Discriminating factors in access to video-EEG for epilepsy surgery in a French tertiary epilepsy center.

Equitable access to care and management is a priority for patients with epilepsy and may vary depending on each country's healthcare system. As this issue has not been specifically addressed in France, we conducted a retrospective study to identify discriminating factors in access to surgery at a French tertiary epilepsy center. Initially, we examined factors previously identified in other countries as influential in surgery access, including age at diagnosis, affected side, gender, years of education, socio-professional categories, and density of general practitioners in the residential area, in 293 consecutive French-native patients with refractory medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). Subsequently, we conducted a case-control study comparing patients born in France with 22 patients born abroad to specifically explore migratory status. The analysis revealed that the only three factors statistically influencing the delay between the onset of epilepsy and entry into video-EEG were early age at onset (associated with a longer delay), pensioner status (associated with a longer delay), and student status (associated with a shorter delay). Migratory status, gender, and socio-economic level (indirectly reflected by the level of education and socio-professional category) were not found to be discriminatory factors in access to video-EEG. Discrepancies between our study and foreign studies may be attributed to differences in healthcare systems and medical coverage among countries. Efforts in France to improve access to surgery should focus on enhancing communication among practitioners to promptly refer any MTLE-HS patient to an epilepsy surgery center, regardless of their age.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial.

BACKGROUND: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. PATIENTS AND METHODS: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. RESULTS: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. CONCLUSIONS: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations. CLINICALTRIALS.GOV NUMBER: NCT01704703. EUDRACT NUMBER: 2012-001955-38.

Techno-economic analysis of the scale-up process of electrochemically-assisted soil remediation.

This work presents a techno-economic study of the scaling-up of the electrochemically-assisted soil remediation (EASR) process of polluted soil. Four scales have been selected for the study: laboratory, bench, pilot and prototype, with a capacity of treating a volume of soil of 1 × 10-4, 2 × 10-3, 0.11 and 21.76 m3, respectively. This study analyses the technical information produced by studies carried out at each scale, and informs about the fixed costs (construction of the electrokinetic remediation reactor, installation of auxiliary services and purchase of analytical equipment) and variable costs (start-up, operation and dismantling of the test) derived from running a test at each of the evaluated scales. The information discussed in based on the experience gained with many evaluations carried out over the last decade at these scales. This information can provide useful guidance for developing a scaling-up of the EASR for many researchers starting on the evaluation of this important environmental remediation technology.

A clinical and neurophysiological motor signature of Unverricht-Lundborg disease.

OBJECTIVES: Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time, contributing along with myoclonus to motor disability. The purpose of the present work was to clarify the motor and neurophysiological characteristics of ULD patients. METHODS: Nine patients with genetically proven ULD were evaluated clinically (medical history collected from patient charts, the Scale for the Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale). Neurophysiological investigations included EEG, surface polymyography, long-loop C-reflexes, somatosensory evoked potentials, EEG jerk-locked back-averaging (JLBA) and oculomotor recordings. All patients underwent brain MRI. Non-parametric Mann-Whitney tests were used to compare ULD patients' oculomotor parameters with those of a matched group of healthy volunteers (HV). RESULTS: Myoclonus was activated by action but was virtually absent at rest and poorly induced by stimuli. Positive myoclonus was multifocal, often rhythmic and of brief duration, with top-down pyramidal temporospatial propagation. Cortical neurophysiology revealed a transient wave preceding myoclonus on EEG JLBA (n=8), enlarged somatosensory evoked potentials (n=7) and positive long-loop C-reflexes at rest (n=5). Compared with HV, ULD patients demonstrated decreased saccadic gain, increased gain dispersion and a higher frequency of hypermetric saccades associated with decreased peak velocity. CONCLUSION: A homogeneous motor pattern was delineated that may represent a ULD clinical and neurophysiological signature. Clinical and neurophysiological findings confirmed the pure cortical origin of the permanent myoclonus. Also, oculomotor findings shed new light on ULD pathophysiology by evidencing combined midbrain and cerebellar dysfunction.

Altered circadian feeding behavior and improvement of metabolic syndrome in obese Tac1-deficient mice.

BACKGROUND: Metabolic function is regulated by the interplay of central and peripheral factors that ultimately regulate food intake (FI) and energy expenditure. The tachykinin substance P (SP) has been identified as a novel regulator of energy balance, however, the mechanisms underlying this effect are ill-defined and conflicting data regarding the role of SP on FI have been reported by different groups. OBJECTIVE: To further characterize the metabolic role of the Tac1 gene products (SP and neurokinin A) in mice through a series of genetic, metabolic and behavioral studies in Tac1-deficient mice. RESULTS: Tac1-/- mice are leaner than controls and display reduced FI and altered feeding circadian rhythm, supported by disrupted expression of the clock genes Cry1/2, Per1/2 in the suprachiasmatic nucleus, mediobasal hypothalamus (MBH) and liver, as well as increased proopiomelanocortin expression in the MBH. Tac1 ablation induced resistance to obesity, improved glucose tolerance, prevented insulin resistance under high-fat diet, increased activation of brown adipose tissue and improved hepatic steatosis. Moreover, deletion of Tac1 in ob/ob mice ameliorated body weight gain in females only but was sufficient to decrease fat and triglyceride content in the liver of males. CONCLUSIONS: These results provide further evidence that Tac1 controls circadian feeding behavior and metabolism in mice through mechanisms that involve the regulation of the melanocortin system. In addition, these studies suggest that the blockade of SP may offer a new method to treat metabolic syndrome.

Outcome of childhood-onset epilepsy from adolescence to adulthood: Transition issues.

This is the second of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper addresses the outcome for some particularly challenging childhood-onset epileptic disorders with the goal of recommending the best approach to transition. We have grouped these disorders in five categories with a few examples for each. The first group includes disorders presenting in childhood that may have late- or adult-onset epilepsy (metabolic and mitochondrial disorders). The second group includes disorders with changing problems in adulthood (tuberous sclerosis complex, Rett syndrome, Dravet syndrome, and autism). A third group includes epilepsies that change with age (Childhood Absence Epilepsy, Juvenile Myoclonic Epilepsy, West Syndrome, and Lennox-Gastaut syndrome). A fourth group consists of epilepsies that vary in symptoms and severity depending on the age of onset (autoimmune encephalitis, Rasmussen's syndrome). A fifth group has epilepsy from structural causes that are less likely to evolve in adulthood. Finally we have included a discussion about the risk of later adulthood cerebrovascular disease and dementia following childhood-onset epilepsy. A detailed knowledge of each of these disorders should assist the process of transition to be certain that attention is paid to the most important age-related symptoms and concerns.

In situ studies of NO reduction by H2 over Pt using surface X-ray diffraction and transmission electron microscopy.

In situ surface X-ray diffraction and transmission electron microscopy at 1 bar show massive material transport of platinum during high-temperature NO reduction with H2. A Pt(110) single-crystal surface shows a wide variety of surface reconstructions and extensive faceting of the surface. Pt nanoparticles change their morphology depending on the gas composition: They are faceted in hydrogen-rich environments, but are more spherical in NO-rich environments, indicating the formation of vicinal surfaces. We conclude that high coverage of NO combined with sufficient mobility of platinum surface atoms is the driving force for the formation of steps on both flat surfaces and nanoparticles. Since the steps that are introduced provide strongly coordinating adsorption sites with potential catalytic benefits, this may be of direct practical relevance for the performance of catalytic nanoparticles under high-pressure conditions.

Lateralizing value of semiology in medial temporal lobe epilepsy.

OBJECTIVES: Analysing the clinical characteristics of seizures constitutes a fundamental aspect of the presurgical evaluation of patients with medial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE-HS), the most frequent form of focal epilepsy accessible to surgery. We sought to retrospectively determine whether objective manifestations could have a reliable lateralizing value in a large population of MTLE-HS patients and if their presence could help to identify those patients who would be seizure free after surgery. MATERIAL AND METHODS: We analysed the frequency and predictive lateralizing value of objective ictal and postictal signs in 391 patients with MTLE-HS (183 left/208 right). Data were derived from chart review and not from blinded videoEEG analysis. Correlation between the presence of reliable lateralizing signs and postoperative outcome was performed in a subgroup of 302 patients who underwent surgery. RESULTS: Contralateral dystonic posturing was the most frequent and reliable lateralizing sign that correctly lateralized the focus in 96% of patients. Unilateral head/eye deviation was noted in 42% of the patients and predicted unilateral focus in 67%. Ipsilateral postictal nose wiping, contralateral clonus and hypokinesia correctly lateralized the focus in 75%, 81%, respectively, and 100 of patients but were less frequently depicted. Postictal aphasia was a strong lateralizing sign for left MLE-HS. The presence of reliable lateralizing signs was not a predictor of seizure freedom. CONCLUSION: Seizure semiology is a simple tool that may permit reliable lateralization of the seizure focus in MTLE-HS. The presence of reliable lateralizing signs is not associated with a better postoperative outcome.

Surgical treatment for mesial temporal lobe epilepsy associated with hippocampal sclerosis.

INTRODUCTION: Hippocampal sclerosis is the most common cause of pharmacoresistant epilepsy amenable for surgical treatment and seizure control. The aim of this article is to review and evaluate the published literature related to the outcome of the surgical treatment of mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) and to describe the future prospects in this field. STATE OF ART: Surgery of MTLE associated with HS achieves long-term seizure freedom in about 70% (62-83%) of cases. Seizure outcome is similar in the pediatric population. Mortality following temporal resection is very rare (<1%) and the rate of definitive neurological complication is low (1%). Gamma knife stereotactic radiosurgery used as a treatment for MTLE would have a slightly worse outcome to that of surgical resection, but would provide neuropsychological advantage. However, the average latency before reducing or stopping seizures is at least 9 months with radiosurgery. Regarding palliative surgery, amygdalohippocampal stimulation has been demonstrated to improve the control of epilepsy in carefully selected patients with intractable MTLE who are not candidates for resective surgery. PERSPECTIVES: Recent progress in the field of imaging and image-guidance should allow to elaborate tailored surgical strategies for each patient in order to achieve seizure freedom. Concerning therapeutics, closed-loop stimulation strategies allow early seizure detection and responsive stimulation. It may be less toxic and more effective than intermittent and continuous neurostimulation. Moreover, stereotactic radiofrequency amygdalohippocampectomy is a recent approach leading to hopeful results. Closed-loop stimulation and stereotactic radiofrequency amygdalohippocampectomy may provide a new treatment option for patients with pharmacoresistant MTLE. CONCLUSIONS: Mesial temporal lobe surgery has been widely evaluated and has become the standard treatment for MTLE associated with HS. Alternative surgical procedures like gamma knife stereotactic radiosurgery and amygdalohippocampal stimulation are currently under assessment, with promising results.

[Evolution of ideas and techniques, and future prospects in epilepsy surgery]. / Évolution des idées et des techniques, et perspectives d'avenir en chirurgie de l'épilepsie.

INTRODUCTION: The aim of this article was to review and evaluate the published literature related to the outcome of epilepsy surgery, while placing it in an historical perspective, and to describe the future prospects in this field. STATE OF ART: Temporal lobe surgery achieves seizure freedom in about 70% of cases. Seizure outcome is similar in the pediatric population. Extratemporal resections impart good results to 40% to 60% of patients, with a better prognosis in the case of frontal lobe surgery. Pediatric hemispherotomy leads to seizure control in about 80% of children. Radiosurgery used as a treatment for temporal mesial epilepsy has an outcome quite similar to that obtained with surgical resection, but provides a neuropsychological advantage. Radiosurgery is also effective in 60% of children treated for seizures related to hypothalamic hamartoma. Regarding palliative surgery, callosotomy and multiple subpial transections show satisfactory outcomes in over 60% of cases. Neuromodulation techniques (vagus nerve stimulation and bilateral stimulation of the anterior nucleus of the thalamus) allow a 50% reduction of seizures in half of patients. PERSPECTIVES: Transcranial magnetic stimulation combined with electroencephalography seems a promising technique because of its diagnostic, prognostic and therapeutic applications. Transcranial ultrasound stimulation, which can reversibly control neuronal activity, is also under consideration. Concerning neuromodulation, trigeminal nerve stimulation may become an alternative to vagus nerve stimulation; while other targets of deep brain stimulation are being evaluated. Also, the possibility of coupling SEEG seizure focus detection with concomitant laser or radiofrequency focus destruction is under development. CONCLUSIONS: Constant evolution of epilepsy surgery has improved patient outcomes over time. Current research and development axes suggest the continuation of this trend and a reduction of the invasiveness of surgical procedures.

Exploring the utility of Geometric Morphometrics to analyse prehistoric hand stencils.

Hand stencils are a remarkable graphic expression in Prehistoric rock art, dating back to 42 ka BP. Although these stencils provide direct impressions of the artists' hands, the characterization of their biological profile (i.e., biological sex and age) is very challenging. Previous studies have attempted this analysis with traditional morphometrics (TM), whereas little research has been undertaken using Geometric Morphometrics (GM), a method widely used in other disciplines but only tentatively employed in rock art studies. However, the large variation in relative finger position in archaeological hands poses the question of whether these representations can be examined through GM, or, in contrast, if this creates an unmanageable error in the results. To address this issue, a 2D hand scans sample of 70 living individuals (F = 35; M = 35) has been collected in three standardized positions (n = 210) and digitized with 32 2D conventional landmarks. Results show that the intra-individual distance (mean Procrustes distance between Pos. 1-2 = 0.132; 2-3 = 0.191; 1-3 = 0.292) is larger than the inter-individual distance (mean in 1 = 0.122; 2 = 0.142; 3 = 0.165). Finally, it has been demonstrated that the relative finger positions, as well as the inclusion of all hand parts in the analysis, have an overshadowing effect on other variables potentially involved in the morphometric variability of the hand, such as biological sex.

Optical coherence tomography angiography analysis of choroidal microvasculature in various forms of diabetic macular edema.

INTRODUCTION: Optical coherence tomography angiography (OCTA) research in diabetic macular edema (DME) has focused on the retinal microvasculature with little attention to the choroid. The goal of this study was to analyze the association between quantitative choroidal OCTA parameters and various forms of DME observed on optical coherence tomography. METHODS: We conducted a retrospective study of 61 eyes of 53 patients with DME. DME was classified as early or advanced, and as sponge-like diffuse retinal thickening (DRT), cystoid macular edema (CME) or serous retinal detachment (SRD). Quantitative OCTA parameters (vessel density [VD] in the superficial capillary plexus [SCP], middle capillary plexus [MCP], deep capillary plexus [DCP] and choriocapillaris [CC]) were recorded. RESULTS: The VD in the CC and SCP was significantly higher in patients with early DME compared to patients with advanced DME (P value<0.01). CC VD was lower in subjects with SRD compared to DRT and CME (P value<0.001). Moreover, it was lower in CME compared to DRT (P value<0.05). No statistical differences were found between VD in the MCP and DCP (P value>0.05). Furthermore, CC VD was lower in patients with increased retinal thickness, disruption of the ellipsoid zone (EZ) or external limiting membrane (ELM), and disorganization of the inner retinal layers (DRIL) (P value<0.05). CONCLUSION: CC ischemia plays an important role in the pathogenesis of DME. We demonstrated a decrease in CC VD in patients with severe DME, SRD, retinal thickening, EZ and/or ELM disruption and DRIL.

Gene expression analysis of Chironomus riparius in response to acute exposure to tire rubber microparticles and leachates.

Tire rubber microparticles (TRPs) entering aquatic ecosystems through stormwater runoffs is a significant challenge. TRPs are formed by the abrasion of tires with the road surface and include chemical additives that are an additional cause for concern. Currently, information on the molecular effects of TRPs, or especially its additives, in freshwater organisms is scarce. To address this problem, an array covering different cellular processes has been designed for the freshwater midge Chironomus riparius. Fourth-instar larvae were exposed to two concentrations of TRPs (1 mg L-1, 10 mg L-1) and tire rubber leachates (TRLs) (0,0125 %, 5 %) to evaluate the transcriptional activity by Real-Time PCR. To assess acute toxicity, larvae were exposed for 24 h and genes related to the endocrine system, stress response, DNA repair mechanisms, immune system, oxidative stress, and detoxification mechanisms were evaluated. The activity of the enzymes: glutathione S-transferase (GST) and catalase was also examined. The main pathway affected was the stress response showing overexpression of HSPs (HSC70.3, HSC70.4, HSC70.5, HSP60). Moreover, there was a reduction of the GSTd3 and catalase disrupting the antioxidant system. The upregulation of InR indicates a potential disturbance in the insulin pathway and ABCB6 activation only in TRPs exposure suggests its potential implication in their transport. However, most of these alterations are caused by TRLs, showing higher toxicity than TRPs. The results obtained in this work provide the first approach at the molecular and cellular levels to elucidate the impact of TRLs in freshwater organisms. To perform a realistic evaluation of the TR effects, additional research is required to assess the TR's long-term effects at the molecular level.

Aneurysmal type 2 neovascularization: A new entity.

PURPOSE: To report three cases of aneurysmal type 2 neovascularization (AT2), a novel entity within the pachychoroid disease (PD) spectrum. METHODS: We conducted an observational retrospective study of three patients with subretinal polyps treated with intravitreal aflibercept. We reviewed clinical and imaging data of the three patients. Best corrected visual acuity (BCVA), central macular thickness (CMT), choroidal subfoveal thickness, choroidal thickness under the polyps and the presence of a dry macula were assessed at baseline and throughout the follow-up. RESULTS: All of the patients showed granular hypoautofluorescence on fundus autofluorescence. Indocyanine green angiography revealed prominent hyperfluorescent branching vascular networks ending in multiple aneurysmal dilatations. Optical coherence tomography (OCT) demonstrated that the aneurysmal lesions were localized in the subretinal space. Additionally, OCT showed retinal pigment epithelial microtears, the double-layer sign and pachyvessels. En face OCT-A perfectly defined prominent telangiectatic branching vascular networks in all the patients, but only revealed polyps in two out of the three patients. Cross-sectional OCT-A demonstrated polyps as patchy circular hypoflow signals in each case. After the intravitreal treatment, BCVA remained unimproved in all of the patients, despite decreased CMT and achievement of a dry macula, as a result of the development of subretinal fibrosis. CONCLUSION: In summary, we describe a new entity within the spectrum of PD, which we have termed AT2. This novel disease is characterized by the presence of aneurysmal dilatations in the subretinal space, along with the typical features of PD, such as choroidal vascular hyperpermeability, thickening of the choroid and pachyvessels.

[Epilepsy and inequality: demographic description and analysis of the difficulty in accessing advanced resources in a population in a small health area]. / Epilepsia y desigualdad: descripción demográfica y análisis de la dificultad para el acceso a recursos avanzados en una población de un área de salud pequeña.

INTRODUCTION: Epilepsy is a very common neurological disease with high morbidity and mortality. Drug-resistant epilepsy (DRE) poses a major therapeutic challenge, even for experts in the field. Despite this, access to advanced resources for this type of patient remains difficult and unequal. The aim of this study is to analyse inequality in a population belonging to a first level hospital. PATIENTS AND METHODS: An analytical observational cross-sectional study was conducted on epileptic patients attending neurology consultations in Area IX of the Murcian Health Service. Demographic, clinical, therapeutic, prognostic and equity variables are described, and significant differences between different subgroups are analysed. RESULTS: The study included 68 patients with a mean age of 42.93 years. Focal epilepsy was the main type (64.7%), and the most commonly used drugs were levetiracetam (33.8%), valproic acid (27.9%) and lamotrigine (22.1%). DRE occurred in 18 patients (26.5% of the total) and only four were under active follow-up in an epilepsy unit, meaning that 71% did not have access to a necessary resource (advanced therapeutic gap). CONCLUSIONS: This study demonstrates that epilepsy inequality continues to be a problem, especially in certain geographical areas, with a lack of access to advanced care for patients who need it most. The solution can be achieved by increasing human and material resources to improve overall patient care, thus strengthening both referral hospitals and epilepsy units.

TITLE: Epilepsia y desigualdad: descripción demográfica y análisis de la dificultad para el acceso a recursos avanzados en una población de un área de salud pequeña.Introducción. La epilepsia es una enfermedad neurológica muy frecuente que implica una elevada morbimortalidad. La epilepsia farmacorresistente (EFR) supone un desafío terapéutico superior, incluso para expertos en la materia. A pesar de ello, el acceso a recursos avanzados para este tipo de pacientes continúa siendo dificultoso y desigual. El objetivo de este estudio es analizar la desigualdad en una población perteneciente a un hospital de primer nivel. Pacientes y métodos. Se llevó a cabo un estudio transversal observacional analítico con pacientes epilépticos que acuden a consultas de neurología del área IX del Servicio Murciano de Salud. Se describen variables demográficas, clínicas, terapéuticas, pronósticas y de equidad, y se analizan diferencias significativas entre distintos subgrupos. Resultados. En el estudio se incluyó a 68 pacientes con una media de edad de 42,93 años. El tipo de epilepsia principal fue la focal (64,7%), y los fármacos más usados fueron el levetiracetam (33,8%), el ácido valproico (27,9%) y la lamotrigina (22,1%). La EFR se dio en 18 pacientes (el 26,5% del total) y sólo cuatro se encontraban en seguimiento activo en una unidad de epilepsia, lo que implica que el 71% no accedía a un recurso necesario (advanced therapeutic gap). Conclusiones. Este estudio demuestra que la desigualdad en la epilepsia continúa siendo un problema, especialmente en ciertas áreas geográficas, con una falta de acceso a atención avanzada en pacientes que más lo necesitan. La solución puede conseguirse aumentando recursos humanos y materiales que mejoren la atención global del paciente, reforzando así tanto los hospitales de referencia como las unidades de epilepsia.

DNA delivery to 'ex vivo' human liver segments.

Hydrodynamic injection is an efficient procedure for liver gene therapy in rodents but with limited efficacy in large animals, using an 'in vivo' adapted regional hydrodynamic gene delivery system. We study the ability of this procedure to mediate gene delivery in human liver segments obtained by surgical resection. Watertight liver segments were retrogradely injected from hepatic vein with a saline solution containing a plasmid bearing the enhanced green fluorescent protein (eGFP) gene, under different conditions of flow rate (1, 10 and 20 ml s(-1)) and final perfused volume. Samples were cultured for 1 to 2 days and used for microscopy and molecular analysis of gene expression. The fluorescent and immunohistochemistry studies indicated that in segments injected at ≥10 ml s(-1), good and wide gene expression was present in the liver sections and the molecular analysis reinforced the histological observation in a quantitative manner (index of apparent gene delivery: 10(2)-10(4) eGFP DNA copy per 100 pg of total DNA; transcription index: 10(5)-2 × 10(6) eGFP RNA copy per 100 ng of total RNA). In addition, injected gold nanoparticles (15 nm diameter) suggested that DNA delivery to hepatocytes must involve a facilitated permeation process without membrane disruption. In summary, we show that retrograde venous injection of watertight human liver segment is an anadromous procedure that results in wide liver gene delivery and good gene expression. However, additional studies will be necessary to clarify the influence of the prolonged ischemia injury to hepatocytes in our model.

Examining hepatitis C virus testing practices in primary care clinics.

Prior studies found that hepatitis C virus (HCV) risk assessment and testing in primary care clinics were suboptimal. We aimed to determine the actual HCV testing rate among patients with HCV risk factors and to identify variables predictive of testing. In order to do so, we performed a prospective cohort study among patients seen in four urban primary care clinics. At the initial visit, patients were given a questionnaire that listed HCV risk factors and they were instructed to check 'yes' or 'no' if they did or did not have a risk factor, respectively. Patients then handed this questionnaire to their physician during their initial visit. Among those who acknowledged having a HCV risk factor via the questionnaire, we determined the subsequent HCV testing rate and calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) to identify variables predictive of testing. Of the 578 individuals who acknowledged having a HCV risk factor via the questionnaire, only 8% (46/578) were tested for HCV within 2 months of their initial visit. Among those tested, 11% (5/46) had a positive HCV antibody test result. The only variable predictive of HCV testing after adjusting for confounders was having a specific HCV risk factor identified and documented in the chart by physicians [16% (26/159) vs 5% (20/419); aOR 4.5, 95% CI 2.1-9.5]. In summary, 92% of patients with a HCV risk factor were not tested for HCV in the primary care setting, and efforts to improve such rates are clearly warranted.