guide computational inferences across diverse organisms. The TDR Targets chemogenomics resource integrates genomic data from human pathogens and model organisms along with information on bioactive compounds and their annotated activities. This report highlights the latest updates on the available data and functionality in TDR Targets 6. Based on chemogenomic network models providing links between inhibitors and targets, the database now incorporates network-driven target prioritizations, and novel visualizations of network subgraphs displaying chemical- and target-similarity neighborhoods along with associated target-compound bioactivity links. Available data can be browsed and queried through a new user interface, that allow users to perform prioritizations of protein targets and chemical inhibitors. As such, TDR Targets now facilitates the investigation of drug repurposing against pathogen targets, which can potentially help in identifying candidate targets for bioactive compounds with previously unknown targets. Fil: Urán Landaburu, Héctor Lionel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Berenstein, Ariel José. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Videla, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Maru, Parag. National Chemical Laboratory; India. Academy of Scientific and Innovative Research; India Fil: Shanmugam, Dhanasekaran. Academy of Scientific and Innovative Research; India. National Chemical Laboratory; India Fil: Chernomoretz, Ariel. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Agüero, Fernan Gonzalo. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina

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.

BACKGROUND AND PURPOSE: Spontaneous or progressive occlusion of the posterior fossa dural sinuses is often observed in patients with vein of Galen malformation, which can affect the clinical course. The aim of this study was to examine the patency of the posterior fossa dural sinuses in patients with vein of Galen malformation and to analyze the clinical and angiographic course of this condition. MATERIALS AND METHODS: We retrospectively reviewed 61 consecutive children with vein of Galen malformations. Clinical presentation, management, outcome, and angiographic change were analyzed for the patients with attention paid to all dural sinus occlusions. RESULTS: Twenty patients (32.8%) demonstrated spontaneous sinus occlusion, mostly in the sigmoid sinus. This condition was not observed in neonates and was first discovered during infancy or childhood. Progression of sinus occlusion was seen in 10 patients, and the conditions of 6 of them deteriorated in accordance with the progression of sinus occlusion. After total or subtotal obliteration of the malformation by transarterial glue embolization, 13 patients recovered to healthy, 3 patients had only mild developmental delay, and 4 patients remained neurologically disabled. CONCLUSIONS: Spontaneous sinus occlusion is not a rare condition and can result in neurologic deterioration in the natural history of untreated vein of Galen malformation. If signs of progressive sinus occlusion are noticed, early arteriovenous shunt reduction or elimination by transarterial glue embolization is expected to prevent permanent brain damage.

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.

Epstein Barr virus (EBV) has a large DNA genome assumed to be stable, but also subject to mutational processes such as nucleotide substitution and recombination, the latter explored to a lesser extent. Moreover, differences in the extent of recombination events across herpes sub-families were recently reported. Given the relevance of recombination in viral evolution and its possible impact in pathogenesis, we aimed to fully characterize and quantify its extension in all available EBV complete genome by assessing global and local recombination rate values (⍴/bp). Our results provide the first EBV recombination map based on recombination rates assessment, both at a global and gene by gene level, where the mean value for the entire genome was 0.035 (HPDI 0.020–0.062) ⍴/bp. We quantified how this evolutionary process changes along the EBV genome, and proved it to be non-homogeneous, since regulatory regions depicted the lowest recombination rate values while repetitive regions the highest signal. Moreover, GC content rich regions seem not to be linked to high recombination rates as previously reported. At an intragenic level, four genes (EBNA3C, EBNA3B, BRRF2 and BBLF2-BBLF3) presented a recombination rate above genome average. We specifically quantified the signal strength among different recombination-initiators previously described features and concluded that those which elicited the greatest amount of changes in ⍴/bp, TGGAG and CCCAG, were two well characterized recombination inducing motifs in eukaryotic cells. Strikingly, although TGGAG was not the most frequently detected DNA motif across the EBV genome (697 hits), it still induced a significantly greater proportion of initiation events (0.025 events/hits) than other more represented motifs, p-value = 0.04; one tailed proportion test. Present results support the idea that diversity and evolution of herpesviruses are impacted by mechanisms, such as recombination, which extends beyond the usual consideration of point mutations.

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.

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

Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in childrenage 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress and/or vascular damage at a fragile joint.To assess children with LCPD for markers of attention deficit hyperactivity disorder (ADHD) relative to their unaffected comparably aged siblings to exclude the contribution of hyperactive behavior versus environmental and/or genetic factors in LCPD.All children followed in the Pediatric Orthopedic Clinic, and their comparably aged siblings, were recruited. ADHD was assessed using the TOVA computerized test and DSM-IV criteria. Quality of life and sleep disorders as ancillary tests were assessed using the Child Health Questionnaire (Parent Form 50), Pediatric Outcomes Data Collection Instrument, and Pediatric Daytime Sleepiness Scale.Sixteen children with LCPD (age 9.1 ± 3.3, 75% males) were compared with their closest-aged siblings (age 9.3 ± 2.6, 30% males). Mean TOVA scores of children with LCPD (-3.79 ± 2.6) and of their non-LCPD siblings (-3.6 ± 4.04) were lower relative to the general population (0 ± 1.8, P0.0001). Both group means were in the ADHD range (≤ -1.8) implying that 73% of this LCPD cohort and 53% of their non-LCPD siblings performed in the ADHD range, relative to 3.6% incidence expected in the general population (P0.0001). Other test results were similar in both groups.Our findings in a small cohort of children with LCPD and their comparably aged siblings do not support an association between LCPD and ADHD. ADHD markers were equally high in the LCPD children and siblings.

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.

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.

The treatment of deep-seeded pediatric brain arteriovenous malformations (AVMs) remains a challenging task. We describe our experience using a new detachable tip microcatheter in the embolization of brain arteriovenous malformations, pial arteriovenous fistulas, and vein of Galen malformations. We describe the safety and efficacy using a new detachable tip microcatheter in the treatment of pediatric deep brain arteriovenous malformations, pial malformations, and vein of Galen malformations. During a period of 9 months from March 2013 through January 2014, 11 pediatric patients in 14 procedures with 27 total injections were selected for treatment with a detachable tip under Food and Drug Administration (FDA) compassionate use exemption and were admitted to our department for treatment of their brain AVM using a liquid embolic agent and a detachable tip microcatheter. The ages of the patients ranged from 3 months to 18 years old. Of the 27 total injections done, the tip detached in seven cases. For the 16 n-BCA injections, the tip detached six times (37.5 %), and for the 11 Onyx injections, the tip detached one time (9 %). There were no cases of premature microcatheter detachment during normal vessel navigation. The introduction of these detachable tip microcatheters allows for a safe and relaxed injection that permits a true circumferential occlusion, and may further permit filling a larger amount of angioarchitecture without the risk of distal migration, or vessel damage during the usual rapid removal of non detachable micocatheters.

Summary Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain’s deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.

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.