Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Atheromatosis of the brain-supplying arteries: Circle of Willis, basilar, vertebral and their branches.

PURPOSE: Atherosclerotic plaques in the brain-supplying arteries are slowly-developing alterations of vascular structures that can lead to neurological impairment due to stenosis and insufficient oxygenation of eloquent brain areas. The aim of this study is to provide detailed demographic information related to the incidence of atherosclerotic plaques in the cerebral arteries. MATERIAL AND METHODS: Forty-eight circles of Willis (21 men, 21 women, mean age: 70.26, six samples unknown) were macroscopically analyzed for length, diameter, and presence of atherosclerotic plaques. Statistical analysis was used to identify potential differences in the locations and frequencies of atherosclerotic plaques in relation to age and sex. RESULTS: The study sample revealed 261 atherosclerotic plaques. The key findings were significant correlations between plaque development and age and between plaque location and age; however, there was no significant sex difference. CONCLUSION: The upper and lower branches of the middle cerebral artery (MCA) were novel locations predisposing to plaque development. A cut-off value at 60 years revealed a significant difference in plaque development and distribution. There were no significant sex differences in the occurrence of atherosclerotic plaques.

In vitro activity of imipenem/relebactam against Gram-negative clinical isolates in two Spanish tertiary hospitals.

OBJECTIVE: The aim of this study was to analyze the activity of the imipenem-relebactam combination (IMI/REL) against a collection of multidrug-resist Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates. METHODS: The study was conducted in two tertiary hospitals in Spain and included 192 clinical isolates of these 3 genera (139 resistant and 53 susceptible to IMI). The MICs for IMI with and without REL (at a fixed concentration of 4 mg/L) were determined by a standard broth microdilution method according to international recommendations. RESULTS: All IMI-susceptible E. coli strains were also susceptible to IMI/REL. Enterobacterales resistant to IMI due to the production of carbapenemases, the MIC50 and MIC90 decreased from 64/256 with IMI to 8/64 mg/L with IMI/REL. This high activity was principally detected among isolates with KPC enzymes. Enterobacterales with class B carbapenemases, P. aeruginosa carrying VIM carbapenemase and A. baumannii strains showed no changes on IMI MIC50 or MIC90 after adding REL. Among P. aeruginosa strains without carbapenemase the MIC for IMI/REL was reduced between 1 to 5 dilutions. CONCLUSIONS: IMI/REL showed high activity against the strains that carry Klebsiella pneumoniae carbapenemase (KPC) and against carbapenem-resistant P. aeruginosa unrelated to the VIM enzyme, mainly AmpC beta lactamase associated with impermeability. Against strains carrying oxacillinase 48 (OXA-48) associated with extended-spectrum beta-lactamase (ESBL), IMI/REL presented activity only slightly better than IMI and had no beneficial effect superior to IMI against A. baumannii.

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (II). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).

INTRODUCTION: For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. AIM: This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. CONCLUSIONS: Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.

TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).Introducción. Desde hace más de una década, tras el Congreso ECTRIMS, se celebra en España la reunión post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo. En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones. Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (I). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).

INTRODUCTION: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). AIM: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. CONCLUSIONS: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.

TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).Introducción. Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones. Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

[The prevalence of multiple sclerosis in the city of Ourense, Galicia, in the north-west of the Iberian Peninsula]. / Prevalencia de la esclerosis múltiple en la ciudad de Ourense, Galicia, noroeste de la Península Ibérica.

INTRODUCTION: Multiple sclerosis is an inflammatory neurodegenerative disease of the central nervous system, which mainly affects young people of working and reproductive age, and represents the first cause of non-traumatic disability in this age group of the population. A north-south latitude gradient is recognised, with prevalence rates increasing as we move away from the equator. This gradient probably represents the genetic predisposition transmitted from the Scandinavian regions through the Viking invasions and could presuppose an influence of the vitamin D deficit related to a lower number of hours of sunshine per year. AIMS: To determine the prevalence and incidence of multiple sclerosis in the city of Ourense, Galicia. PATIENTS AND METHODS: The latitude coordinate of the city of Ourense is 42° 34' N. A retrospective epidemiological study covering the period from 2002 to 2016 was conducted. The prevalence date was 31 December 2016. According to the latest census, the population of the city of Ourense was 105,892 on 1 January 2016. RESULTS: Altogether, 195 cases were recorded, representing a prevalence of 184.1 cases/100,000 inhabitants. In the period 2002-2016, 127 cases of multiple sclerosis were diagnosed, representing an average incidence of 7.86 cases/100,000 inhabitants/year. CONCLUSION: The city of Ourense has the highest prevalence rate of multiple sclerosis of those studied to date in the Iberian Peninsula, with a figure that brings it closer to the data reported in more northern areas under Nordic and Anglo-American influence.

TITLE: Prevalencia de la esclerosis múltiple en la ciudad de Ourense, Galicia, noroeste de la Península Ibérica.Introducción. La esclerosis múltiple es una enfermedad inflamatoria y neurodegenerativa del sistema nervioso central, que afecta fundamentalmente a personas jóvenes en edad laboral y reproductiva, y que representa la primera causa de discapacidad no traumática en este rango etario de la población. Se reconoce un gradiente de latitud norte-sur, con un aumento de las tasas de prevalencia a medida que nos alejamos del ecuador. Este gradiente probablemente representa la predisposición genética transmitida desde las regiones escandinavas a través de las invasiones vikingas y podría presuponer una influencia del déficit de vitamina D en relación con un menor número de horas de sol anuales. Objetivo. Determinar la prevalencia e incidencia de la esclerosis múltiple en la ciudad de Ourense, Galicia. Pacientes y métodos. La ciudad de Ourense tiene una coordenada de latitud de 42° 34' N. Se ha realizado un estudio epidemiológico retrospectivo que abarca desde 2002 a 2016. La fecha de prevalencia fue el 31 de diciembre de 2016. El censo de la población de la ciudad de Ourense a 1 de enero de 2016 era de 105.892 habitantes. Resultados. Se registraron 195 casos, lo que representa una prevalencia de 184,1 casos/100.000 habitantes. En el período 2002-2016 se diagnosticaron 127 casos de esclerosis múltiple, lo que supone una incidencia media de 7,86 casos/ 100.000 habitantes/año. Conclusión. La ciudad de Ourense presenta la tasa de prevalencia de esclerosis múltiple más alta de las estudiadas hasta la actualidad en la Península Ibérica, con una cifra que la aproxima a los datos comunicados en áreas más septentrionales de influencia nórdica y anglosajona.

Utility of lateral flow tests in SARS-CoV-2 infection monitorization.

OBJECTIVE: The diagnosis of SARS-CoV-2 infection is crucial for medical and public health reasons, to allow the best treatment of cases and the best control of the pandemic. Serology testing allows for the detection of asymptomatic infections and 19-COVID cases once the virus has been cleared. We analyzed the usefulness of the SARS-CoV-2 rapid test of Autobio and tried to correlate its pattern with the severity of COVID19 infection. METHODS: We analyzed the accuracy and clinical usefulness of a point-of-care IgM and/or IgG test for SARS-CoV-2 in 35 COVID-19 patients [12 (34.3%) mild-moderate and 23 (65.7%) severe-critical] admitted to a field hospital in Madrid, as well as in 5 controls. RESULTS: The mean time from the first day of symptoms to the antibody test was 28 days (SD: 8.7), similar according to the severity of the disease. All patients with SARS-CoV-2 PCR+ showed the corresponding IgG positivity, while these results were negative in all control individuals. A total of 26 (74%) cases also presented with positive IgM, 19 (83%) were severe-critical cases and 7 (58%) were mild-moderate cases. The IgM response lasted longer in the severe critical cases (mean: 29.7 days; SD: 8.4) compared to the moderate cases (mean: 21.2 days; SD: 2.0).. CONCLUSIONS: Rapid serology tests are useful for the diagnosis of patients with COVID-19 (mainly IgG detection) and may also be correlated with the severity of the infection (based on IgM detection).

12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (II). / XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II).

INTRODUCTION: Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM: To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT: In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed. CONCLUSIONS: Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available.

TITLE: XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II).Introducción. Como cada año, tras la celebración del Congreso del ECTRIMS, reconocidos neurólogos españoles expertos en esclerosis múltiple expusieron en la Reunión Post-ECTRIMS las principales novedades en investigación en este ámbito. Objetivo. Sintetizar el contenido presentado en la XII edición de la Reunión Post-ECTRIMS, que tuvo lugar en septiembre de 2019 en Sevilla y que se presenta en dos partes. Desarrollo. En esta segunda parte, se exponen las evidencias más recientes sobre el uso de tratamientos modificadores de la enfermedad durante el embarazo. Se detallan los resultados de ensayos clínicos en fase 3 en los que se ha evaluado la eficacia y la seguridad de dos potenciales tratamientos modificadores de la enfermedad para la esclerosis múltiple remitente recurrente: ponesimod y ofatumumab. Para las formas progresivas, se revisan los tratamientos modificadores de la enfermedad disponibles y en investigación. En el ámbito de las terapias con células madre, se incluyen los resultados del único ensayo clínico hasta la fecha que compara a pacientes con esclerosis múltiple remitente recurrente tratados con trasplante autólogo de células madre hematopoyéticas y a los tratados con tratamientos modificadores de la enfermedad. No hay grandes novedades sobre tratamientos sintomáticos, aunque la Academia Europea de Neurología ha publicado una guía sobre cuidados paliativos. Se revisan las distintas fuentes de información que recogen datos de farmacovigilancia en el entorno poscomercialización. Conclusiones. Los pacientes diagnosticados en los últimos años tienden a tener una menor gravedad de la esclerosis múltiple, probablemente debido al diagnóstico desde sus estadios más leves y al continuo aumento de tratamientos disponibles.

[12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (I)]. / XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (I).

INTRODUCTION: Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM: To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT: This first part addresses the latest studies on vitamin D deficiency and the discrepancies that currently exist regarding its treatment. The advances made in epigenetics allow us to present this approach as a possible biomarker of multiple sclerosis. An account is provided to explain the growing importance of imaging techniques to detect atrophy and other phenomena that occur during the disease, such as changes in iron concentration or remyelination processes, which allow us to further our understanding of the mechanisms of cortical pathology, and the dimensionality of neurodegeneration during its course. Findings related to immunological mechanisms and advances in potential antigen-specific therapies are discussed. The contribution presents the latest studies on the assessment of cognitive impairment and its rehabilitation, which are becoming increasingly important due to the high prevalence of these disorders and the absence of their systematic assessment in clinical practice. Finally, the unmet social and health needs of multiple sclerosis patients in our country are presented, with emphasis on the current deficits in the system of social protection.

TITLE: XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (I).Introducción. Como cada año, tras la celebración del Congreso ECTRIMS, reconocidos neurólogos españoles expertos en esclerosis múltiple expusieron en la Reunión Post-ECTRIMS las principales novedades en investigación en este ámbito. Objetivo. Sintetizar el contenido presentado en la XII edición de la Reunión Post-ECTRIMS, que tuvo lugar en septiembre de 2019 en Sevilla y que se presenta en dos partes. Desarrollo. Esta primera parte aborda los últimos estudios sobre el déficit de vitamina D y las discrepancias existentes acerca de su tratamiento. Los avances en epigenética realizados permiten presentar esta aproximación como un posible biomarcador de la esclerosis múltiple. Se explica el creciente protagonismo de las técnicas de imagen para detectar la atrofia y otros fenómenos que acontecen durante la enfermedad, como los cambios en la concentración de hierro o los procesos de remielinización, que nos permiten ganar comprensión sobre los mecanismos de la patología cortical, y sobre la dimensionalidad de la neurodegeneración durante su evolución. Se discuten los hallazgos relacionados con los mecanismos inmunológicos y los avances realizados en las potenciales terapias específicas del antígeno. Se presentan los últimos estudios sobre la evaluación del deterioro cognitivo y su rehabilitación, que cobran cada vez más importancia por la alta prevalencia de estas alteraciones y por la ausencia de su evaluación sistemática en la práctica clínica. Por último, se exponen las necesidades sociosanitarias no cubiertas de los pacientes de esclerosis múltiple en nuestro país, poniendo el acento en los déficits actuales del sistema de protección social.

Short-term biological variation of serum thyroid hormones concentrations in clinically healthy cats.

Thyroid disease is common in cats, but little is known about the biologic variability of serum thyroid hormone concentrations and its impact on diagnostic utility in either healthy cats or cats with thyroid disease. The purpose of this study was to determine the biological variation, index of individuality, and reference change values for thyroid hormones and thyroid-stimulating hormone (TSH) in clinically healthy cats. Serum samples for analysis of total thyroxine (T4), triiodothyronine (T3), free T4 by dialysis, and TSH were obtained weekly for 6 wk from 10 healthy cats, then frozen until single-batch analyzed. Data were evaluated for outliers, and we determined the CV within individual cats (CVI) and between individual cats (CVG) for each hormone and the variation between duplicates or analytical variation (CVA). The index of individuality and reference change values for each hormone were then calculated. Serum concentrations of total T4, free T4, T3, and TSH all showed greater variation between cats (CVG) than within cats (CVI). Total and free T4 had an intermediate index of individuality (1.1 and 1.2, respectively), suggesting that these hormones would be best evaluated by a combination of their population-based reference intervals and reference change values. Serum TSH concentrations had high index of individuality (1.8), suggesting this hormone would be best evaluated with reference change values rather than the population-based reference interval. Total T3 also had a high calculated index of individuality (1.8); however, T3 had high ratio of analytical variation (CVA) to within cat variation (CVI), so RCV could not be accurately calculated. This study demonstrates that clinically normal cats show considerable interindividual biological variation in serum thyroid hormone and TSH concentrations, whereas the intraindividual variability in hormone concentrations is much narrower. This suggests that for all serum thyroid hormones, but especially serum TSH and T3 concentrations, comparing individual cat's hormone results to a population-based reference interval may be misleading, especially in those with early or subclinical thyroid disease. Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations of T4, free T4, T3, and TSH for individual cats (ideally when healthy) and applying reference change values to subsequent measurements.

Update in Infectious Diseases 2019.

The IX Course of Antimicrobials and Infectious Diseases update included a review of the main issues in clinical microbiology, epidemiology and clinical aspects for a current approach of infectious pathology. The present introduction summarizes about the most important meetings related to infectious diseases during 2018 (ECCMID, IAS, ASM and ID Week). In addition, the course provides a practical information to focus on nosocomial infection models, with immunosuppressed patients or complex multidrug-resistant pathogens. The closing lecture of this year reviewed the infection during donation process.

Description of carbapenemase-producing Enterobacteriaceae isolates in a Spanish tertiary hospital. Epidemiological analysis and clinical impact.

OBJECTIVE: The aim of the study was to carry out an epidemiological analysis of patients with carbapenemase-producing Enterobacteriaceae (CPE) isolations in our hospital as well as to perform a description of the genotypic temporal evolution of CPE isolated. METHODS: An observational prospective cohort study was performed involving all patients with CPE isolates from clinical samples during November 2014 to November 2016 in a Spanish teaching hospital. Patients were clinically evaluated and classified either as infected or colonized. Information on the consumption of carbapenems in the hospital during the study period was also analyzed. PCR was used for identification of the carbapenemase genes blaKPC, blaVIM, and blaOXA-48. RESULTS: A total of 301 CPE isolates were obtained (107 in 2014, 89 in 2015 and 105 in 2016). Klebsiella pneumoniae (73.4%) was the most prevalent microorganism. Hundred and seventy (56.7%) of carbapenemases detected were blaOXA-48, 73 (24.3%) were blaKPC and 57 (19%) were blaVIM. In year 2014 KPC was predominant while in 2016 OXA-48 predominated. In 2014 we observed a significant association between the medical wards and the ICU with a higher prevalence of OXA-48 (OR 4.15; P<0.001) and VIM (OR 7.40; P<0.001) in the univariate analysis, in the following years there was no association. Regarding the clinical significance of microbiological results after assessing our patients, 60% of isolates represented infection and 40% behaved as colonizers. One third of hospitalized patients with CPE isolation died within 30 days, regardless of whether they were colonized or infected. CONCLUSIONS: We have observed an epidemiological change in the genotypes of our isolates along the study period. A thorough knowledge of the CPE's epidemiological distribution in each hospital is fundamental for optimizing antimicrobial chemotherapy.

Bacterial contamination rate and associated factors during bone and tendon allograft procurement from Spanish donors: exploring the contamination patterns.

BACKGROUND: Allograft contamination during extraction represents a major limiting factor for tissue bank availability. Contamination rates remain persistently high independent of the hospital, country or year considered. AIM: To analyse the factors associated with contamination of bone and tendon samples extracted from Spanish donors. METHODS: Data for 1162 bone and tendon samples extracted from 102 donors between 2014 and 2017 were collected retrospectively from the hospital database. Descriptive statistics, potentially associated factors and correlation of contamination between samples extracted from different anatomical locations of the same donor were analysed. FINDINGS: In total, 227 (19.54%) of the extracted samples [131 (18.49%) bone samples and 96 (20.92%) tendon samples] rendered positive cultures and were discarded. Male sex [odds ratio (OR) 2.023; P=0.019], extraction of >10 samples per donor (OR 1.997; P<0.001) and extraction time >240 min (OR 1.755; P=0.001) were factors independently associated with a higher contamination rate. Meanwhile, the tissue sample type 'bone-patellar tendon-bone' was associated with a significantly lower contamination rate (OR 0.446; P=0.001). Significant correlation between certain localization of contaminated samples and the concordance of bacterial species was also observed. CONCLUSION: Factors related to the extraction procedure, such as total extraction time, extraction sequence, number of samples extracted and anatomical location of extracted samples, play a major role in allograft contamination. Further optimization of procedures, guided by the contamination patterns analysed in this study, should help to increase tissue bank availability.

Update in Infectious Diseases 2018.

VIII Updating Course of Antimicrobials and Infectious Diseases has reviewed useful microbiological, epidemiological and clinical aspects for a current approach of infectious pathology. Present manuscript summarizes a chronicle about the main infection related meetings during 2017 (ECCMID, IAS, ASM and ID Week). In addition, the course proposed a practical approach for understanding different type of pathogens and our selected topics this year were the epidemiology of bacterial nosocomial infection, a practical approach to Clostridium difficile infection patients, a two year selection of the top ten papers about fungal infection and an update in fungal biofilms. Finally, proffesors made a practical approach by main clinical syndromes like sepsis, infections in oncohematological patients, CNS infections in immunosuppressed patients and reviewed the top ten papers in transplant infectious diseases and infection control during the last two years.

Clinical course and pathogenicity of variant rabbit haemorrhagic disease virus in experimentally infected adult and kit rabbits: Significance towards control and spread.

RHDVb has become the dominant RHDV on the Iberian Peninsula. A better understanding of its pathogenicity is required to aid control measures. Thus, the clinical course, humoral immune response, viraemia and kinetics of RHDV-N11 (a Spanish RHDVb isolate) infection in different tissues at both viral RNA and protein levels were studied in experimentally infected young and adult rabbits. The case fatality rate differed between the two age groups, with 21% of kits succumbing while no deaths were observed in adults. Fever and viremia were strongly associated with death, which occurred 48 h post infection (PI) too fast for an effective humoral immune response to be mounted. A significant effect on the number of viral RNA copies with regard to the variables age, tissue and time PI (p < 0.0001 in all cases) was detected. Histological lesions in infected rabbits were consistently more frequent and severe in liver and spleen and additionally intestine in kits, these tissues containing the highest levels of viral RNA and protein. Although no adults showed lesions or virus antigen in intestine, both kits and adults maintained steady viral RNA levels from days 1 to 7 PI in this organ. Analysis revealed the fecal route as the main dissemination route of RHDV-N11. Subclinically infected rabbits had detectable viral RNA in their faeces for up to seven days and thus may play an important role spreading the virus. This study allows a better understanding of the transmission of this virus and improvement of the control strategies for this disease.

Riesgo de pie diabético y déficit de autocuidados en pacientes con Diabetes Mellitus Tipo 2 / Diabetic foot risk and self-care shortfalls among Type 2 Diabetes Mellitus patients / Risco de pé diabético e déficit de autocuidados em pacientes com Diabetes Mellitus Tipo 2

Objetivo: Conocer los factores de riesgo de pie diabético y el nivel de conocimientos sobre autocuidados en una muestra de pacientes con diabetes mellitus tipo 2 (DM2), de un centro de salud urbano. Método: Estudio observacional descriptivo en Atención Primaria. Intervención de enfermería relacionada con pie diabético en una muestra de usuarios diagnosticados de DM2. Recogida de datos de historia clínica, valoración clínica y aplicación de un cuestionario ad hoc sobre factores de riesgo y conocimiento de autocuidados. Análisis estadístico descriptivo e inferencial. Resultados: 42 hombres y 31 mujeres. Media de edad de 69.1 años. El 65.8% fueron diagnosticados de DM2 hace más de 10 años. El valor medio de la HbA1c fue de 6.9%, el cual fue más elevado en los hombres (p=0.02). También, se observó mayor riesgo de complicaciones vasculares y neuropáticas en los hombres (p=0.04); y una mayor presencia de deformidades (helomas y hallux valgus) en las mujeres (p<0.01). Déficit de conocimientos en más de la mitad de los pacientes, relacionado con la hidratación diaria de los pies (p<0.01) y el uso de calzado adecuado (p<0.01). Conclusiones: El control de los factores de riesgo de pie diabético debe ser mejorado por parte de los pacientes de nuestro estudio. El déficit de conocimientos se relacionó con un bajo nivel informativo y con la aplicación inadecuada de las recomendaciones. Se hace necesario formar a los pacientes en estos aspectos y realizar una valoración clínica, según la práctica basada en la evidencia, lo que posiblemente influya en un mejor control del riesgo de pie diabético.

To explore the risk factors associated with diabetic foot, and the level of knowledge on self-care, in a sample of type 2 Diabetes Mellitus patients (DM2) from an urban health center. Method: This is an observational and descriptive study in the area of nursing interventions in Primary Attention. Collected data included clinical history, clinical assessment, and the results of an ad hoc questionnaire on DM2 associated risk factors, and the self-care knowledge level. Descriptive and inferential statistics were calculated. Results: There were 42 male and 31 female patients with a mean age of 69.1 years old. 65.8% had been diagnosed with DM2 longer than 10 years ago. The median value of HbA1c was 6.9%, which was higher among males (p = 0.02). A higher risk of suffering vascular and kidney-related complications was observed among males as well (p = 0.04), whereas a higher presence of deformities such as calluses and hallux valgus was observed among females (p <0.01). Shortfalls in knowledge, including those on daily feet hydration (p < 0.01) and the use of adequate shoes (p<0.01) were observed in more than half of these patients. Conclusions: The control of the related risk factors must be improved by the patients in our study. Moreover, their knowledge shortfalls were related to the inadequate fulfillment of the corresponding recommendations. Thus, and considering the Evidence-Based Practice, it is necessary to better prepare these patients so that they can better control their diabetic foot risks.

Objetivo: Conhecer os fatores de risco de pé diabético e o nível de conhecimentos sobre autocuidados em uma amostra de diabéticos mellitus tipo 2 (DM2), de um centro de saúde urbano. Método: Estudo observacional descritivo em Atenção Primária. Intervenção de enfermagem relacionada com pé diabético em uma amostra de usuários diagnosticados de DM2. Coleta de dados de história clínica, avaliação clínica e aplicação de um questionário ad hoc sobre fatores de risco e conhecimento de autocuidados. Análise estatística descritiva e inferencial. Resultados: 42 homens e 31 mulheres. Média de idade de 69.1 anos. O 65.8% foram diagnosticados de DM2 até mais de 10 anos. A média da HbA1c foi de 6.9%, a qual foi mais elevada nos homens (p=0.02). Também, se observou maior risco de complicações vasculares e neuropáticas nos homens (p=0.04); e uma maior presença de deformidades (helomas e hallux valgus) nas mulheres (p0<.01). Déficit de conhecimentos em mais da metade dos pacientes, relacionado com a hidratação diária dos pés (p<0.01) e o uso de calçado adequado (p<0.01). Conclusões: O controle dos fatores de risco de pé diabético deve ser melhorado por parte dos pacientes de nosso estudo. O déficit de conhecimentos relacionou-se com um baixo nível informativo e com a aplicação inadequada das recomendações. Faz-se necessário formar aos pacientes nestes aspectos e realizar una avaliação clínica, segundo a prática baseada na evidencia, o que possivelmente influencie em um melhor controle do risco de pé diabético.

ELISA for detection of variant rabbit haemorrhagic disease virus RHDV2 antigen in liver extracts.

The emergence and rapid spread of variant of the rabbit hemorrhagic disease virus (RHDV2) require new diagnostic tools to ensure that efficient control measures are adopted. In the present study, a specific sandwich enzyme-linked immunosorbent assay (ELISA) for detection of RHDV2 antigens in rabbit liver homogenates, based on the use of an RHDV2-specific monoclonal antibody (Mab) 2D9 for antigen capture and an anti-RHDV2 goat polyclonal antibody (Pab), was developed. This ELISA was able to successfully detect RHDV2 and RHDV2 recombinant virions with high sensitivity (100%) and specificity (97.22%). No cross-reactions were detected with RHDV G1 viruses while low cross-reactivity was detected with one of the RHDVa samples analyzed. The ELISA afforded good repeatability and had high analytical sensitivity as it was able to detect a dilution 1:163,640 (6.10ng/mL) of purified RHDV-N11 VLPs, which contained approximately 3.4×108molecules/mL particles. The reliable discrimination between closely related viruses is crucial to understand the epidemiology and the interaction of co-existing pathogens. In the work described here we design and validate an ELISA for laboratory based, specific, sensitive and reliable detection of RHDVb/RHDV2. This ELISA is a valuable, specific virological tool for monitoring virus circulation, which will permit a better control of this disease.

A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis. / Guía de tratamiento del deterioro de la marcha con fampridina de liberación prolongada (Fampyra®) en pacientes con esclerosis múltiple.

INTRODUCTION: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT: PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS.