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We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

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The ventilation of buildings is crucial to ensure indoor health, especially when demanding physical activities are carried out indoors, and the pandemic has highlighted the need to develop new management methods to ensure adequate ventilation. In Spain, there are no specific ventilation regulations to prevent the spread of pathogens such as the coronavirus. Therefore, it is necessary to have a theoretical tool for calculating occupancy to maintain sports facilities in optimal safety conditions. The proposed theoretical method is based on the analysis of mathematical expressions from European standardisation documents and uses the concentration of CO2 as a bioeffluent. It is also based on the concept of background and critical concentration, which allows its application to be extrapolated to future crises caused by pathogens. This study presents a unique and novel dataset for sports centres. For this purpose, the calculation methods were applied to the data set provided by Mostoles City Council, Spain, during the pandemic years with the highest incidence of COVID-19, when the government introduced the assimilation of COVID-19 sick leave to occupational accidents. The data on this type of sick leave provided by the City Council correspond to the period between March 2020 and February 2022. Similarly, the data on the average use of sports facilities by activity, provided by the Sports Department, correspond to the years 2020 and 2021. In this way, it was possible to verify the effectiveness in preventing the spread of any type of coronavirus. In conclusion, the implementation of a theoretical occupancy calculation method based on the concentration of carbon dioxide as a bioeffluent can be an effective tool for the management of future crises caused by pathogens or hazardous chemicals in the air, and demonstrated its effectiveness in sports centres such as gyms, sports fields, and indoor swimming pools during the COVID-19 pandemic.

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Antecedentes y objetivos La insuficiencia cardiaca (IC) es una patología compleja con una alta prevalencia, incidencia y mortalidad que conlleva un importante coste sanitario. En España existen unidades de IC (UIC) multidisciplinares, lideradas por cardiología y medicina interna. Nuestro objetivo era conocer su organización actual y adherencia a las últimas recomendaciones científicas. Materiales y métodos Un comité científico formado por cardiólogos e internistas elaboró una encuesta a finales de 2021, que fue enviada a 110 UIC. Setenta y tres de cardiología, acreditadas por SEC-Excelente, y 37 de medicina interna, integradas en el programa UMIPIC. Resultados Se recibieron 83 encuestas cumplimentadas (75,5%); 49 de cardiología y 34 de medicina interna. Los resultados mostraron que las UIC están integradas mayoritariamente por un cardiólogo, internista y enfermería especializada (34,9%). El perfil de paciente atendido en las UIC cardiológicas es muy diferente al paciente de las UMIPIC, siendo estos últimos mayores, con fracción de eyección ventricular izquierda conservada y más carga de comorbilidad. La mayoría de UIC actualmente realizan seguimiento mixto, presencial y telemático (73,5%). Los péptidos natriuréticos son los biomarcadores más utilizados (90%). Se titulan los cuatro grupos farmacológicos fundamentales de tratamiento de la IC a la vez mayoritariamente (85%). Solo 24% de las unidades mantienen una comunicación fluida con atención primaria. Conclusiones Los dos modelos de UIC liderados por cardiología y medicina interna son complementarios, disponen de enfermería especializada, y siguen al paciente de forma mixta, con una adherencia farmacológica muy alta a las últimas recomendaciones científicas. El principal punto de mejora es la coordinación con atención primaria (AU)

Background and objectives Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective was to describe its current organizational model and their adherence to the latest scientific recommendations. Materials and methods In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units [73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine (integrated in UMIPIC program)]. Results We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. Conclusions Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area (AU)

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BACKGROUND AND OBJECTIVES: Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective is to describe its current organizational model and their adherence to the latest scientific recommendations. MATERIALS AND METHODS: In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units. 73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine, (integrated in UMIPIC program). RESULTS: We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. CONCLUSIONS: Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area.

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"Code Stroke" is a multidisciplinary procedure designed to detect acute ischemic strokes and transfer patients for early reperfusion. Selecting these patients requires multimodal imaging with either CT or MRI. 1) Conventional studies without contrast material are obligatory to detect bleeding. Applying the ASPECTS scale, these studies can also identify and quantify areas of early infarction. 2) In candidates for mechanical thrombectomy, angiographic studies are necessary to identify stenoses and obstructions and to evaluate the collateral circulation. 3) Patients with known onset between 6 and 24h or with unknown onset require perfusion studies to distinguish between infracted tissue and recoverable ischemic tissue. Semi-automatic software facilitates diagnosis, but radiologists must interpret its output.

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The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

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Analysis of urine samples from COVID-19 patients by 1H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. Previous studies have identified biomarkers in urine that reflect metabolic alterations in COVID-19 patients. We have used 1H NMR to better define these metabolic alterations since this technique allows us to obtain a broad profile of the metabolites present in urine. This technique offers the advantage that sample preparation is very simple and gives us very complete information on the metabolites present. To detect these alterations, we have compared urine samples from COVID-19 patients (n = 35) with healthy people (n = 18). We used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods to evaluate the differences between the two groups: COVID-19 and healthy controls. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine, and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The alterations in the urinary metabolome shown in this work indicate that SARS-CoV-2 causes a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance.

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INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

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INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

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BACKGROUND: Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. MATERIALS AND METHODS: This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. RESULTS: Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. CONCLUSIONS: This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.

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OBJECTIVE: Determine the incidence and identify factors associated with potentially avoidable hospital readmissions due to uncontrolled symptoms or minor complications after surgery for gynecologic cancers. METHODS: Women who underwent major abdominal or pelvic surgery for a gynecologic malignancy between 2015 and 2017 were identified from the National Surgical Quality Improvement Program targeted hysterectomy dataset. Hospital readmissions within 30 days of surgery were categorized as indicated readmissions or potentially avoidable readmissions by three independent reviewers. Demographic, clinical, and operative covariates were evaluated to determine their association with type of readmission using bivariable tests and adjusted multinomial logistic regression models. RESULTS: A total of 20,986 women were identified. 19,814 (94.4%) were not readmitted, 894 (4.3%) were indicated readmissions, and 278 (1.3%) were potentially avoidable readmissions. Among those readmitted, 24% were potentially avoidable readmissions. Presence of ascites, increasing length of stay, and discharge to facility were associated with an increased risk of indicated and potentially avoidable readmissions. Age < 60 years old (RR 1.4, 95%CI 1.1-1.8), BMI ≥ 30 (RR 1.7, 95%CI 1.3-2.3), history of abdominal/pelvic surgery (RR 1.6, 95%CI 1.2-2.1), cervical cancer (RR 2.1, 95%CI 1.4-3.1), and open surgery (RR 2.1, 95%CI 1.4-3.2) were associated with an increased risk of a potentially avoidable readmission but not with increased risk of an indicated readmission. Median time to readmission did not differ between the two readmission groups (indicated = 8 days; avoidable = 7 days; p = .72). CONCLUSIONS: Among women with gynecologic cancer, 24% of all unplanned readmissions were attributed to uncontrolled symptoms or minor complications that were potentially avoidable. Age <60 years old, history of previous abdominal/pelvic surgery, obesity, cervical cancer, and open surgery were associated with an increase in risk of a potentially avoidable readmission.

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BACKGROUND AND PURPOSE: It has been suggested that silent infarctions (SIs) and hyperintense white matter lesions (WMLs) are related to migraine frequency. We studied their prevalence and anatomical distribution in patients with chronic migraine (CM). METHODS: A total of 96 women with CM [mean age 43 (range 16-65) years] and 29 women with episodic migraine (EM) [mean age 36 (range 16-58) years] underwent 1.5-T magnetic resonance imaging following the CAMERA protocol. The number, size and location of SIs and deep WMLs were recorded and a modified Fazekas scale was applied to assess periventricular WMLs. RESULTS: White matter lesions were found in 59 (61.5%) women with CM and 17 (58.6%) women with EM (odds ratio, 1.13; 95% confidence intervals, 0.48-2.62; P = 0.784). The majority (63% CM and 71% EM) were small deep WMLs. Exclusive periventricular WMLs were exceptional. Of the 739 WMLs seen in patients with CM, 734 (99.3%) were hemispheric and mostly frontal (81%). Posterior fossa WMLs were seen in only five (5.2%) women with CM (always in the pons) and two (6.9%) women with EM. Age >45 years was the only vascular risk factor associated with a higher WML number (median: 0 < 45 years and 3 > 45 years; P = 0.004). We found seven SIs in six women with CM (6.3%). CONCLUSIONS: As compared with the expected prevalence at this age, this study confirms that the prevalence of WMLs, in most cases small, deep and frontal, was increased in CM and EM. However, our results do not support an association of WMLs or SIs with a higher frequency of attacks, but with the presence of vascular risk factors and mainly age >45 years.

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Ante un cambio radical en el comportamiento en un varón de 17 años, a las 12 horas de administrar, en el mismo día, las vacunas contra el Meningococo C, Hepatitis B, Triple Vírica y Varicela, y la detección de un cuadro maníaco a la semana, se sospechó que se tratase de un cuadro de encefalitis post-vacunal. A pesar de la ausencia de hallazgos patológicos en las exploraciones complementarias realizadas, y aunque en la literatura científica no se haya demostrado una asociación temporal a día de hoy, no podemos aceptar ni descartar con certeza la sospecha diagnóstica dado que no contamos con la serología infecciosa o un estudio de anticuerpos en líquido cefalorraquídeo. Los efectos secundarios graves tras vacunaciones no han quedado claramente demostrados, lo que sí está ampliamente demostrado es que la inmunidad adquirida es uno de los mayores logros de la medicina que ha ayudado a erradicar enfermedades potencialmente mortales

A radical behavioral change was observed in a 17-year-old male 12 hours after having received vaccines for Meningococcus C, Hepatitis B, Triple Viral and Varicella on the same day. Moreover a manic episode was detected one week later. It was suspected that this was a case of post-vaccinal encephalitis. In spite of the absence of pathological findings in the complementary explorations carried out and although a temporal association has not been demonstrated to date in the scientific literature, we can not be certain of this diagnostic suspicion since we do not have the infectious serology or a study of antibodies in central spinal fluid. Serious side effects after vaccinations have never been clearly demonstrated, while it has been widely demonstrated that the acquired immunity from these vaccines is one of the greatest achievements of medicine, and this has helped to eradicate life-threatening diseases

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OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

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The Post-ECTRIMS Meeting was held for the eleventh consecutive year in October 2018 in Madrid, with the aim of analysing the advances made in multiple sclerosis that were highlighted at the latest ECTRIMS annual congress. Based on the issues discussed at this meeting, attended by the nation's foremost opinion leaders on multiple sclerosis, two review articles are presented. This second part includes the growing body of evidence confirming the safety of exposure to disease-modifying treatments in women planning a pregnancy, and the beneficial effect of breastfeeding, provided that the disease is not very active. It addresses data showing how the application of the 2017 McDonald criteria in the paediatric population has significantly improved diagnosis compared to the previous criteria. With regard to progressive multiple sclerosis, the results of neuroprotective drugs are inconclusive, but biomarkers are proposed to improve the evaluation of the therapeutic response. Studies on myelin repair treatments suggest that remyelination in multiple sclerosis is possible. Likewise, there are favourable indications for haematopoietic stem cell transplantation, provided that patients are selected appropriately. On the other hand, we also conduct a review of the similarities and differences of the recommendations in the new clinical practice guidelines. Finally, the positive results of cognitive and motor rehabilitation with the use of new technologies point to the systematic incorporation of these tools in the treatment of the disease in the near future.

TITLE: Revision de las novedades presentadas en el Congreso ECTRIMS 2018: XI Reunion Post-ECTRIMS (II).La reunion Post-ECTRIMS se celebro por undecimo año consecutivo el pasado octubre de 2018 en Madrid, con el objetivo de analizar los avances en esclerosis multiple destacados en el ultimo congreso anual ECTRIMS. Fruto de esta reunion, formada por los lideres de opinion en esclerosis multiple de ambito nacional, se presentan dos articulos de revision. En esta segunda parte, se incluye el creciente numero de evidencias que confirman la seguridad de la exposicion a los tratamientos modificadores de la enfermedad en mujeres que planifican un embarazo, y el efecto beneficioso de la lactancia, siempre y cuando la enfermedad no este muy activa. Se abordan los datos que muestran como la aplicacion de los criterios de McDonald de 2017 en poblacion pediatrica ha mejorado considerablemente el diagnostico en comparacion con los criterios anteriores. En cuanto a la esclerosis multiple progresiva, los resultados de los farmacos neuroprotectores son poco concluyentes, pero se proponen biomarcadores para mejorar la evaluacion de la respuesta terapeutica. Los estudios sobre tratamientos de reparacion de la mielina sugieren que la remielinizacion en la esclerosis multiple es posible. De igual manera, se exponen indicios favorables sobre el trasplante de celulas madre hematopoyeticas, siempre que se seleccione adecuadamente a los pacientes. Por otro lado, se revisan las similitudes y diferencias de las recomendaciones de las nuevas guias de practica clinica publicadas. Por ultimo, los resultados positivos de la rehabilitacion cognitiva y motora con el uso de las nuevas tecnologias vaticinan la incorporacion sistematica de estas herramientas en el tratamiento de la enfermedad en un futuro proximo.

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The Post-ECTRIMS Meeting is an emblematic event in Spain which seeks to review and disseminate the main advances in multiple sclerosis presented at the ECTRIMS annual congress. In October 2018, the eleventh Post-ECTRIMS meeting was held in Madrid and was attended by the country's leading experts in multiple sclerosis. As a result of this meeting, we present two articles which outline the most interesting novelties discussed there. This first part includes the latest results obtained regarding the influence of modifiable and non-modifiable risk factors in multiple sclerosis, with emphasis on the progress made in the field of genetics, where the discovery of genes associated with multiple sclerosis has increased exponentially. The complexity of the immune system is addressed and some contributions are made on autoimmunity mechanisms, in which bidirectional relations are observed between immune cells and cells residing in the central nervous system, such as microglial cells and astrocytes. Biomarkers, both in serum and cerebrospinal fluid as well as in imaging, are gaining more and more attention due to their current and, above all, potential role in the diagnosis and prognosis of the disease and in the evaluation of the efficacy of treatments. Finally, the observations made regarding changes in structural and functional connectivity in patients and their relationship with clinical alterations are presented.

TITLE: Revision de las novedades presentadas en el congreso ECTRIMS 2018: XI Reunion Post-ECTRIMS (I).La reunion Post-ECTRIMS es un encuentro emblematico en Espana que persigue revisar y difundir los principales avances en esclerosis multiple presentados en el congreso anual ECTRIMS. En octubre de 2018, la reunion Post-ECTRIMS celebro en Madrid su undecima edicion, contando con los mayores expertos de ambito nacional en esclerosis multiple. Como resultado de esta reunion, se presentan dos articulos donde se recogen las novedades mas destacadas en la misma. En esta primera parte se incluyen los ultimos resultados sobre la influencia de los factores de riesgo modificables y no modificables en la esclerosis multiple, destacando los progresos realizados en el ambito genetico, donde el descubrimiento de genes asociados a la esclerosis multiple ha aumentado exponencialmente. Se aborda la complejidad del sistema inmune y se realizan algunas aportaciones sobre los mecanismos de autoinmunidad, en los que se observan relaciones bidireccionales entre las celulas inmunes y las celulas residentes del sistema nervioso central, como la microglia y los astrocitos. Los biomarcadores, tanto en suero y liquido cefalorraquideo como de imagen, ganan cada vez mas atencion por su papel actual, y sobre todo potencial, en el diagnostico y pronostico de la enfermedad y en la evaluacion de la eficacia de los tratamientos. Por ultimo, se presentan las observaciones realizadas respecto a los cambios en la conectividad estructural y funcional en los pacientes y su relacion con las alteraciones clinicas.

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BACKGROUND: The main cause of endodontic failure is the persistence of microorganisms that cause an intraradicular or extratradicular infection and that become resistant to disinfection measures. The objective of this review is to identify the microbiota associated with endodontic failure, as well as the reasons why these microorganisms are capable of surviving basic disinfection measures. MATERIAL AND METHODS: Systematic search of scientific articles in the databases PubMed with the following keywords "Endodontic Infections", "Endodontic Microbiology", "Endodontic Failure", "Enterococcus Faecalis", "Endodontics Retreatment" was carried out. Case reports and articles with publication date prior to 2000 were not included in this review. RESULTS: Most authors highlight E. faecalis as the main microorganism associated with endodontic failure, nevertheless there are recent studies that isolate, to a greater extent, other bacteria such as Fusobacterium nucleatum and Propionibacterium. DISCUSSION: These microorganisms have in common the following proprieties, which make them able to escape the disinfection measures: the ability to form a biofilm, to locate in areas unreachable to root canal instrumentation techniques, synergism, the ability to express survival genes and activate alternative metabolic pathways.

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Background: The main cause of endodontic failure is the persistence of microorganisms that cause an intraradicular or extratradicular infection and that become resistant to disinfection measures. The objective of this review is to identify the microbiota associated with endodontic failure, as well as the reasons why these microorganisms are capable of surviving basic disinfection measures. Material and Methods: Systematic search of scientific articles in the databases PubMed with the following key-words "Endodontic Infections", "Endodontic Microbiology, "Endodontic Failure", "Enterococcus Faecalis", "Endodontics Retreatment" was carried out. Case reports and articles with publication date prior to 2000 were not included in this review. Results: Most authors highlight E. faecalis as the main microorganism associated with endodontic failure, nevertheless there are recent studies that isolate, to a greater extent, other bacteria such as Fusobacterium nucleatum and Propioni bacterium. Discussion: These microorganisms have in common the following proprieties, which make them able to escape the disinfection measures: the ability to form a biofilm, to locate in areas unreachable to root canal instrumentation techniques, synergism, the ability to express survival genes and activate alternative metabolic pathways

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INTRODUCTION: Cladribine is a prodrug, a synthetic analogue of deoxyadenosine, approved for use as selective immune reconstitution therapy in very active recurring multiple sclerosis in adults. AIMS: To review the development of the drug, its mechanism of action and the efficacy and safety data obtained to date, as well as to establish recommendations of Spanish experts for its use in clinical practice. DEVELOPMENT: The treatment of multiple sclerosis has been simplified with cladribine tablets, and two short courses of administration for two consecutive years (maximum 20 days) are needed to maintain an efficacy of up to four years after the first dose. Results of clinical trials have demonstrated the safety, tolerability and long-term efficacy of cladribine tablets in patients with recurring multiple sclerosis. Thus, patients treated with cladribine presented a significant reduction in the rate of flare-ups, in the risk of disability progression and in the development of new lesions in magnetic resonance imaging compared to those treated with placebo. In terms of safety, the treated patients had a higher frequency of lymphopenia, in relation to its mechanism of action, and of infections by herpes zoster virus. Long-term results with eight years' follow-up have shown that treated patients are not at greater risk of developing serious events, such as malignant neoplasms or opportunistic infections. CONCLUSIONS: Cladribine is the first short-course oral therapy that has been shown to be effective and safe in patients with very active recurring multiple sclerosis, and with a sustained effect over time. The recommendations of Spanish experts on its usage are a fundamental complement to the considerations described by the regulatory agencies.

TITLE: Recomendaciones de uso de cladribina comprimidos en la esclerosis múltiple recurrente.Introducción. La cladribina es un profármaco, análogo sintético de la desoxiadenosina, aprobado como terapia de reconstitución inmune selectiva en la esclerosis múltiple (EM) recurrente muy activa del adulto. Objetivos. Revisar el desarrollo del fármaco, su mecanismo de acción y los datos de eficacia y seguridad obtenidos hasta la fecha, y establecer recomendaciones de manejo por expertos españoles en la práctica clínica. Desarrollo. El tratamiento de la EM se ha simplificado con cladribina comprimidos, y se necesitan dos cursos cortos de administración durante dos años consecutivos (máximo 20 días) para mantener una eficacia de hasta cuatro años tras la primera dosis. Los resultados de los ensayos clínicos han demostrado la seguridad, la tolerabilidad y la eficacia a largo plazo de la cladribina comprimidos en pacientes con EM recurrente. Así, los pacientes tratados con cladribina presentaron una reducción significativa de la tasa de brotes, del riesgo de progresión de la discapacidad y del desarrollo de nuevas lesiones en la resonancia magnética en comparación con los tratados con placebo. En cuanto a la seguridad, los pacientes tratados presentaron una mayor frecuencia de linfopenia, en relación con su mecanismo de acción, y de infecciones por el virus del herpes zóster. Los resultados a largo plazo con ocho años de seguimiento han mostrado que los pacientes tratados no tienen mayor riesgo de desarrollar efectos graves, como neoplasias malignas o infecciones oportunistas. Conclusiones. La cladribina es la primera terapia oral de corta administración que ha demostrado ser eficaz y segura en pacientes con EM recurrente muy activa, y con un efecto sostenido en el tiempo. Las recomendaciones de expertos españoles sobre su manejo suponen un complemento fundamental a las consideraciones descritas por las agencias reguladoras.

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