Advances in the Immunobiological Therapies for Advanced Melanoma. / Nuevos avances de tratamiento inmunobiológico en el melanoma avanzado.

Metastatic or locally advanced unresectable melanoma carries a high morbidity and mortality. However, notable advances have been made in recent years in the systemic treatment of this disease, with the appearance of targeted therapy using tyrosine kinase inhibitors that block the mitogen activated protein kinase pathway, and of modern immunotherapy with immune-modulating monoclonal antibodies. In this paper, we provide an update of available data on new immune therapies and we review the clinical development that led to their approval for use in routine clinical practice.

Distance of the alveolar antral artery from the alveolar crest. Related factors and surgical considerations in sinus floor elevation.

BACKGROUND: In a variable proportion of maxillary sinuses alveolar antral artery is located close to the residual ridge, increasing the chances for haemorrhagic complications during sinus floor elevation procedures. MATERIAL AND METHODS: Retrospective observational study of CBCT explorations performed for implant-treatment planning. The upper first molar area was selected for this study. The relative uncertainty (standard deviation of the measurement divided by its mean and expressed as a percentage from 0% to 100%) was chosen for determining the observational errors. For modeling the chances of AAA detection, the generalized additive models (GAM) approach was chosen. RESULTS: A total of 240 maxillary sinuses were studied (46.25% males) whose median median age was 58 years old (IQR: 52-66). Univariate models showed that the chances for an AAA-alvelar crest distance ≤15mm increase in wider sinuses with lower, subsinusally edentulous crests. When distance is considered as a continuous variable, the best mutivariate model showed an explained deviance of 67% and included AAA diameter, distance AAA-sinus floor, sinus width, and shape, height and width of the residual ridge. Thinner AAAs are found closer to the crest (within the ≤15mm safe distance). CONCLUSIONS: Bearing in mind the inclusion criteria and the limitations of this investigation, it is concluded that there is a high proportion of maxillary sinuses where AAA describes a course close to the alveolar crest (≤15mm), which was classically considered a safe distance for SFE. This position is related to the presence of atrophic crests (depressed ridge form) and wide maxillary sinuses where the distance of the vessel to the floor of the sinus is small. This information may permit a better surgical planning of SFE procedures.

Kidney allograft inflammation and fibrosis, causes and consequences.

This study assessed the development of allograft interstitial fibrosis and inflammation (GIF+"i"), a histologic pattern associated with reduced graft survival. Included are 795 adults, recipients of kidney allografts from 2000 to 2006. GIF+"i" was diagnosed in surveillance and clinical biopsies that had no transplant glomerulopathy. With time, posttransplant increasing number of grafts showed GIF+"i" and these patients had reduced death-censored graft survival (HR = 4.33 (2.49-7.53), p < 0.0001). Development of GIF+"i" was related to prior acute cellular rejection (ACR), BK nephropathy (PVAN), increasing number of HLA mismatches, retransplantation and DGF. However, 46.4% of GIF+"i" cases had no history of ACR or PVAN. Anti-HLA antibodies at transplant did not relate to GIF+"i" and these patients had no increased frequency of new antibody formation posttransplant. Post-ACR biopsies showed that GIF+"i" developed more commonly after clinically and/or histologically more severe ACR. Graft inflammation persisted in 38.7 and 29.6% of grafts 2 and 12 months post-ACR. Twelve months post-ACR, 27.1% of biopsies developed moderate-severe GIF and 51.8% showed GIF and inflammation. Persistent inflammation and progressive GIF is often subclinical but may lead to graft failure. GIF+"i" can be initiated by multiple etiologies but it is often postinfectious or due to persistent cellular immune-mediated injury.

Effects of chitosan coatings on physicochemical and nutritional quality of clementine mandarins cv. 'Oronules'.

A commercial solution of chitosan was applied on mandarins 'Oronules' at different solid content (0.6%, 1.2% and 1.8%). Additionally, one group of mandarins was coated with a polyethylene-shellac commercial wax, and another group remained uncoated (control). Mandarins were stored at 5 °C up to 28 days followed by 7 days at 20 °C simulating retail conditions. One group of mandarins was stored at 20 °C for 9 days simulating direct retail conditions. The commercial wax decreased weight and firmness loss of mandarins compared to uncoated samples, whereas the chitosan coating did not effectively decrease weight loss of mandarins. Chitosan-coated mandarins at the highest solid content retained firmness after cold storage and contained more phenolics than uncoated ones. Although all the coatings restricted gas exchange and modified the internal atmosphere of the mandarins, with a greater effect at higher chitosan concentration, sensory quality was not affected. In general, the internal quality and the health-related properties of mandarins were not negatively affected by coating application. However, there is a need to further improve the water barrier properties of the chitosan coating.

Transient disabling dyskinesias: a predictor of good outcome in subthalamic nucleus deep brain stimulation in Parkinson's disease.

We report 5 of 75 (6.6%) patients with Parkinson's disease (PD) submitted to subthalamic nucleus deep brain stimulation (STN-DBS) who developed transient disabling dyskinesias immediately after surgery. Dyskinesias persisted despite levodopa withdrawal, cessation or reduction of stimulation, and resolved spontaneously in a maximum period of 12 weeks without the need to change stimulation active contact. Compared to the rest of our PD patients submitted to STN-DBS, the dyskinesia group needed a lower levodopa-equivalent daily dosage (LEDD) over the time of follow-up. A microlesion in the STN, probably concealed in cerebral MRI by the electrode-related artifact, could have been involved in the etiopathology of our patients' symptoms. The presence of transient disabling dyskinesia in PD patients immediately after STN-DBS might be a predictor of good outcome as measured by a decrease in the LEDD needed.

[Clinical and economic repercussions of the use of tunneled haemodialysis catheters in a health area]. / Repercusiones clínicas y económicas del uso de catéteres tunelizados de hemodiálisis en un área sanitaria.

INTRODUCTION: Tunneled catheters in hemodialysis are associated with poor prognosis, however, few prospective studies have been designed to specifically evaluate this aspect. The objective has been evaluate the impact of tunneled catheter in patient mortality and costs attributable to this procedure. METHODS: A seven years prospective cohort study was performed in all patients starting hemodialysis in our health care area adjusting for comorbidity and albumin. The study comprised 260 patients with Charlson index 7.05 +/- 2.8 (age 65.5 years, 62.3% males, 25% with diabetes mellitus and 37.7% with a previous cardiovascular event. RESULTS: The first vascular access was a catheter in 47.3%, PTFE in 11.2% and native arteriovenous fistula in 41.5%. Minimum follow-up was one year, with an average of 2.31 years/patient. The mortality risk adjusted for comorbidity was greater among the patients that started with catheterization, HR: 1.86 [1.11-3.05]. This negative effect was observed in 57.30% of those subjected to catheterization at any stage (HR: 1.68 [1.00-2.84] and proved to be time dependent, i.e., the longer catheterization, the greater the risk: HR: 7.66 [3.34-17.54] third versus first tertil. The cost directly attributable to catheter use was 563.31 euros/month. All poor prognosis groups showed lower albumin and hemoglobin levels, without differences in efficacy. CONCLUSION: Tunneled catheter use at any time is associated with an increased risk of death. This effect increases with the duration of catheterization, both circumstances are independent of patient comorbidity at time start of hemodialysis and implies a higher net cost.

[Changes in the pre-transplant bone-mineral metabolism do not affect the initial progress of the renal graft]. / Las alteraciones del metabolismo óseo-mineral pretrasplante no influyen en la evolución inicial del injerto renal.

BACKGROUND: Abnormalities in serum calcium, phosphate, and Parathyroid Hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. One of the most common problems in the first weeks after renal transplantation is Delayed Graft Function (DGF). There are several well-known risk factors for DGF development, but the role of calcium phosphate-PTH homeostasis as a risk factor for early graft dysfunction is controversial. This issue was addressed in the current study. METHODS: Pretransplant PTH, calcium and phosphate values were gathered in 449 patients that received a renal transplant in our center between 1994 and 2007. Other variables expected to influence the risk for delayed graft function were included from the clinical charts. RESULTS: The incidence of DGF was 27.3%. DGF development was significantly associated with recipient age, type and need of renal replacement therapy, peak panel reactive antibodies, transfusion number and donor age. There were no significant differences in the mean pretransplant values of calcium (9.4 +/- 1.0 vs. 9.5 +/- 0.9 mg/dl, p = 0.667), phosphate (5.7 +/- 1.8 vs. 5.5 +/- 1.5 mg/dl, p = 0.457), calcium-phosphate product (53.5 +/- 17.2 vs. 51.8 +/- 14.6 mg(2)/dl(2), p = 0.413) and PTH (315 +/- 312 vs. 340 +/- 350 pg/ml, p = 0.530) between patients with and without DGF. CONCLUSIONS: In our study population pretransplant serum PTH, calcium and phosphorus levels have no influence on the risk for DGF.

[Efficacy of obturator and femoral cutaneous nerve blocks for postoperative analgesia in hip surgery]. / Eficacia del bloqueo de los nervios obturador y femorocutáneo para analgesia postoperatoria en cirugía de cadera.

OBJECTIVES: The treatment of pain after surgery to repair a hip fracture is essential for an early start of rehabilitation and for reducing morbidity and mortality. Given that patients are elderly and have multiple medical conditions, local-regional analgesia can be an effective approach. Our aim was to compare the efficacy of obturator and femoral cutaneous nerve blocks and total intravenous analgesia in terms of level of patient satisfaction, complications, start of rehabilitation, and cost. PATIENTS AND METHODS: Prospective study of 75 patients undergoing surgery to repair hip fractures. Patients were randomized to receive intravenous analgesia only, blockade of both nerves, or blockade of only the obturator nerve. In each group we recorded visual analog scale (VAS) pain scores, satisfaction with postoperative analgesia, time elapsed until start of rehabilitation, need for postoperative analgesics, side effects, and the cost of drugs. RESULTS: Analgesia was significantly more effective in patients with nerve blocks than in those who received only intravenous analgesia (mean [SD] VAS scores, 2.6 [1.4] and 5.6 [0.7], respectively). Patients with nerve blocks also had a pain-free period of more than 24 hours (P < .001), needed fewer doses of supplementary analgesics or other drugs, had fewer side effects (P < .01), started rehabilitation earlier (32.6 [5.4] hours vs 45.7 [8.2] hours), generated less expenditure (2.6 Euros [1.5 Euros]/patient vs 7.0 Euros [0.4 Euros]/patient). The tested techniques had no complications. CONCLUSIONS: The nerve blocks were effective, easy to perform, and safe. They afforded numerous advantages: extended period of postoperative analgesia, fast recovery, lower costs, and no complications.

[De novo heterozygous mutation in the MBD5 gene associated with bilateral band heterotopia and polymicrogyria]. / Mutación de novo en heterocigosis en el gen MBD5 asociada a heterotopía en banda bilateral y polimicrogiria.

INTRODUCTION: The aetiology of autosomal dominant mental retardation type 1, also known as pseudo-Angelman, MBD5-associated neurodevelopmental disorder or MBD5 haploinsufficiency, lies in a microdeletion of chromosome 2q23.1 or in a specific alteration of the MBD5 gene, which constitutes the minimum region affected in the aforementioned microdeletion. AIM: To report the case of a girl with a heterozygous de novo mutation in the MBD5 gene associated with bilateral band heterotopia and polymicrogyria. CASE REPORT: We report the case of an 8-year-old girl who was submitted to a developmental follow-up from the age of 18 months after presenting the association of severe intellectual disability and motor delay, lack of language development, segmental hypotonia, a wide forehead and kyphoscoliosis. Magnetic resonance imaging of the brain revealed the presence of a bilateral band heterotopia and parietooccipital polymicrogiria predominant on the left side. In the exome the de novo heterozygous variant c.397+1G>C was detected in the MBD5 gene. CONCLUSION: This is the first observation of a heterozygous mutation in the MBD5 gene associated with a neuronal migration disorder.

TITLE: Mutación de novo en heterocigosis en el gen MBD5 asociada a heterotopía en banda bilateral y polimicrogiria.Introducción. La etiología del retraso mental autosómico dominante 1, también conocido como pseudo-Angelman, trastorno del neurodesarrollo asociado a MBD5 o haploinsuficiencia MBD5, radica en una microdeleción del cromosoma 2q23.1 o en una alteración específica del gen MBD5, que constituye la mínima región afectada en la citada microdeleción. Objetivo. Comunicar el caso de una niña con una mutación heterocigota y de novo en el gen MBD5 asociada a heterotopía en banda bilateral y polimicrogiria. Caso clínico. Niña de 8 años, seguida evolutivamente desde los 18 meses por presentar la asociación de discapacidad intelectual y retraso motor graves, ausencia de desarrollo del lenguaje, hipotonía segmentaria, frente ancha y cifoescoliosis. En la resonancia magnética cerebral se observó la presencia de una heterotopía en banda bilateral y polimicrogiria parietooccipital de predominio izquierdo. En el exoma se detectó la variante de novo c.397+1G>C en heterocigosis en el gen MBD5. Conclusión. Constituye la primera observación con una mutación heterocigota en el gen MBD5 asociada a un trastorno en la migración neuronal.

Therapeutic criteria in communicating childhood hydrocephalus.

AIM: The aim of this study was to evaluate the usefulness of cerebral blood flow velocity in the middle cerebral artery measured by transcranial Doppler as criteria to therapeutic action in communicating hydrocephalic children. METHODS: In eight non-tumoral communicating hydrocephalic infants, ranging from five to 18 months of age, monitored from 18 to 36 months (mean time of follow-up: 24.25 months), cerebrospinal fluid (CSF) oxypurines (hypoxanthine and xanthine) and uric acid levels were compared by means of the Evans' index, the mean weekly increase in cranial circumference, and the transcranial Doppler measurements. RESULTS: Results indicate that clinical (mean weekly increase in head circumference), radiological (Evans' index), biochemical (oxypurines and uric acid in the CSF), and hemodynamic (transcranial Doppler) criteria have the same role in monitoring infantile hydrocephalus. CONCLUSION: In conclusion the transcranial Doppler measurement can be done noninvasively and examinations can be repeated when needed, obtaining immediate RESULTS: Hence, it is the most adequate monitoring technique in clinical practice.

Mixed Adenoneuroendocrine Carcinoma of the Esophagus: A Case Report and Review of the Literature.

The most frequent presentation of esophageal cancer is adenocarcinoma and squamous cell carcinoma. In recent years, the latter has decreased its incidence increasing the adenocarcinoma. Currently, another type of tumor with a much lower incidence has been described, which has a neuroendocrine component along with another exocrine glandular component and has been classified since 2010 as mixed adenoneuroendocrine carcinoma (MANEC). We present the case of a 68-year-old male with a history of dyspepsia and epigastric pain who after performing a gastroscopy, was diagnosed with a malignant neoplasm of the esophagus. The patient underwent a total esophagectomy with reconstruction by tubular gastroplasty with cervical anastomosis. The final result of the piece after immunohistochemistry revealed that the tumor was composed of one component of adenocarcinoma in 60% together with another component compatible with neuroendocrine in 40%. With these findings and according to the World Health Organization classification of 2010 was diagnosed as esophageal MANEC. MANECs are rare tumors, described in other locations of the digestive tract, the esophagus being an infrequent location. Its preoperative diagnosis is difficult, and it is not until the final analysis of the complete piece by means of specific immunohistochemical techniques when its diagnosis can be established. Its treatment is fundamentally surgical, whereas the adjuvant therapeutic schemes with chemotherapy are not well defined at present because of their low incidence.

[Pontocerebellar hypoplasia type 1: a case report]. / Hipoplasia pontocerebelosa tipo 1: aportación de un caso.

INTRODUCTION: Pontocerebellar hypoplasias constitute a group of hereditary neurodegenerative disorders of uncertain aetiopathogenesis. They have been reported as being associated with deficiencies of complexes in the mitochondrial respiratory chain (MRC) and with congenital disorders of glycosylation. On the basis of clinical and neuropathological criteria, two phenotypes can be distinguished in this condition. Pontocerebellar hypoplasia type 1 is characterised by hypoplasia of the pons and the cerebellum associated with the degeneration of the motor neurons in the anterior horn of the spinal cord. CASE REPORT: A 4-year-old female with symptoms of severe psychomotor retardation associated with microcephaly, important generalised hypotonia, muscle hypotrophy, contractions in the four limbs, absence of stretch reflex and epilepsy with onset in the neonatal period. Magnetic resonance imaging of the brain revealed pontocerebellar hypoplasia. An electroneuromyography showed a trace that was compatible with axonal neuropathy and a biopsy of the deltoid muscle revealed the existence of neurogenic muscular atrophy. In the MRC study conducted in muscle homogenate and in skin fibroblasts, complex IV values were found to be at the lower limits of what could be considered to be normal levels. Results of the genetic study for spinal muscular atrophy were negative. CONCLUSIONS: The case reported here could be included as a case of pontocerebellar hypoplasia type 1. MRC studies can be of interest in cases of pontocerebellar hypoplasia in order to explain the role it plays in this disorder.

[Reversible posterior leukoencephalopathy syndrome: an infrequent complication in the course of haemolytic-uremic syndrome]. / Leucoencefalopatía posterior reversible: una complicación infrecuente en el curso del síndrome hemolítico urémico.

INTRODUCTION: Posterior reversible leukoencephalopathy syndrome (PRLS) is characterised by the sudden and usually transient onset of headaches, visual disorders, decreased awareness and convulsions associated with cerebral oedema in the posterior areas of the brain. Different reports have associated it with numerous processes and possibly with haemolytic-uremic syndrome (HUS). We describe a new case of PRLS within the context of HUS. CASE REPORT: We describe the case of a 4-year-old child with HUS who developed arterial hypertension that did not respond well to treatment and kidney failure that required renal replacement therapy. During the course of the disease the patient presented several transient episodes of headache, a lowered level of consciousness and seizures. Magnetic resonance imaging revealed multiple lesions in the white matter and the cortex that were hyperintense in T2 and hypointense in T1 situated in the bilateral occipital and right frontotemporoparietal regions. The patient made a full clinical recovery in a few days, although an magnetic resonance imaging scan performed at six weeks after the last episode showed partial remission of the lesions and a small cerebral infarction. CONCLUSIONS: The pathogenesis of PRLS is still not fully understood. Its multifactorial origin suggests that several different mechanisms may be involved. In the case reported here, it is possible that the arterial hypertension, retention of fluids and even the sessions of dialysis played a role in its development.

Factores predictores de respuesta completa patológica tras inducción (ypT0N0M0) en cáncer de pulmón no microcítico y resultados a corto plazo: resultados del Grupo Español de Cirugía Torácica Videoasistida (GE-VATS) / Predictive factors of pathological complete response after induction (ypT0N0M0) in non-small cell lung cancer and short-term outcomes: results of the Spanish Group of Video-assisted Thoracic Surgery (GE-VATS)

Introducción Analizar los factores predictores de respuesta patológica completa (RCp) en pacientes con cáncer de pulmón no microcítico (CPNM) sometidos a resección pulmonar anatómica tras terapia de inducción y evaluar los resultados postoperatorios de estos pacientes. Métodos Se incluyeron en el estudio todos los pacientes registrados de forma prospectiva en la base de datos del grupo de trabajo GE-VATS reclutados entre el 20 de diciembre de 2106 y el 20 de marzo de 2018, sometidos a resección pulmonar anatómica por CPNM tras tratamiento de inducción. La población se dividió en dos grupos: pacientes que obtuvieron respuesta completa patológica tras inducción (RCp) y pacientes que no obtuvieron una respuesta patológica completa tras inducción (no-RCp). Se realizó un análisis multivariante mediante una regresión logística binaria para determinar los factores predictores de RCp y se analizaron los resultados postoperatorios de los pacientes. Resultados De los 241 pacientes analizados, 36 pacientes (14,9%) alcanzaron RCp. Los factores predictores de RCp fueron el sexo masculino (OR 2,814, IC 95% 1,015-7,806), la histología de carcinoma escamoso (OR 3,065, IC 95% 1,233-7,619) u otra distinta de adenocarcinoma (ADC) (OR 5788, IC 95% 1,878-17,733), la terapia de inducción que incluye radioterapia (OR 4,096, IC 95% 1,785-9,401) y terapias dirigidas (OR 7,625, IC 95% 2,147-27,077). La ocurrencia de complicaciones respiratorias postoperatorias fue superior en los pacientes que recibieron quimio-radioterapia de inducción (p = 0,032). Conclusiones El sexo masculino, la histología de carcinoma escamoso o diferente de ADC y la terapia de inducción que incluye radioterapia o terapia dirigida son factores predictores positivos para la obtención de RCp. La quimio-radioterapia de inducción se asocia con un mayor riesgo de complicaciones respiratorias postoperatorias (AU)

Introduction To analyze the predictors of pathological complete response (pCR) in not small cells lung carcinoma (NSCLC) patients who underwent anatomical lung resection after induction therapy and to evaluate the postoperative results of these patients. Methods All patients prospectively registered in the database of the GE-VATS working group undergone anatomic lung resection by NSCLC after induction treatment and recruited between December 20th 2016, and March 20th 2018, were included in the study. The population was divided into two groups: patients who obtained a complete pathological response after induction (pCR) and patients who did not obtain a complete pathological response after induction (non-pCR). A multivariate analysis was performed using a binary logistic regression to determine the predictors of pCR and the postoperative results of patients were analyzed. Results Of the 241 patients analyzed, 36 patients (14.9%) achieved pCR. Predictive factors for pCR are male sex (OR 2.814, 95% CI 1.015-7.806), histology of squamous carcinoma (OR 3.065, 95% CI 1.233-7.619) or other than adenocarcinoma (ADC) (OR 5.788, 95% CI 1.878-17.733) and induction therapy that includes radiation therapy (OR 4.096, 95% CI 1.785-9.401) and targeted therapies (OR 7.625, 95% CI 2.147-27.077). Prevalence of postoperative pulmonary complications was higher in patients treated with neoadjuvant chemo-radiotherapy (p = 0.032). Conclusions Male sex, histology of squamous carcinoma or other than ADC, and induction therapy that includes radiotherapy or targeted therapy are positive predictors for obtaining pCR. Induction chemo-radiotherapy is associated with a higher risk of postoperative pulmonary complications (AU)

Diameter of alveolar antral artery in the lateral sinus wall: study of related factors.

To identify the variables that influence the diameter of the artery in the lateral sinus wall, we studied 240 sinuses, focusing on sex, pattern of tooth loss, type of residual crest, thickness of the lateral wall, height and width of the ridge, and width of the sinus.

[Prospective monitoring of vascular access in hemodialysis by means of a multidisciplinary team]. / Seguimiento prospectivo del acceso vascular en hemodialisis mediante un equipo multidisciplinar.

PURPOSE: Nowadays, expert guidelines recommend the monitoring programs of the vascular access (VA) by a multidisciplinary team. MATERIAL AND METHOD: We present the experience over the last five years, of a prospective VA surveillance by a multidisciplinary team. The quality indicators reached are described as the associated factors for survival of the new VA. RESULTS: Three hundred seventeen VA have been studied, 73% were arteriovenous fistulas(AVF) and the rest were polytetrafluoroethylene (PTFE) grafts at 282 patients. The main causes of dysfunctions were elevated dynamic venous pressure (42.5%) and the decreased blood flow (36.4%) with a 88% of positive predictive value. Over the 5 years there was 88 thrombosis (24 AVF and 64 PTFE grafts), that means a hazard thrombosis global rate of 0.15 access/year, which were distributed in 0.06 for AVF and 0.38 in PTFE grafts. Two hundred and one repairs of VA were done: 66.6% were elective repair after a proper review by the multidisciplinary team and the rest of them were done after the AV thrombosis happened. Urgent rescue surgeries were done in 76% of the thrombosis. 62.5% of the patients did not need a catheter after vascular access thrombosis. The complication relation with AVF and PTFE were 11.4% of the total patients hemodialysis hospitalizations. 65.2% of the VA were new access. 57% of patients were properly reviewed in the pre-dialysis unit at least once and 80% of them start haemodialysis with a mature access. The average survival (Kaplan Meier) of the new AVF was 1,575+/-55 days vs 1,087+/-102 of the PTFE grafts (p < 0.008). The survival after 1, 2 and 3 years for the AVF was 89%, 85% and 83% and for the PTFE graft 3% 67% and 51% respectively. The Cox regression has proved that the type of vascular access is the strongest factor associated to VA survival. The survival added of VA repaired due to dysfunction was 1,062 +/- 97 days vs 707 +/- 132 due to thrombosis, log rank 5.17 (p < 0,02). The increasing risk of those repaired after a thrombosis vs dysfunction is 4.2 p < 0,01. CONCLUSIONS: The monitoring of the vascular access by a multidisciplinary team has reached:low rate of thrombosis, high elective number of repairs of the VA, high urgent rescue surgery after a thrombosis and a few number catheter needed and hospitalizations. AVF are associated with greater survival than PTFE. The VA repair due to dysfunction vs thrombosis had a greater survival as well.

[Non-progressive congenital ataxias]. / Ataxias congénitas no progresivas.

INTRODUCTION: Non-progressive congenital ataxias (NPCA) constitute a heterogeneous group of processes linked to diverse aetiological factors that can be either environmentally or genetically determined. The signs of cerebellar compromise, which are preceded by unspecific signs such as early hypotonia, difficulty in sucking or chewing or retarded motor acquisition, become apparent with development or may remain absent when the disorder is very severe. DEVELOPMENT: NPCA can be accompanied by a number of pathologies and their diagnosis can be made easier by the concurrence of symptoms or signs of extra-cerebellar involvement, such as dysmorphic features or abnormalities affecting the skin, heart, bones, blood, eyes or other areas of the central or peripheral nervous system. Neuroimaging usually reveals vermian hypoplasia and/or hypoplasia of the cerebellar hemispheres, but can be normal in certain situations. The article includes a review of the NPCA following the classification proposed by Steinlin in 1998. CONCLUSIONS: The difficulties inherent in diagnosing these processes makes it necessary to deploy a wide range of complementary examinations, especially metabolic tests, before a generic diagnosis of NPCA can be established. Although the progress made in molecular genetics has made it possible to categorise NPCA better, both their causation and their hereditary or sporadic nature remain unknown in about 50% of cases.

[Pyruvate dehydrogenase deficit associated to the C515T mutation in exon 6 of the E1alpha gene]. / Deficit de piruvato deshidrogenasa asociado a la mutacion C515T en el exon 6 del gen E1alpha.

INTRODUCTION: Pyruvate dehydrogenase (PDH) deficiency constitutes the most frequent metabolic origin of congenital lactic acidosis and is also responsible for a less usual form, found exclusively in females, which leads to a dysmorphic syndrome accompanied by severe cerebral malformations. The most common defect affects fraction E1alpha (gene Xp22.1-22.2). AIM: To report the case of a young female with PDH deficiency, dysmorphic syndrome, cerebral deformations and an unidentified mutation in the corresponding gene. CASE REPORT: An 8-month-old female with microcephaly, a narrow forehead, nasal hypoplasia, anteverted nostrils, thin lips, axial hypotonia, epileptic seizures and an umbilical hernia. Magnetic resonance imaging of the brain revealed intense supra- and infratentorial cortico-subcortical atrophy, ventricular dilatation and agenesis of the corpus callosum. Lactic and pyruvic acid concentrations were high both in blood and in cerebrospinal fluid (CSF), and the level of alanine was high in CSF. Muscular histology results were normal. PDH complex activity in fibroblasts and in muscle tissue, as well as that of the mitochondrial respiratory chain complexes in muscle homogenate, were found to be normal. A molecular genetic study of the gene for PDHE1alpha, both in formed elements in the blood and in fibroblasts, showed a C > T change in nucleotide 515 (C515T) of exon 6, which causes a P172L change in the protein. A study of 108 controls ruled out the possibility of a polymorphism. The parents did not have the mutation. CONCLUSIONS: The C515T mutation of exon 6 of the gene for PDH E1alpha is described. Normal activity of the PDH complex in fibroblasts and in muscle tissue does not exclude this condition.

[Retrospective analysis of the effect of a vagus nerve stimulator implanted in paediatric patients with refractory epilepsy]. / Analisis retrospectivo sobre el efecto del estimulador vagal implantado en pacientes pediatricos con epilepsia refractaria.

INTRODUCTION: The vagus nerve stimulator is a therapeutic alternative in patients with epilepsy which is refractory to treatment with antiepileptic drugs that are not candidates for surgical resection. AIM: To analyse the effectiveness of vagus nerve stimulator in the paediatric patients of our centre. PATIENTS AND METHODS: Set of 13 patients implanted between 2008 y 2013. It was registered the frequency of crises prior to implantation, after a year and at the end of the monitoring period. As well, it was recorded the number of antiepileptic drugs used and in a qualitative way the behavioural improvement and the change in the intensity of the crises, besides the apparition of secondary effects and the removal or not of the device. RESULTS: After a year, two years and at the end of the monitoring period it has been a fall in the number of crises about of 61%, 66.7% y 69% respectively, finding one patient free of crises after two years. At the end of the monitoring period, the 23% of those who had reduced their crises had experimented a reduction over 90%. Independently the effect on the number of crises, 77% of the patients presented an improvement in the intensity and the length of the crises, the same average showed a behavioural improvement. The secondary effects appeared in a 30.7% of the patients, being of mild intensity. CONCLUSIONS: Despite the small size of our sample, our results shows that the vagus nerve stimulator has a relevant efficacy over the pediatric drug resistant population, as much in the frequency and intensity of the crises, as over the behaviour.

TITLE: Analisis retrospectivo sobre el efecto del estimulador vagal implantado en pacientes pediatricos con epilepsia refractaria.Introduccion. El estimulador vagal es una alternativa terapeutica en los pacientes con epilepsia refractaria al tratamiento con farmacos antiepilepticos que no son candidatos a cirugia de reseccion. Objetivo. Analizar la eficacia del estimulador vagal en los pacientes pediatricos de nuestro centro. Pacientes y metodos. Conjunto de 13 pacientes implantados entre los años 2008 y 2013. Se registro la frecuencia de crisis previa a la implantacion, al año, a los dos años y al final del seguimiento. Asimismo, se recogio el numero de farmacos antiepilepticos utilizados, de forma cualitativa la mejoria conductual y el cambio en la intensidad de las crisis, asi como la aparicion de efectos secundarios y la retirada o no del dispositivo. Resultados. Al año, a los dos años y al final del seguimiento se habia producido una reduccion en el numero de crisis del 61%, 66,7% y 69%, respectivamente, y uno de los pacientes se encontro libre de crisis a los dos años. Al final del seguimiento, un 23% de los que habian disminuido sus crisis habia experimentado una reduccion superior al 90%. De forma independiente al efecto sobre el numero de crisis, el 77% de los pacientes presento una mejoria en la intensidad y duracion de las crisis, y ese mismo porcentaje mostro una mejoria conductual. Los efectos secundarios aparecieron en un 30,7% de los pacientes y fueron de intensidad leve. Conclusiones. A pesar del pequeño tamaño de la muestra, nuestros resultados indican que el estimulador vagal tiene una eficacia relevante en la poblacion pediatrica farmacorresistente, tanto sobre la frecuencia e intensidad de las crisis como sobre la conducta.