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Resumen Objetivos La indicacion de ventriculostomia endoscopica de tercer ventriculo (VET) en el tratamiento de la hidrocefalia no comunicante esta extensamente aceptada. Existe controversia respecto a la indicacion de un segundo procedimiento (re-VET) cuando el primero ha fallado. El objetivo de este trabajo es recoger los fallos de VET en una serie propia en los que se realizo re-VET y describir los factores relacionados con su pronostico. Metodo Estudio retrospectivo de pacientes pediatricos con fallo de VET tratados mediante una re-VET entre 2003 y 2018. Se registro genero, edad en primera y segunda VET, tiempo hasta fallo de primera VET, etiologia de hidrocefalia, presencia previa de DVP, ETV-SS en primera y segunda VET, hallazgos intraoperatorios, exito del segundo procedimiento y seguimiento. El resultado de ETV-SS se agrupo en puntuacion alta (≥ 80), moderada (50-70) o baja (≤ 40). Se considero fallo de procedimiento endoscopico el deterioro clinico o la ausencia de criterios radiologicos de mejoria (reduccion de tamano ventricular o presencia de artefacto de flujo de VET en area premamilar). Resultados De 97 VET realizadas en este periodo, se registraron 47 fallos, llevandose a cabo 13 re-VET. De ellas, 8 fueron clasificadas como exito (61,53%). La re-VET fue exitosa en 4/4 casos cuya etiologia fue tumoracion tectal o estenosis de acueducto. En el grupo de alta puntuacion ETV-SS hubo mayor porcentaje de exito (75%) que en el grupo de moderada puntuacion (40%). Nueve pacientes presentaban DVP previa a la primera VET y en ellos, el exito fue del 66,6% frente al 50% en el grupo sin DVP previa. Todas las re-VET se llevaron a cabo sin complicaciones. En 11 de los 13 procedimientos se encontro una membrana premamilar cerrada y en los 2 casos restantes una apertura puntiforme. El seguimiento medio tras re-VET fue de 61,23 meses. Conclusion La re-VET es un procedimiento seguro y con una tasa de exito del 61,5% en nuestra serie. La seleccion de pacientes debe ser cautelosa. Factores como edad, etiologia y derivacion previa (factores del ETV-SS) tienen influencia pronostica. Sin embargo, existen factores concretos que indican un pronostico favorable para re-VET, como un mayor tiempo hasta el fallo del primer procedimiento, el hallazgo de estoma cerrado/puntiforme o la perdida de artefacto de flujo en el seguimiento con RM.

Brugada Syndrome is a cardiac channelopathy closely related to lethal arrhythmias and sudden death in people without underlying structural pathology. The diagnosis is usually assumed with electrocardiographic patterns strictly limited to the right precordial leads, V1 or V2; but this is not so at all. In our article, we describe the clinical case of a patient with a novel and different electrocardiographic presentation: the typical diagnostic pattern was presented in a lower lead of the electrocardiogram, and next to it, another pattern was presented in a contiguous lead. In addition, we propose the possible association of a structural pathology (non-compaction cardiomyopathy) with Brugada Syndrome, since both share a possible common genetic origin in the SCN5A gene.

Although intraventricular neuroendoscopy is considered a minimally invasive technique with good results, there is nevertheless a risk of developing certain complications. As no agreement apparently exists concerning the classification of these complications, we aim to propose a form of classification based on the results of our series, comparing them with recent publications. We undertook a retrospective study of 170 children who underwent intraventricular neuroendoscopy between 2003 and September 2020 at our center. Data were recorded on demographic and clinical variables: age, gender, presenting symptoms, etiology, number of procedures, type of procedure, and complications. Complications were divided into two main groups, intraoperative and postoperative, and in subgroups. The intraoperative complications included one group of systemic alterations and another group of surgical problems. The postoperative complications were divided into six groups: systemic, neurologic, hormone, fluid, hemorrhagic and death. A total of 202 neuroendoscopic procedures were performed in 170 children. The mean age at first surgery was 71 months (22-122). The most common etiology of the hydrocephalus was intraventricular tumors (32.9%), followed by aqueductal stenosis (13.5%). The most usual presenting sign was intracranial hypertension. The procedure most used was third ventriculostomy (62.9%). During the procedures, we experienced 5 surgical intraoperative complications (2.47% per procedure). In the postoperative period, there were 23.7% systemic complications per procedure, 12.87% neurologic, 8.41% hormone, 10.9% fluid, 0.5% hemorrhagic, and 0.99% for postoperative death. The rate of complications associated with intraventricular neuroendoscopy was similar in our series to those already published. Comparative studies require standardization for the analysis of neuroendoscopic complications.

La literatura sobre enfermedad –particularmente, sobre epidemias- cuenta con numerosos recursos a la hora de permitirnos profundizar en el conocimiento de la noxa desde un punto de vista no sólo nosológico, sino también sociológico. El presente trabajo analiza éstos y otros aspectos relevantes que se pueden extraer de la lectura de «El Diario del año de la peste», en contraposición a la situación derivada de la pandemia por el Sars-Cov-2. Se han encontrado similitudes significativas entre ambos procesos, sobre todo en lo relativo a las medidas públicas adoptadas y la respuesta social, así como diferencias sustanciales que pueden tener su base en el desarrollo científico-tecnológico que ha culminado en la obtención de las vacunas frente a la Covid 19 en un tiempo récord. Si bien cada epidemia es única, su estudio comparado puede aportar una visión global que sirva de aprendizaje y guía para afrontar posibles crisis sanitarias futuras.

In the late 1980s, craniofacial surgery units reported suboptimal cosmetic results, cranial volume restriction, and intracranial hypertension after anterior cranial vault remodeling in bilateral coronal synostosis associated with severe brachyturricephaly. A possible explanation was a severe associated growth restriction of the posterior calvaria with radiological synostosis at the lambda sutures. “Conventional” or “fixed” posterior cranial vault expansion techniques were developed to address these limitations, sometimes as the first surgical step in a two-staged protocol of total calvarial reconstruction, combined with suboccipital decompression in cases of symptomatic cerebellar tonsillar herniation or, more easily, to resolve the characteristic occipital flattening of lambdoid synostosis. Various surgical approaches have been described; however, the indications for and timing of surgical treatment and postoperative evaluation of results still remain controversial. Although more invasive, conventional posterior cranial vault expansion has proven to be safe and offers a remodeled and protective bony vault immediately after surgery, but the underlying cranial base malformation remained untreated, with implications in the postoperative growth of the facial skeleton. Overcorrection, rigid stabilization, and grafting are also concerns to be addressed.

Intracranial hypertension may be idiopathic or due to multiple etiologies. Some bone dysplasias and chronic shunt overdrainage syndrome may sometimes lead to intracranial hypertension associated with craniocerebral disproportion due to thickening of cranial diploe. The internal cranial expansion procedure has been used for patients with intracranial hypertension, whether or not associated with craniocerebral disproportion. Its purpose is to increase the intracranial volume by drilling down the inner table. This technique enables the craniocerebral disproportion to be improved and intracranial hypertension reduced. In other etiologies of intracranial hypertension with non-thickened diploe, internal cranial expansion may not be enough to resolve the hypertension. For these cases we propose a modification of the technique by expanding the cranial vault outwards; external cranial expansion. We describe this technique as used in a pediatric patient who presented with chronic headache, tonsillar ectopia, and sleep apnea syndrome. This patient also had a multisuture craniosynostosis, a non-thickened diploe, and intracranial hypertension.

Purpose: This study describes the results of septostomy (SPT) in terms of success and analysis of follow-up in a series of pediatric patients diagnosed with unilateral ventricular hydrocephalus (UHV) and biventricular hydrocephalus (BVH)Methods: A total of 29 pediatric patients diagnosed with UVH or BVH were included in this study. In UVH, a neuroendoscopic SPT was performed (sometimes accompanied by NEFPFMO). In those diagnosed with BVH, an SPT combined with VPS was carried out. Demographic, etiological, clinical, and diagnostic variables and percentage of treatment success were collected.Results: During follow-up, SPT was considered successful when no VPS was required in UVH and when only unilateral VPS was implanted in BVH. At the time of surgery, 16 patients needed a ventriculoperitoneal shunt. The first SPT was successful in 22 patients, requiring a second surgery in 7 patients, from the oncological group diagnosed with BHV.Conclusions: The surgical management of UVH and BVH still has some disclosure points to be reviewed. However, SPT seems to be a secure, non-traumatic, and efficient procedure.

To assess the functional outcome in school-age children shunted in the neonatal period due to post-hemorrhagic hydrocephalus (PHH), using the HOQ-Spanish version (HOQ-sv), and to analyze predictors of quality of life in this group. A cross-sectional study was performed between 2015 and 2018. Parents of pediatric patients with PHH attending our neurosurgery outpatient clinic were invited to complete the HOQ-sv and to enroll in the study. Clinical variables regarding the patients’ neonatal course and surgical outcome were recorded. A descriptive analysis was done, and independent variables related to the HOQ scores were studied in univariate and multivariate analyses with regression trees. The study comprised a total of 52 patients. The mean overall HOQ score was 0.67 (on a scale from 0 [worse] to 1 [best]). The quality of life for the PHH children at school age was related to perinatal factors (gestational age at birth, time until shunt surgery, length of hospitalization at the time of shunt implantation, and comorbidity), shunt complications (symptomatic overdrainage, number of shunt revisions, and shunt revisions related to infection during the first year after treatment), and clinical background (seizures, spasticity, Gross Motor Function Classification System level or visual impairment). HOQ dimension scores in school-age children shunted due to PHH in our center were similar to those of referral centers for other etiologies of pediatric hydrocephalus. Future goals should be the prevention of complications related to worse outcomes at the time of diagnosis and to try to improve shunt performance later.

The cystic spinal dysraphism of the cervical and upper thoracic region (CDCT) accounts for only 3.9 to 8% of spina bifida cystica lesions. The presence of external cerebrospinal fluid (CSF) leakage is infrequent and very few authors have reported about surgical complications. We present the case of a new born diagnosed of CDCT C1-C3 with a stalk of fibrovascular tissue, CSF leakage, hydrocephalus, and type Chiari II malformation, discuss about the chosen surgical technique and the associated complications, and make a review of the literature focusing on the main aspects of CDCT. The CDCT with a stalk of neuroglial and/or fibrovascular tissue originates from the dorsal surface of the spinal cord and penetrates into a cervical cystic sac. The presence of CSF leakage, hydrocephalus, and/or type Chiari II malformation can influence to decide the most appropriate surgical technique.

Resumen Introduccion La neuroendoscopia se ha posicionado como un tratamiento eficaz y seguro en los quistes aracnoideos en la edad pediatrica. Realizamos una revision de los pacientes pediatricos con quistes aracnoideos tratados mediante neuroendoscopia en nuestro servicio y analizamos los resultados. Material y metodos Analisis retrospectivo de una serie de 20 pacientes intervenidos entre los anos 2005 y 2018. Las variables recogidas son: genero, edad, presentacion clinica, localizacion del quiste, presencia de hidrocefalia o colecciones extraaxiales, maniobras endoscopicas realizadas y complicaciones. Se considero exito del procedimiento cuando se produjo mejoria de los sintomas y reduccion del tamano del quiste, manteniendose esta situacion hasta final de seguimiento. Resultados La serie consta de 13 varones y 7 mujeres (edad media: 64,6 meses; rango 4-172 meses). La localizacion mas repetida fue supraselar/prepontina (7), seguida de intraventricular (6), despues cuadrigeminales (3), interhemisfericos (2) y silvianos (2). Un 70% (14/20) de pacientes asociaba hidrocefalia en el momento del diagnostico, elevandose hasta el 85% en quistes supraselares/prepontinos o el 100% en cuadrigeminales. Solo 4/14 pacientes precisaron un sistema de derivacion ventriculoperitoneal (mediana de edad al diagnostico: 12,5 meses). De estos 4, 3 desarrollaron un sobredrenaje valvular grave. Se considero exito del procedimiento en 12/20 pacientes (60%) de la serie. Diferenciando por localizacion: 4/7 en supraselares (57%), 1/3 en cuadrigeminales (33%), 4/6 en intraventriculares (66%), 2/2 en interhemisfericos (100%) y 1/2 en silvianos (50%). Por tanto, se registraron 8 fallos de tratamiento, con un tiempo medio hasta el fallo de 12,12 meses (rango: 0-45). De esos 8 pacientes, en 4 se realizo una nueva neuroendoscopia (exito de 2/4), en 2 casos se opto por la colocacion de derivacion ventriculoperitoneal, en un caso por la colocacion de derivacion cistoperitoneal y en el restante se mantuvo una actitud conservadora. El seguimiento medio fue de 52,45 meses (rango 3-129 meses). Conclusiones El tratamiento neuroendoscopico es efectivo y seguro en el tratamiento de los quistes aracnoideos en edad pediatrica, permitiendo ademas en muchos casos el control de la hidrocefalia asociada. El tipo de procedimiento neuroendoscopico y el porcentaje de exito dependen de la localizacion del quiste. Se observa una tendencia de mayor dependencia valvular en pacientes de menor edad. En esos casos, seria recomendable la aplicacion de medidas de prevencion de sobredrenaje.

Furin is a protease that plays a key role in the infection cycle of SARS-CoV-2 by cleaving the viral proteins during the virus particle assembly. In addition, Furin regulates several physiological processes related to cardio-metabolic traits. DNA variants in the FURIN gene are candidates to regulate the risk of developing these traits as well as the susceptibility to severe COVID-19. We genotyped two functional FURIN variants (rs6224/rs4702) in 428 COVID-19 patients in the intensive care unit. The association with death (N = 106) and hypertension, diabetes, and hyperlipidaemia was statistically evaluated. The risk of death was associated with age, hypertension, and hypercholesterolemia. The two FURIN alleles linked to higher expression (rs6224 T and rs4702 A) were significantly increased in the death cases (odds ratio= 1.40 and 1.43). Homozygosis for the two high expression genotypes (rs6224 TT and rs4702 AA) and for the T-A haplotype was associated with an increased risk of hypercholesterolemia. In the multiple logistic regression both, hypercholesterolemia and the TT + AA genotype were significantly associated with death. In conclusion, besides its association with hypercholesterolemia, FURIN variants might be independent risk factors for the risk of death among COVID-19 patients.

Idiopathic intracranial hypertension (IIH) is a clinical syndrome characterised by raised intracranial pressure with no discernible aetiology. It is relatively rare in children and its demographic features may differ from those of adults. The relationship between IIH and venous sinus stenosis (VSS) is well known. As VSS plays an important role in the pathophysiology, treatments have been developed aimed at improving venous blood outflow in refractory IIH. In the last two decades, venous sinus stenting has emerged as a treatment option in cases where stenosis is documented.The scientific literature on paediatric cases of IIH and its treatment with venous sinus stenting was analysed. We present the case of a 6-year-old girl with a life-threatening presentation of IIH, who was treated with transverse sinus stenting and a lumboperitoneal shunt. We summarise the characteristic of paediatric stenting cases reported and review the literature focusing on the main aspects of venous sinus stenting.VSS stenting could be a treatment tool for the acute presentation of IIH with severe symptoms and VSS plus an elevated trans-stenotic pressure gradient. However, in some cases, additional surgical treatment may be necessary.

The aims of our study were to evaluate tumour response in a series of patients with vestibular schwannoma (VS) treated with linear accelerator stereotactic radiosurgery (LINAC-RS), to describe the complications and to analyze the variables associated with the response to treatment.This retrospective descriptive study included 64 patients treated from 2010 to 2016 with a minimum follow-up of one year, excluding patients with neurofibromatosis. Clinical-radiological parameters were evaluated. The treatment was performed using LINAC-RS. The prescribed dose was 12Gy at 90% isodose.The mean age at treatment was 53 years, 56% were women. Ninety-eight percent of the patients had hearing loss, 71% with grade III according to the Gardner-Robertson Classification. The mean volume at treatment was 2.92cc and the mean follow-up, 40.95 months. The overall therapeutic success was 90%, reaching 100% at 12 and 24 months, and 86% after 36 months of follow-up. The radiological result was significantly related to the initial tumour volume (p0.037). In 20 patients there was evidence of transient tumour growth compatible with pseudoprogression. Acute complications were present in 37.5%, and transitory complications in 50%. Chronic complications were found in 20%, with 84% being permanent. The rate of acute complications was lower in patients with regression (p0.016). Chronic complications were more frequent in the 41-60 year old age group (p0.040).In our study, the overall tumour control was in accordance with other published series. The radiological result significantly related to the tumour volume at the commencement of treatment. The rate of acute complications was lower in patients with regression.

This chapter maps the most relevant aspects of the evolution of the free movement of persons and services through the analysis of the main legislative and judicial developments in both fields. After looking at the salient legislative transformations in the last decades and the effects of codification—mostly through Directives 2004/38 and 2006/123—the chapter explores the parameters that delimit the three different freedoms concerned—workers, establishment, and services. A reassessment of the place and scope of the provisions on the free movement of persons is then offered through a critical examination of the interrelationship between the regulatory framework and case law concerning the free movement of persons, the status of Union citizenship, and developments in the distinct but related Area of Freedom, Security and Justice.

In the late 1980s, craniofacial surgery units reported suboptimal cosmetic results, cranial volume restriction, and intracranial hypertension after anterior cranial vault remodeling in bilateral coronal synostosis associated with severe brachyturricephaly. A possible explanation was a severe associated growth restriction of the posterior calvaria with radiological synostosis at the lambda sutures. "Conventional" or "fixed" posterior cranial vault expansion techniques were developed to address these limitations, sometimes as the first surgical step in a two-staged protocol of total calvarial reconstruction, combined with suboccipital decompression in cases of symptomatic cerebellar tonsillar herniation or, more easily, to resolve the characteristic occipital flattening of lambdoid synostosis. Various surgical approaches have been described; however, the indications for and timing of surgical treatment and postoperative evaluation of results still remain controversial. Although more invasive, conventional posterior cranial vault expansion has proven to be safe and offers a remodeled and protective bony vault immediately after surgery, but the underlying cranial base malformation remained untreated, with implications in the postoperative growth of the facial skeleton. Overcorrection, rigid stabilization, and grafting are also concerns to be addressed.

INTRODUCTION: Brain tumors are the most common solid tumors of childhood and optimal therapeutic strategies for many subtypes remain unknown. Bithalamic gliomas, in contrast with unilateral, have frequent mutations in the EGFR oncogene and only rare Histone H3 mutation. These EGFR mutations are small inframe insertions within exon 20 or missense mutations within exon 7 and occur in absence of gene amplification. CASE REPORT: A previously healthy 10-years-old boy with adequate neuropsychomotor development was admitted with a 5-day-long headache. A brain magnetic resonance imaging (MRI) showed an expansive midline lesion with thalamic extension. The tumor showed no diffusion restriction or contrast enhancement. An endoscopic septostomy and biopsy were performed.The histopahotology showed a diffused astrocytoma grade II. The immunohistochemistry was negative for IDH1 and 2, BRAF mutation, P53 and H3K27M. Next generation sequencing (NGS) ruled out histone H3K27M mutation and showed EGFR mutation in exon 7. The patient experimented clinical and radiological disease progression in a few weeks, confirming the high grade glioma despite the histopahological diagnosis.He received radiotherapy (Total dose 54Gy) and after radiation he started target therapy with Osimertinib, a third generation tirosin kinase inhibitor. As a toxiticy, he experienced neutropenia Grade 2. Disease evaluation performed after 2 cycles showed stable disease. DISCUSSION: Our case report represents a distintc molecular class of pediatric-type bithalamic glioma characterized by EGFR alteration and absence of H3K27M mutation. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.

Objetives Indication for endoscopic third ventriculostomy (ETV) in the treatment for noncommunicating hydrocephalus is widely accepted. There is controversy regarding the indication of a second procedure (re-ETV) when the first has failed. The objective of this work is to revise ETV failures in a series in which re-ETV was performed and to describe the factors related to its prognosis. Method Retrospective study of pediatric patients with ETV failure treated by re-ETV between 2003 and 2018. Gender, age in first and second ETV, time to failure of first ETV, etiology of hydrocephalus, previous presence of shunt, ETV-SS in the first and second ETV, intraoperative findings, success of the second procedure and follow-up were collected. The ETV-SS result was grouped into high (≥ 80), moderate (50−70) or low (≤ 40) scores. Endoscopic procedure failure was considered clinical worsening or the absence of radiological criteria for improvement (reduction in ventricular size or presence of ETV flow artifact in the floor of third ventricle). Results Of 97 ETV carried out in this period, 47 failures were registered, with 13 re-ETV performed. Of these, 8 were classified as successful (61.53%). Re-ETV was successful in 4/4 cases in which etiology was tectal tumor or aqueduct stenosis . In the group with a high ETV-SS score there was a higher rate of success (75%) than in the group with a moderate score (40%). 9 patients presented shunt prior to first ETV and in them, success was 66.6% compared to 50% in the group without prior shunt. All re-ETV were performed without complications. In 11 of the 13 procedures a closed stoma was found and the remaining 2 cases, we found a punctate opening. The mean follow-up after re-ETV was 61.23 months. Conclusion The selection of patients for re-VET should be cautious. Factors such as age, etiology, and previous shunt (ETV-SS factors) have prognostic influence. However, there are specific factors which indicate favorable prognostic for re-VET such as a longer time to failure of the first procedure, the finding of a closed/punctate stoma or the loss of flow artifact in the follow-up MRI.

A polymorphism in the LZTFL1 gene located in the chemokine-receptor gene cluster (chromosome 3p) has been associated with the risk of developing COVID-19. The chemokine receptor-5 (CCR5) maps to this region, and the common 32 bp deletion variant (Δ32) has been associated with the extent of inflammatory disease and the outcome in several viral diseases. Several studies have also suggested that the pharmacological targeting of CCR5 could reduce the impact of SARS-CoV-2 infection and the severity of COVID-19. We sought to investigate whether this polymorphism was associated with the risk of moderate-severe COVID-19.We genotyped 294 patients who required hospitalization due to COVID-19 (85 were severe cases) and 460 controls. We found a significantly lower frequency of CCR5-Δ32 among the COVID-19 patients (0.10 vs 0.18 in controls; p=0.002, OR=0.48, 95%CI=0.29-0.76). The difference was mainly due to the reduced frequency of CCR5-Δ32 carriers in the severe, significantly lower than in the non-severe patients (p=0.036). Of note, we did not find deletion-homozygotes among the patients compared to 1% among controls. We also confirmed the association between a LZTFL1 variant and COVID-19. Our study points to CCR5 as a promising target for treatment of COVID-19, but requires validation in additional large cohorts. In confirmed by others, the genetic analysis of CCR5-variants (such as Δ32) might help to identify patients with a higher susceptibility to severe COVID-19.

Apoliprotein B (ApoB) has been associated with hypercholesterolemia and ischemic coronary disease. This study was aimed to determine the effect of two APOB gene variants in the risk of developing early-onset coronary artery disease (EO-CAD) in a Spanish population. The association of these polymorphisms with hypercholesterolemia was also analysed.The study involved a total of 889 healthy population controls (397 male) and 790 EO-CAD cases (636 male; EO-CAD was defined as male60 years and women65 years). All the patients had at least one vessel with angiography documented atherosclerotic lesion. Patients and controls were genotyped for the APOB variants rs1801701 A/G (p.R3638Q) and rs1367117 C/T (p.T98I). Allele and genotype frequencies were compared between the groups (patients vs. controls, hyper-vs. normo-cholesterolemia) by logistic regression. The rs1801701 was significantly associated with EO-CAD in male (OR = 1.44, 95%CI = 1.05-1.99) and female (OR = 2.22, 95%CI = 1.58-3.14). This SNP was significantly associated with hypercholesterolemia in female, with a trend in male. The association with EO-CAD was independent of hypercholesterolemia (multiple logistic regression).A common APOB polymorphism (rs1801701) was an independent risk factor for EO-CAD in our population. The risk-effect was more significant in female than in male.

The H19-IGF2 imprinted gene region could be implicated in the risk of developing impaired renal function (IRF). Our aim was to determine the association of several common H19-IGF2 variants and IRF in a cohort of elderly healthy individuals. The study involved 675 individuals65 years of age, 184 with type 2 diabetes mellitus (T2DM), and 105 with IRF (estimated glomerular filtration rate [eGFR]60). They were genotyped for two common H19 single nucleotide polymorphisms (SNPs) (rs2839698 and rs10732516), one H19-IGF2 intergenic indel (rs201858505), and one indel in the 3'UTR of the IGF2. For the H19 SNPs, we also determined the allele present in the methylated chromosome through genotyping the DNA digested with a methylation-sensitive endonuclease. None of the four H19-IGF2 variants was associated with IRF in our cohort. We found a significantly higher frequency of the 3'UTR IGF2 deletion (D) in the eGFR60 group (p = 0.01; odds ratio = 1.16, 95% confidence interval = 1.10-2.51). This association was independent of age and T2DM, two strong predictors of IRF. In conclusion, a common indel variant in the 3'UTR of the IGF2 gene was associated with the risk of IRF. This association could be explained by the role of IGF2 in podocyte survival, through regulation of IGF2 expression by differential binding of miRNAs to the indel sequences. Functional studies should be necessary to clarify this issue.

Purely internal situations – Fundamental freedoms – Attribution of powers –Ullens de Schooten– Reverse discrimination – Non-discriminatory obstacles – EU citizenship – Preliminary rulings – Jurisdiction of the Court of Justice – Conditions of admissibility of preliminary references