Practical consensus for the treatment and follow-up of primary aldosteronism: a multidisciplinary consensus document.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).

Screening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).

Post-event follow-up costs in patients with atherosclerotic cardiovascular disease in Spain.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is one of the main causes of morbidity and mortality in developed countries and entails high resources use and costs for health systems. The risk of suffering future cardiovascular (CV) events and the consequent resources use is higher in those patients who have already had a previous cardiovascular event. The objective of the study was to determine the average annual cost of patients with a new or recurrent atherosclerotic CV event during the 2 years after the event. Methodology: Retrospective observational study of electronic medical records of patients from the BIG-PAC® database (7 integrated health areas of 7 Autonomous Communities; n = 1.8 million). Patients with a new or recurrent episode of ASCVD (angina, acute myocardial infarction, transient ischemic attack, stroke, or peripheral arterial disease) between 1-Jan-2017 and 31-Dec-2018 were included. The resources use within two years of the diagnosis was estimated in order to estimate the average cost of patient follow-up. Results: A total of 26,976 patients with an ASCVD episode were identified during the recruitment period; Out of them, 6,798 had a recurrent event during the follow-up period and 2,414 died. The average costs per patient were €11,171 during the first year and €9,944 during the second year. Discussion: Patients with ASCVD represent a significant economic burden for the health system and for society. Despite the perception that drug costs in the follow-up of chronic patients imply a high percentage of the costs, these accounted for only one tenth of the total amount. Implementing preventive programs and increasing the control of cardiovascular risk factors may have a significant social and health impact by helping to reduce mortality and costs for the Spanish National Health System. The costs derived from pharmacological treatments were obtained from the NHS pricing nomenclator database (https://www.sanidad.gob.es/profesionales/nomenclator.do).

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Documento de consenso sobre el abordaje de la hiperpotasemia / Consensus document on the management of hyperkalaemia

La hiperpotasemia es una alteración electrolítica frecuente con consecuencias potencialmente graves a corto, medio y largo plazo, tanto en términos de morbilidad y mortalidad como de consumo de recursos del Sistema Nacional de Salud. El abordaje de la hiperpotasemia por diversas especialidades médicas y la reciente disponibilidad de nuevos tratamientos farmacológicos específicos hace necesaria una acción unificada y actualizada. El presente documento de consenso entre las sociedades científicas más directamente implicadas en el abordaje de la hiperpotasemia (Sociedad Española de Cardiología, Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Medicina Interna, Sociedad Española de Medicina de Urgencias y Emergencias y Sociedad Española de Nefrología) repasa, en primer lugar, aspectos básicos del balance de potasio y de la potasemia, centrándose posteriormente en el concepto, epidemiología, fisiopatología, y abordaje diagnóstico y terapéutico de la hiperpotasemia. Se han revisado las evidencias y los principales estudios publicados con el objetivo de que sea una herramienta útil en el abordaje multidisciplinar del paciente con hiperpotasemia (AU)

Hyperkalaemia is a common electrolyte imbalance with potentially serious short-, medium- and long-term consequences on morbidity and mortality rates and the use of national health service resources. The fact that different medical specialities can manage hyperkalaemia makes it important to have a unified approach, and the recent availability of new specific drug treatments means that the approach needs to be updated. This consensus document from the scientific societies most directly involved in the management of hyperkalaemia (Sociedad Española de Cardiología [Spanish Society of Cardiology], Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition], Sociedad Española de Medicina Interna [Spanish Society of Internal Medicine], Sociedad Española de Medicina de Urgencias y Emergencias [Spanish Society of Emergency Medicine and Emergencies] and Sociedad Española de Nefrología [Spanish Society of Nephrology]) first of all reviews basic aspects of potassium balance and blood potassium. Then it goes on to focus on the concept, epidemiology, pathophysiology and diagnostic and therapeutic approaches to hyperkalaemia. The available evidence and the main published studies have been reviewed with the aim of providing a useful tool in the multidisciplinary approach to patients with hyperkalaemia (AU)

Evolocumab como tratamiento de la dislipemia secundaria a lorlatinib / Evolocumab as treatment in lorlatinib-related hyperlipidemia

Los anticuerpos monoclonales anti-PCSK9 han demostrado reducción de eventos cardiovasculares en pacientes con enfermedad vascular ateroesclerótica1. Sin embargo, no está descrito su uso en el tratamiento de la dislipemia secundaria a lorlatinib, un inhibidor competitivo de la quinasa del linfoma anaplásico de tercera generación, indicado en cáncer de pulmón no microcítico avanzado ALK+.(AU)

Anti-PCSK9 monoclonal antibodies have reduced the risk of cardiovascular events in patients with atheroesclerosis cardiovascular disease. However, its use has not been described in hyperlipidemia associated with lorlatinib, a third-generation ALK tyrosin kinasa inhibitor approved as treatment for ALK-positive non-small cell lung cancer.(AU)

Evolocumab as treatment in lorlatinib-related hyperlipidemia. / Evolocumab como tratamiento de la dislipemia secundaria a lorlatinib.

Anti-PCSK9 monoclonal antibodies have reduced the risk of cardiovascular events in patients with atheroesclerosis cardiovascular disease. However, its use has not been described in hyperlipidemia associated with lorlatinib, a third-generation ALK tyrosin kinasa inhibitor approved as treatment for ALK-positive non-small cell lung cancer.

Actualización sobre las nuevas formas de consumo de tabaco / Update on new forms of tobacco use

El tabaquismo sigue siendo la principal causa de morbimortalidad a nivel mundial. Por su clara influencia en las enfermedades cardiovasculares y respiratorias, es un factor importante en la consulta de medicina interna. Aunque la tasa de abandono del hábito tabáquico está ascendiendo en los últimos años, existe un porcentaje de pacientes que continúan fumando porque no pueden o no quieren cesar el hábito, a pesar de haber probado las terapias farmacológicas y no farmacológicas existentes. Para este grupo de paciente existen unas estrategias que se basan en intervenciones destinadas a reducir los efectos negativos del tabaco sin la necesidad de extinguir por completo su consumo. En esta revisión se contempla como gracias a la ausencia de combustión de la materia orgánica que se da en el cigarrillo convencional, en snus, cigarrillo electrónico y productos de tabaco calentado se genera un nivel significativamente inferior de sustancias tóxicas.(AU)

Smoking remains the leading cause of morbidity and mortality worldwide. Because of its clear influence on cardiovascular and respiratory diseases, it is an important factor in internal medicine consultations. Although the rate of smoking cessation has been increasing in recent years, there is a percentage of patients who continue to smoke because they are unable or unwilling to quit, despite having tried existing pharmacological and non-pharmacological therapies. For this group of patients there are strategies based on interventions aimed at reducing the negative effects of smoking without the need for complete cessation. In this review it is shown that due to the absence of combustion of organic matter in conventional cigarettes, snus, e-cigarettes and heated tobacco products generate significantly lower levels of toxic substances.(AU)

Treatment patterns and use of healthcare resources of patients with atherosclerotic cardiovascular disease and hypercholesterolemia and patients with familial hypercholesterolemia in Spain: Protocol of the Reality study.

Background: Atherosclerotic cardiovascular diseases (ASCVD) and dyslipidemia are associated to a higher risk of cardiovascular events, mortality, use of healthcare resources and costs. In Spain, the evidence about the administration of lipid-lowering treatments in clinical practice, and their clinical effectiveness in patients with ASCVD and hypercholesterolemia and patients with FH is scarce. Therefore, a multidisciplinary working group of cardiologists, family physicians, internal medicine specialists and neurologists was gathered for the Reality study. The aim of this study is to describe the demographic and clinical characteristics, comorbidities, and concomitant medication of patients with ASCVD and hypercholesterolemia and of patients with familial hypercholesterolemia (FH). The use of healthcare resources and costs associated to the management of these diseases after their diagnosis were also considered. Methods: This is an observational and retrospective study, based on the BIG-PAC® database, which includes the electronic medical registries (EMRs) of 1.8 million people from 7 Autonomous Communities in Spain (including public primary care centers and hospitals). The study includes patients who had a new or recurrent episode of ASCVD during the recruitment period (from 01/01/2017 to 31/12/2018). The index date will be defined as the date of the ASCVD event, and the follow-up period will be 24 months. According to their first diagnosis in the database, patients will be classified as ASCVD (5 groups: stable/unstable angina, acute myocardial infarction, ischemic stroke, transient ischemic attack, and peripheral arterial disease) or FH. Discussion: This study aims to analyze the treatment patterns and use of healthcare resources of ASCVD and FH in Spain. The prevalence of these disorders will also be estimated. Due to the high morbidity and mortality associated with these diseases, it is expected that our study will provide useful information for healthcare systems and decision makers to improve the management of these disabling diseases.

Update on new forms of tobacco use. / Actualización sobre las nuevas formas de consumo de tabaco.

Smoking remains the leading cause of morbidity and mortality worldwide. Because of its clear influence on cardiovascular and respiratory diseases, it is an important factor in internal medicine consultations. Although the rate of smoking cessation has been increasing in recent years, there is a percentage of patients who continue to smoke because they are unable or unwilling to quit, despite having tried existing pharmacological and non-pharmacological therapies. For this group of patients there are strategies based on interventions aimed at reducing the negative effects of smoking without the need for complete cessation. In this review it is shown that due to the absence of combustion of organic matter in conventional cigarettes, snus, e-cigarettes and heated tobacco products generate significantly lower levels of toxic substances.

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

International public awareness of peripheral artery disease.

Background: Peripheral artery disease (PAD) of the lower limbs is a common condition with considerable global burden. Some country-specific studies suggest low levels of public awareness. To our knowledge public awareness of PAD has never been assessed simultaneously in several countries worldwide. Patients and methods: This was an international, general public, internet-based quantitative survey assessing vascular health and disease understanding. Questionnaires included 23 closed-ended multiple-choice, Likert scale and binary choice questions. Data were collected from 9,098 survey respondents from nine countries in Europe, North and Latin America during May-June 2018. Results: Overall, familiarity with PAD was low (57% of respondents were "not at all familiar", and 9% were "moderately" or "very familiar"). Knowledge about PAD health consequences was limited, with 55% of all respondents not being aware of limb consequences of PAD. There were disparities in PAD familiarity levels between countries; highest levels of self-reported awareness were in Germany and Poland where 13% reported to be "very" or "moderately" familiar with PAD, and lowest in Scandinavian countries (5%, 3% and 2% of respondents in Norway, Sweden and Denmark, respectively). There were disparities in awareness according to age. Respondents aged 25-34 were most familiar with PAD, with 12% stating that they were "moderately" or "very" familiar with the condition, whereas those aged 18-24 were the least familiar with PAD (7% "moderately" or "very" familiar with PAD). In the 45-54, 55-64 and 65+ age groups, 9% said they were "moderately" or "very" familiar with the term. There was no important gender-based difference in PAD familiarity. Conclusions: On an international level, public self-reported PAD awareness is low, even though PAD is a common condition with considerable burden. Campaigns to increase PAD awareness are needed to reduce delays in diagnosis and to motivate people to control PAD risk factors.

Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia.

BACKGROUND: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250 mg of prednisone daily and use of equivalent doses greater than or equal to 250 mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250 mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250 mg prednisone daily) versus patients with glucocorticoids doses <250 mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250 mg have a more favorable evolution (less mortality and less admission to ICU).

INTRODUCCIÓN: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides. MÉTODOS: Estudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250 mg de prednisona y dosis diarias equivalentes mayores o iguales a 250 mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante. RESULTADOS: De los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30­1,66]), tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11­1,08]) y tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus pacientes con dosis de glucocorticoides < 250 mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10­0,88]). CONCLUSIÓN: Los resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250 mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI).

Clinical Characteristics, Frailty, and Mortality of Residents With COVID-19 in Nursing Homes of a Region of Madrid.

OBJECTIVES: To describe the clinical characteristics, 30-day mortality, and associated factors of patients living in nursing homes (NH) with COVID-19, from March 20 to June 1, 2020. DESIGN: This is a retrospective study. A geriatric hospital-based team acted as a consultant and coordinated the care of older people living in NHs from the hospital. SETTING AND PARTICIPANTS: A total of 630 patients aged 70 and older with Coronavirus Disease 2019 COVID-19 living in 55 NHs. METHODS: A logistic regression was performed to analyze the factors associated with mortality. In addition, Kaplan-Meier curves were applied according to mortality and its associated factors using the log-rank Mantel-Cox test. RESULTS: The diagnosis of COVID-19 was mainly made by clinical compatibility (N = 430). Median age was 87 years, 64.6% were women and 45.9% were transferred to be cared for at the hospital. A total of 282 patients died (44.7%) within the 30 days of first attention by the team. A severe form of COVID-19 occurred in 473 patients, and the most frequent symptoms were dyspnea (n = 332) and altered level of consciousness (n = 301). According to multiple logistic regression, male sex (P = .019), the Clinical Frailty Score (CFS) ≥6 (P = .004), dementia (P = .012), dyspnea (P < .001), and having a severe form of COVID-19 (P = .001), were associated with mortality, whereas age and care setting were not. CONCLUSIONS AND IMPLICATIONS: Mortality of the residents living in NHs with COVID-19 was almost 45%. The altered level of consciousness as an atypical presentation of COVID-19 should be considered in this population. A severe form of the disease, present in more than three-quarters of patients, was associated with mortality, apart from the male sex, CFS ≥6, dementia, and dyspnea, whereas age and care setting were not. These findings may also help to recognize patients in which the Advance Care Planning process is especially urgent to assist in the decisions about their care.

Effect of intravenous iron on functional outcomes in hip fracture: a randomised controlled trial.

OBJECTIVES: to determine the safety and effect of intravenous iron sucrose on functional outcomes, delirium, nosocomial infections and transfusion requirements in older patients with hip fracture. DESIGN: single-centre randomised, double-blind, placebo-controlled clinical trial. SETTING AND PARTICIPANTS: orthogeriatric share care service at an academic tertiary care hospital. A total of 253 patients were recruited: 126 patients were assigned to intravenous iron and 127 to placebo. METHODS: on days 1, 3 and 5 after admission, the iron group received 200 mg Venofer® (iron sucrose) in 100 ml saline and the placebo group 100 ml saline. The primary outcome was absolute functional gain, considered as Barthel index (BI) at discharge minus BI on admission. Secondary outcomes included incidence of postoperative delirium according to the confusion assessment method, proportion of patients recovering prior functional status at 3 months, postoperative transfusion requirements, haemoglobin at 3 months, incidence of nosocomial infections and safety. RESULTS: the median participant age was 87 (interquartile range, 82.5-91.5) years. Most patients were female (72.7%), and the median previous BI was 81(59-95). No significant effect of intravenous iron was observed for the primary outcome: the median AFG score was 17.1 points (4.8-23.3) in the intravenous iron group and 16 points (6-26) in the placebo group (P = 0.369). No significant treatment effects were observed for other functional outcomes or secondary end points. CONCLUSION: while we found no impact of intravenous iron sucrose on functional recovery, incidence of postoperative delirium, transfusion requirements, haemoglobin at 3 months, mortality and nosocomial infections rates in older patients with hip fracture, we did find that the intervention was safe.

[Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia]. / Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2.

INTRODUCTION: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU).

Atención al ictus agudo durante la pandemia por COVID-19. Recomendaciones Plan Ictus Madrid / Acute stroke care during the COVID-19 pandemic. Ictus Madrid Program

INTRODUCCIÓN: La pandemia por COVID-19 ha obligado a una reorganización de los sistemas sanitarios y una saturación excepcional de sus recursos. En este contexto es vital asegurar la atención al ictus agudo y optimizar los procesos asistenciales del código ictus para reducir el riesgo de contagios y racionalizar el uso de recursos hospitalarios. Para ello desde el Grupo multidisciplinar Ictus Madrid proponemos una serie de recomendaciones. MÉTODOS: Revisión bibliográfica no sistemática de las publicaciones disponibles con los términos "stroke" y "covid-19" o "coronavirus" o "SARS-COV-2", así como otras conocidas por los autores. En base a ésta se redacta un documento de recomendaciones que es sometido a consenso por el Grupo multidisciplinar Ictus Madrid y su Comité de Neurología. RESULTADOS: Las recomendaciones se estructuran en cinco líneas fundamentales: (1) Coordinar la actuación para garantizar el acceso la asistencia hospitalaria de los pacientes con ictus, (2) Reconocer a los pacientes con ictus potencialmente infectados por COVID-19, (3) Organización adecuada para garantizar la protección de los profesionales sanitarios frente al riesgo de contagio por COVID-19, (4) la realización de Neuroimagen y otros procedimientos que conlleven contactos de riesgo de infección COVID-19 hay que procurar reducirlos y asegurar la protección, y (5) alta y seguimiento seguros procurando optimizar la ocupación hospitalaria. Resumimos el procedimiento de forma esquemática con el acrónimo CORONA (COordinar, Reconocer, Organizar, Neuroimagen, Alta). CONCLUSIONES: Estas recomendaciones pueden servir de apoyo para la organización del sistema sanitario en la atención al ictus agudo y la optimización de sus recursos, garantizando la protección de sus profesionales

BACKGROUND: The COVID-19 pandemic has forced a reorganization of healthcare systems and an exceptional saturation of their resources. In this context, it is vital to ensure acute stroke care and optimize the care processes of the stroke code to reduce the risk of contagion and rationalize the use of hospital resources. To do this, the Ictus Madrid multidisciplinary group proposes a series of recommendations. METHODS: Non-systematic bibliographic review of the available publications with the terms "stroke" and "covid-19" or "coronavirus" or "SARS-COV-2", as well as other already known for the authors. We provide a document of recommendations as a result of the consensus of the Ictus Madrid multidisciplinary group and its Neurology Committee. RESULTS: Our recommendations are structured on five lines: (1) Coordinate to guarantee the access to hospital care for stroke patients, (2) Recognize potentially COVID-19 infected stroke patients, (3) Organize to ensure the protection of healthcare professionals from COVID-19 infections, (4) Neuroimaging and other procedures potentially associated to risks for COVID-19 infection should be reduced and secured to avoid contagion, and (5) At home as soon as posible and supported follow-up to optimize hospital occupancy. The procedure is shown summarized under the acronym CORONA (Coordinate, Recognize, Organize, Neuroimaging, At home). CONCLUSIONS: These recommendations can support the organization of healthcare services for acute stroke care and the optimization of their resources, guaranteeing the protection of healthcare professionals

Visfatin/eNampt induces endothelial dysfunction in vivo: a role for Toll-Like Receptor 4 and NLRP3 inflammasome.

Visfatin/extracellular-nicotinamide-phosphoribosyltranferase-(eNampt) is a multifaceted adipokine enhanced in type-2-diabetes and obesity. Visfatin/eNampt cause in vitro endothelial dysfunction and vascular inflammation, although whether the same effects are achieved in vivo is unknown. Toll-like receptor-4 (TLR4), a main surface pattern recognition receptor of innate immune system is a potential target for visfatin/eNampt. We studied its capacity to generate vascular dysfunction in vivo, focusing on TLR4 role and downstream activation of nod-like-receptor-protein-3 (NLRP3)-inflammasome. 4 month-old C57BL/6 mice were exposed to 7 days infusion of visfatin/eNampt, alone or together with FK 866 (Nampt enzymatic inhibitor), CLI 095 (TLR4 blocker), MCC 950 (NLRP3-inflammasome inhibitor), or anakinra (interleukin(IL)-1-receptor antagonist). Endothelial dysfunction was tested in isolated microvessels. In human umbilical endothelial cells (HUVEC), proteins related to the NLRP3-inflammasome phosphorylated p-65, NLRP3, caspase-1, pro-IL-1ß, and mature IL-1ß were determined by Western blot, while the inflammasome related apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC-specks) was studied by immunofluorescence. Impaired endothelium-dependent relaxations were observed in isolated mesenteric microvessels from visfatin/eNampt-infused mice. This effect was attenuated by co-treatment with FK 866 or CLI 095, supporting a role for Nampt enzymatic activity and TLR4 activation. Moreover, cultured HUVEC exposed to visfatin/eNampt showed higher expression and activation of NLRP3-inflammasome. Again, this effect relied on Nampt enzymatic activity and TLR4 activation, and it was abrogated by the inflammasome assembly blockade with MCC 950. The endothelial dysfunction evoked by visfatin/eNampt infusion in vivo was also sensitive to both MCC 950 and anakinra treatments, suggesting that the NLRP3-inflammasome-driven tissular release of IL-1ß is the final mediator of endothelial damage. We conclude that Visfatin/eNampt produces in vivo vascular dysfunction in mice by a Nampt-dependent TLR4-mediated pathway, involving NLRP3-inflammasome and paracrine IL-1ß. Thus, those targets may become therapeutic strategies for attenuating the adipokine-mediated vascular dysfunction associated to obesity and/or type-2-diabetes.